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Sample records for response die modulation

  1. Can Arousal Modulate Response Inhibition?

    ERIC Educational Resources Information Center

    Weinbach, Noam; Kalanthroff, Eyal; Avnit, Amir; Henik, Avishai

    2015-01-01

    The goal of the present study was to examine if and how arousal can modulate response inhibition. Two competing hypotheses can be drawn from previous literature. One holds that alerting cues that elevate arousal should result in an impulsive response and therefore impair response inhibition. The other suggests that alerting enhances processing of…

  2. Modulating macrophage response to biomaterials

    NASA Astrophysics Data System (ADS)

    Zaveri, Toral

    Macrophages recruited to the site of biomaterial implantation are the primary mediators of the chronic foreign body response to implanted materials. Since foreign body response limits performance and functional life of numerous implanted biomaterials/medical devices, various approaches have been investigated to modulate macrophage interactions with biomaterial surfaces to mitigate this response. In this work we have explored two independent approaches to modulate the macrophage inflammatory response to biomaterials. The first approach targets surface integrins, cell surface receptors that mediate cell adhesion to biomaterials through adhesive proteins spontaneously adsorbed on biomaterial surfaces. The second approach involves surface modification of biomaterials using nanotopographic features since nanotopography has been reported to modulate cell adhesion and viability in a cell type-dependent manner. More specifically, Zinc Oxide (ZnO) nanorod surface was investigated for its role in modulating macrophage adhesion and survival in vitro and foreign body response in vivo. For the first approach, we have investigated the role of integrin Mac-1 and RGD-binding integrins in the in-vivo osteolysis response and macrophage inflammatory processes of phagocytosis as well as inflammatory cytokine secretion in response to particulate biomaterials. We have also investigated the in vivo foreign body response (FBR) to subcutaneously implanted biomaterials by evaluating the thickness of fibrous capsule formed around the implants after 2 weeks of implantation. The role of Mac-1 integrin was isolated using a Mac-1 KO mouse and comparing it to a WT control. The role of RGD binding integrins in FBR was investigated by coating the implanted biomaterial with ELVAX(TM) polymer loaded with Echistatin which contains the RGD sequence. For the in-vivo osteolysis study and to study the in-vitro macrophage response to particulate biomaterials, we used the RGD peptide encapsulated in ELVAX

  3. Modeling and Analysis of The Pressure Die Casting Using Response Surface Methodology

    NASA Astrophysics Data System (ADS)

    Kittur, Jayant K.; Herwadkar, T. V.; Parappagoudar, M. B.

    2010-10-01

    Pressure die casting is successfully used in the manufacture of Aluminum alloys components for automobile and many other industries. Die casting is a process involving many process parameters having complex relationship with the quality of the cast product. Though various process parameters have influence on the quality of die cast component, major influence is seen by the die casting machine parameters and their proper settings. In the present work, non-linear regression models have been developed for making predictions and analyzing the effect of die casting machine parameters on the performance characteristics of die casting process. Design of Experiments (DOE) with Response Surface Methodology (RSM) has been used to analyze the effect of effect of input parameters and their interaction on the response and further used to develop nonlinear input-output relationships. Die casting machine parameters, namely, fast shot velocity, slow shot to fast shot change over point, intensification pressure and holding time have been considered as the input variables. The quality characteristics of the cast product were determined by porosity, hardness and surface rough roughness (output/responses). Design of experiments has been used to plan the experiments and analyze the impact of variables on the quality of casting. On the other-hand Response Surface Methodology (Central Composite Design) is utilized to develop non-linear input-output relationships (regression models). The developed regression models have been tested for their statistical adequacy through ANOVA test. The practical usefulness of these models has been tested with some test cases. These models can be used to make the predictions about different quality characteristics, for the known set of die casting machine parameters, without conducting the experiments.

  4. Modeling and Analysis of The Pressure Die Casting Using Response Surface Methodology

    SciTech Connect

    Kittur, Jayant K.; Herwadkar, T. V.; Parappagoudar, M. B.

    2010-10-26

    Pressure die casting is successfully used in the manufacture of Aluminum alloys components for automobile and many other industries. Die casting is a process involving many process parameters having complex relationship with the quality of the cast product. Though various process parameters have influence on the quality of die cast component, major influence is seen by the die casting machine parameters and their proper settings. In the present work, non-linear regression models have been developed for making predictions and analyzing the effect of die casting machine parameters on the performance characteristics of die casting process. Design of Experiments (DOE) with Response Surface Methodology (RSM) has been used to analyze the effect of effect of input parameters and their interaction on the response and further used to develop nonlinear input-output relationships. Die casting machine parameters, namely, fast shot velocity, slow shot to fast shot change over point, intensification pressure and holding time have been considered as the input variables. The quality characteristics of the cast product were determined by porosity, hardness and surface rough roughness (output/responses). Design of experiments has been used to plan the experiments and analyze the impact of variables on the quality of casting. On the other-hand Response Surface Methodology (Central Composite Design) is utilized to develop non-linear input-output relationships (regression models). The developed regression models have been tested for their statistical adequacy through ANOVA test. The practical usefulness of these models has been tested with some test cases. These models can be used to make the predictions about different quality characteristics, for the known set of die casting machine parameters, without conducting the experiments.

  5. Regional vegetation die-off in response to global-change-type drought

    USGS Publications Warehouse

    Breshears, D.D.; Cobb, N.S.; Rich, P.M.; Price, K.P.; Allen, C.D.; Balice, R.G.; Romme, W.H.; Kastens, J.H.; Floyd, M. Lisa; Belnap, J.; Anderson, J.J.; Myers, O.B.; Meyer, Clifton W.

    2005-01-01

    Future drought is projected to occur under warmer temperature conditions as climate change progresses, referred to here as global-change-type drought, yet quantitative assessments of the triggers and potential extent of drought-induced vegetation die-off remain pivotal uncertainties in assessing climate-change impacts. Of particular concern is regional-scale mortality of overstory trees, which rapidly alters ecosystem type, associated ecosystem properties, and land surface conditions for decades. Here, we quantify regional-scale vegetation die-off across southwestern North American woodlands in 2002-2003 in response to drought and associated bark beetle infestations. At an intensively studied site within the region, we quantified that after 15 months of depleted soil water content, >90% of the dominant, overstory tree species (Pinus edulis, a pin??on) died. The die-off was reflected in changes in a remotely sensed index of vegetation greenness (Normalized Difference Vegetation Index), not only at the intensively studied site but also across the region, extending over 12,000 km2 or more; aerial and field surveys confirmed the general extent of the die-off. Notably, the recent drought was warmer than the previous subcontinental drought of the 1950s. The limited, available observations suggest that die-off from the recent drought was more extensive than that from the previous drought, extending into wetter sites within the tree species' distribution. Our results quantify a trigger leading to rapid, drought-induced die-off of overstory woody plants at subcontinental scale and highlight the potential for such die-off to be more severe and extensive for future global-change-type drought under warmer conditions. ?? 2005 by The National Academy of Sciences of the USA.

  6. On the spectral response of PV modules

    NASA Astrophysics Data System (ADS)

    Ye, J. Y.; Guo, S.; Walsh, T. M.; Hishikawa, Y.; Stangl, R. A.

    2014-09-01

    The spectral response of silicon wafer based and thin-film photovoltaic (PV) modules is studied using simulation and experimental methods. Circuit simulations show that the module spectral response (SR) depends on (1) the SR of the cells, (2) the shunt resistance Rshunt of the cells, and (3) the bypass diodes of the module. For realistic Rshunt values, the module SR is significantly higher than the minimal SR of the individual cells (which would be the module SR in the case of infinite Rshunt). Round-robin tests using different experimental methods (partial illumination and full-area illumination) to determine the SR of a wafer-based module and a thin-film silicon module were conducted. Both SR methods are found to agree reasonably well. However, circuit simulations indicate that if only one cell, or a few cells, within the module have significantly different characteristics but not known, the results may differ considerably. The partial illumination method can access the SR of the individual cells within a module, but it possibly requires a long measurement time in order to measure the SR and Rshunt of each cell for confirming the SR of the whole module. In contrast, full-area illumination methods measure the module SR directly, but they cannot access the cell SRs if problematic cells exist. An uncertainty analysis of the full-area illumination method is conducted, which reveals that—if the calibrated reference cell is chosen properly—the calibration uncertainty of the reference cell itself is the main source of uncertainty.

  7. Extrathalamic Modulation of Cortical Responsiveness

    DTIC Science & Technology

    1994-08-01

    H.; Gratton , G. 31. McCarthy, G.; Wood, C. C.; Williamson, P. D.; Spencer, D. D. Task- Cognitive psychophysiology and human information processing...monkey: The role of task relevance, stim- 19. Gabriel , M.; Sparenborg, S. P.; Donchin, E. Macropotentials re- ulus probability, and behavioral response

  8. Attentional Modulation of Eye Torsion Responses

    NASA Technical Reports Server (NTRS)

    Stevenson, Scott B.; Mahadevan, Madhumitha S.; Mulligan, Jeffrey B.

    2016-01-01

    Eye movements generally have both reflexive and voluntary aspects, but torsional eye movements are usually thought of as a reflexive response to image rotation around the line of sight (torsional OKN) or to head roll (torsional VOR). In this study we asked whether torsional responses could be modulated by attention in a case where two stimuli rotated independently, and whether attention would influence the latency of responses. The display consisted of rear-projected radial "pinwheel" gratings, with an inner annulus segment extending from the center to 22 degrees eccentricity, and an outer annulus segment extending from 22 degrees out to 45 degrees eccentricity. The two segments rotated around the center in independent random walks, stepping randomly 4 degrees clockwise or counterclockwise at 60 Hz. Subjects were asked to attend to one or the other while keeping fixation steady at the center of the display. To encourage attention on one or the other segment of the display, subjects were asked to move a joystick in synchrony with the back and forth rotations of one part of the image while ignoring the other. Eye torsion was recorded with the scleral search coil technique, sampled at 500 Hz. All four subjects showed roughly 50% stronger torsion responses to the attended compared to unattended segments. Latency varied from 100 to 150 msec across subjects and was unchanged by attention. These findings suggest that attention can influence eye movement responses that are not typically under voluntary control.

  9. [Modulation of immune response by bacterial lipopolysaccharides].

    PubMed

    Aldapa-Vega, Gustavo; Pastelín-Palacios, Rodolfo; Isibasi, Armando; Moreno-Eutimio, Mario A; López-Macías, Constantino

    2016-01-01

    Lipopolysaccharide (LPS) is a molecule that is profusely found on the outer membrane of Gram-negative bacteria and is also a potent stimulator of the immune response. As the main molecule on the bacterial surface, is also the most biologically active. The immune response of the host is activated by the recognition of LPS through Toll-like receptor 4 (TLR4) and this receptor-ligand interaction is closely linked to LPS structure. Microorganisms have evolved systems to control the expression and structure of LPS, producing structural variants that are used for modulating the host immune responses during infection. Examples of this include Helicobacter pylori, Francisella tularensis, Chlamydia trachomatis and Salmonella spp. High concentrations of LPS can cause fever, increased heart rate and lead to septic shock and death. However, at relatively low concentrations some LPS are highly active immunomodulators, which can induce non-specific resistance to invading microorganisms. The elucidation of the molecular and cellular mechanisms involved in the recognition of LPS and its structural variants has been fundamental to understand inflammation and is currently a pivotal field of research to understand the innate immune response, inflammation, the complex host-pathogen relationship and has important implications for the rational development of new immunomodulators and adjuvants.

  10. Nutritional modulation of the inflammatory bowel response.

    PubMed

    Ioannidis, Orestis; Varnalidis, Ioannis; Paraskevas, George; Botsios, Dimitrios

    2011-01-01

    Crohn's disease and ulcerative colitis represent distinct phenotypic forms of inflammatory bowel disease and continue to be a common cause of morbidity. The corticosteroids and the immunomodulatory drugs, which are the basis of treatment for the inflammatory bowel diseases, do not assure always satisfactory outcomes. Nutrition has been used in order to modify the inflammatory response of various chronic inflammatory diseases, including Crohn's disease and ulcerative colitis. In the pathogenesis of inflammatory bowel diseases, the intestinal microflora and the intestinal mucosal disorders play a crucial role. Also, the release of reactive oxygen species is a significant factor of initiation and preservation of the inflammatory reaction in these diseases. The advantages of the nutritional treatment derive from the sequestration of intraluminal agents which may promote the inflammatory bowel response or, alternatively, nutrition is able to modify the immune response, reducing the uncontrolled inflammatory reaction. Furthermore, nutrition can enhance the mucosal barrier function and consists a significant source of antioxidants. This review focuses on certain nutritional components that modulate the inflammatory response of the bowel and aims to present a rational thesis regarding the use of nutritional agents in the management of inflammatory bowel diseases.

  11. Corticofugal modulation of peripheral auditory responses

    PubMed Central

    Terreros, Gonzalo; Delano, Paul H.

    2015-01-01

    The auditory efferent system originates in the auditory cortex and projects to the medial geniculate body (MGB), inferior colliculus (IC), cochlear nucleus (CN) and superior olivary complex (SOC) reaching the cochlea through olivocochlear (OC) fibers. This unique neuronal network is organized in several afferent-efferent feedback loops including: the (i) colliculo-thalamic-cortico-collicular; (ii) cortico-(collicular)-OC; and (iii) cortico-(collicular)-CN pathways. Recent experiments demonstrate that blocking ongoing auditory-cortex activity with pharmacological and physical methods modulates the amplitude of cochlear potentials. In addition, auditory-cortex microstimulation independently modulates cochlear sensitivity and the strength of the OC reflex. In this mini-review, anatomical and physiological evidence supporting the presence of a functional efferent network from the auditory cortex to the cochlear receptor is presented. Special emphasis is given to the corticofugal effects on initial auditory processing, that is, on CN, auditory nerve and cochlear responses. A working model of three parallel pathways from the auditory cortex to the cochlea and auditory nerve is proposed. PMID:26483647

  12. Baseline blood oxygenation modulates response amplitude

    PubMed Central

    Lu, Hanzhang; Zhao, Chenguang; Ge, Yulin; Lewis-Amezcua, Kelly

    2008-01-01

    Although BOLD fMRI provides a useful tool for probing neuronal activities, large inter-subject variations in signal amplitude are commonly observed. Understanding the physiologic basis for these variations will have a significant impact on many fMRI studies. First, the physiologic modulator can be used as a regressor to reduce variations across subjects, thereby improving statistical power for detecting group differences. Second, if a pathologic condition or a drug treatment is shown to change fMRI responses, monitoring this modulatory parameter is useful in correctly interpreting the fMRI changes to neuronal deficits/recruitments. Here we present evidence that the task-evoked fMRI signals are modulated by baseline blood oxygenation. To measure global blood oxygenation, we used a recently developed technique, T2-Relaxation-Under-Spin-Tagging MRI, yielding baseline oxygenation of 63.7±7.2% in sagittal sinus with an estimation error of 1.3%. It was found that individuals with higher baseline oxygenation tend to have a smaller fMRI signal and vice versa. For every 10% difference in baseline oxygenation across subjects, the BOLD and cerebral blood flow signal differ by -0.4% and -30.0%, respectively, when using visual stimulation. TRUST MRI is a useful measurement for fMRI studies to control for the modulatory effects of baseline oxygenation that are unique to each subject. PMID:18666103

  13. Generals die in friendly fire, or modeling immune response to HIV

    NASA Astrophysics Data System (ADS)

    Rouzine, Igor M.; Murali-Krishna, Kaja; Ahmed, Rafi

    2005-12-01

    We develop a kinetic model for CD8 T lymphocytes (CTL) whose purpose is to kill cells infected with viruses and intracellular parasites. Using a set of first-order nonlinear differential equations, the model predicts how numbers of different cell types involved in CTL response depend on time. The model postulates that CTL response requires continuous presence of professional antigen-presenting cells (APC) comprised of macrophages and dendritic cells. It assumes that any virus present in excess of a threshold level activates APC that, in turn, activate CTL that expand in number and become armed "effector" cells. In the end, APC are deactivated after virus is cleared. The lack of signal from APC causes effector cells to differentiate, by default, into "transitory cells" that either die, or, in a small part, become long-lived memory cells. Viruses capable of infecting APC will cause premature retirement of effector CTL. If transitory cells encounter virus, which takes place after the premature depletion, CTL become anergic (unresponsive to external stimuli). The model is designed to fit recent experiments on primary CTL response to simian immunodeficiency virus closely related to HIV and lymphocytic choriomeningitis virus. The two viruses are known to infect APC and make them targets for CTL they are supposed to control. Both viruses cause premature depletion and anergy of CTL and persist in the host for life.

  14. Peroxiredoxin 5 modulates immune response in Drosophila

    PubMed Central

    Radyuk, Svetlana N.; Michalak, Katarzyna; Klichko, Vladimir I.; Benes, Judith; Orr, William C.

    2010-01-01

    Background Peroxiredoxins are redox-sensing enzymes with multiple cellular functions. Previously, we reported on the potent antioxidant function of Drosophila peroxiredoxin 5 (dPrx5). Studies with mammalian and human cells suggest that peroxiredoxins can modulate immune-related signaling. Methods Survivorship studies and bacteriological analysis were used to determine resistance of flies to fungal and bacterial infections. RT-PCR and immunoblot analyses determined expression of dPrx5 and immunity factors in response to bacterial challenge. Double mutants for dprx5 gene and genes comprising the Imd/Relish and dTak1/Basket branches of the immune signaling pathways were used in epistatic analysis. Results The dprx5 mutant flies were more resistant to bacterial infection than controls, while flies overexpressing dPrx5 were more susceptible. The enhanced resistance to bacteria was accompanied by rapid induction of the Imd-dependent antimicrobial peptides, phosphorylation of the JNK kinase Basket and altered transcriptional profiling of the transient response genes, puckered, ets21C and relish, while the opposite effects were observed in flies over-expressing dPrx5. Epistatic analysis of double mutants, using attacin D and Puckered as read outs of activation of the Imd and JNK pathways, implicated dPrx5 function in the control of the dTak1-JNK arm of immune signaling. Conclusions Differential effects on fly survivorship suggested a trade-off between the antioxidant and immune functions of dPrx5. Molecular and epistatic analyses identified dPrx5 as a negative regulator in the dTak1-JNK arm of immune signaling. General significance Our findings suggest that peroxiredoxins play an important modulatory role in the Drosophila immune response. PMID:20600624

  15. Simulation of differential die-away instrument's response to asymmetrically burned spent nuclear fuel

    NASA Astrophysics Data System (ADS)

    Martinik, Tomas; Henzl, Vladimir; Grape, Sophie; Svärd, Staffan Jacobsson; Jansson, Peter; Swinhoe, Martyn T.; Tobin, Stephen J.

    2015-07-01

    Previous simulation studies of Differential Die-Away (DDA) instrument's response to active interrogation of spent nuclear fuel from a pressurized water reactor (PWR) yielded promising results in terms of its capability to accurately measure or estimate basic spent fuel assembly (SFA) characteristics, such as multiplication, initial enrichment (IE) and burn-up (BU) as well as the total plutonium content. These studies were however performed only for a subset of idealized SFAs with a symmetric BU with respect to its longitudinal axis. Therefore, to complement the previous results, additional simulations have been performed of the DDA instrument's response to interrogation of asymmetrically burned spent nuclear fuel in order to determine whether detailed assay of SFAs from all 4 sides will be necessary in real life applications or whether a cost and time saving single sided assay could be used to achieve results of similar quality as previously reported in case of symmetrically burned SFAs. The results of this study suggest that DDA instrument response depends on the position of the individual neutron detectors and in fact can be split in two modes. The first mode, measured by the back detectors, is not significantly sensitive to the spatial distribution of fissile isotopes and neutron absorbers, but rather reflects the total amount of both contributors as in the cases of symmetrically burned SFAs. In contrary, the second mode, measured by the front detectors, yields certain sensitivity to the orientation of the asymmetrically burned SFA inside the assaying instrument. This study thus provides evidence that the DDA instrument can potentially be utilized as necessary in both ways, i.e. a quick determination of the average SFA characteristics in a single assay, as well as a more detailed characterization involving several DDA observables through assay of the SFA from all of its four sides that can possibly map the burn-up distribution and/or identify diversion or

  16. Low-concentration photovoltaic module with reflective compound parabolic concentrator fabricated by roll-to-roll slot-die coating and 3D printing.

    PubMed

    Lee, Hyungman; Lim, Heonkwang; Park, Sungsik; Lee, Dongjin

    2016-12-26

    We fabricate a low-concentration photovoltaic (LCPV) module with a reflective compound parabolic concentrator (CPC) using roll-to-roll (R2R) slot-die coating and 3D printing technologies. A highly reflective silver thin-film is coated on a flexible plastic substrate, and the CPC frame is manufactured via 3D printing. The slot-die-coated silver film with thickness of more than 100 nm stably exhibits 95% reflectivity at 550 nm. Further, CPC concentrators with concentration ratios of 4X and 3X are assembled into silicon solar cells and characterized. Although the fill factor and maximum voltage slightly decrease, power and efficiency increase by factors of 3.51 and 2.63 with respect to the no-CPC-module case. Our approach can be used to optimize the design of various engineering products.

  17. Cellular response to modulated radiation fields

    NASA Astrophysics Data System (ADS)

    Claridge Mackonis, E.; Suchowerska, N.; Zhang, M.; Ebert, M.; McKenzie, D. R.; Jackson, M.

    2007-09-01

    Cell survival following exposure to spatially modulated beams, as created by intensity-modulated radiotherapy (IMRT), is investigated. In vitro experiments were performed using malignant melanoma cells (MM576) exposed to a therapeutic megavoltage photon beam. We compared cell survival in modulated fields with cell survival in uniform control fields. Three different spatial modulations of the field were used: a control 'uniform' field in which all cells in a flask were uniformly exposed; a 'quarter' field in which 25% of cells at one end of the flask were exposed and a 'striped' field in which 25% of cells were exposed in three parallel stripes. The cell survival in both the shielded and unshielded regions of the modulated fields, as determined by a clonogenic assay, were compared to the cell survival in the uniform field. We have distinguished three ways in which cell survival is influenced by the fate of neighbouring cells. The first of these (type I effect) is the previously reported classical Bystander effect, where cell survival is reduced when communicating with irradiated cells. We find two new types of Bystander effect. The type II effect is an observed increase in cell survival when nearby cells receive a lethal dose. The type III effect is an increase in the survival of cells receiving a high dose of radiation, when nearby cells receive a low dose. These observations of the Bystander effects emphasize the need for improved radiobiological models, which include communicated effects and account for the effects of modulated dose distribution.

  18. Differential die-away analysis system response modeling and detector design

    NASA Astrophysics Data System (ADS)

    Jordan, K. A.; Gozani, T.; Vujic, J.

    2008-05-01

    Differential die-away-analysis (DDAA) is a sensitive technique to detect presence of fissile materials such as 235U and 239Pu. DDAA uses a high-energy (14 MeV) pulsed neutron generator to interrogate a shipping container. The signature is a fast neutron signal hundreds of microseconds after the cessation of the neutron pulse. This fast neutron signal has decay time identical to the thermal neutron diffusion decay time of the inspected cargo. The theoretical aspects of a cargo inspection system based on the differential die-away technique are explored. A detailed mathematical model of the system is developed, and experimental results validating this model are presented.

  19. Response of Plasmonic Terahertz Detectors to Modulated Signals

    NASA Astrophysics Data System (ADS)

    Rudin, Sergey; Rupper, Greg; Reed, Meredith; Shur, Michael

    We present theoretical study of the response of two-dimensional gated electron gas to an amplitude modulated signals with carrier frequency in the terahertz range. Our model is based on complete hydrodynamic equations, and includes effects of viscosity, pressure gradients and thermal transport in the conduction channel of a high electron mobility semiconductor transistor. The modulation response was evaluated as a function of modulation frequency for a range of mobility values in different semiconductor materials. Maximum modulation frequency was evaluated as a function of channel mobility, with typical values in the subterahertz range of frequencies. Our analysis shows that short channel field effect transistors operating in the plasmonic regime meets the requirements for applications as terahertz detectors and modulators in high-speed wireless communication circuits.

  20. Response of plasmonic terahertz detectors to amplitude modulated signals

    NASA Astrophysics Data System (ADS)

    Rupper, Greg; Rudin, Sergey; Shur, Michael

    2015-09-01

    We present theoretical study of the response of two-dimensional gated electron gas to an amplitude modulated signals with carrier frequency in the terahertz range. The model is based on complete hydrodynamic equations, and includes effects of viscosity, pressure gradients and thermal transport in the conduction channel of a high electron mobility semiconductor transistor (HEMT). The modulation response was evaluated as a function of modulation frequency fM for a wide range of mobility values. Maximum modulation frequency fMAX was evaluated as a function of channel mobility, with typical values of fMAX in the subterahertz range of frequencies. Our analysis shows that short channel field effect transistors operating in the plasmonic regime can meet all the requirements for applications as terahertz detectors and modulators in ultra high-speed wireless communication circuits.

  1. An NCME Instructional Module on Polytomous Item Response Theory Models

    ERIC Educational Resources Information Center

    Penfield, Randall David

    2014-01-01

    A polytomous item is one for which the responses are scored according to three or more categories. Given the increasing use of polytomous items in assessment practices, item response theory (IRT) models specialized for polytomous items are becoming increasingly common. The purpose of this ITEMS module is to provide an accessible overview of…

  2. The Angry Dying Patient.

    PubMed

    Houston, Robert E.

    1999-02-01

    Over 25 years ago, Kubler-Ross identified anger as a predictable part of the dying process. When the dying patient becomes angry in the clinical setting, all types of communication become strained. Physicians can help the angry dying patient through this difficult time by using 10 rules of engagement. When physicians engage and empathize with these patients, they improve the patient's response to pain and they reduce patient suffering. When physicians educate patients on their normal responses to dying and enlist them in the process of family reconciliation, they can impact the end-of-life experience in a positive way.

  3. Torso flexion modulates stiffness and reflex response.

    PubMed

    Granata, K P; Rogers, E

    2007-08-01

    Neuromuscular factors that contribute to spinal stability include trunk stiffness from passive and active tissues as well as active feedback from reflex response in the paraspinal muscles. Trunk flexion postures are a recognized risk factor for occupational low-back pain and may influence these stabilizing control factors. Sixteen healthy adult subjects participated in an experiment to record trunk stiffness and paraspinal muscle reflex gain during voluntary isometric trunk extension exertions. The protocol was designed to achieve trunk flexion without concomitant influences of external gravitational moment, i.e., decouple the effects of trunk flexion posture from trunk moment. Systems identification analyses identified reflex gain by quantifying the relation between applied force disturbances and time-dependent EMG response in the lumbar paraspinal muscles. Trunk stiffness was characterized from a second order model describing the dynamic relation between the force disturbances versus the kinematic response of the torso. Trunk stiffness increased significantly with flexion angle and exertion level. This was attributed to passive tissue contributions to stiffness. Reflex gain declined significantly with trunk flexion angle but increased with exertion level. These trends were attributed to correlated changes in baseline EMG recruitment in the lumbar paraspinal muscles. Female subjects demonstrated greater reflex gain than males and the decline in reflex gain with flexion angle was greater in females than in males. Results reveal that torso flexion influences neuromuscular factors that control spinal stability and suggest that posture may contribute to the risk of instability injury.

  4. Modulation of stimulus contrast on the human pupil orienting response.

    PubMed

    Wang, Chin-An; Munoz, Douglas P

    2014-09-01

    The sudden appearance of a novel stimulus initiates a series of responses to orient the body for appropriate actions, including not only shifts of gaze and attention, but also transient pupil dilation. Modulation of pupil dynamics by stimulus properties is less understood, although its effects on other components of orienting have been extensively explored. Microstimulation of the superior colliculus evoked transient pupil dilation, and the initial component of pupil dilation evoked by microstimulation was similar to that elicited by the presentation of salient sensory stimuli, suggesting a coordinated role of the superior colliculus on this behavior, although evidence in humans is yet to be established. To examine pupil orienting responses in humans, we presented visual stimuli while participants fixated on a central visual spot. Transient pupil dilation in humans was elicited after presentation of a visual stimulus in the periphery. The evoked pupil responses were modulated systematically by stimulus contrast, with faster and larger pupil responses triggered by higher contrast stimuli. The pupil response onset latencies for high contrast stimuli were similar to those produced by the light reflex and significantly faster than the darkness reflex, suggesting that the initial component of pupil dilation is probably mediated by inhibition of the parasympathetic pathway. The contrast modulation was pronounced under different levels of baseline pupil size. Together, our results demonstrate visual contrast modulation on the orienting pupil response in humans.

  5. FTO modulates fibrogenic responses in obstructive nephropathy.

    PubMed

    Wang, Chao-Yung; Shie, Shian-Sen; Tsai, Ming-Lung; Yang, Chia-Hung; Hung, Kuo-Chun; Wang, Chun-Chieh; Hsieh, I-Chang; Wen, Ming-Shien

    2016-01-04

    Genome-wide association studies have shown that variants in fat mass and obesity-associated (FTO) gene are robustly associated with body mass index and obesity. These FTO variants are also associated with end stage renal disease and all-cause mortality in chronic kidney diseases. However, the exact role of FTO in kidneys is currently unknown. Here we show that FTO expression is increased after ureteral obstruction and renal fibrosis. Deficiency of the FTO gene attenuates the fibrogenic responses induced by ureteral obstruction in the kidney. Renal tubular cells deficient of FTO produce less α-SMA after TGF-β stimulation. FTO is indispensable for the extracellular matrix synthesis after ureteral obstruction in kidneys. Indeed, global gene transcriptions amplitude is reduced in FTO deficient kidneys after ureteral obstruction. These data establish the importance of FTO in renal fibrosis, which may have potential therapeutic implications.

  6. Attention modulates responses in the human lateral geniculate nucleus.

    PubMed

    O'Connor, Daniel H; Fukui, Miki M; Pinsk, Mark A; Kastner, Sabine

    2002-11-01

    Attentional mechanisms are important for selecting relevant information and filtering out irrelevant information from cluttered visual scenes. Selective attention has previously been shown to affect neural activity in both extrastriate and striate visual cortex. Here, evidence from functional brain imaging shows that attentional response modulation is not confined to cortical processing, but can occur as early as the thalamic level. We found that attention modulated neural activity in the human lateral geniculate nucleus (LGN) in several ways: it enhanced neural responses to attended stimuli, attenuated responses to ignored stimuli and increased baseline activity in the absence of visual stimulation. The LGN, traditionally viewed as the gateway to visual cortex, may also serve as a 'gatekeeper' in controlling attentional response gain.

  7. Response function of modulated grid Faraday cup plasma instruments

    NASA Technical Reports Server (NTRS)

    Barnett, A.; Olbert, S.

    1986-01-01

    Modulated grid Faraday cup plasma analyzers are a very useful tool for making in situ measurements of space plasmas. One of their great attributes is that their simplicity permits their angular response function to be calculated theoretically. An expression is derived for this response function by computing the trajectories of the charged particles inside the cup. The Voyager plasma science experiment is used as a specific example. Two approximations to the rigorous response function useful for data analysis are discussed. Multisensor analysis of solar wind data indicates that the formulas represent the true cup response function for all angles of incidence with a maximum error of only a few percent.

  8. Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation.

    PubMed

    Canli, T; Congdon, E; Gutknecht, L; Constable, R T; Lesch, K P

    2005-11-01

    The tryptophan hydroxylase-2 gene (TPH2) codes for the enzyme of serotonin (5-HT) synthesis in the brain and variation of TPH2 has been implicated in disorders of emotion regulation. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that a potentially functional variant of TPH2 modulates amygdala responsiveness to emotional stimuli of both negative and positive valence.

  9. Modulation of taste responsiveness by the satiation hormone peptide YY

    PubMed Central

    La Sala, Michael S.; Hurtado, Maria D.; Brown, Alicia R.; Bohórquez, Diego V.; Liddle, Rodger A.; Herzog, Herbert; Zolotukhin, Sergei; Dotson, Cedrick D.

    2013-01-01

    It has been hypothesized that the peripheral taste system may be modulated in the context of an animal's metabolic state. One purported mechanism for this phenomenon is that circulating gastrointestinal peptides modulate the functioning of the peripheral gustatory system. Recent evidence suggests endocrine signaling in the oral cavity can influence food intake (FI) and satiety. We hypothesized that these hormones may be affecting FI by influencing taste perception. We used immunohistochemistry along with genetic knockout models and the specific reconstitution of peptide YY (PYY) in saliva using gene therapy protocols to identify a role for PYY signaling in taste. We show that PYY is expressed in subsets of taste cells in murine taste buds. We also show, using brief-access testing with PYY knockouts, that PYY signaling modulates responsiveness to bitter-tasting stimuli, as well as to lipid emulsions. We show that salivary PYY augmentation, via viral vector therapy, rescues behavioral responsiveness to a lipid emulsion but not to bitter stimuli and that this response is likely mediated via activation of Y2 receptors localized apically in taste cells. Our findings suggest distinct functions for PYY produced locally in taste cells vs. that circulating systemically.—La Sala, M. S., Hurtado, M. D., Brown, A. R., Bohórquez, D. V., Liddle, R. A., Herzog, H., Zolotukhin, S., Dotson, C. D. Modulation of taste responsiveness by the satiation hormone peptide YY. PMID:24043261

  10. Modulation of Response to Environmental Stimulation in Autistic Children.

    ERIC Educational Resources Information Center

    Kootz, John P.; And Others

    1982-01-01

    Autistic children's blood pressure, heart rate, peripheral blood flow (PBF), and peripheral vascular resistance (PVR) were measured during three types of tasks (reaction time, social interaction, at rest). Disturbances in filtering environmental stimulation and modulating response to novelty may be part of the basic pathology of autism apparent…

  11. Micromechanical die attachment surcharge

    DOEpatents

    Filter, William F.; Hohimer, John P.

    2002-01-01

    An attachment structure is disclosed for attaching a die to a supporting substrate without the use of adhesives or solder. The attachment structure, which can be formed by micromachining, functions purely mechanically in utilizing a plurality of shaped pillars (e.g. round, square or polygonal and solid, hollow or slotted) that are formed on one of the die or supporting substrate and which can be urged into contact with various types of mating structures including other pillars, a deformable layer or a plurality of receptacles that are formed on the other of the die or supporting substrate, thereby forming a friction bond that holds the die to the supporting substrate. The attachment structure can further include an alignment structure for precise positioning of the die and supporting substrate to facilitate mounting the die to the supporting substrate. The attachment structure has applications for mounting semiconductor die containing a microelectromechanical (MEM) device, a microsensor or an integrated circuit (IC), and can be used to form a multichip module. The attachment structure is particularly useful for mounting die containing released MEM devices since these devices are fragile and can otherwise be damaged or degraded by adhesive or solder mounting.

  12. Halophyte die-off in response to anthropogenic impacts on tidal flats

    NASA Astrophysics Data System (ADS)

    Lee, Yoon-Kyung; Park, Wook; Choi, Jong-Kuk; Ryu, Joo-Hyung; Won, Joong-Sun

    2014-12-01

    This study analyzed an abrupt change in halophyte populations, especially the annual plant Suaeda japonica. The boundaries and distributions of S. japonica and Phragmites australis were determined based on the decision tree classifier of TerraSAR-X, SAVI of Landsat ETM+, and density slicing of aerial photography. A large patch of S. japonica in the eastern parts of Donggum-do, South Korea, disappeared in 2007, while populations have been stable in the western parts of the island. To understand the reason behind the sudden die-off, mean sea level was analyzed based on gaged tidal data. Sedimentation rate was measured using Vernier caliper and RTK leveling data. Sedimentation rate between 2006 and 2007 was above the threshold at which S. japonica can germinate. After the loss of an 11-ha S. japonica patch from the eastern part of Donggum-do, sedimentation was accelerated because of a decrease in tidal current caused by a series of land reclamation projects. The increased monthly exposure duration due to continuous sediment accretion altered the type of salt marsh. Our results imply that accumulated effects from a series of coastal construction projects around Ganghwa-do can change not only tide and current hydrodynamics, but also sedimentation and erosion rates, which can cause large halophyte patches to disappear.

  13. An optimizing process of profiled cross-sectional aluminum alloy porthole die extrusion using response surface methodology

    NASA Astrophysics Data System (ADS)

    Zhou, Fujian; Li, Feng; Shi, Liansheng; Jiang, Hongwei

    2016-03-01

    The porthole die extrusion process of profiled cross-section hollow aluminum alloy is influenced by numerous factors, which brings inconvenience to the process design. In this paper, 7075 aluminum alloy is taken as an example, the fitting model of the ultimate load is analyzed by variance and regression analysis using response surface method (RSM). The influences of extrusion speed, friction factor and initial temperature on the change of extruded ultimate load are investigated systematically, and the important influence factors (initial temperature > friction factor > extrusion speed) to the load are determined eventually. By comparison, the error between the ultimate load model obtained after fitting and the calculated value is only 2.4%, further verifying the reliability of this model. The optimal objective is to minimize the ultimate load, then the optimum technological parameters are obtained by optimizing the process, where the initial temperature, the extrusion speed and the friction factor are 430∘C, 2.28mm/s and 0.31, respectively. The results provide a theoretical basis for the scientific design of the porthole die extrusion process of profiled cross-section hollow aluminum alloy.

  14. Reprogramming immune responses via microRNA modulation

    PubMed Central

    Cubillos-Ruiz, Juan R.; Rutkowski, Melanie R; Tchou, Julia; Conejo-Garcia, Jose R.

    2013-01-01

    It is becoming increasingly clear that there are unique sets of miRNAs that have distinct governing roles in several aspects of both innate and adaptive immune responses. In addition, new tools allow selective modulation of the expression of individual miRNAs, both in vitro and in vivo. Here, we summarize recent advances in our understanding of how miRNAs drive the activity of immune cells, and how their modulation in vivo opens new avenues for diagnostic and therapeutic interventions in multiple diseases, from immunodeficiency to cancer. PMID:25285232

  15. Transient pupil response is modulated by contrast-based saliency.

    PubMed

    Wang, Chin-An; Boehnke, Susan E; Itti, Laurent; Munoz, Douglas P

    2014-01-08

    The sudden appearance of a novel stimulus in the environment initiates a series of orienting responses that include coordinated shifts of gaze and attention, and also transient changes in pupil size. Although numerous studies have identified a significant effect of stimulus saliency on shifts of gaze and attention, saliency effects on pupil size are less understood. To examine salience-evoked pupil responses, we presented visual, auditory, or audiovisual stimuli while monkeys fixated a central visual spot. Transient pupil dilation was elicited after visual stimulus presentation regardless of target luminance relative to background, and auditory stimuli also evoked similar pupil responses. Importantly, the evoked pupil response was modulated by contrast-based saliency, with faster and larger pupil responses following the presentation of more salient stimuli. The initial transient component of pupil dilation was qualitatively similar to that evoked by weak microstimulation of the midbrain superior colliculus. The pupil responses elicited by audiovisual stimuli were well predicted by a linear summation of each modality response. Together, the results suggest that the transient pupil response, as one component of orienting, is modulated by contrast-based saliency, and the superior colliculus is likely involved in its coordination.

  16. Modulation of immune response in experimental Chagas disease.

    PubMed

    Basso, Beatriz

    2013-02-20

    Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage's role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response (modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi

  17. SPHERICAL DIE

    DOEpatents

    Livingston, J.P.

    1959-01-27

    A die is presented for pressing powdered materials into a hemispherical shape of uniforin density and wall thickness comprising a fcmale and male die element held in a stationary spaced relation with the space being equivalent to the wall thickness and defining the hemispherical shape, a pressing ring linearly moveable along the male die element, an inlet to fill the space with powdered materials, a guiding system for moving the pressing ring along the male die element so as to press the powdered material and a heating system for heating the male element so that the powdered material is heated while being pressed.

  18. Attentional Modulation of Auditory Steady-State Responses

    PubMed Central

    Mahajan, Yatin; Davis, Chris; Kim, Jeesun

    2014-01-01

    Auditory selective attention enables task-relevant auditory events to be enhanced and irrelevant ones suppressed. In the present study we used a frequency tagging paradigm to investigate the effects of attention on auditory steady state responses (ASSR). The ASSR was elicited by simultaneously presenting two different streams of white noise, amplitude modulated at either 16 and 23.5 Hz or 32.5 and 40 Hz. The two different frequencies were presented to each ear and participants were instructed to selectively attend to one ear or the other (confirmed by behavioral evidence). The results revealed that modulation of ASSR by selective attention depended on the modulation frequencies used and whether the activation was contralateral or ipsilateral. Attention enhanced the ASSR for contralateral activation from either ear for 16 Hz and suppressed the ASSR for ipsilateral activation for 16 Hz and 23.5 Hz. For modulation frequencies of 32.5 or 40 Hz attention did not affect the ASSR. We propose that the pattern of enhancement and inhibition may be due to binaural suppressive effects on ipsilateral stimulation and the dominance of contralateral hemisphere during dichotic listening. In addition to the influence of cortical processing asymmetries, these results may also reflect a bias towards inhibitory ipsilateral and excitatory contralateral activation present at the level of inferior colliculus. That the effect of attention was clearest for the lower modulation frequencies suggests that such effects are likely mediated by cortical brain structures or by those in close proximity to cortex. PMID:25334021

  19. Perceived reputation of others modulates empathic neural responses.

    PubMed

    Zheng, Li; Wang, Qianfeng; Cheng, Xuemei; Li, Lin; Yang, Guang; Sun, Lining; Ling, Xiaoli; Guo, Xiuyan

    2016-01-01

    Empathy enables us to understand and share the emotional and affective states of another person and plays a key role in social behaviors. The current study investigated whether and how empathic neural responses to pain were modulated by the perceived reputation of others. Action histories reflecting individuals' past cooperation or betrayal actions in the repeated prisoner's dilemma game were introduced as an index of reputation. We assessed brain activity with functional magnetic resonance imaging while the participants observed individuals with a good or bad reputation receiving or not receiving pain. The results indicated that the participants exhibited reduced empathic responses in AI and dACC to the individual who had a bad reputation relative to the one who had a good reputation, suggesting that their empathy for pain was modulated by the perceived reputation of others.

  20. ESTRADIOL RAPIDLY MODULATES ODOR RESPONSES IN MOUSE VOMERONASAL SENSORY NEURONS

    PubMed Central

    CHERIAN, S.; LAM, Y. WAI; MCDANIELS, I.; STRUZIAK, M.; DELAY, R. J.

    2014-01-01

    In rodents, many social behaviors are driven by the sense of smell. The vomeronasal organ (VNO), part of the accessory olfactory system mediates many of these chemically driven behaviors. The VNO is heavily vascularized, and is readily accessible to circulating peptide or steroid hormones. Potentially, this allows circulating hormones to alter behavior through modulating the output of the primary sensory neurons in the VNO, the vomeronasal sensory neurons (VSNs). Based on this, we hypothesized that steroid hormones, in particular 17β-estradiol, would modulate activity of VSNs. In this paper, we show that the estrogen receptors, GPR30 and ERα, were present in VSNs and that estradiol may be synthesized locally in the VNO. Our results also showed that 17β-estradiol decreased responses of isolated VSNs to dilute urine, a potent natural stimulus, with respect to current amplitudes and depolarization. Further, 17β-estradiol increased the latency of the first action potential (AP) and the AP amplitude. Additionally, calcium responses to sulfated steroids (present in the low molecular weight fraction of urine) that act as ligands for apical vomeronasal receptors were decreased by 17β-estradiol. In conclusion, we show that estradiol modulates odorant responses mediated by VSNs and hence paves the way for future studies to better understand the mechanisms by which odorant mediated behavior is altered by endocrine status of the animal. PMID:24680884

  1. Goals and task difficulty expectations modulate striatal responses to feedback.

    PubMed

    DePasque Swanson, Samantha; Tricomi, Elizabeth

    2014-06-01

    The striatum plays a critical role in learning from reward, and it has been implicated in learning from performance-related feedback as well. Positive and negative performance-related feedback is known to engage the striatum during learning by eliciting a response similar to the reinforcement signal for extrinsic rewards and punishments. Feedback is an important tool used to teach new skills and promote healthful lifestyle changes, so it is important to understand how motivational contexts can modulate its effectiveness at promoting learning. While it is known that striatal responses scale with subjective factors influencing the desirability of rewards, it is less clear how expectations and goals might modulate the striatal responses to cognitive feedback during learning. We used functional magnetic resonance imaging to investigate the effects of task difficulty expectations and achievement goals on feedback processing during learning. We found that individuals who scored high in normative goals, which reflect a desire to outperform other students academically, showed the strongest effects of our manipulation. High levels of normative goals were associated with greater performance gains and exaggerated striatal sensitivity to positive versus negative feedback during blocks that were expected to be more difficult. Our findings suggest that normative goals may enhance performance when difficulty expectations are high, while at the same time modulating the subjective value of feedback as processed in the striatum.

  2. Simulation of differential die-away instrument’s response to asymmetrically burned spent nuclear fuel

    SciTech Connect

    Martinik, Tomas; Henzl, Vladimir; Grape, Sophie; Svard, Staffan Jacobsson; Jansson, Peter; Swinhoe, Martyn T.; Tobin, Stephen J.

    2015-03-04

    Here, previous simulation studies of Differential Die–Away (DDA) instrument’s response to active interrogation of spent nuclear fuel from a pressurized water reactor (PWR) yielded promising results in terms of its capability to accurately measure or estimate basic spent fuel assembly (SFA) characteristics, such as multiplication, initial enrichment (IE) and burn-up (BU) as well as the total plutonium content. These studies were however performed only for a subset of idealized SFAs with a symmetric BU with respect to its longitudinal axis. Therefore, to complement the previous results, additional simulations have been performed of the DDA instrument’s response to interrogation of asymmetrically burned spent nuclear fuel in order to determine whether detailed assay of SFAs from all 4 sides will be necessary in real life applications or whether a cost and time saving single sided assay could be used to achieve results of similar quality as previously reported in case of symmetrically burned SFAs.

  3. Serotonin differentially modulates responses to tones and frequency-modulated sweeps in the inferior colliculus.

    PubMed

    Hurley, L M; Pollak, G D

    1999-09-15

    Although almost all auditory brainstem nuclei receive serotonergic innervation, little is known about its effects on auditory neurons. We address this question by evaluating the effects of serotonin on sound-evoked activity of neurons in the inferior colliculus (IC) of Mexican free-tailed bats. Two types of auditory stimuli were used: tone bursts at the neuron's best frequency and frequency-modulated (FM) sweeps with a variety of spectral and temporal structures. There were two main findings. First, serotonin changed tone-evoked responses in 66% of the IC neurons sampled. Second, the influence of serotonin often depended on the type of signal presented. Although serotonin depressed tone-evoked responses in most neurons, its effects on responses to FM sweeps were evenly mixed between depression and facilitation. Thus in most cells serotonin had a different effect on tone-evoked responses than it did on FM-evoked responses. In some neurons serotonin depressed responses evoked by tone bursts but left the responses to FM sweeps unchanged, whereas in others serotonin had little or no effect on responses to tone bursts but substantially facilitated responses to FM sweeps. In addition, serotonin could differentially affect responses to various FM sweeps that differed in temporal or spectral structure. Previous studies have revealed that the efficacy of the serotonergic innervation is partially modulated by sensory stimuli and by behavioral states. Thus our results suggest that the population activity evoked by a particular sound is not simply a consequence of the hard wiring that connects the IC to lower and higher regions but rather is highly dynamic because of the functional reconfigurations induced by serotonin and almost certainly other neuromodulators as well.

  4. Modulation of Untruthful Responses with Non-Invasive Brain Stimulation

    PubMed Central

    Fecteau, Shirley; Boggio, Paulo; Fregni, Felipe; Pascual-Leone, Alvaro

    2013-01-01

    Deceptive abilities have long been studied in relation to personality traits. More recently, studies explored the neural substrates associated with deceptive skills suggesting a critical role of the prefrontal cortex. Here we investigated whether non-invasive brain stimulation over the dorsolateral prefrontal cortex (DLPFC) could modulate generation of untruthful responses about subject’s personal life across contexts (i.e., deceiving on guilt-free questions on daily activities; generating previously memorized lies about past experience; and producing spontaneous lies about past experience), as well as across modality responses (verbal and motor responses). Results reveal that real, but not sham, transcranial direct current stimulation (tDCS) over the DLPFC can reduce response latency for untruthful over truthful answers across contexts and modality responses. Also, contexts of lies seem to incur a different hemispheric laterality. These findings add up to previous studies demonstrating that it is possible to modulate some processes involved in generation of untruthful answers by applying non-invasive brain stimulation over the DLPFC and extend these findings by showing a differential hemispheric contribution of DLPFCs according to contexts. PMID:23550273

  5. Modulation of Intestinal Epithelial Defense Responses by Probiotic Bacteria.

    PubMed

    Wan, L Y M; Chen, Z J; Shah, N P; El-Nezami, H

    2016-12-09

    Probiotics are live microorganisms, which when administered in food confer numerous health benefits. In previous studies about beneficial effects of probiotic bacteria to health, particularly in the fields of intestinal mucosa defense responses, specific probiotics, in a strain-dependent manner, show certain degree of potential to reinforce the integrity of intestinal epithelium and/or regulate some immune components. The mechanism of probiotic action is an area of interest. Among all possible routes of modulation by probiotics of intestinal epithelial cell-mediated defense responses, modulations of intestinal barrier function, innate, and adaptive mucosal immune responses, as well as signaling pathways are considered to play important role in the intestinal defense responses against pathogenic bacteria. This review summarizes the beneficial effects of probiotic bacteria to intestinal health together with the mechanisms affected by probiotic bacteria: barrier function, innate, and adaptive defense responses such as secretion of mucins, defensins, trefoil factors, immunoglobulin A (IgA), Toll-like receptors (TLRs), cytokines, gut associated lymphoid tissues, and signaling pathways.

  6. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia

    PubMed Central

    Thakor, Avnesh S; Allison, Beth J; Niu, Youguo; Botting, Kimberley J; Serón-Ferré, Maria; Herrera, Emilio A; Giussani, Dino A

    2015-01-01

    Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability. PMID:25908097

  7. The response function of modulated grid Faraday cup plasma instruments

    NASA Astrophysics Data System (ADS)

    Barnett, A.; Olbert, S.

    Modulated grid Faraday cup plasma analyzers are a very useful tool for making in situ measurements of space plasmas. One of their great attributes is that their simplicity permits their angular response function to be calculated theoretically. An expression is derived for this response function by computing the trajectories of the charged particles inside the cup. The Voyager Plasma Science (PLS) experiment is used as a specific example. Two approximations to the rigorous response function useful for data analysis are discussed. The theoretical formulas were tested by multi-sensor analysis of solar wind data. The tests indicate that the formulas represent the true cup response function for all angles of incidence with a maximum error of only a few percent.

  8. The response function of modulated grid Faraday cup plasma instruments

    NASA Technical Reports Server (NTRS)

    Barnett, A.; Olbert, S.

    1986-01-01

    Modulated grid Faraday cup plasma analyzers are a very useful tool for making in situ measurements of space plasmas. One of their great attributes is that their simplicity permits their angular response function to be calculated theoretically. An expression is derived for this response function by computing the trajectories of the charged particles inside the cup. The Voyager Plasma Science (PLS) experiment is used as a specific example. Two approximations to the rigorous response function useful for data analysis are discussed. The theoretical formulas were tested by multi-sensor analysis of solar wind data. The tests indicate that the formulas represent the true cup response function for all angles of incidence with a maximum error of only a few percent.

  9. Visual-induced expectations modulate auditory cortical responses

    PubMed Central

    van Wassenhove, Virginie; Grzeczkowski, Lukasz

    2015-01-01

    Active sensing has important consequences on multisensory processing (Schroeder et al., 2010). Here, we asked whether in the absence of saccades, the position of the eyes and the timing of transient color changes of visual stimuli could selectively affect the excitability of auditory cortex by predicting the “where” and the “when” of a sound, respectively. Human participants were recorded with magnetoencephalography (MEG) while maintaining the position of their eyes on the left, right, or center of the screen. Participants counted color changes of the fixation cross while neglecting sounds which could be presented to the left, right, or both ears. First, clear alpha power increases were observed in auditory cortices, consistent with participants' attention directed to visual inputs. Second, color changes elicited robust modulations of auditory cortex responses (“when” prediction) seen as ramping activity, early alpha phase-locked responses, and enhanced high-gamma band responses in the contralateral side of sound presentation. Third, no modulations of auditory evoked or oscillatory activity were found to be specific to eye position. Altogether, our results suggest that visual transience can automatically elicit a prediction of “when” a sound will occur by changing the excitability of auditory cortices irrespective of the attended modality, eye position or spatial congruency of auditory and visual events. To the contrary, auditory cortical responses were not significantly affected by eye position suggesting that “where” predictions may require active sensing or saccadic reset to modulate auditory cortex responses, notably in the absence of spatial orientation to sounds. PMID:25705174

  10. Simulation of differential die-away instrument’s response to asymmetrically burned spent nuclear fuel

    DOE PAGES

    Martinik, Tomas; Henzl, Vladimir; Grape, Sophie; ...

    2015-03-04

    Here, previous simulation studies of Differential Die–Away (DDA) instrument’s response to active interrogation of spent nuclear fuel from a pressurized water reactor (PWR) yielded promising results in terms of its capability to accurately measure or estimate basic spent fuel assembly (SFA) characteristics, such as multiplication, initial enrichment (IE) and burn-up (BU) as well as the total plutonium content. These studies were however performed only for a subset of idealized SFAs with a symmetric BU with respect to its longitudinal axis. Therefore, to complement the previous results, additional simulations have been performed of the DDA instrument’s response to interrogation of asymmetricallymore » burned spent nuclear fuel in order to determine whether detailed assay of SFAs from all 4 sides will be necessary in real life applications or whether a cost and time saving single sided assay could be used to achieve results of similar quality as previously reported in case of symmetrically burned SFAs.« less

  11. Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses

    PubMed Central

    Ashbrook, M J; McDonough, K L; Pituch, J J; Christopherson, P L; Cornell, T T; Selewski, D T; Shanley, T P; Blatt, N B

    2015-01-01

    Citrate, a central component of cellular metabolism, is a widely used anti-coagulant due to its ability to chelate calcium. Adenosine triphosphate (ATP)-citrate lyase, which metabolizes citrate, has been shown to be essential for inflammation, but the ability of exogenous citrate to impact inflammatory signalling cascades remains largely unknown. We hypothesized that citrate would modulate inflammatory responses as both a cellular metabolite and calcium chelator, and tested this hypothesis by determining how clinically relevant levels of citrate modulate monocyte proinflammatory responses to lipopolysaccharide (LPS) in a human acute monocytic leukaemia cell line (THP-1). In normal medium (0·4 mM calcium), citrate inhibited LPS-induced tumour necrosis factor (TNF)-α and interleukin (IL)-8 transcripts, whereas in medium supplemented with calcium (1·4 mM), TNF-α and IL-8 levels increased and appeared independent of calcium chelation. Using an IL-8–luciferase plasmid construct, the same increased response was observed in the activation of the IL-8 promoter region, suggesting transcriptional regulation. Tricarballylic acid, an inhibitor of ATP-citrate lyase, blocked the ability of citrate to augment TNF-α, linking citrate's augmentation effect with its metabolism by ATP-citrate lyase. In the presence of citrate, increased histone acetylation was observed in the TNF-α and IL-8 promoter regions of THP-1 cells. We observed that citrate can both augment and inhibit proinflammatory cytokine production via modulation of inflammatory gene transactivation. These findings suggest that citrate anti-coagulation may alter immune function through complex interactions with the inflammatory response. PMID:25619261

  12. Glycan-Based Cell Targeting To Modulate Immune Responses.

    PubMed

    Johannssen, Timo; Lepenies, Bernd

    2017-04-01

    Glycosylation is an integral post-translational modification present in more than half of all eukaryotic proteins. It affects key protein functions, including folding, stability, and immunogenicity. Glycoengineering approaches, such as the use of bacterial N-glycosylation systems, or expression systems, including yeasts, insect cells, and mammalian cells, have enabled access to defined and homogenous glycoproteins. Given that glycan structures on proteins can be recognized by host lectin receptors, they may facilitate cell-specific targeting and immune modulation. Myeloid C-type lectin receptors (CLRs) expressed by antigen-presenting cells are attractive targets to shape immune responses. Multivalent glycan display on nanoparticles, liposomes, or dendrimers has successfully enabled CLR targeting. In this review, we discuss novel strategies to access defined glycan structures and highlight CLR targeting approaches for immune modulation.

  13. Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

    PubMed

    Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

    2016-06-01

    Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain.

  14. The immune response and its therapeutic modulation in bronchiectasis.

    PubMed

    Daheshia, Massoud; Prahl, James D; Carmichael, Jacob J; Parrish, John S; Seda, Gilbert

    2012-01-01

    Bronchiectasis (BC) is a chronic pulmonary disease with tremendous morbidity and significant mortality. As pathogen infection has been advocated as a triggering insult in the development of BC, a central role for the immune response in this process seems obvious. Inflammatory cells are present in both the airways as well as the lung parenchyma, and multiple mediators of immune cells including proteases and cytokines or their humoral products are increased locally or in the periphery. Interestingly, a defect in the immune system or suppression of immune response during conditions such as immunodeficiency may well predispose one to the devastating effects of BC. Thus, the outcome of an active immune response as detrimental or protective in the pathogenesis of BC may be dependent on the state of the patient's immunity, the severity of infection, and the magnitude of immune response. Here we reassess the function of the innate and acquired immunity in BC, the major sites of immune response, and the nature of the bioactive mediators. Furthermore, the potential link(s) between an ongoing immune response and structural alterations accompanying the disease and the success of therapies that can modulate the nature and extent of immune response in BC are elaborated upon.

  15. Monte Carlo Simulation of Response Time for Velocity Modulation Transistors

    NASA Astrophysics Data System (ADS)

    Maezawa, Koichi; Mizutani, Takashi; Tomizawa, Masaaki

    1992-03-01

    We have studied the response time for velocity modulation transistors (VMTs) using particle Monte Carlo simulation. The intrinsic VMT model with zero gate-source spacing was used to avoid the change in total number of electrons due to the difference in source resistances between the two channels. The results show that the response time for VMTs is about half that for ordinary high electron mobility transistors (HEMTs). The remaining factor limiting the response time is the electron redistribution in the channel, which is shown to be caused by the difference in velocity-electric field characteristics in the two channels. A “virtual” VMT model with a single channel, where the impurity concentration is changed abruptly at a certain moment, has also been studied to clarify the effect of electron redistribution.

  16. Integrin-directed modulation of macrophage responses to biomaterials.

    PubMed

    Zaveri, Toral D; Lewis, Jamal S; Dolgova, Natalia V; Clare-Salzler, Michael J; Keselowsky, Benjamin G

    2014-04-01

    Macrophages are the primary mediator of chronic inflammatory responses to implanted biomaterials, in cases when the material is either in particulate or bulk form. Chronic inflammation limits the performance and functional life of numerous implanted medical devices, and modulating macrophage interactions with biomaterials to mitigate this response would be beneficial. The integrin family of cell surface receptors mediates cell adhesion through binding to adhesive proteins nonspecifically adsorbed onto biomaterial surfaces. In this work, the roles of integrin Mac-1 (αMβ2) and RGD-binding integrins were investigated using model systems for both particulate and bulk biomaterials. Specifically, the macrophage functions of phagocytosis and inflammatory cytokine secretion in response to a model particulate material, polystyrene microparticles were investigated. Opsonizing proteins modulated microparticle uptake, and integrin Mac-1 and RGD-binding integrins were found to control microparticle uptake in an opsonin-dependent manner. The presence of adsorbed endotoxin did not affect microparticle uptake levels, but was required for the production of inflammatory cytokines in response to microparticles. Furthermore, it was demonstrated that integrin Mac-1 and RGD-binding integrins influence the in vivo foreign body response to a bulk biomaterial, subcutaneously implanted polyethylene terephthalate. A thinner foreign body capsule was formed when integrin Mac-1 was absent (~30% thinner) or when RGD-binding integrins were blocked by controlled release of a blocking peptide (~45% thinner). These findings indicate integrin Mac-1 and RGD-binding integrins are involved and may serve as therapeutic targets to mitigate macrophage inflammatory responses to both particulate and bulk biomaterials.

  17. Social hierarchy modulates neural responses of empathy for pain

    PubMed Central

    Feng, Chunliang; Li, Zhihao; Feng, Xue; Wang, Lili; Tian, Tengxiang

    2016-01-01

    Recent evidence indicates that empathic responses to others’ pain are modulated by various situational and individual factors. However, few studies have examined how empathy and underlying brain functions are modulated by social hierarchies, which permeate human society with an enormous impact on social behavior and cognition. In this study, social hierarchies were established based on incidental skill in a perceptual task in which all participants were mediumly ranked. Afterwards, participants were scanned with functional magnetic resonance imaging while watching inferior-status or superior-status targets receiving painful or non-painful stimulation. The results revealed that painful stimulation applied to inferior-status targets induced higher activations in the anterior insula (AI) and anterior medial cingulate cortex (aMCC), whereas these empathic brain activations were significantly attenuated in response to superior-status targets’ pain. Further, this neural empathic bias to inferior-status targets was accompanied by stronger functional couplings of AI with brain regions important in emotional processing (i.e. thalamus) and cognitive control (i.e. middle frontal gyrus). Our findings indicate that emotional sharing with others’ pain is shaped by relative positions in a social hierarchy such that underlying empathic neural responses are biased toward inferior-status compared with superior-status individuals. PMID:26516169

  18. A Computational Model of Cellular Response to Modulated Radiation Fields

    SciTech Connect

    McMahon, Stephen J.; Butterworth, Karl T.; McGarry, Conor K.; Trainor, Colman; O'Sullivan, Joe M.; Hounsell, Alan R.; Prise, Kevin M.

    2012-09-01

    Purpose: To develop a model to describe the response of cell populations to spatially modulated radiation exposures of relevance to advanced radiotherapies. Materials and Methods: A Monte Carlo model of cellular radiation response was developed. This model incorporated damage from both direct radiation and intercellular communication including bystander signaling. The predictions of this model were compared to previously measured survival curves for a normal human fibroblast line (AGO1522) and prostate tumor cells (DU145) exposed to spatially modulated fields. Results: The model was found to be able to accurately reproduce cell survival both in populations which were directly exposed to radiation and those which were outside the primary treatment field. The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells. The bystander effect contribution varies strongly with dose, falling from a high of 80% at low doses to 25% and 50% at 4 Gy for AGO1522 and DU145 cells, respectively. This was verified using the inducible nitric oxide synthase inhibitor aminoguanidine to inhibit the bystander effect in cells exposed to different doses, which showed significantly larger reductions in cell killing at lower doses. Conclusions: The model presented in this work accurately reproduces cell survival following modulated radiation exposures, both in and out of the primary treatment field, by incorporating a bystander component. In addition, the model suggests that the bystander effect is responsible for a significant portion of cell killing in uniformly irradiated cells, 50% and 70% at doses of 2 Gy in AGO1522 and DU145 cells, respectively. This description is a significant departure from accepted radiobiological models and may have a significant impact on optimization of treatment planning approaches if proven to be applicable in vivo.

  19. Engineering biomaterials surfaces to modulate the host response.

    PubMed

    Yu, Kai; Mei, Yan; Hadjesfandiari, Narges; Kizhakkedathu, Jayachandran N

    2014-12-01

    Undesirable host response is responsible for the surface induced thrombus generation, activation of the complement system and the inflammatory reactions by the blood-contacting biomaterials. The surface interaction of biomaterials with different blood components is thought to be the critical factor that dictates the host response to biomaterials. Surface engineering can be utilized as a method to enhance the biocompatibility and tailor the biological response to biomaterials. This review provides a brief account of various polymer brush based approaches used for biomaterials surface modification, both passive and bioactive, to make the material surfaces biocompatible and antibacterial. Initially we discuss the utilization of polymer brushes with different structure and chemistry as a novel strategy to design the surface non-fouling that passively prevent the subsequent biological responses. Further we explore the utility of different bioactive agents including peptides, carbohydrates and proteins which can be conjugated the polymer brush to make the surface actively interact with the body and modulate the host response. A number of such avenues have also been explored in this review.

  20. Tissue engineering tools for modulation of the immune response

    PubMed Central

    Boehler, Ryan M.; Graham, John G.; Shea, Lonnie D.

    2012-01-01

    Tissue engineering scaffolds have emerged as a powerful tool within regenerative medicine. These materials are being designed to create environments that promote regeneration through a combination of: (i) scaffold architecture, (ii) the use of scaffolds as vehicles for transplanting progenitor cells, and/or (iii) localized delivery of inductive factors or genes encoding for these inductive factors. This review describes the techniques associated with each of these components. Additionally, the immune response is increasingly recognized as a factor influencing regeneration. The immune reaction to an implant begins with an acute response to the injury and innate recognition of foreign materials, with the subsequent chronic immune response involving specific recognition of antigens (e.g., transplanted cells) by the adaptive immune response, which can eventually lead to rejection of the implant. Thus, we also describe the impact of each component on the immune response, and strategies (e.g., material design, anti-inflammatory cytokine delivery, and immune cell recruitment/transplantation) to modulate, yet not eliminate, the local immune response in order to promote regeneration, which represents another important tool for regenerative medicine. PMID:21988690

  1. Bifidobacterium bifidum PRL2010 Modulates the Host Innate Immune Response

    PubMed Central

    Turroni, Francesca; Taverniti, Valentina; Ruas-Madiedo, Patricia; Duranti, Sabrina; Guglielmetti, Simone; Lugli, Gabriele Andrea; Gioiosa, Laura; Palanza, Paola; Margolles, Abelardo; van Sinderen, Douwe

    2014-01-01

    Here, we describe data obtained from transcriptome profiling of human cell lines and intestinal cells of a murine model upon exposure and colonization, respectively, with Bifidobacterium bifidum PRL2010. Significant changes were detected in the transcription of genes that are known to be involved in innate immunity. Furthermore, results from enzyme-linked immunosorbent assays (ELISAs) showed that exposure to B. bifidum PRL2010 causes enhanced production of interleukin 6 (IL-6) and IL-8 cytokines, presumably through NF-κB activation. The obtained global transcription profiles strongly suggest that Bifidobacterium bifidum PRL2010 modulates the innate immune response of the host. PMID:24242237

  2. Modulation Response of Twin Optically Coupled Diode Lasers

    DTIC Science & Technology

    2008-03-27

    the past year and a half. I would also like to thank Dr . Kovanis and Maj. Niday for their wisdom and guidance. v Table of Contents Page Abstract...set of subscripts to arrive at dR dt̂ = N̂R (40) dθ dt̂ = −αN̂ (41) T dN̂ dt̂ = P̂ − N̂ − (1 + 2N̂)R2. (42) To find the infinitesimal modulation...response Equations (40-42) are linearized about their steady state values. The steady state values are found by equating dR dt in Equa- tion (40) to zero

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

    PubMed

    Gómez-González, Susana; Ojeda, Fernando; Torres-Morales, Patricio; Palma, Jazmín E

    2016-01-01

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

  4. Motivational orientation modulates the neural response to reward.

    PubMed

    Linke, Julia; Kirsch, Peter; King, Andrea V; Gass, Achim; Hennerici, Michael G; Bongers, André; Wessa, Michèle

    2010-02-01

    Motivational orientation defines the source of motivation for an individual to perform a particular action and can either originate from internal desires (e.g., interest) or external compensation (e.g., money). To this end, motivational orientation should influence the way positive or negative feedback is processed during learning situations and this might in turn have an impact on the learning process. In the present study, we thus investigated whether motivational orientation, i.e., extrinsic and intrinsic motivation modulates the neural response to reward and punishment as well as learning from reward and punishment in 33 healthy individuals. To assess neural responses to reward, punishment and learning of reward contingencies we employed a probabilistic reversal learning task during functional magnetic resonance imaging. Extrinsic and intrinsic motivation were assessed with a self-report questionnaire. Rewarding trials fostered activation in the medial orbitofrontal cortex and anterior cingulate gyrus (ACC) as well as the amygdala and nucleus accumbens, whereas for punishment an increased neural response was observed in the medial and inferior prefrontal cortex, the superior parietal cortex and the insula. High extrinsic motivation was positively correlated to increased neural responses to reward in the ACC, amygdala and putamen, whereas a negative relationship between intrinsic motivation and brain activation in these brain regions was observed. These findings show that motivational orientation indeed modulates the responsiveness to reward delivery in major components of the human reward system and therefore extends previous results showing a significant influence of individual differences in reward-related personality traits on the neural processing of reward.

  5. Laminar circuit organization and response modulation in mouse visual cortex

    PubMed Central

    Olivas, Nicholas D.; Quintanar-Zilinskas, Victor; Nenadic, Zoran; Xu, Xiangmin

    2012-01-01

    The mouse has become an increasingly important animal model for visual system studies, but few studies have investigated local functional circuit organization of mouse visual cortex. Here we used our newly developed mapping technique combining laser scanning photostimulation (LSPS) with fast voltage-sensitive dye (VSD) imaging to examine the spatial organization and temporal dynamics of laminar circuit responses in living slice preparations of mouse primary visual cortex (V1). During experiments, LSPS using caged glutamate provided spatially restricted neuronal activation in a specific cortical layer, and evoked responses from the stimulated layer to its functionally connected regions were detected by VSD imaging. In this study, we first provided a detailed analysis of spatiotemporal activation patterns at specific V1 laminar locations and measured local circuit connectivity. Then we examined the role of cortical inhibition in the propagation of evoked cortical responses by comparing circuit activity patterns in control and in the presence of GABAa receptor antagonists. We found that GABAergic inhibition was critical in restricting layer-specific excitatory activity spread and maintaining topographical projections. In addition, we investigated how AMPA and NMDA receptors influenced cortical responses and found that blocking AMPA receptors abolished interlaminar functional projections, and the NMDA receptor activity was important in controlling visual cortical circuit excitability and modulating activity propagation. The NMDA receptor antagonist reduced neuronal population activity in time-dependent and laminar-specific manners. Finally, we used the quantitative information derived from the mapping experiments and presented computational modeling analysis of V1 circuit organization. Taken together, the present study has provided important new information about mouse V1 circuit organization and response modulation. PMID:23060751

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

    PubMed Central

    Gómez-González, Susana; Ojeda, Fernando; Torres-Morales, Patricio; Palma, Jazmín E.

    2016-01-01

    Post-fire recruitment by seeds is regarded as an adaptive response in fire-prone ecosystems. Nevertheless, little is known about which heritable seed traits are functional to the main signals of fire (heat and smoke), thus having the potential to evolve. Here, we explored whether three seed traits (pubescence, dormancy and shape) and fire regime modulate seed response to fire cues(heat and smoke). As a model study system, we used Helenium aromaticum (Asteraceae), a native annual forb from the Chilean matorral, where fires are anthropogenic. We related seed trait values with fitness responses (germination and survival) after exposure to heat-shock and smoke experimental treatments on seeds from 10 H. aromaticum wild populations. We performed a phenotypic selection experiment to examine the relationship of seed traits with post-treatment fitness within a population (adaptive hypothesis). We then explored whether fire frequency in natural habitats was associated with trait expression across populations, and with germination and survival responses to experimental fire-cues. We found that populations subjected to higher fire frequency had, in average, more rounded and pubescent seeds than populations from rarely burned areas. Populations with more rounded and pubescent seeds were more resistant to 80°C heat-shock and smoke treatments.There was correlated selection on seed traits: pubescent-rounded or glabrouscent-elongated seeds had the highest probability of germinating after heat-shock treatments. Seed pubescence and shape in H. aromaticum are heritable traits that modulate adaptive responses to fire. Our results provide new insights into the process of plant adaptation to fire and highlight the relevance of human-made fires as a strong evolutionary agent in the Anthropocene. PMID:27438267

  7. Do plants modulate biomass allocation in response to petroleum pollution?

    PubMed

    Nie, Ming; Yang, Qiang; Jiang, Li-Fen; Fang, Chang-Ming; Chen, Jia-Kuan; Li, Bo

    2010-12-23

    Biomass allocation is an important plant trait that responds plastically to environmental heterogeneities. However, the effects on this trait of pollutants owing to human activities remain largely unknown. In this study, we investigated the response of biomass allocation of Phragmites australis to petroleum pollution by a ¹³CO₂ pulse-labelling technique. Our data show that plant biomass significantly decreased under petroleum pollution, but the root-shoot ratio for both plant biomass and ¹³C increased with increasing petroleum concentration, suggesting that plants could increase biomass allocation to roots in petroleum-polluted soil. Furthermore, assimilated ¹³C was found to be significantly higher in soil, microbial biomass and soil respiration after soils were polluted by petroleum. These results suggested that the carbon released from roots is rapidly turned over by soil microbes under petroleum pollution. This study found that plants can modulate biomass allocation in response to petroleum pollution.

  8. miRNA modulation of the cellular stress response.

    PubMed

    Babar, Imran A; Slack, Frank J; Weidhaas, Joanne B

    2008-04-01

    Cellular stress responses are potent and dynamic, allowing cells to effectively counteract diverse stresses. These pathways are crucial not only for maintaining normal cellular homeostasis, but also for protecting cells from what would otherwise lead to their demise. A novel class of genes, termed miRNAs, has recently been implicated in the cellular stress response. For example, it has been demonstrated that a cardiac-specific miRNA that is not required for normal development is requisite for a normal cardiac stress response in mice. In addition, we have found that a miRNA family is able to modulate the cellular response to cytotoxic cancer treatment both in vitro and in vivo. In this review, we will discuss these and other important developments in the field. In particular, we will focus on studies that have linked miRNAs to the genotoxic stress response and will suggest how this connection may be both important for our understanding of biology and pertinent for the development of novel cancer therapies.

  9. Modulation of amygdala response to task-irrelevant emotion.

    PubMed

    Sebastian, Catherine L; McCrory, Eamon J; De Brito, Stephane A; Viding, Essi

    2017-01-24

    It has been shown that as cognitive demands of a non-emotional task increase, amygdala response to task-irrelevant emotional stimuli is reduced. However, it remains unclear whether effects are due to altered task demands, or altered perceptual input associated with task demands. Here, we present fMRI data from 20 adult males during a novel cognitive conflict task in which the requirement to scan emotional information was necessary for task performance and held constant across levels of cognitive conflict. Response to fearful facial expressions was attenuated under high (vs. low) conflict conditions, as indexed by both slower reaction times (RTs) and reduced right amygdala response. Psychophysiological interaction (PPI) analysis showed that increased amygdala response to fear in the low conflict condition was accompanied by increased functional coupling with middle frontal gyrus, a prefrontal region previously associated with emotion regulation during cognitive task performance. These data suggest that amygdala response to emotion is modulated as a function of task demands, even when perceptual inputs are closely matched across load conditions. PPI data also show that, in particular emotional contexts, increased functional coupling of amygdala with prefrontal cortex can paradoxically occur when executive demands are lower.

  10. Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

    PubMed Central

    León, Alex; Elgueda, Diego; Silva, María A.; Hamamé, Carlos M.; Delano, Paul H.

    2012-01-01

    Background The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/Principal Findings Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. Conclusions/Significance These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects

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

    PubMed

    Hawley, John A

    2013-01-01

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

  12. Living and dying for sex. A theory of aging based on the modulation of cell cycle signaling by reproductive hormones.

    PubMed

    Bowen, Richard L; Atwood, Craig S

    2004-01-01

    A mechanistic understanding of aging has yet to be described; this paper puts forth a new theory that has the potential to explain aging in all sexually reproductive life forms. The theory also puts forth a new definition of aging - any change in an organism over time. This definition includes not only the changes associated with the loss of function (i.e. senescence, the commonly accepted definition of aging), but also the changes associated with the gain of function (growth and development). Using this definition, the rate of aging would be synonymous with the rate of change. The rate of change/aging is most rapid during the fetal period when organisms develop from a single cell at conception to a multicellular organism at birth. Therefore, 'fetal aging' would be determined by factors regulating the rate of mitogenesis, differentiation, and cell death. We suggest that these factors also are responsible for regulating aging throughout life. Thus, whatever controls mitogenesis, differentiation and cell death must also control aging. Since life-extending modalities consistently affect reproduction, and reproductive hormones are known to regulate mitogenesis and differentiation, we propose that aging is primarily regulated by the hormones that control reproduction (hence, the Reproductive-Cell Cycle Theory of Aging). In mammals, reproduction is controlled by the hypothalamic-pituitary-gonadal (HPG) axis hormones. Longevity inducing interventions, including caloric restriction, decrease fertility by suppressing HPG axis hormones and HPG hormones are known to affect signaling through the well-documented longevity regulating GH/IGF-1/PI3K/Akt/Forkhead pathway. This is exemplified by genetic alterations in Caenorhabditis elegans where homologues of the HPG axis pathways, as well as the daf-2 and daf-9 pathways, all converge on daf-16, the homologue of human Forkhead that functions in the regulation of cell cycle events. In summary, we propose that the hormones that

  13. Neural response to reward anticipation is modulated by Gray's impulsivity.

    PubMed

    Hahn, Tim; Dresler, Thomas; Ehlis, Ann-Christine; Plichta, Michael M; Heinzel, Sebastian; Polak, Thomas; Lesch, Klaus-Peter; Breuer, Felix; Jakob, Peter M; Fallgatter, Andreas J

    2009-07-15

    According to the Reinforcement Sensitivity Theory (RST), Gray's dimension of impulsivity, reflecting human trait reward sensitivity, determines the extent to which stimuli activate the Behavioural Approach System (BAS). The potential neural underpinnings of the BAS, however, remain poorly understood. In the present study, we examined the association between Gray's impulsivity as defined by the RST and event-related fMRI BOLD-response to anticipation of reward in twenty healthy human subjects in brain regions previously associated with reward processing. Anticipation of reward during a Monetary Incentive Delay Task elicited activation in key components of the human reward circuitry such as the ventral striatum, the amygdala and the orbitofrontal cortex. Interindividual differences in Gray's impulsivity accounted for a significant amount of variance of the reward-related BOLD-response in the ventral striatum and the orbitofrontal cortex. Specifically, higher trait reward sensitivity was associated with increased activation in response to cues indicating potential reward. Extending previous evidence, here we show that variance in functional brain activation during anticipation of reward is attributed to interindividual differences regarding Gray's dimension of impulsivity. Thus, trait reward sensitivity contributes to the modulation of responsiveness in major components of the human reward system which thereby display a core property of the BAS. Generally, fostering our understanding of the neural underpinnings of the association of reward-related interindividual differences in affective traits might aid researchers in quest for custom-tailored treatments of psychiatric disorders, further disentangling the complex relationship between personality traits, emotion, and health.

  14. Attention modulates the dorsal striatum response to love stimuli.

    PubMed

    Langeslag, Sandra J E; van der Veen, Frederik M; Röder, Christian H

    2014-02-01

    In previous functional magnetic resonance imaging (fMRI) studies concerning romantic love, several brain regions including the caudate and putamen have consistently been found to be more responsive to beloved-related than control stimuli. In those studies, infatuated individuals were typically instructed to passively view the stimuli or to think of the viewed person. In the current study, we examined how the instruction to attend to, or ignore the beloved modulates the response of these brain areas. Infatuated individuals performed an oddball task in which pictures of their beloved and friend served as targets and distractors. The dorsal striatum showed greater activation for the beloved than friend, but only when they were targets. The dorsal striatum actually tended to show less activation for the beloved than the friend when they were distractors. The longer the love and relationship duration, the smaller the response of the dorsal striatum to beloved-distractor stimuli was. We interpret our findings in terms of reinforcement learning. By virtue of using a cognitive task with a full factorial design, we show that the dorsal striatum is not activated by beloved-related information per se, but only by beloved-related information that is attended.

  15. Personality traits modulate neural responses to emotions expressed in music.

    PubMed

    Park, Mona; Hennig-Fast, Kristina; Bao, Yan; Carl, Petra; Pöppel, Ernst; Welker, Lorenz; Reiser, Maximilian; Meindl, Thomas; Gutyrchik, Evgeny

    2013-07-26

    Music communicates and evokes emotions. The number of studies on the neural correlates of musical emotion processing is increasing but few have investigated the factors that modulate these neural activations. Previous research has shown that personality traits account for individual variability of neural responses. In this study, we used functional magnetic resonance imaging (fMRI) to investigate how the dimensions Extraversion and Neuroticism are related to differences in brain reactivity to musical stimuli expressing the emotions happiness, sadness and fear. 12 participants (7 female, M=20.33 years) completed the NEO-Five Factor Inventory (NEO-FFI) and were scanned while performing a passive listening task. Neurofunctional analyses revealed significant positive correlations between Neuroticism scores and activations in bilateral basal ganglia, insula and orbitofrontal cortex in response to music expressing happiness. Extraversion scores were marginally negatively correlated with activations in the right amygdala in response to music expressing fear. Our findings show that subjects' personality may have a predictive power in the neural correlates of musical emotion processing and should be considered in the context of experimental group homogeneity.

  16. Modulation of vaccine response by concomitant probiotic administration

    PubMed Central

    Maidens, Catherine; Childs, Caroline; Przemska, Agnieszka; Dayel, Iman Bin; Yaqoob, Parveen

    2013-01-01

    Evidence suggests that probiotic bacteria modulate both innate and adaptive immunity in the host, and in some situations can result in reduced severity of common illnesses, such as acute rotavirus infection and respiratory infections. Responses to vaccination are increasingly being used to provide high quality information on the immunomodulatory effects of dietary components in humans. The present review focuses on the effect of probiotic administration upon vaccination response. The majority of studies investigating the impact of probiotics on responses to vaccination have been conducted in healthy adults, and at best they show modest effects of probiotics on serum or salivary IgA titres. Studies in infants and in elderly subjects are very limited, and it is too early to draw any firm conclusions regarding the potential for probiotics to act as adjuvants in vaccination. Although some studies are comparable in terms of duration of the intervention, age and characteristics of the subjects, most differ in terms of the probiotic selected. Further well designed, randomized, placebo‐controlled studies are needed to understand fully the immunomodulatory properties of probiotics, whether the effects exerted are strain‐dependent and age‐dependent and their clinical relevance in enhancing immune protection following vaccination. PMID:22845346

  17. Modulation of Primary Immune Response by Different Vaccine Adjuvants

    PubMed Central

    Ciabattini, Annalisa; Pettini, Elena; Fiorino, Fabio; Pastore, Gabiria; Andersen, Peter; Pozzi, Gianni; Medaglini, Donata

    2016-01-01

    Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Here early biomarkers of adjuvanticity after primary immunization were investigated using four different adjuvants combined with the chimeric tuberculosis vaccine antigen H56. C57BL/6 mice were immunized by the subcutaneous route with different vaccine formulations, and the modulation of primary CD4+ T cell and B cell responses was assessed within draining lymph nodes, blood, and spleen, 7 and 12 days after priming. Vaccine formulations containing the liposome system CAF01 or a squalene-based oil-in-water emulsion (o/w squalene), but not aluminum hydroxide (alum) or CpG ODN 1826, elicited a significant primary antigen-specific CD4+ T cell response compared to antigen alone, 7 days after immunization. The effector function of activated CD4+ T cells was skewed toward a Th1/Th17 response by CAF01, while a Th1/Th2 response was elicited by o/w squalene. Differentiation of B cells in short-lived plasma cells, and subsequent early H56-specific IgG secretion, was observed in mice immunized with o/w squalene or CpG adjuvants. Tested adjuvants promoted the germinal center reaction with different magnitude. These results show that the immunological activity of different adjuvants can be characterized by profiling early immunization biomarkers after primary immunization. These data and this approach could give an important contribution to the rational development of heterologous prime–boost vaccine immunization protocols. PMID:27781036

  18. Estradiol modulates Kiss1 neuronal response to ghrelin

    PubMed Central

    Frazao, Renata; Lemko, Heather M. Dungan; da Silva, Regina P.; Ratra, Dhirender V.; Lee, Charlotte E.; Williams, Kevin W.; Zigman, Jeffrey M.

    2014-01-01

    Ghrelin is a metabolic signal regulating energy homeostasis. Circulating ghrelin levels rise during starvation and fall after a meal, and therefore, ghrelin may function as a signal of negative energy balance. Ghrelin may also act as a modulator of reproductive physiology, as acute ghrelin administration suppresses gonadotropin secretion and inhibits the neuroendocrine reproductive axis. Interestingly, ghrelin's effect in female metabolism varies according to the estrogen milieu predicting an interaction between ghrelin and estrogens, likely at the hypothalamic level. Here, we show that ghrelin receptor (GHSR) and estrogen receptor-α (ERα) are coexpressed in several hypothalamic sites. Higher levels of circulating estradiol increased the expression of GHSR mRNA and the co-xpression of GHSR mRNA and ERα selectively in the arcuate nucleus (ARC). Subsets of preoptic and ARC Kiss1 neurons coexpressed GHSR. Increased colocalization was observed in ARC Kiss1 neurons of ovariectomized estradiol-treated (OVX + E2; 80%) compared with ovariectomized oil-treated (OVX; 25%) mice. Acute actions of ghrelin on ARC Kiss1 neurons were also modulated by estradiol; 75 and 22% of Kiss1 neurons of OVX + E2 and OVX mice, respectively, depolarized in response to ghrelin. Our findings indicate that ghrelin and estradiol may interact in several hypothalamic sites. In the ARC, high levels of E2 increase GHSR mRNA expression, modifying the colocalization rate with ERα and Kiss1 and the proportion of Kiss1 neurons acutely responding to ghrelin. Our findings indicate that E2 alters the responsiveness of kisspeptin neurons to metabolic signals, potentially acting as a critical player in the metabolic control of the reproductive physiology. PMID:24473434

  19. YY1 modulates taxane response in epithelial ovarian cancer

    SciTech Connect

    Matsumura, Noriomi; Huang, Zhiqing; Baba, Tsukasa; Lee, Paula S.; Barnett, Jason C.; Mori, Seiichi; Chang, Jeffrey T.; Kuo, Wen-Lin; Gusberg, Alison H.; Whitaker, Regina S.; Gray, JoeW.; Fujii, Shingo; Berchuck, Andrew; Murphy, Susan K.

    2008-10-10

    The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed decisions regarding chemotherapeutic choice. Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer (SEOC) were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary SEOC and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using siRNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in SEOC and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA crosslinking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1

  20. Hormonal modulation of the heat shock response: insights from fish with divergent cortisol stress responses.

    PubMed

    LeBlanc, Sacha; Höglund, Erik; Gilmour, Kathleen M; Currie, Suzanne

    2012-01-01

    Acute temperature stress in animals results in increases in heat shock proteins (HSPs) and stress hormones. There is evidence that stress hormones influence the magnitude of the heat shock response; however, their role is equivocal. To determine whether and how stress hormones may affect the heat shock response, we capitalized on two lines of rainbow trout specifically bred for their high (HR) and low (LR) cortisol response to stress. We predicted that LR fish, with a low cortisol but high catecholamine response to stress, would induce higher levels of HSPs after acute heat stress than HR trout. We found that HR fish have significantly higher increases in both catecholamines and cortisol compared with LR fish, and LR fish had no appreciable stress hormone response to heat shock. This unexpected finding prevented further interpretation of the hormonal modulation of the heat shock response but provided insight into stress-coping styles and environmental stress. HR fish also had a significantly greater and faster heat shock response and less oxidative protein damage than LR fish. Despite these clear differences in the physiological and cellular responses to heat shock, there were no differences in the thermal tolerance of HR and LR fish. Our results support the hypothesis that responsiveness to environmental change underpins the physiological differences in stress-coping styles. Here, we demonstrate that the heat shock response is a distinguishing feature of the HR and LR lines and suggest that it may have been coselected with the hormonal responses to stress.

  1. The Importance of TLR2 and Macrophages in Modulating a Humoral Response after Encountering Streptococcus pneumoniae

    DTIC Science & Technology

    2008-03-26

    Response after Encountering Streptococcus Pneumoniae " Brian Schae:5 ,Ph.D. Department of Microbi ogy & Immunology Committee Chairperson Masters...Macrophages in Modulating a Humoral Response after Encountering Streptococcus Pneumoniae " is appropriately acknowledged and, beyond brief excerpts, is...Dissertation: The importance of TLR2 and macrophages in modulating a humoral response after encountering Streptococcus pneumoniae Sam Vasilevsky

  2. Using Module Analysis for Multiple Choice Responses: A New Method Applied to Force Concept Inventory Data

    ERIC Educational Resources Information Center

    Brewe, Eric; Bruun, Jesper; Bearden, Ian G.

    2016-01-01

    We describe "Module Analysis for Multiple Choice Responses" (MAMCR), a new methodology for carrying out network analysis on responses to multiple choice assessments. This method is used to identify modules of non-normative responses which can then be interpreted as an alternative to factor analysis. MAMCR allows us to identify conceptual…

  3. Modulation of host responses by oral commensal bacteria

    PubMed Central

    Devine, Deirdre A.; Marsh, Philip D.; Meade, Josephine

    2015-01-01

    Immunomodulatory commensal bacteria are proposed to be essential for maintaining healthy tissues, having multiple roles including priming immune responses to ensure rapid and efficient defences against pathogens. The default state of oral tissues, like the gut, is one of inflammation which may be balanced by regulatory mechanisms and the activities of anti-inflammatory resident bacteria that modulate Toll-like receptor (TLR) signalling or NF-κB activation, or influence the development and activities of immune cells. However, the widespread ability of normal resident organisms to suppress inflammation could impose an unsustainable burden on the immune system and compromise responses to pathogens. Immunosuppressive resident bacteria have been isolated from the mouth and, for example, may constitute 30% of the resident streptococci in plaque or on the tongue. Their roles in oral health and dysbiosis remain to be determined. A wide range of bacterial components and/or products can mediate immunomodulatory activity, raising the possibility of development of alternative strategies for therapy and health promotion using probiotics, prebiotics, or commensal-derived immunomodulatory molecules. PMID:25661061

  4. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity

    PubMed Central

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  5. Modulation of Autophagy by Sorafenib: Effects on Treatment Response

    PubMed Central

    Prieto-Domínguez, Nestor; Ordóñez, Raquel; Fernández, Anna; García-Palomo, Andres; Muntané, Jordi; González-Gallego, Javier; Mauriz, José L.

    2016-01-01

    The multikinase inhibitor sorafenib is, at present, the only drug approved for the treatment of hepatocellular carcinoma (HCC), one of the most lethal types of cancer worldwide. However, the increase in the number of sorafenib tumor resistant cells reduces efficiency. A better knowledge of the intracellular mechanism of the drug leading to reduced cell survival could help to improve the benefits of sorafenib therapy. Autophagy is a bulk cellular degradation process activated in a broad range of stress situations, which allows cells to degrade misfolded proteins or dysfunctional organelles. This cellular route can induce survival or death, depending on cell status and media signals. Sorafenib, alone or in combination with other drugs is able to induce autophagy, but cell response to the drug depends on the complex integrative crosstalk of different intracellular signals. In cancerous cells, autophagy can be regulated by different cellular pathways (Akt-related mammalian target of rapamycin (mTOR) inhibition, 5′ AMP-activated protein kinase (AMPK) induction, dissociation of B-cell lymphoma 2 (Bcl-2) family proteins from Beclin-1), or effects of some miRNAs. Inhibition of mTOR signaling by sorafenib and diminished interaction between Beclin-1 and myeloid cell leukemia 1 (Mcl-1) have been related to induction of autophagy in HCC. Furthermore, changes in some miRNAs, such as miR-30α, are able to modulate autophagy and modify sensitivity in sorafenib-resistant cells. However, although AMPK phosphorylation by sorafenib seems to play a role in the antiproliferative action of the drug, it does not relate with modulation of autophagy. In this review, we present an updated overview of the effects of sorafenib on autophagy and its related activation pathways, analyzing in detail the involvement of autophagy on sorafenib sensitivity and resistance. PMID:27375485

  6. Polyamine depletion inhibits the autophagic response modulating Trypanosoma cruzi infectivity

    PubMed Central

    Vanrell, María C.; Cueto, Juan A.; Barclay, Jeremías J.; Carrillo, Carolina; Colombo, María I.; Gottlieb, Roberta A.; Romano, Patricia S.

    2013-01-01

    Autophagy is a cell process that in normal conditions serves to recycle cytoplasmic components and aged or damaged organelles. The autophagic pathway has been implicated in many physiological and pathological situations, even during the course of infection by intracellular pathogens. Many compounds are currently used to positively or negatively modulate the autophagic response. Recently it was demonstrated that the polyamine spermidine is a physiological inducer of autophagy in eukaryotic cells. We have previously shown that the etiological agent of Chagas disease, the protozoan parasite Trypanosoma cruzi, interacts with autophagic compartments during host cell invasion and that preactivation of autophagy significantly increases host cell colonization by this parasite. In the present report we have analyzed the effect of polyamine depletion on the autophagic response of the host cell and on T. cruzi infectivity. Our data showed that depleting intracellular polyamines by inhibiting the biosynthetic enzyme ornithine decarboxylase with difluoromethylornithine (DFMO) suppressed the induction of autophagy in response to starvation or rapamycin treatment in two cell lines. This effect was associated with a decrease in the levels of LC3 and ATG5, two proteins required for autophagosome formation. As a consequence of inhibiting host cell autophagy, DFMO impaired T. cruzi colonization, indicating that polyamines and autophagy facilitate parasite infection. Thus, our results point to DFMO as a novel autophagy inhibitor. While other autophagy inhibitors such as wortmannin and 3-methyladenine are nonspecific and potentially toxic, DFMO is an FDA-approved drug that may have value in limiting autophagy and the spread of the infection in Chagas disease and possibly other pathological settings. PMID:23697944

  7. Frequency Modulated Translocational Oscillations of Nrf2 Mediate the Antioxidant Response Element Cytoprotective Transcriptional Response

    PubMed Central

    Xue, Mingzhan; Momiji, Hiroshi; Rabbani, Naila; Barker, Guy; Bretschneider, Till; Shmygol, Anatoly; Rand, David A.

    2015-01-01

    Abstract Aims: Stress responsive signaling coordinated by nuclear factor erythroid 2-related factor 2 (Nrf2) provides an adaptive response for protection of cells against toxic insults, oxidative stress and metabolic dysfunction. Nrf2 regulates a battery of protective genes by binding to regulatory antioxidant response elements (AREs). The aim of this study was to examine how Nrf2 signals cell stress status and regulates transcription to maintain homeostasis. Results: In live cell microscopy we observed that Nrf2 undergoes autonomous translocational frequency-modulated oscillations between cytoplasm and nucleus. Oscillations occurred in quiescence and when cells were stimulated at physiological levels of activators, they decrease in period and amplitude and then evoke a cytoprotective transcriptional response. We propose a mechanism whereby oscillations are produced by negative feedback involving successive de-phosphorylation and phosphorylation steps. Nrf2 was inactivated in the nucleus and reactivated on return to the cytoplasm. Increased frequency of Nrf2 on return to the cytoplasm with increased reactivation or refresh-rate under stress conditions activated the transcriptional response mediating cytoprotective effects. The serine/threonine-protein phosphatase PGAM5, member of the Nrf2 interactome, was a key regulatory component. Innovation: We found that Nrf2 is activated in cells without change in total cellular Nrf2 protein concentration. Regulation of ARE-linked protective gene transcription occurs rather through translocational oscillations of Nrf2. We discovered cytoplasmic refresh rate of Nrf2 is important in maintaining and regulating the transcriptional response and links stress challenge to increased cytoplasmic surveillance. We found silencing and inhibition of PGAM5 provides potent activation of Nrf2. Conclusion: Frequency modulated translocational oscillations of Nrf2 mediate the ARE-linked cytoprotective transcriptional response. Antioxid. Redox

  8. SHORT- AND LONG-TERM MODULATION OF THE EXERCISE VENTILATORY RESPONSE

    PubMed Central

    Babb, Tony G; Wood, Helen E; Mitchell, Gordon S

    2011-01-01

    The importance of adaptive control strategies (modulation and plasticity) in the control of breathing during exercise has become recognized only in recent years. In this review we discuss new evidence for modulation of the exercise ventilatory response in humans, specifically, short-and long-term modulation. Short-term modulation is proposed to be an important regulatory mechanism that helps maintain blood gas homeostasis during exercise. PMID:20164813

  9. Tamibarotene modulates the local immune response in experimental periodontitis.

    PubMed

    Jin, Ying; Wang, Linyuan; Liu, Dixin; Lin, Xiaoping

    2014-12-01

    Tamibarotene (Am80), a synthetic retinoic acid receptor (RAR), is an agonist with high specificity for RARα and RARβ. Retinoid agonists have been shown to inhibit Th17 cell polarization and to enhance forkhead box P3 (Foxp3) expression during the course of inflammatory diseases. The aim of this study was to evaluate the previously unrecognized role of Am80 in regulating the immune responses of periodontitis within the oral microenvironment. The experimental model of periodontitis in mice was induced by oral infection with Porphyromonas gingivalis (P. gingivalis) W83. Our results indicated that Am80 effectively suppressed alveolar bone resorption induced by P. gingivalis W83 and decreased the number of osteoclasts. We clarified that these effects were closely associated with the reduced percentage of CD4(+) retinoid-related orphan receptor (ROR)γt(+) cells and increased the percentage of CD4(+) Foxp3(+) cells in the gingival tissues, cervical lymph nodes (CLNs), and spleen. Furthermore, in P. gingivalis-infected mice, Am80 down-regulated mRNA expression levels of interleukin-17A (IL-17A), receptor activator of nuclear factor-kappa beta ligand (RANKL), monocyte chemotactic protein-1 (MCP-1), IL-6, and IL-1β. Simultaneously, Am80 up-regulated expression levels of IL-10 and transforming growth factor-β1 (TGF-β1) in gingival tissues and the CLNs. Our results suggest that Am80 could protect against periodontal bone resorption, primarily through the modulation of immune responses in the oral microenvironment, and demonstrate the potential of Am80 as a novel clinical strategy for preventing periodontitis.

  10. Retinoblastoma loss modulates DNA damage response favoring tumor progression.

    PubMed

    Seoane, Marcos; Iglesias, Pablo; Gonzalez, Teresa; Dominguez, Fernando; Fraga, Maximo; Aliste, Carlos; Forteza, Jeronimo; Costoya, Jose A

    2008-01-01

    Senescence is one of the main barriers against tumor progression. Oncogenic signals in primary cells result in oncogene-induced senescence (OIS), crucial for protection against cancer development. It has been described in premalignant lesions that OIS requires DNA damage response (DDR) activation, safeguard of the integrity of the genome. Here we demonstrate how the cellular mechanisms involved in oncogenic transformation in a model of glioma uncouple OIS and DDR. We use this tumor type as a paradigm of oncogenic transformation. In human gliomas most of the genetic alterations that have been previously identified result in abnormal activation of cell growth signaling pathways and deregulation of cell cycle, features recapitulated in our model by oncogenic Ras expression and retinoblastoma (Rb) inactivation respectively. In this scenario, the absence of pRb confers a proliferative advantage and activates DDR to a greater extent in a DNA lesion-independent fashion than cells that express only HRas(V12). Moreover, Rb loss inactivates the stress kinase DDR-associated p38MAPK by specific Wip1-dependent dephosphorylation. Thus, Rb loss acts as a switch mediating the transition between premalignant lesions and cancer through DDR modulation. These findings may have important implications for the understanding the biology of gliomas and anticipate a new target, Wip1 phosphatase, for novel therapeutic strategies.

  11. Systemic corazonin signalling modulates stress responses and metabolism in Drosophila

    PubMed Central

    Kubrak, Olga I.; Lushchak, Oleh V.; Zandawala, Meet

    2016-01-01

    Stress triggers cellular and systemic reactions in organisms to restore homeostasis. For instance, metabolic stress, experienced during starvation, elicits a hormonal response that reallocates resources to enable food search and readjustment of physiology. Mammalian gonadotropin-releasing hormone (GnRH) and its insect orthologue, adipokinetic hormone (AKH), are known for their roles in modulating stress-related behaviour. Here we show that corazonin (Crz), a peptide homologous to AKH/GnRH, also alters stress physiology in Drosophila. The Crz receptor (CrzR) is expressed in salivary glands and adipocytes of the liver-like fat body, and CrzR knockdown targeted simultaneously to both these tissues increases the fly's resistance to starvation, desiccation and oxidative stress, reduces feeding, alters expression of transcripts of Drosophila insulin-like peptides (DILPs), and affects gene expression in the fat body. Furthermore, in starved flies, CrzR-knockdown increases circulating and stored carbohydrates. Thus, our findings indicate that elevated systemic Crz signalling during stress coordinates increased food intake and diminished energy stores to regain metabolic homeostasis. Our study suggests that an ancient stress-peptide in Urbilateria evolved to give rise to present-day GnRH, AKH and Crz signalling systems. PMID:27810969

  12. Keratinocytes can modulate and directly initiate nociceptive responses

    PubMed Central

    Baumbauer, Kyle M; DeBerry, Jennifer J; Adelman, Peter C; Miller, Richard H; Hachisuka, Junichi; Lee, Kuan Hsien; Ross, Sarah E; Koerber, H Richard; Davis, Brian M; Albers, Kathryn M

    2015-01-01

    How thermal, mechanical and chemical stimuli applied to the skin are transduced into signals transmitted by peripheral neurons to the CNS is an area of intense study. Several studies indicate that transduction mechanisms are intrinsic to cutaneous neurons and that epidermal keratinocytes only modulate this transduction. Using mice expressing channelrhodopsin (ChR2) in keratinocytes we show that blue light activation of the epidermis alone can produce action potentials (APs) in multiple types of cutaneous sensory neurons including SA1, A-HTMR, CM, CH, CMC, CMH and CMHC fiber types. In loss of function studies, yellow light stimulation of keratinocytes that express halorhodopsin reduced AP generation in response to naturalistic stimuli. These findings support the idea that intrinsic sensory transduction mechanisms in epidermal keratinocytes can directly elicit AP firing in nociceptive as well as tactile sensory afferents and suggest a significantly expanded role for the epidermis in sensory processing. DOI: http://dx.doi.org/10.7554/eLife.09674.001 PMID:26329459

  13. Fetal Sex Modulates Developmental Response to Maternal Malnutrition

    PubMed Central

    Gonzalez-Bulnes, Antonio; Torres-Rovira, Laura; Astiz, Susana; Ovilo, Cristina; Sanchez-Sanchez, Raul; Gomez-Fidalgo, Ernesto; Perez-Solana, Mariluz; Martin-Lluch, Mercedes; Garcia-Contreras, Consuelo; Vazquez-Gomez, Marta

    2015-01-01

    The incidence of obesity and metabolic diseases is dramatically high in rapidly developing countries. Causes have been related to intrinsic ethnic features with development of a thrifty genotype for adapting to food scarcity, prenatal programming by undernutrition, and postnatal exposure to obesogenic lifestyle. Observational studies in humans and experimental studies in animal models evidence that the adaptive responses of the offspring may be modulated by their sex. In the contemporary context of world globalization, the new question arising is the existence and extent of sex-related differences in developmental and metabolic traits in case of mixed-race. Hence, in the current study, using a swine model, we compared male and female fetuses that were crossbred from mothers with thrifty genotype and fathers without thrifty genotype. Female conceptuses evidence stronger protective strategies for their adequate growth and postnatal survival. In brief, both male and female fetuses developed a brain-sparing effect but female fetuses were still able to maintain the development of other viscerae than the brain (mainly liver, intestine and kidneys) at the expense of carcass development. Furthermore, these morphometric differences were reinforced by differences in nutrient availability (glucose and cholesterol) favoring female fetuses with severe developmental predicament. These findings set the basis for further studies aiming to increase the knowledge on the interaction between genetic and environmental factors in the determination of adult phenotype PMID:26544862

  14. BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy.

    PubMed

    Slone, William L; Moses, Blake S; Hare, Ian; Evans, Rebecca; Piktel, Debbie; Gibson, Laura F

    2016-04-26

    The bone marrow niche has a significant impact on acute lymphoblastic leukemia (ALL) cell phenotype. Of clinical relevance is the frequency with which quiescent leukemic cells, in this niche, survive treatment and contribute to relapse. This study suggests that marrow microenvironment regulation of BCL6 in ALL is one factor that may be involved in the transition between proliferative and quiescent states of ALL cells. Utilizing ALL cell lines, and primary patient tumor cells we observed that tumor cell BCL6 protein abundance is decreased in the presence of primary human bone marrow stromal cells (BMSC) and osteoblasts (HOB). Chemical inhibition, or shRNA knockdown, of BCL6 in ALL cells resulted in diminished ALL proliferation. As many chemotherapy regimens require tumor cell proliferation for optimal efficacy, we investigated the consequences of constitutive BCL6 expression in leukemic cells during co-culture with BMSC or HOB. Forced chronic expression of BCL6 during co-culture with BMSC or HOB sensitized the tumor to chemotherapy induced cell death. Combination treatment of caffeine, which increases BCL6 expression in ALL cells, with chemotherapy extended the event free survival of mice. These data suggest that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response.

  15. BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy

    PubMed Central

    Slone, William L.; Moses, Blake S.; Hare, Ian; Evans, Rebecca; Piktel, Debbie; Gibson, Laura F.

    2016-01-01

    The bone marrow niche has a significant impact on acute lymphoblastic leukemia (ALL) cell phenotype. Of clinical relevance is the frequency with which quiescent leukemic cells, in this niche, survive treatment and contribute to relapse. This study suggests that marrow microenvironment regulation of BCL6 in ALL is one factor that may be involved in the transition between proliferative and quiescent states of ALL cells. Utilizing ALL cell lines, and primary patient tumor cells we observed that tumor cell BCL6 protein abundance is decreased in the presence of primary human bone marrow stromal cells (BMSC) and osteoblasts (HOB). Chemical inhibition, or shRNA knockdown, of BCL6 in ALL cells resulted in diminished ALL proliferation. As many chemotherapy regimens require tumor cell proliferation for optimal efficacy, we investigated the consequences of constitutive BCL6 expression in leukemic cells during co-culture with BMSC or HOB. Forced chronic expression of BCL6 during co-culture with BMSC or HOB sensitized the tumor to chemotherapy induced cell death. Combination treatment of caffeine, which increases BCL6 expression in ALL cells, with chemotherapy extended the event free survival of mice. These data suggest that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response. PMID:27015556

  16. Dies1/VISTA expression loss is a recurrent event in gastric cancer due to epigenetic regulation.

    PubMed

    Oliveira, Patrícia; Carvalho, Joana; Rocha, Sara; Azevedo, Mafalda; Reis, Inês; Camilo, Vânia; Sousa, Bárbara; Valente, Sofia; Paredes, Joana; Almeida, Raquel; Huntsman, David; Oliveira, Carla

    2016-10-10

    Dies1/VISTA induces embryonic stem-cell differentiation, via BMP-pathway, but also acts as inflammation regulator and immune-response modulator. Dies1 inhibition in a melanoma-mouse model led to increased tumour-infiltrating T-cells and decreased tumour growth, emphasizing Dies1 relevance in tumour-microenvironment. Dies1 is involved in cell de/differentiation, inflammation and cancer processes, which mimic those associated with Epithelial-to-Mesenchymal-Transition (EMT). Despite this axis linking Dies1 with EMT and cancer, its expression, modulation and relevance in these contexts is unknown. To address this, we analysed Dies1 expression, its regulation by promoter-methylation and miR-125a-5p overexpression, and its association with BMP-pathway downstream-effectors, in a TGFβ1-induced EMT-model, cancer cell-lines and primary samples. We detected promoter-methylation as a mechanism controlling Dies1 expression in our EMT-model and in several cancer cell-lines. We showed that the relationship between Dies1 expression and BMP-pathway effectors observed in the EMT-model, was not present in all cell-lines, suggesting that Dies1 has other cell-specific effectors, beyond the BMP-pathway. We further demonstrated that: Dies1 expression loss is a recurrent event in GC, caused by promoter methylation and/or miR-125a-5p overexpression and; GC-microenvironment myofibroblasts overexpress Dies1. Our findings highlight Dies1 as a novel player in GC, with distinct roles within tumour cells and in the tumour-microenvironment.

  17. Dies1/VISTA expression loss is a recurrent event in gastric cancer due to epigenetic regulation

    PubMed Central

    Oliveira, Patrícia; Carvalho, Joana; Rocha, Sara; Azevedo, Mafalda; Reis, Inês; Camilo, Vânia; Sousa, Bárbara; Valente, Sofia; Paredes, Joana; Almeida, Raquel; Huntsman, David; Oliveira, Carla

    2016-01-01

    Dies1/VISTA induces embryonic stem-cell differentiation, via BMP-pathway, but also acts as inflammation regulator and immune-response modulator. Dies1 inhibition in a melanoma-mouse model led to increased tumour-infiltrating T-cells and decreased tumour growth, emphasizing Dies1 relevance in tumour-microenvironment. Dies1 is involved in cell de/differentiation, inflammation and cancer processes, which mimic those associated with Epithelial-to-Mesenchymal-Transition (EMT). Despite this axis linking Dies1 with EMT and cancer, its expression, modulation and relevance in these contexts is unknown. To address this, we analysed Dies1 expression, its regulation by promoter-methylation and miR-125a-5p overexpression, and its association with BMP-pathway downstream-effectors, in a TGFβ1-induced EMT-model, cancer cell-lines and primary samples. We detected promoter-methylation as a mechanism controlling Dies1 expression in our EMT-model and in several cancer cell-lines. We showed that the relationship between Dies1 expression and BMP-pathway effectors observed in the EMT-model, was not present in all cell-lines, suggesting that Dies1 has other cell-specific effectors, beyond the BMP-pathway. We further demonstrated that: Dies1 expression loss is a recurrent event in GC, caused by promoter methylation and/or miR-125a-5p overexpression and; GC-microenvironment myofibroblasts overexpress Dies1. Our findings highlight Dies1 as a novel player in GC, with distinct roles within tumour cells and in the tumour-microenvironment. PMID:27721458

  18. Developmental Changes in Hemodynamic Responses and Cardiovagal Modulation during Isometric Handgrip Exercise

    PubMed Central

    Goulopoulou, Styliani; Fernhall, Bo; Kanaley, Jill A.

    2010-01-01

    The purpose of this study was to examine differences in pressor response and cardiovagal modulation during isometric handgrip exercise (IHG) between children and adults. Beat-to-beat heart rate (HR) and blood pressure were measured in 23 prepubertal children and 23 adults at baseline and during IHG. Cardiovagal modulation was quantified by analysis of HR variability. Mean arterial pressure responses to IHG were greater in adults compared to children (P < .05) whereas there were no group differences in HR responses (P > .05). Children had a greater reduction in cardiovagal modulation in response to IHG compared to adults (P < .05). Changes in mean arterial pressure during IHG were correlated with baseline cardiovagal modulation and force produced during isometric contraction (P < .05). In conclusion, differences in pressor reflex response between children and adults cannot be solely explained by differences in autonomic modulation and appear to be associated with factors contributing to the force produced during isometric contraction. PMID:20862202

  19. Tree die-off in response to global change-type drought: mortality insights from a decade of plant water potential measurements

    USGS Publications Warehouse

    Breshears, D.D.; Myers, O.B.; Meyer, Clifton W.; Barnes, F.J.; Zou, C.B.; Allen, C.D.; McDowell, N.G.; Pockman, W. T.

    2009-01-01

    Global climate change is projected to produce warmer, longer, and more frequent droughts, referred to here as "global change-type droughts", which have the potential to trigger widespread tree die-off. However, droughtinduced tree mortality cannot be predicted with confidence, because long-term field observations of plant water stress prior to, and culminating in, mortality are rare, precluding the development and testing of mechanisms. Here, we document plant water stress in two widely distributed, co-occurring species, pi??on pine (Pinus edulis) and juniper (Juniperus monosperma), over more than a decade, leading up to regional-scale die-off of pi??on pine trees in response to global change-related drought. Pi??on leaf water potentials remained substantially below their zero carbon assimilation point for at least 10 months prior to dying, in contrast to those of juniper, which rarely dropped below their zero-assimilation point. These data suggest that pi??on mortality was driven by protracted water stress, leading to carbon starvation and associated increases in susceptibility to other disturbances (eg bark beetles), a finding that should help to improve predictions of mortality during drought. ?? The Ecological Society of America.

  20. Detection of innate immune response modulating impurities in therapeutic proteins.

    PubMed

    Haile, Lydia Asrat; Puig, Montserrat; Kelley-Baker, Logan; Verthelyi, Daniela

    2015-01-01

    Therapeutic proteins can contain multiple impurities, some of which are variants of the product, while others are derived from the cell substrate and the manufacturing process. Such impurities, even when present at trace levels, have the potential to activate innate immune cells in peripheral blood or embedded in tissues causing expression of cytokines and chemokines, increasing antigen uptake, facilitating processing and presentation by antigen presenting cells, and fostering product immunogenicity. Currently, while products are tested for host cell protein content, assays to control innate immune response modulating impurities (IIRMIs) in products are focused mainly on endotoxin and nucleic acids, however, depending on the cell substrate and the manufacturing process, numerous other IIRMI could be present. In these studies we assess two approaches that allow for the detection of a broader subset of IIRMIs. In the first, we use commercial cell lines transfected with Toll like receptors (TLR) to detect receptor-specific agonists. This method is sensitive to trace levels of IIRMI and provides information of the type of IIRMIs present but is limited by the availability of stably transfected cell lines and requires pre-existing knowledge of the IIRMIs likely to be present in the product. Alternatively, the use of a combination of macrophage cell lines of human and mouse origin allows for the detection of a broader spectrum of impurities, but does not identify the source of the activation. Importantly, for either system the lower limit of detection (LLOD) of impurities was similar to that of PBMC and it was not modified by the therapeutic protein tested, even in settings where the product had inherent immune modulatory properties. Together these data indicate that a cell-based assay approach could be used to screen products for the presence of IIRMIs and inform immunogenicity risk assessments, particularly in the context of comparability exercises.

  1. Using module analysis for multiple choice responses: A new method applied to Force Concept Inventory data

    NASA Astrophysics Data System (ADS)

    Brewe, Eric; Bruun, Jesper; Bearden, Ian G.

    2016-12-01

    We describe Module Analysis for Multiple Choice Responses (MAMCR), a new methodology for carrying out network analysis on responses to multiple choice assessments. This method is used to identify modules of non-normative responses which can then be interpreted as an alternative to factor analysis. MAMCR allows us to identify conceptual modules that are present in student responses that are more specific than the broad categorization of questions that is possible with factor analysis and to incorporate non-normative responses. Thus, this method may prove to have greater utility in helping to modify instruction. In MAMCR the responses to a multiple choice assessment are first treated as a bipartite, student X response, network which is then projected into a response X response network. We then use data reduction and community detection techniques to identify modules of non-normative responses. To illustrate the utility of the method we have analyzed one cohort of postinstruction Force Concept Inventory (FCI) responses. From this analysis, we find nine modules which we then interpret. The first three modules include the following: Impetus Force, More Force Yields More Results, and Force as Competition or Undistinguished Velocity and Acceleration. This method has a variety of potential uses particularly to help classroom instructors in using multiple choice assessments as diagnostic instruments beyond the Force Concept Inventory.

  2. Transient Response of Cadmium Telluride Modules to Light Exposure: Preprint

    SciTech Connect

    Deline, C.; del Cueto, J.; Albin, D. S.; Petersen, C.; Tyler, L.; TamizhMani, G.

    2011-07-01

    Commercial cadmium telluride (CdTe) photovoltaic (PV) modules from three different manufacturers were monitored for performance changes during indoor and outdoor light-exposure. Short-term transients in Voc were recorded on some modules, with characteristic times of ~1.1 hours. Outdoor performance data shows a similar drop in Voc after early morning light exposure. Preliminary analysis of FF changes show light-induced changes on multiple time scales, including a long time scale.

  3. Sputtered protective coatings for die casting dies

    NASA Technical Reports Server (NTRS)

    Mirtich, M. J.; Nieh, C. Y.; Wallace, J. F.

    1981-01-01

    This investigation determined whether selected ion beam sputtered coatings on H-13 die steel would have the potential of improving the thermal fatigue behavior of the steel used as a die in aluminum die casting. The coatings were selected to test candidate insulators and metals capable of providing protection of the die surface. The studies indicate that 1 micrometer thick W and Pt coatings reduced the thermal fatigue more than any other coating tested and are candidates to be used on a die surface to increase die life.

  4. Multivalent proteoglycan modulation of FGF mitogenic responses in perivascular cells.

    PubMed

    Cattaruzza, Sabrina; Ozerdem, Ugur; Denzel, Martin; Ranscht, Barbara; Bulian, Pietro; Cavallaro, Ugo; Zanocco, Daniela; Colombatti, Alfonso; Stallcup, William B; Perris, Roberto

    2013-04-01

    Sprouting of angiogenic perivascular cells is thought to be highly dependent upon autocrine and paracrine growth factor stimulation. Accordingly, we report that corneal angiogenesis induced by ectopic FGF implantation is strongly impaired in NG2/CSPG4 proteoglycan (PG) null mice known to harbour a putative deficit in pericyte proliferation/mobilization. Conversely, no significant differences were seen between wild type and knockout corneas when VEGF was used as an angiocrine factor. Perturbed responsiveness of NG2-deficient pericytes to paracrine and autocrine stimulation by several FGFs could be confirmed in cells isolated from NG2 null mice, while proliferation induced by other growth factors was equivalent in wild type and knockout cells. Identical results were obtained after siRNA-mediated knock-down of NG2 in human smooth muscle-like cell lines, as also demonstrated by the decreased levels of FGF receptor phosphorylation detected in these NG2 deprived cells. Binding assays with recombinant proteins and molecular interactions examined on live cells asserted that FGF-2 bound to NG2 in a glycosaminoglycan-independent, core protein-mediated manner and that the PG was alone capable of retaining FGF-2 on the cell membrane for subsequent receptor presentation. The use of dominant-negative mutant cells, engineered by combined transduction of NG2 deletion constructs and siRNA knock-down of the endogenous PG, allowed us to establish that the FGF co-receptor activity of NG2 is entirely mediated by its extracellular portion. In fact, forced overexpression of the NG2 ectodomain in human smooth muscle-like cells increased their FGF-2-induced mitosis and compensated for low levels of FGF receptor surface expression, in a manner equivalent to that produced by overexpression of the full-length NG2. Upon FGF binding, the cytoplasmic domain of NG2 is phosphorylated, but there is no evidence that this event elicits signal transductions that could bypass the FGFR-mediated ones

  5. Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats

    PubMed Central

    Semionatto, Isadora Ferraz; Raminelli, Adrieli Oliveira; Alves, Angelica Cristina; Capitelli, Caroline Santos; Chriguer, Rosangela Soares

    2017-01-01

    Background Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. Methods We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. Results No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). Discussion The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. Conclusion These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats. PMID:28099586

  6. Odorant response properties of individual neurons in an olfactory glomerular module

    PubMed Central

    Kikuta, Shu; Fletcher, Max L.; Homma, Ryota; Yamasoba, Tatsuya; Nagayama, Shin

    2013-01-01

    Summary Neuronal networks that are directly associated with glomeruli in the olfactory bulb are thought to comprise functional modules. However, this has not yet been experimentally proven. In this study, we explored the anatomical and functional architecture of glomerular modules using in vivo two-photon calcium imaging. Surprisingly, the deep portions of the glomerular modules showed considerable spatial overlap with other modules. Juxtaglomerular cells showed similar excitatory odorant response profiles to presynaptic olfactory sensory neuron inputs. Mitral cells exhibited a more sharply tuned molecular receptive range compared to juxtaglomerular cells, and their odorant response profiles varied depending on their interneuronal horizontal distances. These data suggest that glomerular modules are composed of functionally distinct neurons, and that homogenous odor inputs to each glomerulus may be parsed and processed in different fashions within the modules before being sent to higher olfactory centers. PMID:23522047

  7. [Role of interoceptive signalization in modulating emotional-behavioral responses].

    PubMed

    Emel'ianenko, I V; Raĭtses, V S

    1976-03-01

    Chronic experiments were conducted on rabbits; electrodes were implanted into the deep structures of the brain. Stimulation of gastric receptors led to modulation of the emotional-behavioristic reactions induced by electric stimulation of the hypothalamus, the amygdala and the hypocampus. The effect depended on the intensity of interoceptive stimulation and peculiarities of the emotional reaction with own cerebral control systems.

  8. Wege in die Zukunft

    NASA Astrophysics Data System (ADS)

    Kauermann, Göran; Mosler, Karl

    Die Zukunft stellt große Herausforderungen an die Arbeit der Deutschen Statistischen Gesellschaft. Sie betreffen die gestiegenen Anforderungen der Nutzer von Statistik, die Kommunikationsmöglichkeiten des Internets sowie die Dynamik der statistischen Wissenschaften und ihrer Anwendungsgebiete. Das Kapitel 5 beschreibt, wie sich die Gesellschaft diesen Herausforderungen stellt und welche Ziele sie sich in der wissenschaftlichen Zusammenarbeit und im Kampf gegen das Innumeratentum gesetzt hat.

  9. Optimization of coherent optical OFDM transmitter using DP-IQ modulator with nonlinear response

    NASA Astrophysics Data System (ADS)

    Chang, Sun Hyok; Kang, Hun-Sik; Moon, Sang-Rok; Lee, Joon Ki

    2016-07-01

    In this paper, we investigate the performance of dual polarization orthogonal frequency division multiplexing (DP-OFDM) signal generation when the signal is generated by a DP-IQ optical modulator. The DP-IQ optical modulator is made of four parallel Mach-Zehnder modulators (MZMs) which have nonlinear responses and limited extinction ratios. We analyze the effects of the MZM in the DP-OFDM signal generation by numerical simulation. The operating conditions of the DP-IQ modulator are optimized to have the best performance of the DP-OFDM signal.

  10. Optimize the modulation response of twisted-nematic liquid crystal displays as pure phase spatial light modulators

    NASA Astrophysics Data System (ADS)

    Ma, Baiheng; Peng, Fei; Kang, Mingwu; Zhou, Jiawu

    2014-11-01

    Twisted-nematic liquid crystal displays (TN-LCD) are widely used in numerous research fields of optics working as spatial light modulators. Approaches to obtaining desired intensity or phase modulation by TN-LCD have been extensively studied based on the knowledge of TN-LCD's internal structure parameters, e.g., the orientation of LC molecules at the surfaces, the twist angle, the thickness of the LC layer, and the birefringence of the material. Generally TN-LCD placed between two linear polarizers (P) produces coupled intensity and phase modulation. To obtain the commonly used pure phase modulation, quarter wave plates (QWP) are often used in front of and/or behind the LCD. In this paper, we present a method to optimize the optical modulation properties of the TN-LCD to obtain pure phase modulation in the configuration of P-QWP-LCD-QWP-P each with proper orientation. Firstly an improved method for determining the Jones matrix of the TN-LCD without knowing its internal parameters is presented, which is based on the macroscopical Jones matrix descriptions for TN-LCD, linear polarizer and QWP. Only three sets of intensity measurements are needed for the complete determination of the TN-LCD's Jones matrix for a single wavelength. Then Jones matrix calculations are carried out to determine the orientations of the polarizers and QWPs for pure phase modulation response. In addition, we prove that the phase modulation depth (PMD) of the TN-LCD can be further increased provided that the mean intensity transmission is decreased to a lower level, which is very useful when the TN-LCD is used as a phase modulator and the ratio between the intensities of the desired diffracted order relative to the other diffracted orders is required higher. Experimental results coincide well with the optical modulation properties of the TN-LCD predicted by our determined Jones matrix. In contrast to the traditional method which requires knowledge of the TN-LCD's internal structure parameters

  11. Dopamine modulates the plasticity of mechanosensory responses in Caenorhabditis elegans

    PubMed Central

    Sanyal, Suparna; Wintle, Richard F; Kindt, Katie S; Nuttley, William M; Arvan, Rokhand; Fitzmaurice, Paul; Bigras, Eve; Merz, David C; Hébert, Terence E; van der Kooy, Derek; Schafer, William R; Culotti, Joseph G; Van Tol, Hubert H M

    2004-01-01

    Dopamine-modulated behaviors, including information processing and reward, are subject to behavioral plasticity. Disruption of these behaviors is thought to support drug addictions and psychoses. The plasticity of dopamine-mediated behaviors, for example, habituation and sensitization, are not well understood at the molecular level. We show that in the nematode Caenorhabditis elegans, a D1-like dopamine receptor gene (dop-1) modulates the plasticity of mechanosensory behaviors in which dopamine had not been implicated previously. A mutant of dop-1 displayed faster habituation to nonlocalized mechanical stimulation. This phenotype was rescued by the introduction of a wild-type copy of the gene. The dop-1 gene is expressed in mechanosensory neurons, particularly the ALM and PLM neurons. Selective expression of the dop-1 gene in mechanosensory neurons using the mec-7 promoter rescues the mechanosensory deficit in dop-1 mutant animals. The tyrosine hydroxylase-deficient C. elegans mutant (cat-2) also displays these specific behavioral deficits. These observations provide genetic evidence that dopamine signaling modulates behavioral plasticity in C. elegans. PMID:14739932

  12. Modulation response of an injection locked quantum-dash Fabry Perot laser at 1550nm

    NASA Astrophysics Data System (ADS)

    Pochet, M.; Naderi, N. A.; Grillot, F.; Terry, N.; Kovanis, V.; Lester, L. F.

    2009-02-01

    The microwave domain modulation response of an injection-locked laser system is analyzed in the context of a Quantum Dash Fabry-Perot laser. This work demonstrates the applicability of a newly-derived modulation response function by using it to least-squares fit data collected on an injection-locked system with a Quantum-Dash Fabry-Perot semiconductor slave laser. The maximum injection strength, linewidth enhancement factor, coupled phase between the master and slave, and field enhancement factor characterizing the deviation of the locked slave laser from its freerunning value are extracted by least-squares fitting the collected data with the function. The extracted values are then compared with theoretically expected values under the given detuning conditions. The correlation between the frequency of the resonance peak of the modulation response at the positive frequency detuning edge and a pole in the modulation response function under this detuning condition is illustrated. The calculation of the injection strength based on the experimental operating conditions is verified by applying the modulation response function to the experimental data. With the modulation response function, injection-locked behaviors can be accurately simulated in the microwave domain and used to predict operating conditions ideal for high-performance RF links.

  13. Waking State: Rapid Variations Modulate Neural and Behavioral Responses

    PubMed Central

    McGinley, Matthew J.; Vinck, Martin; Reimer, Jacob; Batista-Brito, Renata; Zagha, Edward; Cadwell, Cathryn R.

    2015-01-01

    The state of the brain and body constantly varies on rapid and slow time scales. These variations contribute to the apparent noisiness of sensory responses at both the neural and behavioral level. Recent investigations of rapid state changes in awake, behaving animals have provided insight into the mechanisms by which optimal sensory encoding and behavioral performance are achieved. Fluctuations in state, as indexed by pupillometry, impact both the “signal” (sensory evoked response) and the “noise” (spontaneous activity) of cortical responses. By taking these fluctuations into account, neural response (co-)variability is significantly reduced, revealing the brain to be more reliable and predictable than previously thought. PMID:26402600

  14. Regulating the ethylene response of a plant by modulation of F-box proteins

    DOEpatents

    Guo, Hongwei [Beijing, CN; Ecker, Joseph R [Carlsbad, CA

    2014-01-07

    The relationship between F-box proteins and proteins invovled in the ethylene response in plants is described. In particular, F-box proteins may bind to proteins involved in the ethylene response and target them for degradation by the ubiquitin/proteasome pathway. The transcription factor EIN3 is a key transcription factor mediating ethylne-regulated gene expression and morphological responses. EIN3 is degraded through a ubiquitin/proteasome pathway mediated by F-box proteins EBF1 and EBF2. The link between F-box proteins and the ethylene response is a key step in modulating or regulating the response of a plant to ethylene. Described herein are transgenic plants having an altered sensitivity to ethylene, and methods for making transgenic plant haing an althered sensitivity to ethylene by modulating the level of activity of F-box proteins. Methods of altering the ethylene response in a plant by modulating the activity or expression of an F-box protein are described. Also described are methods of identifying compounds that modulate the ethylene response in plants by modulating the level of F-box protein expression or activity.

  15. Response Modality Modulator PRP Interference, Even When Task 1 is a no-go trial

    NASA Technical Reports Server (NTRS)

    VanSelst, Mark; Johnston, James C.; Shafto, Michael (Technical Monitor)

    1997-01-01

    In a Psychological Refractory Period paradigm where the first task requires one of several possible responses on some trials (the go trials), but no response on other (no-go) trials, response modality modulates the amount of interference on Task 2 processing. This is true even when Task 1 is no-go trial. Differences in the cost of switching response sets between processing for Task 1 and Task 2 may provide an account of this surprising phenomenon.

  16. Personality traits modulate emotional and physiological responses to stress

    PubMed Central

    Childs, Emma; White, Tara L.; de Wit, Harriet

    2014-01-01

    An individual’s susceptibility to psychological and physical disorders associated with chronic stress exposure e.g., cardiovascular and infectious disease, may also be predicted by their reactivity to acute stress. One factor associated with both stress resilience and health outcomes is personality. An understanding of how personality influences responses to acute stress may shed light upon individual differences in susceptibility to chronic stress-linked disease. This study examined relationships between personality and acute responses to stress in 125 healthy adults, using hierarchical linear regression. We assessed personality traits using the Multidimensional Personality Questionnaire (MPQ-BF), and responses to acute stress (cortisol, heart rate, blood pressure, mood) using a standardised laboratory psychosocial stress task, the Trier Social Stress Test (TSST). Individuals with high Negative Emotionality exhibited greater emotional distress and lower blood pressure responses to the TSST. Individuals with high Agentic Positive Emotionality exhibited prolonged heart rate responses to stress, whereas those with high Communal Positive Emotionality exhibited smaller cortisol and blood pressure responses. Separate personality traits differentially predicted emotional, cardiovascular, and cortisol responses to a psychosocial stressor in healthy volunteers. Future research investigating the association of personality with chronic stress-related disease may provide further clues to the relationship between acute stress reactivity and susceptibility to disease. PMID:25036730

  17. Selective attention modulates human auditory brainstem responses: relative contributions of frequency and spatial cues.

    PubMed

    Lehmann, Alexandre; Schönwiesner, Marc

    2014-01-01

    Selective attention is the mechanism that allows focusing one's attention on a particular stimulus while filtering out a range of other stimuli, for instance, on a single conversation in a noisy room. Attending to one sound source rather than another changes activity in the human auditory cortex, but it is unclear whether attention to different acoustic features, such as voice pitch and speaker location, modulates subcortical activity. Studies using a dichotic listening paradigm indicated that auditory brainstem processing may be modulated by the direction of attention. We investigated whether endogenous selective attention to one of two speech signals affects amplitude and phase locking in auditory brainstem responses when the signals were either discriminable by frequency content alone, or by frequency content and spatial location. Frequency-following responses to the speech sounds were significantly modulated in both conditions. The modulation was specific to the task-relevant frequency band. The effect was stronger when both frequency and spatial information were available. Patterns of response were variable between participants, and were correlated with psychophysical discriminability of the stimuli, suggesting that the modulation was biologically relevant. Our results demonstrate that auditory brainstem responses are susceptible to efferent modulation related to behavioral goals. Furthermore they suggest that mechanisms of selective attention actively shape activity at early subcortical processing stages according to task relevance and based on frequency and spatial cues.

  18. Biting intentions modulate digastric reflex responses to sudden unloading of the jaw.

    PubMed

    Johansson, Anders S; Pruszynski, J Andrew; Edin, Benoni B; Westberg, Karl-Gunnar

    2014-09-01

    Reflex responses in jaw-opening muscles can be evoked when a brittle object cracks between the teeth and suddenly unloads the jaw. We hypothesized that this reflex response is flexible and, as such, is modulated according to the instructed goal of biting through an object. Study participants performed two different biting tasks when holding a peanut half stacked on a chocolate piece between their incisors. In one task, they were asked to split the peanut half only (single-split task), and in the other task, they were asked to split both the peanut and the chocolate in one action (double-split task). In both tasks, the peanut split evoked a jaw-opening muscle response, quantified from electromyogram (EMG) recordings of the digastric muscle in a window 20-60 ms following peanut split. Consistent with our hypothesis, we found that the jaw-opening muscle response in the single-split trials was about twice the size of the jaw-opening muscle response in the double-split trials. A linear model that predicted the jaw-opening muscle response on a single-trial basis indicated that task settings played a significant role in this modulation but also that the presplit digastric muscle activity contributed to the modulation. These findings demonstrate that, like reflex responses to mechanical perturbations in limb muscles, reflex responses in jaw muscles not only show gain-scaling but also are modulated by subject intent.

  19. An NCME Instructional Module on Latent DIF Analysis Using Mixture Item Response Models

    ERIC Educational Resources Information Center

    Cho, Sun-Joo; Suh, Youngsuk; Lee, Woo-yeol

    2016-01-01

    The purpose of this ITEMS module is to provide an introduction to differential item functioning (DIF) analysis using mixture item response models. The mixture item response models for DIF analysis involve comparing item profiles across latent groups, instead of manifest groups. First, an overview of DIF analysis based on latent groups, called…

  20. Molecular modulation of airway epithelial ciliary response to sneezing.

    PubMed

    Zhao, Ke-Qing; Cowan, Andrew T; Lee, Robert J; Goldstein, Natalia; Droguett, Karla; Chen, Bei; Zheng, Chunquan; Villalon, Manuel; Palmer, James N; Kreindler, James L; Cohen, Noam A

    2012-08-01

    Our purpose was to evaluate the effect of the mechanical force of a sneeze on sinonasal cilia function and determine the molecular mechanism responsible for eliciting the ciliary response to a sneeze. A novel model was developed to deliver a stimulation simulating a sneeze (55 mmHg for 50 ms) at 26°C to the apical surface of mouse and human nasal epithelial cells. Ciliary beating was visualized, and changes in ciliary beat frequency (CBF) were determined. To interrogate the molecular cascades driving sneeze-induced changes of CBF, pharmacologic manipulation of intra- and extracellular calcium, purinergic, PKA, and nitric oxide (NO) signaling were performed. CBF rapidly increases by ≥150% in response to a sneeze, which is dependent on the release of adenosine triphosphate (ATP), calcium influx, and PKA activation. Furthermore, apical release of ATP is independent of calcium influx, but calcium influx and subsequent increase in CBF are dependent on the ATP release. Lastly, we observed a blunted ciliary response in surgical specimens derived from patients with chronic rhinosinusitis compared to control patients. Apical ATP release with subsequent calcium mobilization and PKA activation are involved in sinonasal ciliary response to sneezing, which is blunted in patients with upper-airway disease.

  1. Do competitors modulate rare plant response to precipitation change?

    USGS Publications Warehouse

    Levine, J.M.; Kathryn, Mceachern A.; Cowan, C.

    2010-01-01

    Ecologists increasingly suspect that climate change will directly impact species physiology, demography, and phenology, but also indirectly affect these measures via changes to the surrounding community. Unfortunately, few studies examine both the direct and indirect pathways of impact. Doing so is important because altered competitive pressures can reduce or magnify the direct responses of a focal species to climate change. Here, we examine the effects of changing rainfall on three rare annual plant species in the presence and absence of competition on the California Channel Islands. We used rain-out shelters and hand watering to exclude and augment early, late, and season-long rainfall, spanning the wide range of precipitation change forecast for the region. In the absence of competition, droughts reduced the population growth rates of two of three focal annuals, while increased rainfall was only sometimes beneficial, As compared to the focal species, the dominant competitors were more sensitive to the precipitation treatments, benefiting from increased season-long precipitation and harmed by droughts. Importantly, the response of two of three competitors to the precipitation treatments tended to be positively correlated with those of the focal annuals. Although this leads to the expectation that increased competition will counter the direct benefits of favorable conditions, such indirect effects of precipitation change proved weak to nonexistent in our experiment. Competitors had little influence on the precipitation response of two focal species, due to their low sensitivity to competition and highly variable precipitation responses. Competition did affect how our third focal species responded to precipitation change, but this effect only approached significance, and whether it truly resulted from competitor response to precipitation change was unclear. Our work suggests that even when competitors respond to climate change, these responses may have little

  2. Growth plate cartilage shows different strain patterns in response to static versus dynamic mechanical modulation.

    PubMed

    Kaviani, Rosa; Londono, Irene; Parent, Stefan; Moldovan, Florina; Villemure, Isabelle

    2016-08-01

    Longitudinal growth of long bones and vertebrae occurs in growth plate cartilage. This process is partly regulated by mechanical forces, which are one of the underlying reasons for progression of growth deformities such as idiopathic adolescent scoliosis and early-onset scoliosis. This concept of mechanical modulation of bone growth is also exploited in the development of fusionless treatments of these deformities. However, the optimal loading condition for the mechanical modulation of growth plate remains to be identified. The objective of this study was to evaluate the effects of in vitro static versus dynamic modulation and of dynamic loading parameters, such as frequency and amplitude, on the mechanical responses and histomorphology of growth plate explants. Growth plate explants from distal ulnae of 4-week-old swines were extracted and randomly distributed among six experimental groups: baseline ([Formula: see text]), control ([Formula: see text]), static ([Formula: see text]) and dynamic ([Formula: see text]). For static and dynamic groups, mechanical modulation was performed in vitro using an Indexed CartiGen bioreactor. A stress relaxation test combined with confocal microscopy and digital image correlation was used to characterize the mechanical responses of each explant in terms of peak stress, equilibrium stress, equilibrium modulus of elasticity and strain pattern. Histomorphometrical measurements were performed on toluidine blue tissue sections using a semi-automatic custom-developed MATLAB toolbox. Results suggest that compared to dynamic modulation, static modulation changes the strain pattern of the tissue and thus is more detrimental for tissue biomechanics, while the histomorphological parameters are not affected by mechanical modulation. Also, under dynamic modulation, changing the frequency or amplitude does not affect the biomechanical response of the tissue. Results of this study will be useful in finding optimal and non-damaging parameters

  3. Immune response modulation by curcumin in a latex allergy model

    PubMed Central

    Kurup, Viswanath P; Barrios, Christy S; Raju, Raghavan; Johnson, Bryon D; Levy, Michael B; Fink, Jordan N

    2007-01-01

    Background There has been a worldwide increase in allergy and asthma over the last few decades, particularly in industrially developed nations. This resulted in a renewed interest to understand the pathogenesis of allergy in recent years. The progress made in the pathogenesis of allergic disease has led to the exploration of novel alternative therapies, which include herbal medicines as well. Curcumin, present in turmeric, a frequently used spice in Asia has been shown to have anti-allergic and inflammatory potential. Methods We used a murine model of latex allergy to investigate the role of curcumin as an immunomodulator. BALB/c mice were exposed to latex allergens and developed latex allergy with a Th2 type of immune response. These animals were treated with curcumin and the immunological and inflammatory responses were evaluated. Results Animals exposed to latex showed enhanced serum IgE, latex specific IgG1, IL-4, IL-5, IL-13, eosinophils and inflammation in the lungs. Intragastric treatment of latex-sensitized mice with curcumin demonstrated a diminished Th2 response with a concurrent reduction in lung inflammation. Eosinophilia in curcumin-treated mice was markedly reduced, co-stimulatory molecule expression (CD80, CD86, and OX40L) on antigen-presenting cells was decreased, and expression of MMP-9, OAT, and TSLP genes was also attenuated. Conclusion These results suggest that curcumin has potential therapeutic value for controlling allergic responses resulting from exposure to allergens. PMID:17254346

  4. Differential modulation by extracellular ATP of carotid chemosensory responses.

    PubMed

    Spergel, D; Lahiri, S

    1993-06-01

    The possibility that the carotid body has ATP surface receptors that mediate O2 chemoreception was tested. To distinguish between the event(s) initiating chemoreception and those at the neurotransmitter level, we also tested the chemosensory response to nicotine before and after ATP administration. Carotid bodies from cats anesthetized with pentobarbital sodium were perfused and superfused in vitro with modified Tyrode solution (PCO2 < 1 Torr, pH 7.4, 36 degrees C) equilibrated at PO2 > 400 or approximately 150 Torr while chemosensory discharge was recorded extracellularly. ATP and adenosine 5'-[gamma-thio]triphosphate stimulated discharge with similar dose dependence, whereas adenosine had little effect. ATP infusion for > or = 2 min evoked an initial stimulation of discharge followed by a decline to baseline (desensitization). Desensitization did not affect the response to hypoxia (perfusate flow interruption) but inhibited the response to nicotine (4-nmol pulse). Therefore, 1) the carotid body has surface ATP receptors that may mediate the chemosensory response to nicotine but not to hypoxia and 2) nicotinic receptors are not required for carotid body O2 chemoreception.

  5. Human Neuromagnetic Steady-State Responses to Amplitude-Modulated Tones, Speech, and Music

    PubMed Central

    Parkkonen, Lauri; Hari, Riitta

    2014-01-01

    Objectives: Auditory steady-state responses that can be elicited by various periodic sounds inform about subcortical and early cortical auditory processing. Steady-state responses to amplitude-modulated pure tones have been used to scrutinize binaural interaction by frequency-tagging the two ears’ inputs at different frequencies. Unlike pure tones, speech and music are physically very complex, as they include many frequency components, pauses, and large temporal variations. To examine the utility of magnetoencephalographic (MEG) steady-state fields (SSFs) in the study of early cortical processing of complex natural sounds, the authors tested the extent to which amplitude-modulated speech and music can elicit reliable SSFs. Design: MEG responses were recorded to 90-s-long binaural tones, speech, and music, amplitude-modulated at 41.1 Hz at four different depths (25, 50, 75, and 100%). The subjects were 11 healthy, normal-hearing adults. MEG signals were averaged in phase with the modulation frequency, and the sources of the resulting SSFs were modeled by current dipoles. After the MEG recording, intelligibility of the speech, musical quality of the music stimuli, naturalness of music and speech stimuli, and the perceived deterioration caused by the modulation were evaluated on visual analog scales. Results: The perceived quality of the stimuli decreased as a function of increasing modulation depth, more strongly for music than speech; yet, all subjects considered the speech intelligible even at the 100% modulation. SSFs were the strongest to tones and the weakest to speech stimuli; the amplitudes increased with increasing modulation depth for all stimuli. SSFs to tones were reliably detectable at all modulation depths (in all subjects in the right hemisphere, in 9 subjects in the left hemisphere) and to music stimuli at 50 to 100% depths, whereas speech usually elicited clear SSFs only at 100% depth. The hemispheric balance of SSFs was toward the right hemisphere

  6. Immune modulation in response to stress and relaxation.

    PubMed

    Mahbub-E-Sobhani; Haque, N; Salma, U; Ahmed, A

    2011-03-15

    Traditional medical science has kept the mind separate from the body. Recently people realize the effect of mind on health and psychoneuroimmunology is the new evolved science that describes the interactions between psyche and soma. In this review through a typical psycho-neuro-endocrino-immune network the effects of psychological stress (acute, brief naturalistic and chronic) and relaxation on immune modulation has been shown. From this network Corticotrophin Releasing Factor (CRF), Adrenocorticotrophic Hormone (ACTH), Glucocorticoids (GC), alpha-endorphin and Met-enkephalin are found as important endocrine components and T cells, B cells, monocytes/macrophages, Natural Killer (NK) cells and their cytokines that is Tumor Necrosis Factor-alpha (TNF-alpha), Interferon Gamma (IFN-alpha) and interleukins such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12 etc. are found as important immune components. Finally, it has been shown that, acute, brief naturalistic and chronic stress have different immune modulatory activities which are harmful to one's homeostasis and relaxation can help to maintain that homeostasis.

  7. Mallotus roxburghianus modulates antioxidant responses in pancreas of diabetic rats.

    PubMed

    Roy, V K; Chenkual, L; Gurusubramanian, G

    2016-03-01

    Mallotus roxburghianus has long been used by Mizo tribal people for the treatment of diabetes. Scientific validation at known doses may provide information about its safety and efficacy. Methanolic leaf extract of M. roxburghianus (MRME 100 and 400mg/kg) was tested in comparison with normal and alloxan diabetic rats for 28 days p.o. in terms of body and pancreatic weight, blood glucose level, antioxidant enzymes, expression of visfatin and PCNA, histopathology and histomorphometric measurements of pancreas. The results were evaluated statistically using ANOVA, correlation and regression and Principal component analysis (PCO). MRME (100 and 400mg/kg) treatment significantly (p<0.0001) decreased the body weight, blood glucose level, improved the mass and size of pancreas, elevated the levels of antioxidant enzymes and up regulate the expression of visfatin and PCNA. PCO analysis was good to fitness and prediction distinguishes the therapeutic effects of M. roxburghianus from the alloxan induced diabetic rats. MRME has significant role in protecting animals from alloxan-induced diabetic oxidative stress in pancreas and exhibited promising antihyperglycaemic and antioxidant activities along with significant reversal of disturbed antioxidant status and lipid peroxidative damage. Pancreatic architecture and physiology under diabetic oxidative stress have been significantly modulated by MRME and validated as a drug candidate for antidiabetic treatment. M. roxburghianus treatment restores the antioxidant enzyme system and rejuvenates the islets mass in alloxanized rat by accelerating visfatin and PCNA expression in pancreatic tissue.

  8. Adult attachment style modulates neural responses in a mentalizing task.

    PubMed

    Schneider-Hassloff, H; Straube, B; Nuscheler, B; Wemken, G; Kircher, T

    2015-09-10

    Adult attachment style (AAS) is a personality trait that affects social cognition. Behavioral data suggest that AAS influences mentalizing proficiency, i.e. the ability to predict and explain people's behavior with reference to mental states, but the neural correlates are unknown. We here tested how the AAS dimensions "avoidance" (AV) and "anxiety" (ANX) modulate neural correlates of mentalizing. We measured brain activation using functional magnetic resonance imaging (fMRI) in 164 healthy subjects during an interactive mentalizing paradigm (Prisoner's Dilemma Game). AAS was assessed with the Relationship Scales Questionnaire, including the subscales AV and ANX. Our task elicited a strong activation of the mentalizing network, including bilateral precuneus, (anterior, middle, and posterior) cingulate cortices, temporal poles, inferior frontal gyri (IFG), temporoparietal junctions, superior medial frontal gyri as well as right medial orbital frontal gyrus, superior temporal gyrus, middle frontal gyrus (MFG), and amygdala. We found that AV is positively and ANX negatively correlated with task-associated neural activity in the right amygdala, MFG, midcingulate cortex, and superior parietal lobule, and in bilateral IFG. These data suggest that avoidantly attached adults activate brain areas implicated in emotion regulation and cognitive control to a larger extent than anxiously attached individuals during mentalizing.

  9. Response of Rhesus Macaques (Macaca mulatta) to the Body of a Group Member That Died from a Fatal Attack

    PubMed Central

    Buhl, Jacqueline S.; Aure, Bonn; Ruiz-Lambides, Angelina; Gonzalez-Martinez, Janis; Platt, Michael L.; Brent, Lauren J. N.

    2013-01-01

    Among animals that form social bonds, the death of a conspecific may be a significant social event, representing the loss of an ally and resulting in disruptions to the dominance hierarchy. Despite this potential biological importance, we have only limited knowledge of animals' reactions to the death of a group member. This is particularly true of responses to dead adults, as most reports describe the responses of mothers to dead infants. Here, we describe in detail and provide video evidence of the behavioral responses of a group of free-ranging rhesus macaques (Macaca mulatta) immediately after the death of a mid-ranking adult male as a result of a fatal attack. High-ranking male members of the group, suspected to have carried out the attack, dragged and bit the dead body, exhibiting a rate of aggression 20 times greater than baseline levels. Lower-ranking individuals approached and inspected the body by looking closely, smelling, and grooming the fur. There was inconclusive evidence that these rhesus macaques found the death of a conspecific stressful: Levels of grooming between group members after the fatal attack were significantly higher than baseline levels, and higher than levels of grooming after nonfatal attacks. However, when grooming levels were adjusted based on the assumption that individuals positioned close to the body, i.e., those visible to researchers, were more likely to be engaged in grooming than those positioned farther away, this difference from baseline was no longer significant. The rate of self-directed behaviors after the fatal attack was also not different from baseline. Many of the behaviors we observed directed toward the body (aggression, inspection) have been previously reported in chimpanzees and geladas, and are similar to reactions sometimes displayed by humans. As such, this report represents a potentially valuable contribution the nascent field of nonhuman primate thanatology. PMID:23459587

  10. PRMT5 modulates the metabolic response to fasting signals.

    PubMed

    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.

  11. Modulation of immune responses in stress by Yoga

    PubMed Central

    Arora, Sarika; Bhattacharjee, Jayashree

    2008-01-01

    Stress is a constant factor in today's fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS) and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress. PMID:21829284

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

    PubMed Central

    Walter, Susanna A.; Forsgren, Mikael; Lundengård, Karin; Simon, Rozalyn; Torkildsen Nilsson, Maritha; Söderfeldt, Birgitta; Lundberg, Peter; Engström, Maria

    2016-01-01

    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. PMID:26930498

  13. A circuit for pupil orienting responses: implications for cognitive modulation of pupil size.

    PubMed

    Wang, Chin-An; Munoz, Douglas P

    2015-08-01

    Pupil size, as a component of orienting, changes rapidly in response to local salient events in the environment, in addition to its well-known illumination-dependent modulation. Recent research has shown that visual, auditory, or audiovisual stimuli can elicit transient pupil dilation, and the timing and size of the evoked responses are systematically modulated by stimulus salience. Moreover, weak microstimulation of the superior colliculus (SC), a midbrain structure involved in eye movements and attention, evokes similar transient pupil dilation, suggesting that the SC coordinates the orienting response which includes transient pupil dilation. Projections from the SC to the pupil control circuitry provide a novel neural substrate underlying pupil modulation by various cognitive processes.

  14. Pupil size directly modulates the feedforward response in human primary visual cortex independently of attention.

    PubMed

    Bombeke, Klaas; Duthoo, Wout; Mueller, Sven C; Hopf, Jens-Max; Boehler, C Nico

    2016-02-15

    Controversy revolves around the question of whether psychological factors like attention and emotion can influence the initial feedforward response in primary visual cortex (V1). Although traditionally, the electrophysiological correlate of this response in humans (the C1 component) has been found to be unaltered by psychological influences, a number of recent studies have described attentional and emotional modulations. Yet, research into psychological effects on the feedforward V1 response has neglected possible direct contributions of concomitant pupil-size modulations, which are known to also occur under various conditions of attentional load and emotional state. Here we tested the hypothesis that such pupil-size differences themselves directly affect the feedforward V1 response. We report data from two complementary experiments, in which we used procedures that modulate pupil size without differences in attentional load or emotion while simultaneously recording pupil-size and EEG data. Our results confirm that pupil size indeed directly influences the feedforward V1 response, showing an inverse relationship between pupil size and early V1 activity. While it is unclear in how far this effect represents a functionally-relevant adaptation, it identifies pupil-size differences as an important modulating factor of the feedforward response of V1 and could hence represent a confounding variable in research investigating the neural influence of psychological factors on early visual processing.

  15. Modulation of Human Immune Response by Fungal Biocontrol Agents

    PubMed Central

    Konstantinovas, Cibele; de Oliveira Mendes, Tiago A.; Vannier-Santos, Marcos A.; Lima-Santos, Jane

    2017-01-01

    Although the vast majority of biological control agents is generally regarded as safe for humans and environment, the increased exposure of agriculture workers, and consumer population to fungal substances may affect the immune system. Those compounds may be associated with both intense stimulation, resulting in IgE-mediated allergy and immune downmodulation induced by molecules such as cyclosporin A and mycotoxins. This review discusses the potential effects of biocontrol fungal components on human immune responses, possibly associated to infectious, inflammatory diseases, and defective defenses. PMID:28217107

  16. Modulating the pituitary-adrenal response to stress

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.

    1975-01-01

    Serotonin is believed to be a transmitter or regulator of neuronal function. A possible relationship between the pituitary-adrenal secretion of steroids and brain serotonin in the rat was investigated by evaluating the effects of altering brain 5-hydroxy tryptamine (HT) levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. The approach was either to inhibit brain 5-HT synthesis with para-chlorophenyl alanine or to raise its level with precursors such as tryptophan or 5-hydroxy tryptophan.

  17. Modulation of Human Immune Response by Fungal Biocontrol Agents.

    PubMed

    Konstantinovas, Cibele; de Oliveira Mendes, Tiago A; Vannier-Santos, Marcos A; Lima-Santos, Jane

    2017-01-01

    Although the vast majority of biological control agents is generally regarded as safe for humans and environment, the increased exposure of agriculture workers, and consumer population to fungal substances may affect the immune system. Those compounds may be associated with both intense stimulation, resulting in IgE-mediated allergy and immune downmodulation induced by molecules such as cyclosporin A and mycotoxins. This review discusses the potential effects of biocontrol fungal components on human immune responses, possibly associated to infectious, inflammatory diseases, and defective defenses.

  18. 'Green revolution' genes encode mutant gibberellin response modulators.

    PubMed

    Peng, J; Richards, D E; Hartley, N M; Murphy, G P; Devos, K M; Flintham, J E; Beales, J; Fish, L J; Worland, A J; Pelica, F; Sudhakar, D; Christou, P; Snape, J W; Gale, M D; Harberd, N P

    1999-07-15

    World wheat grain yields increased substantially in the 1960s and 1970s because farmers rapidly adopted the new varieties and cultivation methods of the so-called 'green revolution'. The new varieties are shorter, increase grain yield at the expense of straw biomass, and are more resistant to damage by wind and rain. These wheats are short because they respond abnormally to the plant growth hormone gibberellin. This reduced response to gibberellin is conferred by mutant dwarfing alleles at one of two Reduced height-1 (Rht-B1 and Rht-D1) loci. Here we show that Rht-B1/Rht-D1 and maize dwarf-8 (d8) are orthologues of the Arabidopsis Gibberellin Insensitive (GAI) gene. These genes encode proteins that resemble nuclear transcription factors and contain an SH2-like domain, indicating that phosphotyrosine may participate in gibberellin signalling. Six different orthologous dwarfing mutant alleles encode proteins that are altered in a conserved amino-terminal gibberellin signalling domain. Transgenic rice plants containing a mutant GAI allele give reduced responses to gibberellin and are dwarfed, indicating that mutant GAI orthologues could be used to increase yield in a wide range of crop species.

  19. Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation

    PubMed Central

    Sánchez, Jon Andoni; Alfonso, Amparo; Rodriguez, Ines; Alonso, Eva; Cifuentes, José Manuel; Bermudez, Roberto; Rateb, Mostafa E.; Jaspars, Marcel; Houssen, Wael E.; Ebel, Rainer; Tabudravu, Jioji; Botana, Luís M.

    2016-01-01

    The modulation of the immune system can have multiple applications such as cancer treatment, and a wide type of processes involving inflammation where the potent chemotactic agent cyclophilin A (Cyp A) is implicated. The Porifera phylum, in which Spongionella is encompassed, is the main producer of marine bioactive compounds. Four secondary metabolites obtained from Spongionella (Gracilin H, A, L, and Tetrahydroaplysulphurin-1) were described to hit Cyp A and to block the release of inflammation mediators. Based on these results, some role of Spongionella compounds on other steps of the signaling pathway mediated by this chemotactic agent can be hypothesized. In the present paper, we studied the effect of these four compounds on the surface membrane CD147 receptor expression, on the extracellular levels of Cyp A and on the ability to migrate of concanavalin (Con A)-activated T lymphocytes. Similar to a well-known immunosuppressive agent cyclosporine A (CsA), Gracilin H, A, L, and tetrahydroaplysulphurin-1 were able to reduce the CD147 membrane expression and to block the release of Cyp A to the medium. Besides, by using Cyp A as chemotactic agent, T cell migration was inhibited when cells were previously incubated with Gracilin A and Gracilin L. These positive results lead us to test the in vivo effect of Gracilin H and L in a mouse ear delayed hypersensitive reaction. Thus, both compounds efficiently reduce the ear swelling as well as the inflammatory cell infiltration. These results provide more evidences for their potential therapeutic application in immune-related diseases of Spongionella compounds. PMID:27822214

  20. Urokinase receptor modulates cellular and angiogenic responses in obstructive nephropathy.

    PubMed

    Zhang, Guoqiang; Kim, Heungsoo; Cai, Xiaohe; Lopez-Guisa, Jesus M; Carmeliet, Peter; Eddy, Allison A

    2003-05-01

    Interstitial cells have been implicated in the pathogenesis of renal fibrosis. Given that the urokinase receptor (uPAR) is known to play a role in cell adhesion, migration, and angiogenesis, the present study was designed to evaluate the role of uPAR in the regulation of the phenotypic composition of interstitial cells (macrophages, myofibroblasts, capillaries) in response to chronic renal injury. Groups of uPAR wild-type (+/+) and knockout (-/-) mice were investigated between 3 and 14 d after unilateral ureteral obstruction (UUO) or sham surgery (n = 8 mice per group). The density of F4/80+ interstitial macrophages (Mphi) was significantly lower in the -/- mice (3.3 +/- 0.4 versus 6.9 +/- 1.7% area at day 3 UUO; 10.8 +/- 1.6 versus 15.7 +/- 1.0% at day 14 UUO; -/- versus +/+). In contrast, in the -/- mice there were significantly more alpha smooth muscle actin (alphaSMA)-positive cells (12.9 +/- 3.2 versus 7.8 +/- 1.5% area at day 3 UUO; 21.0 +/- 4.7 versus 9.7 +/- 1.9% at day 14 UUO) and CD34-positive endothelial cells (8.4 +/- 1.9 versus 4.0 +/- 1.1% area at day 14 UUO). These differences were associated with significantly more interstitial fibrosis in the -/- mice based on Sirius red staining (4.6 +/- 0.9 versus 2.3 +/- 0.9% area at 14 d UUO). Absence of the uPAR scavenger receptor was associated with significantly greater accumulation of plasminogen activator inhibitor-1 protein (PAI-1) (20.5 +/- 3.5 versus 9.1 +/- 2.9% area, day 14 UUO) and vitronectin protein (2.4 +/- 1.1 versus 0.9 +/- 0.4% area, day 14 UUO). By immunostaining alphaSMA+ cells, CD34+ cells, vitronectin and PAI-1 co-localized to the same tubulointerstitial area. The number of apoptotic cells increased in response to UUO but was significantly higher in the -/- mice (2.0 +/- 0.2 versus 1.2 +/- 0.2 per 100 tubulointerstitial cells, day 14 UUO) while the number of proliferating cells was significantly lower in the uPAR-/- mice. These data suggest that uPAR deficiency suppresses renal Mphi

  1. Attention to primes modulates affective priming of pronunciation responses.

    PubMed

    De Houwer, Jan; Randell, Tom

    2002-01-01

    In studies on affective priming of pronunciation responses, two words are presented on each trial and participants are asked to read the second word out loud. Whereas some studies revealed shorter reaction times when the two words had the same valence than when they had a different valence, other studies either found no effect of affective congruence or revealed a reversed effect. In the present experiments, a significant effect of affective congruence only emerged when filler trials were presented in which the prime and target were identical and participants were instructed to attend to the primes (Experiment 2). No effects were found when participants were merely instructed to attend to or ignore the primes (Experiment 1), or when affectively incongruent filler trials were presented and participants were instructed to ignore the primes (Experiment 2).

  2. Acute Exercise Modulates Feature-selective Responses in Human Cortex.

    PubMed

    Bullock, Tom; Elliott, James C; Serences, John T; Giesbrecht, Barry

    2017-04-01

    An organism's current behavioral state influences ongoing brain activity. Nonhuman mammalian and invertebrate brains exhibit large increases in the gain of feature-selective neural responses in sensory cortex during locomotion, suggesting that the visual system becomes more sensitive when actively exploring the environment. This raises the possibility that human vision is also more sensitive during active movement. To investigate this possibility, we used an inverted encoding model technique to estimate feature-selective neural response profiles from EEG data acquired from participants performing an orientation discrimination task. Participants (n = 18) fixated at the center of a flickering (15 Hz) circular grating presented at one of nine different orientations and monitored for a brief shift in orientation that occurred on every trial. Participants completed the task while seated on a stationary exercise bike at rest and during low- and high-intensity cycling. We found evidence for inverted-U effects; such that the peak of the reconstructed feature-selective tuning profiles was highest during low-intensity exercise compared with those estimated during rest and high-intensity exercise. When modeled, these effects were driven by changes in the gain of the tuning curve and in the profile bandwidth during low-intensity exercise relative to rest. Thus, despite profound differences in visual pathways across species, these data show that sensitivity in human visual cortex is also enhanced during locomotive behavior. Our results reveal the nature of exercise-induced gain on feature-selective coding in human sensory cortex and provide valuable evidence linking the neural mechanisms of behavior state across species.

  3. When the forest dies: the response of forest soil fungi to a bark beetle-induced tree dieback.

    PubMed

    Stursová, Martina; Snajdr, Jaroslav; Cajthaml, Tomáš; Bárta, Jiří; Santrůčková, Hana; Baldrian, Petr

    2014-09-01

    Coniferous forests cover extensive areas of the boreal and temperate zones. Owing to their primary production and C storage, they have an important role in the global carbon balance. Forest disturbances such as forest fires, windthrows or insect pest outbreaks have a substantial effect on the functioning of these ecosystems. Recent decades have seen an increase in the areas affected by disturbances in both North America and Europe, with indications that this increase is due to both local human activity and global climate change. Here we examine the structural and functional response of the litter and soil microbial community in a Picea abies forest to tree dieback following an invasion of the bark beetle Ips typographus, with a specific focus on the fungal community. The insect-induced disturbance rapidly and profoundly changed vegetation and nutrient availability by killing spruce trees so that the readily available root exudates were replaced by more recalcitrant, polymeric plant biomass components. Owing to the dramatic decrease in photosynthesis, the rate of decomposition processes in the ecosystem decreased as soon as the one-time litter input had been processed. The fungal community showed profound changes, including a decrease in biomass (2.5-fold in the litter and 12-fold in the soil) together with the disappearance of fungi symbiotic with tree roots and a relative increase in saprotrophic taxa. Within the latter group, successive changes reflected the changing availability of needle litter and woody debris. Bacterial biomass appeared to be either unaffected or increased after the disturbance, resulting in a substantial increase in the bacterial/fungal biomass ratio.

  4. When the forest dies: the response of forest soil fungi to a bark beetle-induced tree dieback

    PubMed Central

    Štursová, Martina; Šnajdr, Jaroslav; Cajthaml, Tomáš; Bárta, Jiří; Šantrůčková, Hana; Baldrian, Petr

    2014-01-01

    Coniferous forests cover extensive areas of the boreal and temperate zones. Owing to their primary production and C storage, they have an important role in the global carbon balance. Forest disturbances such as forest fires, windthrows or insect pest outbreaks have a substantial effect on the functioning of these ecosystems. Recent decades have seen an increase in the areas affected by disturbances in both North America and Europe, with indications that this increase is due to both local human activity and global climate change. Here we examine the structural and functional response of the litter and soil microbial community in a Picea abies forest to tree dieback following an invasion of the bark beetle Ips typographus, with a specific focus on the fungal community. The insect-induced disturbance rapidly and profoundly changed vegetation and nutrient availability by killing spruce trees so that the readily available root exudates were replaced by more recalcitrant, polymeric plant biomass components. Owing to the dramatic decrease in photosynthesis, the rate of decomposition processes in the ecosystem decreased as soon as the one-time litter input had been processed. The fungal community showed profound changes, including a decrease in biomass (2.5-fold in the litter and 12-fold in the soil) together with the disappearance of fungi symbiotic with tree roots and a relative increase in saprotrophic taxa. Within the latter group, successive changes reflected the changing availability of needle litter and woody debris. Bacterial biomass appeared to be either unaffected or increased after the disturbance, resulting in a substantial increase in the bacterial/fungal biomass ratio. PMID:24671082

  5. Displaced capillary dies

    DOEpatents

    Kalejs, Juris P.; Chalmers, Bruce; Surek, Thomas

    1984-01-01

    An asymmetrical shaped capillary die made exclusively of graphite is used to grow silicon ribbon which is capable of being made into solar cells that are more efficient than cells produced from ribbon made using a symmetrically shaped die.

  6. Displaced capillary dies

    DOEpatents

    Kalejs, Juris P.; Chalmers, Bruce; Surek, Thomas

    1982-01-01

    An asymmetrical shaped capillary die made exclusively of graphite is used to grow silicon ribbon which is capable of being made into solar cells that are more efficient than cells produced from ribbon made using a symmetrically shaped die.

  7. Vestibular activation differentially modulates human early visual cortex and V5/MT excitability and response entropy.

    PubMed

    Seemungal, Barry M; Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

    2013-01-01

    Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC.

  8. Dissociable Neural Response Signatures for Slow Amplitude and Frequency Modulation in Human Auditory Cortex

    PubMed Central

    Henry, Molly J.; Obleser, Jonas

    2013-01-01

    Natural auditory stimuli are characterized by slow fluctuations in amplitude and frequency. However, the degree to which the neural responses to slow amplitude modulation (AM) and frequency modulation (FM) are capable of conveying independent time-varying information, particularly with respect to speech communication, is unclear. In the current electroencephalography (EEG) study, participants listened to amplitude- and frequency-modulated narrow-band noises with a 3-Hz modulation rate, and the resulting neural responses were compared. Spectral analyses revealed similar spectral amplitude peaks for AM and FM at the stimulation frequency (3 Hz), but amplitude at the second harmonic frequency (6 Hz) was much higher for FM than for AM. Moreover, the phase delay of neural responses with respect to the full-band stimulus envelope was shorter for FM than for AM. Finally, the critical analysis involved classification of single trials as being in response to either AM or FM based on either phase or amplitude information. Time-varying phase, but not amplitude, was sufficient to accurately classify AM and FM stimuli based on single-trial neural responses. Taken together, the current results support the dissociable nature of cortical signatures of slow AM and FM. These cortical signatures potentially provide an efficient means to dissect simultaneously communicated slow temporal and spectral information in acoustic communication signals. PMID:24205309

  9. Modulation of T cell response by Phellinus linteus.

    PubMed

    Lin, Chun-Jung; Lien, Hsiu-Man; Lin, Hwai-Jeng; Huang, Chao-Lu; Kao, Min-Chuan; Chen, Yu-An; Wang, Chien-Kuo; Chang, Hsiao-Yun; Chang, Yin-Kuang; Wu, Hua-Shan; Lai, Chih-Ho

    2016-01-01

    Phellinus linteus, a species of mushroom, has been shown to contribute to health benefits, such as anti-inflammatory activity and immunomodulatory efficacy. The aim of this study was to analyze the most effective constituents of P. linteus fermented broths, polysaccharides, and to evaluate their immunoregulatory effects on T cells. Four fermented broths (PL1-4) and the dialyzate medium (MD) were prepared from P. linteus mycelia, and the polysaccharide contents of each were analyzed. The P. linteus samples were tested for biological activity in the regulation of T cell activation. In T cells, the production of mitogen-induced interleukin (IL)-2 and cell cycle progression were dose-responsively inhibited by PL3 and MD, primarily through cell-cycle arrest in S phase. PL3 broth, which contained large quantities of polysaccharides, significantly decreased the ratio of interferon-gamma (IFN-γ) to interleukin 4 (IL-4) in T cells. Thus, P. linteus fermented broths produced additive effects on the regulation of the Th1/Th2 balance and show promise for the development of immunomodulatory therapeutics.

  10. WWOX modulates the ATR-mediated DNA damage checkpoint response.

    PubMed

    Abu-Odeh, Mohammad; Hereema, Nyla A; Aqeilan, Rami I

    2016-01-26

    For many decades genomic instability is considered one of the hallmarks of cancer. Role of the tumor suppressor WWOX (WW domain-containing oxidoreductase) in DNA damage response upon double strand breaks has been recently revealed. Here we demonstrate unforeseen functions for WWOX upon DNA single strand breaks (SSBs) checkpoint activation. We found that WWOX levels are induced following SSBs and accumulate in the nucleus. WWOX deficiency is associated with reduced activation of ataxia telangiectasia and Rad3-related protein (ATR) checkpoint proteins and increased chromosomal breaks. At the molecular level, we show that upon SSBs WWOX is modified at lysine 274 by ubiquitination mediated by the ubiquitin E3 ligase ITCH and interacts with ataxia telangiectasia-mutated (ATM). Interestingly, ATM inhibition was associated with reduced activation of ATR checkpoint proteins suggesting that WWOX manipulation of ATR checkpoint proteins is ATM-dependent. Taken together, the present findings indicate that WWOX plays a key role in ATR checkpoint activation, while its absence might facilitate genomic instability.

  11. WWOX modulates the ATR-mediated DNA damage checkpoint response

    PubMed Central

    Abu-Odeh, Mohammad; Hereema, Nyla A.; Aqeilan, Rami I.

    2016-01-01

    For many decades genomic instability is considered one of the hallmarks of cancer. Role of the tumor suppressor WWOX (WW domain-containing oxidoreductase) in DNA damage response upon double strand breaks has been recently revealed. Here we demonstrate unforeseen functions for WWOX upon DNA single strand breaks (SSBs) checkpoint activation. We found that WWOX levels are induced following SSBs and accumulate in the nucleus. WWOX deficiency is associated with reduced activation of ataxia telangiectasia and Rad3-related protein (ATR) checkpoint proteins and increased chromosomal breaks. At the molecular level, we show that upon SSBs WWOX is modified at lysine 274 by ubiquitination mediated by the ubiquitin E3 ligase ITCH and interacts with ataxia telangiectasia-mutated (ATM). Interestingly, ATM inhibition was associated with reduced activation of ATR checkpoint proteins suggesting that WWOX manipulation of ATR checkpoint proteins is ATM-dependent. Taken together, the present findings indicate that WWOX plays a key role in ATR checkpoint activation, while its absence might facilitate genomic instability. PMID:26675548

  12. Melatonin Regulates Root Architecture by Modulating Auxin Response in Rice

    PubMed Central

    Liang, Chengzhen; Li, Aifu; Yu, Hua; Li, Wenzhen; Liang, Chengzhi; Guo, Sandui; Zhang, Rui; Chu, Chengcai

    2017-01-01

    It has been suggested that melatonin acts as an important regulator in controlling root growth and development, but the underlying molecular mechanism driving this relationship remains undetermined. In this study, we demonstrated that melatonin acts as a potent molecule to govern root architecture in rice. Treatments with melatonin significantly inhibited embryonic root growth, and promoted lateral root formation and development. Genome-wide expression profiling by RNA-sequencing revealed auxin-related genes were significantly activated under melatonin treatment. Moreover, several transcription factors and candidate cis-regulatory elements involved in root growth and developments, as well as auxin-related processes, were over-represented in both co-up and -down differentially expressed genes, suggesting that melatonin-mediated root growth occurs in an auxin signal pathway-dependent manner. Further, gravitropic response analysis determined that melatonin affects auxin-regulated processes in rice root. These data show that melatonin shapes root architecture by directly or indirectly activating the auxin signaling pathway. PMID:28223997

  13. Optically addressed and submillisecond response phase only liquid crystal spatial light modulator

    NASA Astrophysics Data System (ADS)

    Zhao, Xiangjie; Duan, Jiazhu; Zhang, Dayong; Luo, Yongquan

    2014-10-01

    Liquid crystal based phase only spatial light modulator has attracted many research interests since last decades because of its superior advantage. Until now the liquid crystal spatial light modulator has been applied in many fields, but the response speed of nematic LC limited its further application. In this paper, an optically addressed phase only LC spatial light modulator was proposed based on polymer network liquid crystal. Morphology effect on the light scattering of PNLC was studied, which was mainly consisted of fiber and fiber bundles. The morphology nearly determined the light scattering and electro-optical property. Due to the high threshold voltage, to address the PNLC phase modulator was also concerned. Optical addressing method was proposed, in which BSO crystal was selected to replace one of the glass substrate. The response speed of PNLC was so fast that the reorientation of liquid crystal director will follow the change of effective voltage applied on LC layer, which was related with the voltage signal and especially with electron transport of photo-induced carriers due to diffusion and drift. The on state dynamic response of phase change was investigated. Based on this device, beam steering was also achieved by loading 488nm laser strip on the optical addressed phase only spatial light modulator.

  14. To live or to die? Evidence of variable drivers of wood d13C reveal different responses to disturbance in co-occurring oaks

    NASA Astrophysics Data System (ADS)

    Reed, A. S.; Stephen, F. M.; Billings, S. A.

    2011-12-01

    A major oak decline event in recent decades in Northwest Arkansas permits insight into disturbance impacts on forests, which is important for understanding global carbon, nutrient and climate cycles given projections of increasing disturbance event frequency in the future. The decline event, associated with an increase in population of a native, wood-boring insect, followed a cycle of droughts and resulted in a mosaic of apparently healthy red oaks (Quercus rubra) neighboring severely declining trees of the same species. Tree-ring evidence suggests decreased growth rates following increases in the insect's population decades prior to visible external decline symptoms (i.e. decreased crown coverage, mortality), but only in trees destined to die during the insect outbreak. Reasons why some trees experienced mortality and some remained healthy are unclear. Through analysis of stable isotopes of carbon (δ13C) and oxygen (δ18O) in wood and leaf δ13C and nitrogen among co-occurring trees, we can infer differential responses of red oaks to disturbance and associated resilience to mortality. Tree-ring a-cellulose δ13C varied from -27.3to -23.0%, and δ18O values varied from 27.5 to 31.8%. Neither δ13C nor δ18O exhibited signficant differences between healthy and declining trees. However, declining trees exhibited a significant, positive relationship between δ13C and δ18O (p <0.05, r2=0.15) prior to peak insect infestation. In contrast, apparently healthy individuals did not exhibit a significant relationship between these parameters, but exhibited significant, positive relationships between current year leaf δ13C and nitrogen content (p<0.05, r2=0.77). These results suggest that healthy and declining trees had different strategies for coping with insect infestation. Correlation between tree-ring δ13C and δ18O in dying trees suggests that trees destined to die during the infestation regulated their δ13C values primarily via stomatal conductance, a mechanism that

  15. The Ambiguous Dying Syndrome

    ERIC Educational Resources Information Center

    Bern-Klug, Mercedes

    2004-01-01

    More than one-half of the 2.4 million deaths that will occur in the United States in 2004 will be immediately preceded by a time in which the likelihood of dying can best be described as "ambiguous." Many people die without ever being considered "dying" or "at the end of life." These people may miss out on the…

  16. cGMP modulates responses to queen mandibular pheromone in worker honey bees

    PubMed Central

    Fussnecker, Brendon L.; McKenzie, Alexander M.; Grozinger, Christina M.

    2013-01-01

    Responses to social cues, such as pheromones, can be modified by genotype, physiology, or environmental context. Honey bee queens produce a pheromone (queen mandibular pheromone; QMP) which regulates aspects of worker bee behavior and physiology. Forager bees are less responsive to QMP than young bees engaged in brood care, suggesting that physiological changes associated with behavioral maturation modulate response to this pheromone. Since 3′, 5′-cyclic guanosine monophosphate (cGMP) is a major regulator of behavioral maturation in workers, we examined its role in modulating worker responses to QMP. Treatment with a cGMP analog resulted in significant reductions in both behavioral and physiological responses to QMP in young caged workers. Treatment significantly reduced attraction to QMP and inhibited the QMP-mediated increase in vitellogenin RNA levels in the fat bodies of worker bees. Genome-wide analysis of brain gene expression patterns demonstrated that cGMP has a larger effect on expression levels than QMP, and that QMP has specific effects in the presence of cGMP, suggesting that some responses to QMP may be dependent on an individual bees' physiological state. Our data suggest that cGMP-mediated processes play a role in modulating responses to QMP in honey bees at the behavioral, physiological, and molecular levels. PMID:21626397

  17. Oxytocin, but not vassopressin, modulates nociceptive responses in dorsal horn neurons.

    PubMed

    Rojas-Piloni, Gerardo; Gerardo, Rojas-Piloni; Mejía-Rodríguez, Rosalinda; Rosalinda, Mejía-Rodríguez; Martínez-Lorenzana, Guadalupe; Guadalupe, Martínez-Lorenzana; Condés-Lara, Miguel; Miguel, Condés-Lara

    2010-05-26

    Oxytocin (OT) and vasopressin (VP) are synthesized and secreted by the paraventricular hypothalamic nucleus (PVN), and both peptides have been implicated in the pain modulatory system. In the spinal cord, activation of OT-containing axons modulates nociceptive neuronal responses in dorsal horn neurons; however, it is not known whether the direct VPergic descending projection participates. Here, we show that both PVN electrical stimulation and topical application of OT in the vicinity of identified and recorded dorsal horn WDR selectively inhibit Adelta and C-fiber responses. In contrast, the topical administration of VP on the same neurons did not affect the nociceptive responses. In addition, the reduction in nociceptive responses caused by PVN stimulation or OT administration was blocked with a selective OT antagonist. The results suggest that the VP descending projection does not modulate the antinociceptive effects mediated by the PVN on dorsal horn neurons; instead, it is the hypothalamic-spinal OT projection that regulates nociceptive information.

  18. Preserved emotional modulation of motor response time despite psychomotor slowing in young-old adults.

    PubMed

    Hälbig, Thomas D; Creighton, Judy; Assuras, Stephanie; Borod, Joan C; Tse, Winona; Gracies, Jean-Michel; Foldi, Nancy S; Kaufmann, Horacio; Olanow, C Warren; Voustianiouk, Andrei

    2011-08-01

    Whereas aging affects cognitive and psychomotor processes negatively, the impact of aging on emotional processing is less clear. Using an "old-new" binary decision task, we ascertained the modulation of response latencies after presentation of neutral and emotional pictures in "young" (M = 27.1 years) and "young-old" adults with a mean age below 60 (M = 57.7 years). Stimuli varied on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Young-old adults had significantly longer reaction times. However, young and young-old adults showed the exact same pattern of response time modulation by emotional stimuli: Response latencies were longer for high-arousal than for low-arousal pictures and longer for negative than for positive or neutral stimuli. This result suggests that the specific effects of implicitly processed emotional valence and arousal information on behavioral response time are preserved in young-old adults despite significant age-related psychomotor decline.

  19. Project S.P.I.C.E.: Special Partnership in Career Education. Rights and Responsibility Teaching Module.

    ERIC Educational Resources Information Center

    Emerson, Debby H.; And Others

    The rights and responsibility teaching module is one of a series of six modules prepared by Project SPICE (Special Partnership in Career Education) as a means of providing career awareness information to educable mentally handicapped students (ages 11-to-13 years). After an overview, a module profile is provided which charts the activities, and…

  20. An Evaluation of the Response Modulation Hypothesis in Relation to Attention-Deficit/ Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Farmer, Richard F.; Rucklidge, Julia J.

    2006-01-01

    Several hypotheses related to Newman's (e.g., Patterson & Newman, 1993) response modulation hypothesis were examined among adolescents with attention-deficit/hyperactivity disorder (ADHD; n = 18) and normal controls (n = 23). Consistent with predictions, youth with ADHD committed more passive avoidance errors (PAEs) than controls during the latter…

  1. Stress Response Recruits the Hippocampal Endocannabinoid System for the Modulation of Fear Memory

    ERIC Educational Resources Information Center

    Alvares, Lucas de Oliveira; Engelke, Douglas Senna; Diehl, Felipe; Scheffer-Teixeira, Robson; Haubrich, Josue; Cassini, Lindsey de Freitas; Molina, Victor Alejandro; Quillfeldt, Jorge Alberto

    2010-01-01

    The modulation of memory processes is one of the several functions of the endocannabinoid system (ECS) in the brain, with CB1 receptors highly expressed in areas such as the dorsal hippocampus. Experimental evidence suggested an important role of the ECS in aversively motivated memories. Similarly, glucocorticoids released in response to stress…

  2. The Response Scale for the Intellectual Disability Module of the WHOQOL: 5-Point or 3-Point?

    ERIC Educational Resources Information Center

    Fang, J.; Fleck, M. P.; Green, A.; McVilly, K.; Hao, Y.; Tan, W.; Fu, R.; Power, M.

    2011-01-01

    Objective: To deal with the question of whether a 5-point response Likert scale should be changed to a 3-point scale when used in the field testing of people with intellectual disabilities (IDs), which was raised after the pilot study of World Health Organization Quality of Life (WHOQOL)-DIS, a module being developed with the World Health…

  3. An NCME Instructional Module on Estimating Item Response Theory Models Using Markov Chain Monte Carlo Methods

    ERIC Educational Resources Information Center

    Kim, Jee-Seon; Bolt, Daniel M.

    2007-01-01

    The purpose of this ITEMS module is to provide an introduction to Markov chain Monte Carlo (MCMC) estimation for item response models. A brief description of Bayesian inference is followed by an overview of the various facets of MCMC algorithms, including discussion of prior specification, sampling procedures, and methods for evaluating chain…

  4. An NCME Instructional Module on Item-Fit Statistics for Item Response Theory Models

    ERIC Educational Resources Information Center

    Ames, Allison J.; Penfield, Randall D.

    2015-01-01

    Drawing valid inferences from item response theory (IRT) models is contingent upon a good fit of the data to the model. Violations of model-data fit have numerous consequences, limiting the usefulness and applicability of the model. This instructional module provides an overview of methods used for evaluating the fit of IRT models. Upon completing…

  5. Individual Differences in Mathematical Competence Modulate Brain Responses to Arithmetic Errors: An fMRI Study

    ERIC Educational Resources Information Center

    Ansari, Daniel; Grabner, Roland H.; Koschutnig, Karl; Reishofer, Gernot; Ebner, Franz

    2011-01-01

    Data from both neuropsychological and neuroimaging studies have implicated the left inferior parietal cortex in calculation. Comparatively less attention has been paid to the neural responses associated with the commission of calculation errors and how the processing of arithmetic errors is modulated by individual differences in mathematical…

  6. Baseline and Modulated Acoustic Startle Responses in Adolescent Girls with Posttraumatic Stress Disorder

    ERIC Educational Resources Information Center

    Lipschitz, Deborah S.; Mayes, Linda M.; Rasmusson, Ann M.; Anyan, Walter; Billingslea, Eileen; Gueorguieva, Ralitza; Southwick, Steven M.

    2005-01-01

    Objective: To assess baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder (PTSD). Method: Twenty-eight adolescent girls with PTSD and 23 healthy control girls were recruited for participation in the study. Acoustic stimuli were bursts of white noise of 104 dB presented biaurally through…

  7. HIGH PRESSURE DIES

    DOEpatents

    Wilson, W.B.

    1960-05-31

    A press was invented for subjecting specimens of bismuth, urania, yttria, or thoria to high pressures and temperatures. The press comprises die parts enclosing a space in which is placed an electric heater thermally insulated from the die parts so as not to damage them by heat. The die parts comprise two opposed inner frustoconical parts and an outer part having a double frustoconical recess receiving the inner parts. The die space decreases in size as the inner die parts move toward one another against the outer part and the inner parts, though very hard, do not fracture because of the mode of support provided by the outer part.

  8. Preexisting antigen-specific immune responses are modulated by oral KLH feeding in humans.

    PubMed

    Hostmann, Arwed; Meyer, Tim; Maul, Jochen; Preiss, Jan; Boortz, Bertram; Thiel, Andreas; Duchmann, Rainer; Ullrich, Reiner

    2015-07-01

    Oral tolerance is the antigen-specific inhibition of a systemic immune response after oral antigen uptake and well established in animal models. We recently showed that keyhole limpet hemocyanin (KLH) feeding modulates subsequently induced systemic immune responses in humans as well. In the present study, we investigated whether oral KLH can also modulate preexisting antigen-specific systemic B- and T-cell responses. We induced delayed-type hypersensitivity (DTH) reactions as well as systemic KLH-specific B- and T-cell responses by subcutaneous KLH injections. Subsequent oral KLH administration decreased the small proportion of antigen-specific CD4(+) T cells positive for the cytokine IL-17 at the end of the feeding regimen even further. After reimmunization, there was no difference in DTH reactions and the KLH-specific B-cell responses, but KLH-fed volunteers had an increased proportion of antigen-specific CD4(+) T cells positive for IL-10 and a reduced proportion of antigen-specific CD4(+) T cells positive for the skin-homing receptor cutaneous lymphocyte antigen and IL-2 and IFN-γ. Taken together, oral KLH can modulate a preexisting systemic KLH-specific immune response. These results suggest that feeding antigen may offer therapeutic strategies for the suppression of unwanted immune reactions in humans.

  9. A surface ice module for wind turbine dynamic response simulation using FAST

    DOE PAGES

    Yu, Bingbin; Karr, Dale G.; Song, Huimin; ...

    2016-06-03

    It is a fact that developing offshore wind energy has become more and more serious worldwide in recent years. Many of the promising offshore wind farm locations are in cold regions that may have ice cover during wintertime. The challenge of possible ice loads on offshore wind turbines raises the demand of modeling capacity of dynamic wind turbine response under the joint action of ice, wind, wave, and current. The simulation software FAST is an open source computer-aided engineering (CAE) package maintained by the National Renewable Energy Laboratory. In this paper, a new module of FAST for assessing the dynamicmore » response of offshore wind turbines subjected to ice forcing is presented. In the ice module, several models are presented which involve both prescribed forcing and coupled response. For conditions in which the ice forcing is essentially decoupled from the structural response, ice forces are established from existing models for brittle and ductile ice failure. For conditions in which the ice failure and the structural response are coupled, such as lock-in conditions, a rate-dependent ice model is described, which is developed in conjunction with a new modularization framework for FAST. In this paper, analytical ice mechanics models are presented that incorporate ice floe forcing, deformation, and failure. For lower speeds, forces slowly build until the ice strength is reached and ice fails resulting in a quasi-static condition. For intermediate speeds, the ice failure can be coupled with the structural response and resulting in coinciding periods of the ice failure and the structural response. A third regime occurs at high speeds of encounter in which brittle fracturing of the ice feature occurs in a random pattern, which results in a random vibration excitation of the structure. An example wind turbine response is simulated under ice loading of each of the presented models. This module adds to FAST the capabilities for analyzing the response of wind

  10. A surface ice module for wind turbine dynamic response simulation using FAST

    SciTech Connect

    Yu, Bingbin; Karr, Dale G.; Song, Huimin; Sirnivas, Senu

    2016-06-03

    It is a fact that developing offshore wind energy has become more and more serious worldwide in recent years. Many of the promising offshore wind farm locations are in cold regions that may have ice cover during wintertime. The challenge of possible ice loads on offshore wind turbines raises the demand of modeling capacity of dynamic wind turbine response under the joint action of ice, wind, wave, and current. The simulation software FAST is an open source computer-aided engineering (CAE) package maintained by the National Renewable Energy Laboratory. In this paper, a new module of FAST for assessing the dynamic response of offshore wind turbines subjected to ice forcing is presented. In the ice module, several models are presented which involve both prescribed forcing and coupled response. For conditions in which the ice forcing is essentially decoupled from the structural response, ice forces are established from existing models for brittle and ductile ice failure. For conditions in which the ice failure and the structural response are coupled, such as lock-in conditions, a rate-dependent ice model is described, which is developed in conjunction with a new modularization framework for FAST. In this paper, analytical ice mechanics models are presented that incorporate ice floe forcing, deformation, and failure. For lower speeds, forces slowly build until the ice strength is reached and ice fails resulting in a quasi-static condition. For intermediate speeds, the ice failure can be coupled with the structural response and resulting in coinciding periods of the ice failure and the structural response. A third regime occurs at high speeds of encounter in which brittle fracturing of the ice feature occurs in a random pattern, which results in a random vibration excitation of the structure. An example wind turbine response is simulated under ice loading of each of the presented models. This module adds to FAST the capabilities for analyzing the response of wind

  11. Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress

    PubMed Central

    Picard, Martin; McManus, Meagan J.; Gray, Jason D.; Nasca, Carla; Moffat, Cynthia; Kopinski, Piotr K.; Seifert, Erin L.; McEwen, Bruce S.; Wallace, Douglas C.

    2015-01-01

    The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism’s multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic–pituitary–adrenal axis, sympathetic adrenal–medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases. PMID:26627253

  12. Size matters: plasticity in metabolic scaling shows body-size may modulate responses to climate change

    PubMed Central

    Carey, Nicholas; Sigwart, Julia D.

    2014-01-01

    Variability in metabolic scaling in animals, the relationship between metabolic rate (R) and body mass (M), has been a source of debate and controversy for decades. R is proportional to Mb, the precise value of b much debated, but historically considered equal in all organisms. Recent metabolic theory, however, predicts b to vary among species with ecology and metabolic level, and may also vary within species under different abiotic conditions. Under climate change, most species will experience increased temperatures, and marine organisms will experience the additional stressor of decreased seawater pH (‘ocean acidification’). Responses to these environmental changes are modulated by myriad species-specific factors. Body-size is a fundamental biological parameter, but its modulating role is relatively unexplored. Here, we show that changes to metabolic scaling reveal asymmetric responses to stressors across body-size ranges; b is systematically decreased under increasing temperature in three grazing molluscs, indicating smaller individuals were more responsive to warming. Larger individuals were, however, more responsive to reduced seawater pH in low temperatures. These alterations to the allometry of metabolism highlight abiotic control of metabolic scaling, and indicate that responses to climate warming and ocean acidification may be modulated by body-size. PMID:25122741

  13. Size matters: plasticity in metabolic scaling shows body-size may modulate responses to climate change.

    PubMed

    Carey, Nicholas; Sigwart, Julia D

    2014-08-01

    Variability in metabolic scaling in animals, the relationship between metabolic rate ( R: ) and body mass ( M: ), has been a source of debate and controversy for decades. R: is proportional to MB: , the precise value of B: much debated, but historically considered equal in all organisms. Recent metabolic theory, however, predicts B: to vary among species with ecology and metabolic level, and may also vary within species under different abiotic conditions. Under climate change, most species will experience increased temperatures, and marine organisms will experience the additional stressor of decreased seawater pH ('ocean acidification'). Responses to these environmental changes are modulated by myriad species-specific factors. Body-size is a fundamental biological parameter, but its modulating role is relatively unexplored. Here, we show that changes to metabolic scaling reveal asymmetric responses to stressors across body-size ranges; B: is systematically decreased under increasing temperature in three grazing molluscs, indicating smaller individuals were more responsive to warming. Larger individuals were, however, more responsive to reduced seawater pH in low temperatures. These alterations to the allometry of metabolism highlight abiotic control of metabolic scaling, and indicate that responses to climate warming and ocean acidification may be modulated by body-size.

  14. Morphology effect on the light scattering and dynamic response of polymer network liquid crystal phase modulator.

    PubMed

    Xiangjie, Zhao; Cangli, Liu; Jiazhu, Duan; Jiancheng, Zeng; Dayong, Zhang; Yongquan, Luo

    2014-06-16

    Polymer network liquid crystal (PNLC) was one of the most potential liquid crystal for submillisecond response phase modulation, which was possible to be applied in submillisecond response phase only spatial light modulator. But until now the light scattering when liquid crystal director was reoriented by external electric field limited its phase modulation application. Dynamic response of phase change when high voltage was applied was also not elucidated. The mechanism that determines the light scattering was studied by analyzing the polymer network morphology by SEM method. Samples were prepared by varying the polymerization temperature, UV curing intensity and polymerization time. The morphology effect on the dynamic response of phase change was studied, in which high voltage was usually applied and electro-striction effect was often induced. The experimental results indicate that the polymer network morphology was mainly characterized by cross linked single fibrils, cross linked fibril bundles or even both. Although the formation of fibril bundle usually induced large light scattering, such a polymer network could endure higher voltage. In contrast, although the formation of cross linked single fibrils induced small light scattering, such a polymer network cannot endure higher voltage. There is a tradeoff between the light scattering and high voltage endurance. The electro-optical properties such as threshold voltage and response time were taken to verify our conclusion. For future application, the monomer molecular structure, the liquid crystal solvent and the polymerization conditions should be optimized to generate optimal polymer network morphology.

  15. Local modulation of human brain responses by circadian rhythmicity and sleep debt.

    PubMed

    Muto, Vincenzo; Jaspar, Mathieu; Meyer, Christelle; Kussé, Caroline; Chellappa, Sarah L; Degueldre, Christian; Balteau, Evelyne; Shaffii-Le Bourdiec, Anahita; Luxen, André; Middleton, Benita; Archer, Simon N; Phillips, Christophe; Collette, Fabienne; Vandewalle, Gilles; Dijk, Derk-Jan; Maquet, Pierre

    2016-08-12

    Human performance is modulated by circadian rhythmicity and homeostatic sleep pressure. Whether and how this interaction is represented at the regional brain level has not been established. We quantified changes in brain responses to a sustained-attention task during 13 functional magnetic resonance imaging sessions scheduled across the circadian cycle, during 42 hours of wakefulness and after recovery sleep, in 33 healthy participants. Cortical responses showed significant circadian rhythmicity, the phase of which varied across brain regions. Cortical responses also significantly decreased with accrued sleep debt. Subcortical areas exhibited primarily a circadian modulation that closely followed the melatonin profile. These findings expand our understanding of the mechanisms involved in maintaining cognition during the day and its deterioration during sleep deprivation and circadian misalignment.

  16. Differential modulation of auditory responses to attended and unattended speech in different listening conditions

    PubMed Central

    Kong, Ying-Yee; Mullangi, Ala; Ding, Nai

    2014-01-01

    This study investigates how top-down attention modulates neural tracking of the speech envelope in different listening conditions. In the quiet conditions, a single speech stream was presented and the subjects paid attention to the speech stream (active listening) or watched a silent movie instead (passive listening). In the competing speaker (CS) conditions, two speakers of opposite genders were presented diotically. Ongoing electroencephalographic (EEG) responses were measured in each condition and cross-correlated with the speech envelope of each speaker at different time lags. In quiet, active and passive listening resulted in similar neural responses to the speech envelope. In the CS conditions, however, the shape of the cross-correlation function was remarkably different between the attended and unattended speech. The cross-correlation with the attended speech showed stronger N1 and P2 responses but a weaker P1 response compared with the cross-correlation with the unattended speech. Furthermore, the N1 response to the attended speech in the CS condition was enhanced and delayed compared with the active listening condition in quiet, while the P2 response to the unattended speaker in the CS condition was attenuated compared with the passive listening in quiet. Taken together, these results demonstrate that top-down attention differentially modulates envelope-tracking neural activity at different time lags and suggest that top-down attention can both enhance the neural responses to the attended sound stream and suppress the responses to the unattended sound stream. PMID:25124153

  17. Differential modulation of auditory responses to attended and unattended speech in different listening conditions.

    PubMed

    Kong, Ying-Yee; Mullangi, Ala; Ding, Nai

    2014-10-01

    This study investigates how top-down attention modulates neural tracking of the speech envelope in different listening conditions. In the quiet conditions, a single speech stream was presented and the subjects paid attention to the speech stream (active listening) or watched a silent movie instead (passive listening). In the competing speaker (CS) conditions, two speakers of opposite genders were presented diotically. Ongoing electroencephalographic (EEG) responses were measured in each condition and cross-correlated with the speech envelope of each speaker at different time lags. In quiet, active and passive listening resulted in similar neural responses to the speech envelope. In the CS conditions, however, the shape of the cross-correlation function was remarkably different between the attended and unattended speech. The cross-correlation with the attended speech showed stronger N1 and P2 responses but a weaker P1 response compared to the cross-correlation with the unattended speech. Furthermore, the N1 response to the attended speech in the CS condition was enhanced and delayed compared with the active listening condition in quiet, while the P2 response to the unattended speaker in the CS condition was attenuated compared with the passive listening in quiet. Taken together, these results demonstrate that top-down attention differentially modulates envelope-tracking neural activity at different time lags and suggest that top-down attention can both enhance the neural responses to the attended sound stream and suppress the responses to the unattended sound stream.

  18. Computational identification of genetic subnetwork modules associated with maize defense response to Fusarium verticillioides

    PubMed Central

    2015-01-01

    Background Maize, a crop of global significance, is vulnerable to a variety of biotic stresses resulting in economic losses. Fusarium verticillioides (teleomorph Gibberella moniliformis) is one of the key fungal pathogens of maize, causing ear rots and stalk rots. To better understand the genetic mechanisms involved in maize defense as well as F. verticillioides virulence, a systematic investigation of the host-pathogen interaction is needed. The aim of this study was to computationally identify potential maize subnetwork modules associated with its defense response against F. verticillioides. Results We obtained time-course RNA-seq data from B73 maize inoculated with wild type F. verticillioides and a loss-of-virulence mutant, and subsequently established a computational pipeline for network-based comparative analysis. Specifically, we first analyzed the RNA-seq data by a cointegration-correlation-expression approach, where maize genes were jointly analyzed with known F. verticillioides virulence genes to find candidate maize genes likely associated with the defense mechanism. We predicted maize co-expression networks around the selected maize candidate genes based on partial correlation, and subsequently searched for subnetwork modules that were differentially activated when inoculated with two different fungal strains. Based on our analysis pipeline, we identified four potential maize defense subnetwork modules. Two were directly associated with maize defense response and were associated with significant GO terms such as GO:0009817 (defense response to fungus) and GO:0009620 (response to fungus). The other two predicted modules were indirectly involved in the defense response, where the most significant GO terms associated with these modules were GO:0046914 (transition metal ion binding) and GO:0046686 (response to cadmium ion). Conclusion Through our RNA-seq data analysis, we have shown that a network-based approach can enhance our understanding of the

  19. A Computational Model of Inferior Colliculus Responses to Amplitude Modulated Sounds in Young and Aged Rats

    PubMed Central

    Rabang, Cal F.; Parthasarathy, Aravindakshan; Venkataraman, Yamini; Fisher, Zachery L.; Gardner, Stephanie M.; Bartlett, Edward L.

    2012-01-01

    The inferior colliculus (IC) receives ascending excitatory and inhibitory inputs from multiple sources, but how these auditory inputs converge to generate IC spike patterns is poorly understood. Simulating patterns of in vivo spike train data from cellular and synaptic models creates a powerful framework to identify factors that contribute to changes in IC responses, such as those resulting in age-related loss of temporal processing. A conductance-based single neuron IC model was constructed, and its responses were compared to those observed during in vivo IC recordings in rats. IC spike patterns were evoked using amplitude-modulated tone or noise carriers at 20–40 dB above threshold and were classified as low-pass, band-pass, band-reject, all-pass, or complex based on their rate modulation transfer function tuning shape. Their temporal modulation transfer functions were also measured. These spike patterns provided experimental measures of rate, vector strength, and firing pattern for comparison with model outputs. Patterns of excitatory and inhibitory synaptic convergence to IC neurons were based on anatomical studies and generalized input tuning for modulation frequency. Responses of modeled ascending inputs were derived from experimental data from previous studies. Adapting and sustained IC intrinsic models were created, with adaptation created via calcium-activated potassium currents. Short-term synaptic plasticity was incorporated into the model in the form of synaptic depression, which was shown to have a substantial effect on the magnitude and time course of the IC response. The most commonly observed IC response sub-types were recreated and enabled dissociation of inherited response properties from those that were generated in IC. Furthermore, the model was used to make predictions about the consequences of reduction in inhibition for age-related loss of temporal processing due to a reduction in GABA seen anatomically with age. PMID:23129994

  20. Modulation of shark prey capture kinematics in response to sensory deprivation.

    PubMed

    Gardiner, Jayne M; Atema, Jelle; Hueter, Robert E; Motta, Philip J

    2017-02-01

    The ability of predators to modulate prey capture in response to the size, location, and behavior of prey is critical to successful feeding on a variety of prey types. Modulating in response to changes in sensory information may be critical to successful foraging in a variety of environments. Three shark species with different feeding morphologies and behaviors were filmed using high-speed videography while capturing live prey: the ram-feeding blacktip shark, the ram-biting bonnethead, and the suction-feeding nurse shark. Sharks were examined intact and after sensory information was blocked (olfaction, vision, mechanoreception, and electroreception, alone and in combination), to elucidate the contribution of the senses to the kinematics of prey capture. In response to sensory deprivation, the blacktip shark demonstrated the greatest amount of modulation, followed by the nurse shark. In the absence of olfaction, blacktip sharks open the jaws slowly, suggestive of less motivation. Without lateral line cues, blacktip sharks capture prey from greater horizontal angles using increased ram. When visual cues are absent, blacktip sharks elevate the head earlier and to a greater degree, allowing them to overcome imprecise position of the prey relative to the mouth, and capture prey using decreased ram, while suction remains unchanged. When visual cues are absent, nurse sharks open the mouth wider, extend the labial cartilages further, and increase suction while simultaneously decreasing ram. Unlike some bony fish, neither species switches feeding modalities (i.e. from ram to suction or vice versa). Bonnetheads failed to open the mouth when electrosensory cues were blocked, but otherwise little to no modulation was found in this species. These results suggest that prey capture may be less plastic in elasmobranchs than in bony fishes, possibly due to anatomical differences, and that the ability to modulate feeding kinematics in response to available sensory information varies

  1. Non-uniform spatial response of the LCoS spatial light modulator

    NASA Astrophysics Data System (ADS)

    Lopez, Víctor; González-Vega, Arturo; Aguilar, Alberto; Landgrave, J. E. A.; García-Márquez, Jorge

    2016-05-01

    Liquid crystal on silicon (LCoS) spatial light modulators have been considered for a wide variety of scientific applications, due to their phase modulation capability and high spatial resolution. Nevertheless, their intrinsic characteristics, like the extensively studied depolarization and phase shift fluctuations, can make their behavior significantly distant from the ideal and somewhat unpredictable. Here, we present the characterization of a different source of uncertainty: the non-uniform spatial response of the LCoS, which is fundamentally different to the static aberrations of the panel. We measured local deviations of ±22% from the expected phase shift, resulting in non-negligible effects for phase modulation measurements, phase shifting interferometry, wavefront correction, and speckle interferometry.

  2. Delayed response of a fermion pair condensate to a modulation of the interaction strength

    NASA Astrophysics Data System (ADS)

    Plata, J.

    2009-09-01

    The effect of a sinusoidal modulation of the interaction strength on a fermion pair condensate is analytically studied. The system is described by a generalization of the coupled fermion-boson model that incorporates a time-dependent intermode coupling induced via a magnetic Feshbach resonance. Nontrivial effects are shown to emerge depending on the relative magnitude of the modulation period and the relaxation time of the condensate. Specifically, a nonadiabatic modulation drives the system out of thermal equilibrium: the external field induces a variation of the quasiparticle energies, and, in turn, a disequilibrium of the associated populations. The subsequent relaxation process is studied and an analytical description of the gap dynamics is obtained. Recent experimental findings are explained: the delay observed in the response to the applied field is understood as a temperature effect linked to the condensate relaxation time.

  3. Die singulation method

    DOEpatents

    Swiler, Thomas P.; Garcia, Ernest J.; Francis, Kathryn M.

    2013-06-11

    A method is disclosed for singulating die from a semiconductor substrate (e.g. a semiconductor-on-insulator substrate or a bulk silicon substrate) containing an oxide layer (e.g. silicon dioxide or a silicate glass) and one or more semiconductor layers (e.g. monocrystalline or polycrystalline silicon) located above the oxide layer. The method etches trenches through the substrate and through each semiconductor layer about the die being singulated, with the trenches being offset from each other around at least a part of the die so that the oxide layer between the trenches holds the substrate and die together. The trenches can be anisotropically etched using a Deep Reactive Ion Etching (DRIE) process. After the trenches are etched, the oxide layer between the trenches can be etched away with an HF etchant to singulate the die. A release fixture can be located near one side of the substrate to receive the singulated die.

  4. Die singulation method

    DOEpatents

    Swiler, Thomas P [Albuquerque, NM; Garcia, Ernest J [Albuquerque, NM; Francis, Kathryn M [Rio Rancho, NM

    2014-01-07

    A method is disclosed for singulating die from a semiconductor substrate (e.g. a semiconductor-on-insulator substrate or a bulk silicon substrate) containing an oxide layer (e.g. silicon dioxide or a silicate glass) and one or more semiconductor layers (e.g. monocrystalline or polycrystalline silicon) located above the oxide layer. The method etches trenches through the substrate and through each semiconductor layer about the die being singulated, with the trenches being offset from each other around at least a part of the die so that the oxide layer between the trenches holds the substrate and die together. The trenches can be anisotropically etched using a Deep Reactive Ion Etching (DRIE) process. After the trenches are etched, the oxide layer between the trenches can be etched away with a HF etchant to singulate the die. A release fixture can be located near one side of the substrate to receive the singulated die.

  5. Sputtered protective coatings for die casting dies

    NASA Technical Reports Server (NTRS)

    Mirtich, M. J.; Nieh, C.-Y.; Wallace, J. F.

    1981-01-01

    Three experimental research designs investigating candidate materials and processes involved in protective die surface coating procedures by sputter deposition, using ion beam technologies, are discussed. Various pre-test results show that none of the coatings remained completely intact for 15,000 test cycles. The longest lifetime was observed for coatings such as tungsten, platinum, and molybdenum which reduced thermal fatigue, but exhibited oxidation and suppressed crack initiation only as long as the coating did not fracture. Final test results confirmed earlier findings and coatings with Pt and W proved to be the candidate materials to be used on a die surface to increase die life. In the W-coated specimens, which remained intact on the surface after thermal fatigue testing, no oxidation was found under the coating, although a few cracks formed on the surface where the coating broke down. Further research is planned.

  6. Near-infrared Light Responsive Synthetic c-di-GMP Module for Optogenetic Applications

    PubMed Central

    2015-01-01

    Enormous potential of cell-based therapeutics is hindered by the lack of effective means to control genetically engineered cells in mammalian tissues. Here, we describe a synthetic module for remote photocontrol of engineered cells that can be adapted for such applications. The module involves photoactivated synthesis of cyclic dimeric GMP (c-di-GMP), a stable small molecule that is not produced by higher eukaryotes and therefore is suitable for orthogonal regulation. The key component of the photocontrol module is an engineered bacteriophytochrome diguanylate cyclase, which synthesizes c-di-GMP from GTP in a light-dependent manner. Bacteriophytochromes are particularly attractive photoreceptors because they respond to light in the near-infrared window of the spectrum, where absorption by mammalian tissues is minimal, and also because their chromophore, biliverdin IXα, is naturally available in mammalian cells. The second component of the photocontrol module, a c-di-GMP phosphodiesterase, maintains near-zero background levels of c-di-GMP in the absence of light, which enhances the photodynamic range of c-di-GMP concentrations. In the E. coli model used in this study, the intracellular c-di-GMP levels could be upregulated by light by >50-fold. Various c-di-GMP-responsive proteins and riboswitches identified in bacteria can be linked downstream of the c-di-GMP-mediated photocontrol module for orthogonal regulation of biological activities in mammals as well as in other organisms lacking c-di-GMP signaling. Here, we linked the photocontrol module to a gene expression output via a c-di-GMP-responsive transcription factor and achieved a 40-fold photoactivation of gene expression. PMID:24926804

  7. Extrusion die and method

    DOEpatents

    Lipp, G. Daniel

    1994-04-26

    A method and die apparatus for manufacturing a honeycomb body of rhombic cell cross-section by extrusion through an extrusion die of triangular cell discharge slot configuration, the die incorporating feedholes at selected slot intersections only, such that slot segments communicating directly with the feedholes discharge web material and slot segments not so connected do not discharge web material, whereby a rhombic cell cross-section in the extruded body is provided.

  8. Module-Based Analysis of Robustness Tradeoffs in the Heat Shock Response System

    PubMed Central

    Iwasaki, Rei; Ohtake, Hisao; Doyle, John C; Grigorova, Irina; Gross, Carol A; Khammash, Mustafa

    2006-01-01

    Biological systems have evolved complex regulatory mechanisms, even in situations where much simpler designs seem to be sufficient for generating nominal functionality. Using module-based analysis coupled with rigorous mathematical comparisons, we propose that in analogy to control engineering architectures, the complexity of cellular systems and the presence of hierarchical modular structures can be attributed to the necessity of achieving robustness. We employ the Escherichia coli heat shock response system, a strongly conserved cellular mechanism, as an example to explore the design principles of such modular architectures. In the heat shock response system, the sigma-factor σ32 is a central regulator that integrates multiple feedforward and feedback modules. Each of these modules provides a different type of robustness with its inherent tradeoffs in terms of transient response and efficiency. We demonstrate how the overall architecture of the system balances such tradeoffs. An extensive mathematical exploration nevertheless points to the existence of an array of alternative strategies for the existing heat shock response that could exhibit similar behavior. We therefore deduce that the evolutionary constraints facing the system might have steered its architecture toward one of many robustly functional solutions. PMID:16863396

  9. Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study

    PubMed Central

    2010-01-01

    Background Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately describe the complexity of metabolic responses to mild anti-inflammatory therapy. Methods To address this limitation, we used an integrative omics approach to characterize modulation of inflammation in overweight men during an intervention with the non-steroidal anti-inflammatory drug diclofenac. Measured parameters included 80 plasma proteins, >300 plasma metabolites (lipids, free fatty acids, oxylipids and polar compounds) and an array of peripheral blood mononuclear cells (PBMC) gene expression products. These measures were submitted to multivariate and correlation analysis and were used for construction of biological response networks. Results A panel of genes, proteins and metabolites, including PGE2 and TNF-alpha, were identified that describe a diclofenac-response network (68 genes in PBMC, 1 plasma protein and 4 plasma metabolites). Novel candidate markers of inflammatory modulation included PBMC expression of annexin A1 and caspase 8, and the arachidonic acid metabolite 5,6-DHET. Conclusion In this study the integrated analysis of a wide range of parameters allowed the development of a network of markers responding to inflammatory modulation, thereby providing insight into the complex process of inflammation and ways to assess changes in inflammatory status associated with obesity. Trial registration The study is registered as NCT00221052 in clinicaltrials.gov database. PMID:20178593

  10. Dopamine modulates carotid nerve responses induced by acetylcholine on the cat petrosal ganglion in vitro.

    PubMed

    Alcayaga, J; Varas, R; Arroyo, J; Iturriaga, R; Zapata, P

    1999-06-12

    We have recently reported that application of acetylcholine (ACh) or nicotine to the petrosal ganglion-the sensory ganglion of the glossopharyngeal nerve-elicits a burst of discharges in the carotid nerve branch, innervating the carotid body and sinus, but not in the glossopharyngeal branch, innervating the tongue and pharynx. Thus, the perikarya of sensory neurons for the carotid bifurcation exhibit selective cholinosensitivity. Since dopamine (DA) modulates carotid nerve chemosensory activity, we searched for the presence of DA sensitivity at the perikarya of these neurons in the cat petrosal ganglion superfused in vitro. Applications of DA in doses of up to 5 mg to the ganglion did not modify the rate of spontaneous discharges in the carotid nerve. However, if DA was applied 30 s before ACh injections, ACh-evoked reactions were modified: low doses of DA enhanced the subsequent responses to ACh, while high doses of DA depressed the responses to ACh. This depressant effect of DA on ACh responses was partially antagonized by adding spiroperone to the superfusate. Our results show that the response to ACh of petrosal ganglion neurons projecting through the carotid nerve is modulated by DA acting on D(2) receptors located in the somata of these neurons. Thus, dopaminergic modulation of cholinosensitivity could be shared also by the membranes of peripheral endings and perikarya of primary sensory neurons involved in arterial chemoreception.

  11. Modulation of the Contrast Response Function by Electrical Microstimulation of the Macaque Frontal Eye Field

    PubMed Central

    Ekstrom, Leeland B.; Roelfsema, Pieter R.; Arsenault, John T.; Kolster, Hauke; Vanduffel, Wim

    2009-01-01

    Spatial attention influences representations in visual cortical areas as well as perception. Some models predict a contrast gain, while others a response or activity gain when attention is directed to a contrast varying stimulus. Recent evidence has indicated that microstimulating the Frontal Eye Field (FEF) can produce modulations of V4 neuronal firing rates that resemble spatial attention-like effects, and we have shown similar modulations of functional magnetic resonance imaging activity throughout the visual system. Here, we used fMRI in awake, fixating monkeys to first measure the response in twelve visual cortical areas to stimuli of varying luminance contrast. Next, we simultaneously microstimulated sub-regions of the FEF with movement fields that overlapped the stimulus locations and measured how microstimulation modulated these contrast response functions (CRFs) throughout visual cortex. In general, we found evidence for a non-proportional scaling of the CRF under these conditions, resembling a contrast gain effect. Representations of low contrast stimuli were enhanced by stimulation of the FEF below the threshold needed to evoke saccades, while high contrast stimuli were unaffected or in some areas even suppressed. Further, we measured a characteristic spatial pattern of enhancement and suppression across the cortical surface, from which we propose a simple schematic of this contrast-dependent fMRI response. PMID:19710320

  12. Individual differences in attentional modulation of cortical responses correlate with selective attention performance.

    PubMed

    Choi, Inyong; Wang, Le; Bharadwaj, Hari; Shinn-Cunningham, Barbara

    2014-08-01

    Many studies have shown that attention modulates the cortical representation of an auditory scene, emphasizing an attended source while suppressing competing sources. Yet, individual differences in the strength of this attentional modulation and their relationship with selective attention ability are poorly understood. Here, we ask whether differences in how strongly attention modulates cortical responses reflect differences in normal-hearing listeners' selective auditory attention ability. We asked listeners to attend to one of three competing melodies and identify its pitch contour while we measured cortical electroencephalographic responses. The three melodies were either from widely separated pitch ranges ("easy trials"), or from a narrow, overlapping pitch range ("hard trials"). The melodies started at slightly different times; listeners attended either the leading or lagging melody. Because of the timing of the onsets, the leading melody drew attention exogenously. In contrast, attending the lagging melody required listeners to direct top-down attention volitionally. We quantified how attention amplified auditory N1 response to the attended melody and found large individual differences in the N1 amplification, even though only correctly answered trials were used to quantify the ERP gain. Importantly, listeners with the strongest amplification of N1 response to the lagging melody in the easy trials were the best performers across other types of trials. Our results raise the possibility that individual differences in the strength of top-down gain control reflect inherent differences in the ability to control top-down attention.

  13. Direct sensorimotor corticospinal modulation of dorsal horn neuronal C-fiber responses in the rat.

    PubMed

    Rojas-Piloni, Gerardo; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rodríguez-Jiménez, Javier

    2010-09-10

    Clinically, the stimulation of motor cortical areas has been used to alleviate certain pain conditions. However, the attempts to understand the mechanisms of cortical nociceptive modulation at the spinal cord level have yielded controversial results. The objectives of the present work were to: 1) determine the effects of activating and suppressing the activity of sensorimotor cortical neurons on the nociceptive electrophysiological responses of the segmental C-fibers, and 2) evaluate the contribution of direct and indirect corticospinal projections in segmental nociceptive modulation. By means of a bipolar matrix of stimulation electrodes we mapped the stimulation of cortical areas that modulate C-fiber evoked field potentials in the dorsal horn. In addition, suppressing the cortical activity by means of cortical spreading depression, we observed that the C-fiber evoked field potentials in the dorsal horn are facilitated when cortical activity is suppressed specifically in sensorimotor cortex. Moreover, the C-fiber evoked field potentials were inhibited during spontaneous activation of cortical projecting neurons. Furthermore, after a lesion of the pyramidal tract contralateral to the spinal cord recording sites, the cortical action was suppressed. Our results show that corticospinal tract fibers arising from the sensorimotor cortex modulate directly the nociceptive C-fiber evoked responses of the dorsal horn.

  14. Perceptual demand modulates activation of human auditory cortex in response to task-irrelevant sounds.

    PubMed

    Sabri, Merav; Humphries, Colin; Verber, Matthew; Mangalathu, Jain; Desai, Anjali; Binder, Jeffrey R; Liebenthal, Einat

    2013-09-01

    In the visual modality, perceptual demand on a goal-directed task has been shown to modulate the extent to which irrelevant information can be disregarded at a sensory-perceptual stage of processing. In the auditory modality, the effect of perceptual demand on neural representations of task-irrelevant sounds is unclear. We compared simultaneous ERPs and fMRI responses associated with task-irrelevant sounds across parametrically modulated perceptual task demands in a dichotic-listening paradigm. Participants performed a signal detection task in one ear (Attend ear) while ignoring task-irrelevant syllable sounds in the other ear (Ignore ear). Results revealed modulation of syllable processing by auditory perceptual demand in an ROI in middle left superior temporal gyrus and in negative ERP activity 130-230 msec post stimulus onset. Increasing the perceptual demand in the Attend ear was associated with a reduced neural response in both fMRI and ERP to task-irrelevant sounds. These findings are in support of a selection model whereby ongoing perceptual demands modulate task-irrelevant sound processing in auditory cortex.

  15. Utilizing the response patterns of a temperature modulated chemoresistive gas sensor for gas diagnosis

    NASA Astrophysics Data System (ADS)

    Amini, Amir; Ghafarinia, Vahid

    2011-02-01

    The observed features in the temporal response patterns of a temperature-modulated chemoresistive gas sensor were used for gas diagnosis. The patterns were recorded for clean air and air contaminated with different levels of some volatile organic compounds while a staircase heating voltage waveform had been applied to the microheater of a tin oxide gas sensor that modulated its operating temperature. Combining the steady-state and transient parameters of the recorded responses in the 50-400°C range resulted in discriminatory feature vectors which were utilized for contaminant classification. The information content of these feature vectors was proved sufficient for discrimination of methanol, ethanol, 1-butanol, and acetone contaminations in a wide concentration range.

  16. Disrupting SMA activity modulates explicit and implicit emotional responses: an rTMS study.

    PubMed

    Rodigari, Alessia; Oliveri, Massimiliano

    2014-09-05

    Supplementary Motor Area (SMA) has been considered as an interface between the emotional/motivational system and motor effector system. Here, we investigated whether it is possible to modulate emotional responses using non-invasive brain stimulation of the SMA. 1Hz repetitive transcranial magnetic stimulation (rTMS) trains were applied over the SMA of healthy subjects performing a task requiring to judge the valence and arousal of emotional stimuli. rTMS trains over the SMA increased the perceived valence of emotionally negative visual stimuli, while decreasing the perceived valence of emotionally positive ones. The modulatory effect on emotional valence was specific for stimuli with emotional content, since it was not observed for neutral visual stimuli. The effect was also specific for the site of stimulation, since rTMS of the visual cortex failed to modulate either perceived valence or arousal. These findings provide the first example of neuromodulation of emotional responses based on non-invasive brain stimulation.

  17. Insulin signaling genes modulate nicotine-induced behavioral responses in C. elegans

    PubMed Central

    Wescott, Seth A.; Ronan, Elizabeth A.; Xu, X.Z. Shawn

    2015-01-01

    Insulin signaling has been suggested to modulate nicotine dependence, but the underlying genetic evidence has been lacking. Here, we used the nematode, C. elegans, to investigate whether genetic alterations in the insulin signaling pathway affect behavioral responses to nicotine. To do so, we challenged drug-naïve C. elegans with an acute dose of nicotine [100 μM] while recording changes in their locomotion speed. While nicotine treatment stimulated locomotion speed in wild-type C. elegans, the same treatment reduced locomotion speed in mutants defective in insulin signaling. This phenotype could be suppressed by mutations in daf-16, a gene encoding a FOXO transcription factor that acts downstream of insulin signaling. Our data suggest that insulin signaling genes, daf-2, age-1, pdk-1, akt-1, and akt-2 modulate behavioral responses to nicotine in C. elegans, revealing a genetic link between nicotine behavior and insulin signaling. PMID:26317299

  18. Modulation of Immune Response by Organophosphorus Pesticides: Fishes as a Potential Model in Immunotoxicology

    PubMed Central

    Díaz-Resendiz, K. J. G.; Toledo-Ibarra, G. A.; Girón-Pérez, M. I.

    2015-01-01

    Immune response is modulated by different substances that are present in the environment. Nevertheless, some of these may cause an immunotoxic effect. In this paper, the effect of organophosphorus pesticides (frequent substances spilled in aquatic ecosystems) on the immune system of fishes and in immunotoxicology is reviewed. Furthermore, some cellular and molecular mechanisms that might be involved in immunoregulation mechanisms of organophosphorus pesticides are discussed. PMID:25973431

  19. Modulation of immune response by organophosphorus pesticides: fishes as a potential model in immunotoxicology.

    PubMed

    Díaz-Resendiz, K J G; Toledo-Ibarra, G A; Girón-Pérez, M I

    2015-01-01

    Immune response is modulated by different substances that are present in the environment. Nevertheless, some of these may cause an immunotoxic effect. In this paper, the effect of organophosphorus pesticides (frequent substances spilled in aquatic ecosystems) on the immune system of fishes and in immunotoxicology is reviewed. Furthermore, some cellular and molecular mechanisms that might be involved in immunoregulation mechanisms of organophosphorus pesticides are discussed.

  20. Die Soldering in Aluminium Die Casting

    SciTech Connect

    Han, Q.; Kenik, E.A.; Viswanathan, S.

    2000-03-15

    Two types of tests, dipping tests and dip-coating tests were carried out on small steel cylinders using pure aluminum and 380 alloy to investigate the mechanism of die soldering during aluminum die casting. Optical and scanning electron microscopy were used to study the morphology and composition of the phases formed during soldering. A soldering mechanism is postulated based on experimental observations. A soldering critical temperature is postulated at which iron begins to react with aluminum to form an aluminum-rich liquid phase and solid intermetallic compounds. When the temperature at the die surface is higher than this critical temperature, the aluminum-rich phase is liquid and joins the die with the casting during the subsequent solidification. The paper discusses the mechanism of soldering for the case of pure aluminum and 380 alloy casting in a steel mold, the factors that promote soldering, and the strength of the bond formed when soldering occurs. conditions, an aluminum-rich soldering layer may also form over the intermetallic layer. Although a significant amount of research has been conducted on the nature of these intermetallics, little is known about the conditions under which soldering occurs.

  1. Is Dying Young Worse than Dying Old?

    ERIC Educational Resources Information Center

    Jecker, Nancy S.; Schneiderman, Lawrence J.

    1994-01-01

    Notes that, in contemporary Western society, people feel death of small child is greater injustice than death of older adult and experience correspondingly greater sorrow, anger, regret, or bitterness when very young person dies. Contrasts these attitudes with those of ancient Greece and shows relevance that different attitudes toward death have…

  2. The aryl hydrocarbon receptor modulates acute and late mast cell responses.

    PubMed

    Sibilano, Riccardo; Frossi, Barbara; Calvaruso, Marco; Danelli, Luca; Betto, Elena; Dall'Agnese, Alessandra; Tripodo, Claudio; Colombo, Mario P; Pucillo, Carlo E; Gri, Giorgia

    2012-07-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics as well as physiological ligands. These compounds may modulate inflammatory responses and contribute to the rising prevalence of allergic diseases observed in industrialized countries. Mast cells (MCs), located within tissues at the boundary of the external environment, represent a potential target of AhR ligands. In this study, we report that murine and human MCs constitutively express AhR, and its activation by the high-affinity ligand 6-formylindolo[3,2-b]carbazole (FICZ) determines a boost in degranulation. On the contrary, repeated exposure to FICZ inhibits MC degranulation. Accordingly, histamine release, in an in vivo passive systemic anaphylactic model, is exacerbated by a single dose and is attenuated by repetitive stimulation of AhR. FICZ-exposed MCs produce reactive oxygen species and IL-6 in response to cAMP-dependent signals. Moreover, AhR-activated MCs produce IL-17, a critical player in chronic inflammation and autoimmunity, suggesting a novel pathway for MC activation in the pathogenesis of these diseases. Indeed, histological analysis of patients with chronic obstructive pulmonary disease revealed an enrichment in AhR/IL-6 and AhR/IL-17 double-positive MCs within bronchial lamina propria. Thus, tissue-resident MCs could translate external chemical challenges through AhR by modulating allergic responses and contributing to the generation of inflammation-related diseases.

  3. Impaired early visual response modulations to spatial information in chronic schizophrenia

    PubMed Central

    Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

    2011-01-01

    Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

  4. Modulation by octopamine of olfactory responses to nonpheromone odorants in the cockroach, Periplaneta americana L.

    PubMed

    Zhukovskaya, Marianna I

    2012-06-01

    Olfactory receptor cells in insects are modulated by neurohormones. Recordings from cockroach olfactory sensilla showed that a subset of sensory neurons increase their responses to selected nonpheromone odorants after octopamine application. With octopamine application, recordings demonstrated increased firing rates by the short but not the long alcohol-sensitive sensilla to the nonpheromone volatile, hexan-1-ol. Within the same sensillum, individual receptor cells are shown to be modulated independently from each other, indicating that the octopamine receptors reside in the receptor not in the accessory cells. A uniform decrease in the amplitude of electroantennogram, which is odorant independent, is suggested to reflect the rise in octopamine concentration in the antennal hemolymph. Perception of general odorants measured as behavioral responses changed qualitatively under octopamine treatment: namely, repulsive hexan-1-ol became neutral, whereas neutral eucalyptol became attractive. Octopamine induced a change in male behavioral responses to general odors that were essentially the same as in the state of sexual arousal. Our findings suggest that sensitivity to odors having different biological significances is modulated selectively at the peripheral as well as other levels of olfactory processing.

  5. Extrusion die and method

    DOEpatents

    Lipp, G. Daniel

    1994-05-03

    A method and die apparatus for manufacturing a honeycomb body of triangular cell cross-section and high cell density, the die having a combination of (i) feedholes feeding slot intersections and (ii) feedholes feeding slot segments not supplied from slot intersections, whereby a reduction in feedhole count is achieved while still retaining good extrusion efficiency and extrudate uniformity.

  6. Regulating the ethylene response of a plant by modulation of F-box proteins

    DOEpatents

    Guo, Hongwei [Beijing, CN; Ecker, Joseph R [Carlsbad, CA

    2011-03-08

    The invention relates to transgenic plants having reduced sensitivity to ethylene as a result of having a recombinant nucleic acid encoding an F-box protein that interacts with a EIN3 involved in an ethylene response of plants, and a method of producing a transgenic plant with reduced ethylene sensitivity by transforming the plant with a nucleic acid sequence encoding an F-box protein. The inventions also relates to methods of altering the ethylene response in a plant by modulating the activity or expression of an F-box protein.

  7. Materials approaches for modulating neural tissue responses to implanted microelectrodes through mechanical and biochemical means

    PubMed Central

    Sommakia, Salah; Lee, Heui C.; Gaire, Janak; Otto, Kevin J.

    2014-01-01

    Implantable intracortical microelectrodes face an uphill struggle for widespread clinical use. Their potential for treating a wide range of traumatic and degenerative neural disease is hampered by their unreliability in chronic settings. A major factor in this decline in chronic performance is a reactive response of brain tissue, which aims to isolate the implanted device from the rest of the healthy tissue. In this review we present a discussion of materials approaches aimed at modulating the reactive tissue response through mechanical and biochemical means. Benefits and challenges associated with these approaches are analyzed, and the importance of multimodal solutions tested in emerging animal models are presented. PMID:25530703

  8. Modulation of Auditory Responses to Speech vs. Nonspeech Stimuli during Speech Movement Planning

    PubMed Central

    Daliri, Ayoub; Max, Ludo

    2016-01-01

    Previously, we showed that the N100 amplitude in long latency auditory evoked potentials (LLAEPs) elicited by pure tone probe stimuli is modulated when the stimuli are delivered during speech movement planning as compared with no-speaking control conditions. Given that we probed the auditory system only with pure tones, it remained unknown whether the nature and magnitude of this pre-speech auditory modulation depends on the type of auditory stimulus. Thus, here, we asked whether the effect of speech movement planning on auditory processing varies depending on the type of auditory stimulus. In an experiment with nine adult subjects, we recorded LLAEPs that were elicited by either pure tones or speech syllables when these stimuli were presented prior to speech onset in a delayed-response speaking condition vs. a silent reading control condition. Results showed no statistically significant difference in pre-speech modulation of the N100 amplitude (early stages of auditory processing) for the speech stimuli as compared with the nonspeech stimuli. However, the amplitude of the P200 component (later stages of auditory processing) showed a statistically significant pre-speech modulation that was specific to the speech stimuli only. Hence, the overall results from this study indicate that, immediately prior to speech onset, modulation of the auditory system has a general effect on early processing stages but a speech-specific effect on later processing stages. This finding is consistent with the hypothesis that pre-speech auditory modulation may play a role in priming the auditory system for its role in monitoring auditory feedback during speech production. PMID:27242494

  9. Controlled release strategies for modulating immune responses to promote tissue regeneration.

    PubMed

    Dumont, Courtney M; Park, Jonghyuck; Shea, Lonnie D

    2015-12-10

    Advances in the field of tissue engineering have enhanced the potential of regenerative medicine, yet the efficacy of these strategies remains incomplete, and is limited by the innate and adaptive immune responses. The immune response associated with injury or disease combined with that mounted to biomaterials, transplanted cells, proteins, and gene therapies vectors can contribute to the inability to fully restore tissue function. Blocking immune responses such as with anti-inflammatory or immunosuppressive agents are either ineffective, as the immune response contributes significantly to regeneration, or have significant side effects. This review describes targeted strategies to modulate the immune response in order to limit tissue damage following injury, promote an anti-inflammatory environment that leads to regeneration, and induce antigen (Ag)-specific tolerance that can target degenerative diseases that destroy tissues and promote engraftment of transplanted cells. Focusing on targeted immuno-modulation, we describe local delivery techniques to sites of inflammation as well as systemic approaches that preferentially target subsets of immune populations.

  10. Polarized immune responses modulated by layered double hydroxides nanoparticle conjugated with CpG.

    PubMed

    Yan, Shiyu; Rolfe, Barbara E; Zhang, Bing; Mohammed, Yousuf H; Gu, Wenyi; Xu, Zhi P

    2014-11-01

    Modulation of the immune response is an important step in the induction of protective humoral and cellular immunity against pathogens. In this study, we investigated the possibility of using a nanomaterial conjugated with the toll-like receptor (TLR) ligand CpG to modulate the immune response towards the preferred polarity. MgAl-layered double hydroxide (LDH) nanomaterial has a very similar chemical composition to Alum, an FDA approved adjuvant for human vaccination. We used a model antigen, ovalbumin (OVA) to demonstrate that MgAl-LDH had comparable adjuvant activity to Alum, but much weaker inflammation. Conjugation of TLR9 ligand CpG to LDH nanoparticles significantly enhanced the antibody response and promoted a switch from Th2 toward Th1 response, demonstrated by a change in the IgG2a:IgG1 ratio. Moreover, immunization of mice with CpG-OVA-conjugated LDH before challenge with OVA-expressing B16/F10 tumor cells retarded tumor growth. Together, these data indicate that LDH nanomaterial can be used as an immune adjuvant to promote Th1 or Th2 dominant immune responses suitable for vaccination purposes.

  11. Modulation of visual responses by behavioral state in mouse visual cortex.

    PubMed

    Niell, Cristopher M; Stryker, Michael P

    2010-02-25

    Studies of visual processing in rodents have conventionally been performed on anesthetized animals, precluding examination of the effects of behavior on visually evoked responses. We have now studied the response properties of neurons in primary visual cortex of awake mice that were allowed to run on a freely rotating spherical treadmill with their heads fixed. Most neurons showed more than a doubling of visually evoked firing rate as the animal transitioned from standing still to running, without changes in spontaneous firing or stimulus selectivity. Tuning properties in the awake animal were similar to those measured previously in anesthetized animals. Response magnitude in the lateral geniculate nucleus did not increase with locomotion, demonstrating that the striking change in responsiveness did not result from peripheral effects at the eye. Interestingly, some narrow-spiking cells were spontaneously active during running but suppressed by visual stimuli. These results demonstrate powerful cell-type-specific modulation of visual processing by behavioral state in awake mice.

  12. Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells

    PubMed Central

    Shenoda, Botros B.; Ajit, Seena K.

    2016-01-01

    Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs) can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages. PMID:27660518

  13. Conservation of Modules but not Phenotype in Bacterial Response to Environmental Stress

    SciTech Connect

    Timberlake, Sonia; Joachimiak, Marcin; Joyner, Dominique; Chakraborty, Romy; Baumohl, Jason; Dehal, Paramvir; Arkin, Adam; Hazen, Terry; Alm, Eric

    2010-05-17

    Microbes live in changing environments and change their phenotype via gene regulation in response. Although this transcriptional response is important for fitness, very little is known about how it evolves in microbes. We started by asking a number of high-level questions about the evolution of transcriptional phenotype: (1) To what extent is transcriptional response conserved, i.e. do conserved genes respond similarly to the same condition; (2) To what extent are transcriptional modules conserved; and (3) Does there exist a general stress response to a variety of stressors? To illuminate these questions, we analyzed more than 500 microarray experiments across the bacterial domain. We looked for conservation of transcriptional regulation both in close sister species and vastly divergent clades. In addition, we produced and analyzed an extensive in-house compendium of environmental stress data in three metal-reducing bacteria.

  14. B1-kinin receptors modulate Mesobuthus tamulus venom-induced vasosensory reflex responses in anesthetized rats

    PubMed Central

    Singh, Sanjeev K.; Deshpande, Shripad B.

    2016-01-01

    Objective: Intra-arterial injection of Mesobuthus tamulus (BT) venom produces reflex vasosensory responses modulating cardiorespiratory parameters in albino rats. The present study was conducted to understand the role of kinin receptors in modulating vasosensory reflexes evoked by BT venom. Materials and Methods: In urethane-anesthetized rats, tracheostomy was performed to keep the airway patent. The femoral artery was cannulated proximally, as well as distally, to record the blood pressure (BP) and to inject the chemicals, respectively. Electrocardiographic and respiratory excursions were recorded to compute the heart rate (HR) and respiratory rate (RR). A group of animals was pretreated with saline/kinin receptor antagonists intra-arterially (B1/B2 receptor antagonists) before the injection of venom. Results: After intra-arterial injection of BT venom (1 mg/kg), there was an immediate increase in RR, which reached to 40% within 30 s, followed by a decrease of 40%. Further, there was sustained increase in RR (50%) up to 60 min. The BP started to increase at 40 s, peaking at 5 min (50%), and remained above the initial level up to 60 min. The bradycardiac response started after 5 min which peaked (50% of initial) at 25 min and remained at that level up to 60 min. In B1 receptor antagonist (des-Arg) pretreated animals, venom-induced cardiovascular responses were attenuated (by 20–25% in mean arterial pressure and HR) significantly but not in B2 receptor antagonist (Hoe-140) pretreated animals. Either of the antagonists failed to alter the RR responses. Conclusions: BT venom-induced vasosensory reflex responses modulating cardiovascular parameters are mediated via B1-kinin receptors in anesthetized rats. PMID:27756949

  15. Serotonin modulates the effects of Pavlovian aversive predictions on response vigor.

    PubMed

    Crockett, Molly J; Clark, Luke; Apergis-Schoute, Annemieke M; Morein-Zamir, Sharon; Robbins, Trevor W

    2012-09-01

    Updated theoretical accounts of the role of serotonin (5-HT) in motivation propose that 5-HT operates at the intersection of aversion and inhibition, promoting withdrawal in the face of aversive predictions. However, the specific cognitive mechanisms through which 5-HT modulates withdrawal behavior remain poorly understood. Behavioral inhibition in response to punishments reflects at least two concurrent processes: instrumental aversive predictions linking stimuli, responses, and punishments, and Pavlovian aversive predictions linking stimuli and punishments irrespective of response. In the current study, we examined to what extent 5-HT modulates the impact of instrumental vs Pavlovian aversive predictions on behavioral inhibition. We used acute tryptophan depletion to lower central 5-HT levels in healthy volunteers, and observed behavior in a novel task designed to measure the influence of Pavlovian and instrumental aversive predictions on choice (response bias) and response vigor (response latencies). After placebo treatment, participants were biased against responding on the button that led to punishment, and they were slower to respond in a punished context, relative to a non-punished context. Specifically, participants slowed their responses in the presence of stimuli predictive of punishments. Tryptophan depletion removed the bias against responding on the punished button, and abolished slowing in the presence of punished stimuli, irrespective of response. We suggest that this set of results can be explained by a role for 5-HT in Pavlovian aversive predictions. These findings suggest additional specificity for the influence of 5-HT on aversively motivated behavioral inhibition and extend recent models of the role of 5-HT in aversive predictions.

  16. Ethylene plays multiple nonprimary roles in modulating the gravitropic response in tomato

    NASA Technical Reports Server (NTRS)

    Madlung, A.; Behringer, F. J.; Lomax, T. L.; Davies, E. (Principal Investigator)

    1999-01-01

    Ethylene is known to interact with auxin in regulating stem growth, and yet evidence for the role of ethylene in tropic responses is contradictory. Our analysis of four mutants of tomato (Lycopersicon esculentum) altered in their response to gravity, auxin, and/or ethylene revealed concentration-dependent modulation of shoot gravitropism by ethylene. Ethylene inhibitors reduce wild-type gravicurvature, and extremely low (0.0005-0.001 microliter L-1) ethylene concentrations can restore the reduced gravitropic response of the auxin-resistant dgt (diageotropica) mutant to wild-type levels. Slightly higher concentrations of ethylene inhibit the gravitropic response of all but the ethylene-insensitive nr (never-ripe) mutant. The gravitropic responses of nr and the constitutive-response mutant epi (epinastic) are slightly and significantly delayed, respectively, but otherwise normal. The reversal of shoot gravicurvature by red light in the lz-2 (lazy-2) mutant is not affected by ethylene. Taken together, these data indicate that, although ethylene does not play a primary role in the gravitropic response of tomato, low levels of ethylene are necessary for a full gravitropic response, and moderate levels of the hormone specifically inhibit gravicurvature in a manner different from ethylene inhibition of overall growth.

  17. Goal-dependent modulation of the long-latency stretch response at the shoulder, elbow, and wrist.

    PubMed

    Weiler, Jeffrey; Gribble, Paul L; Pruszynski, J Andrew

    2015-12-01

    Many studies have demonstrated that muscle activity 50-100 ms after a mechanical perturbation (i.e., the long-latency stretch response) can be modulated in a manner that reflects voluntary motor control. These previous studies typically assessed modulation of the long-latency stretch response from individual muscles rather than how this response is concurrently modulated across multiple muscles. Here we investigated such concurrent modulation by having participants execute goal-directed reaches to visual targets after mechanical perturbations of the shoulder, elbow, or wrist while measuring activity from six muscles that articulate these joints. We found that shoulder, elbow, and wrist muscles displayed goal-dependent modulation of the long-latency stretch response, that the relative magnitude of participants' goal-dependent activity was similar across muscles, that the temporal onset of goal-dependent muscle activity was not reliably different across the three joints, and that shoulder muscles displayed goal-dependent activity appropriate for counteracting intersegmental dynamics. We also observed that the long-latency stretch response of wrist muscles displayed goal-dependent modulation after elbow perturbations and that the long-latency stretch response of elbow muscles displayed goal-dependent modulation after wrist perturbations. This pattern likely arises because motion at either joint could bring the hand to the visual target and suggests that the nervous system rapidly exploits such simple kinematic redundancy when processing sensory feedback to support goal-directed actions.

  18. Goal-dependent modulation of the long-latency stretch response at the shoulder, elbow, and wrist

    PubMed Central

    Gribble, Paul L.; Pruszynski, J. Andrew

    2015-01-01

    Many studies have demonstrated that muscle activity 50–100 ms after a mechanical perturbation (i.e., the long-latency stretch response) can be modulated in a manner that reflects voluntary motor control. These previous studies typically assessed modulation of the long-latency stretch response from individual muscles rather than how this response is concurrently modulated across multiple muscles. Here we investigated such concurrent modulation by having participants execute goal-directed reaches to visual targets after mechanical perturbations of the shoulder, elbow, or wrist while measuring activity from six muscles that articulate these joints. We found that shoulder, elbow, and wrist muscles displayed goal-dependent modulation of the long-latency stretch response, that the relative magnitude of participants' goal-dependent activity was similar across muscles, that the temporal onset of goal-dependent muscle activity was not reliably different across the three joints, and that shoulder muscles displayed goal-dependent activity appropriate for counteracting intersegmental dynamics. We also observed that the long-latency stretch response of wrist muscles displayed goal-dependent modulation after elbow perturbations and that the long-latency stretch response of elbow muscles displayed goal-dependent modulation after wrist perturbations. This pattern likely arises because motion at either joint could bring the hand to the visual target and suggests that the nervous system rapidly exploits such simple kinematic redundancy when processing sensory feedback to support goal-directed actions. PMID:26445871

  19. Responsive nanoporous metals: recoverable modulations on strength and shape by watering

    NASA Astrophysics Data System (ADS)

    Ye, Xing-Long; Liu, Ling-Zhi; Jin, Hai-Jun

    2016-08-01

    Many biological materials can readily modulate their mechanical properties and shape by interacting with water in the surrounding environment, which is essential to their high performance in application. In contrast, typical inorganic materials (such as the metals) cannot change their strength and shape without involving thermal/mechanical treatments. By introducing nano-scale porous structure and exploiting a simple physical concept—the water-capillarity in nanopores, here we report that a ‘dead’ metal can be transformed into a ‘smart’ material with water-responsive properties. We demonstrate that the apparent strength, volume and shape of nanoporous Au and Au(Pt) can be modulated in situ, dramatically and recoverably, in response to water-dipping and partial-drying. The amplitude of strength-modulation reaches 20 MPa, which is nearly 50% of the yield strength at initial state. This approach also leads to reversible length change up to 1.3% in nanoporous Au and a large reversible bending motion of a bi-layer strip with tip displacement of ∼20 mm, which may be used for actuation. This method is simple and effective, occurring in situ under ambient conditions and requiring no external power, analogous to biological materials. The findings may open up novel applications in many areas such as micro-robotics and bio-medical devices.

  20. Responsive nanoporous metals: recoverable modulations on strength and shape by watering.

    PubMed

    Ye, Xing-Long; Liu, Ling-Zhi; Jin, Hai-Jun

    2016-08-12

    Many biological materials can readily modulate their mechanical properties and shape by interacting with water in the surrounding environment, which is essential to their high performance in application. In contrast, typical inorganic materials (such as the metals) cannot change their strength and shape without involving thermal/mechanical treatments. By introducing nano-scale porous structure and exploiting a simple physical concept-the water-capillarity in nanopores, here we report that a 'dead' metal can be transformed into a 'smart' material with water-responsive properties. We demonstrate that the apparent strength, volume and shape of nanoporous Au and Au(Pt) can be modulated in situ, dramatically and recoverably, in response to water-dipping and partial-drying. The amplitude of strength-modulation reaches 20 MPa, which is nearly 50% of the yield strength at initial state. This approach also leads to reversible length change up to 1.3% in nanoporous Au and a large reversible bending motion of a bi-layer strip with tip displacement of ∼20 mm, which may be used for actuation. This method is simple and effective, occurring in situ under ambient conditions and requiring no external power, analogous to biological materials. The findings may open up novel applications in many areas such as micro-robotics and bio-medical devices.

  1. Gentiana asclepiadea and Armoracia rusticana can modulate the adaptive response induced by zeocin in human lymphocytes.

    PubMed

    Hudecova, A; Hasplova, K; Kellovska, L; Ikreniova, M; Miadokova, E; Galova, E; Horvathova, E; Vaculcikova, D; Gregan, F; Dusinska, M

    2012-01-01

    Zeocin is a member of bleomycin/phleomycin family of antibiotics isolated from Streptomyces verticullus. This unique radiomimetic antibiotic is known to bind to DNA and induce oxidative stress in different organisms producing predominantly single- and double- strand breaks, as well as a DNA base loss resulting in apurinic/apyrimidinic (AP) sites. The aim of this study was to induce an adaptive response (AR) by zeocin in freshly isolated human lymphocytes from blood and to observe whether plant extracts could modulate this response. The AR was evaluated by the comet assay. The optimal conditions for the AR induction and modulation were determined as: 2 h-intertreatment time (in PBS, at 4°C) given after a priming dose (50 µg/ml) of zeocin treatment. Genotoxic impact of zeocin to lymphocytes was modulated by plant extracts isolated from Gentiana asclepiadea (methanolic and aqueous haulm extracts, 0.25 mg/ml) and Armoracia rusticana (methanolic root extract, 0.025 mg/ml). These extracts enhanced the AR and also decreased DNA damage caused by zeocin (after 0, 1 and 4 h-recovery time after the test dose of zeocin application) to more than 50%. These results support important position of plants containing many biologically active compounds in the field of pharmacology and medicine.

  2. Modulation of auditory brainstem responses by serotonin and specific serotonin receptors.

    PubMed

    Papesh, Melissa A; Hurley, Laura M

    2016-02-01

    The neuromodulator serotonin is found throughout the auditory system from the cochlea to the cortex. Although effects of serotonin have been reported at the level of single neurons in many brainstem nuclei, how these effects correspond to more integrated measures of auditory processing has not been well-explored. In the present study, we aimed to characterize the effects of serotonin on far-field auditory brainstem responses (ABR) across a wide range of stimulus frequencies and intensities. Using a mouse model, we investigated the consequences of systemic serotonin depletion, as well as the selective stimulation and suppression of the 5-HT1 and 5-HT2 receptors, on ABR latency and amplitude. Stimuli included tone pips spanning four octaves presented over a forty dB range. Depletion of serotonin reduced the ABR latencies in Wave II and later waves, suggesting that serotonergic effects occur as early as the cochlear nucleus. Further, agonists and antagonists of specific serotonergic receptors had different profiles of effects on ABR latencies and amplitudes across waves and frequencies, suggestive of distinct effects of these agents on auditory processing. Finally, most serotonergic effects were more pronounced at lower ABR frequencies, suggesting larger or more directional modulation of low-frequency processing. This is the first study to describe the effects of serotonin on ABR responses across a wide range of stimulus frequencies and amplitudes, and it presents an important step in understanding how serotonergic modulation of auditory brainstem processing may contribute to modulation of auditory perception.

  3. A Critical Role for CLSP2 in the Modulation of Antifungal Immune Response in Mosquitoes.

    PubMed

    Wang, Yan-Hong; Hu, Yang; Xing, Long-Sheng; Jiang, Hong; Hu, Song-Nian; Raikhel, Alexander S; Zou, Zhen

    2015-06-01

    Entomopathogenic fungi represent a promising class of bio-insecticides for mosquito control. Thus, detailed knowledge of the molecular mechanisms governing anti-fungal immune response in mosquitoes is essential. In this study, we show that CLSP2 is a modulator of immune responses during anti-fungal infection in the mosquito Aedes aegypti. With a fungal infection, the expression of the CLSP2 gene is elevated. CLSP2 is cleaved upon challenge with Beauveria bassiana conidia, and the liberated CLSP2 CTL-type domain binds to fungal cell components and B. bassiana conidia. Furthermore, CLPS2 RNA interference silencing significantly increases the resistance to the fungal challenge. RNA-sequencing transcriptome analysis showed that the majority of immune genes were highly upregulated in the CLSP2-depleted mosquitoes infected with the fungus. The up-regulated immune gene cohorts belong to melanization and Toll pathways, but not to the IMD or JAK-STAT. A thioester-containing protein (TEP22), a member of α2-macroglobulin family, has been implicated in the CLSP2-modulated mosquito antifungal defense. Our study has contributed to a greater understanding of immune-modulating mechanisms in mosquitoes.

  4. Die Kometenmission Rosetta

    NASA Astrophysics Data System (ADS)

    Krüger, Harald

    2016-11-01

    Die Rosetta-Mission ist ein Meilenstein in der Erforschung der Kometen und ihrer Entstehung. Eine der größten üerraschungen war die unregelmäßge hantelförmige Gestalt des Zielkometen 67P/Tschurjumow-Gerassimenko. Er besteht wahrscheinlich aus zwei Einzelkörpern, die durch ihre Schwerkraft aneinander gehalten werden. Seine Oberfläche ist sehr rau und zeigt eine sehr vielf ältige Morphologie, die auf eine Vielzahl von ablaufenden Prozessen hindeutet. Der Kometenkern ist vermutlich auf Gr ößnskalen von mehr als etwa 10 bis 100 Metern homogen, Inhomogenitäten auf kleineren Skalen k nnten f r seine Aktivä t verantwortlich sein. Diese ist auf kleine Gebiete konzentriert, und auch Oberflächenveränderungen, die sich innerhalb von einigen Tagen bis wenigen Wochen abspielen, sind lokal. Im Kometenmaterial wurde eine Vielzahl an organischen Substanzen gemessen, die zum Teil als Schlüsselmoleküle für die Synthese der Grundbausteine des Lebens gelten, wie wir es kennen.

  5. Empathic neural responses are modulated by the perceived fairness of others

    PubMed Central

    Singer, Tania; Seymour, Ben; O'Doherty, John P.; Stephan, Klaas E.; Dolan, Raymond J.; Frith, Chris D.

    2009-01-01

    The neural processes underlying empathy are a subject of intense interest within the social neurosciences1-3. However, very little is known about how brain empathic responses are modulated by the affective link between individuals. We show here that empathic responses are modulated by learned preferences, a result consistent with economic models of social preferences4-7. We engaged male and female volunteers in an economic game, in which two confederates played fairly or unfairly, and then measured brain activity with functional magnetic resonance imaging while these same volunteers observed the confederates receiving pain. Both sexes exhibited empathy-related activation in pain-related brain areas (fronto-insular and anterior cingulate cortices) towards fair players. However, these empathy-related responses were significantly reduced in males when observing an unfair person receiving pain. This effect was accompanied by increased activation in reward-related areas, correlated with an expressed desire for revenge. We conclude that in men (at least) empathic responses are shaped by valuation of other people's social behaviour, such that they empathize with fair opponents while favouring the physical punishment of unfair opponents, a finding that echoes recent evidence for altruistic punishment. PMID:16421576

  6. IDO2 Modulates T Cell-Dependent Autoimmune Responses through a B Cell-Intrinsic Mechanism.

    PubMed

    Merlo, Lauren M F; DuHadaway, James B; Grabler, Samantha; Prendergast, George C; Muller, Alexander J; Mandik-Nayak, Laura

    2016-06-01

    Mechanistic insight into how adaptive immune responses are modified along the self-nonself continuum may offer more effective opportunities to treat autoimmune disease, cancer, and other sterile inflammatory disorders. Recent genetic studies in the KRN mouse model of rheumatoid arthritis demonstrate that the immunomodulatory molecule IDO2 modifies responses to self-antigens; however, the mechanisms involved are obscure. In this study, we show that IDO2 exerts a critical function in B cells to support the generation of autoimmunity. In experiments with IDO2-deficient mice, adoptive transplant experiments demonstrated that IDO2 expression in B cells was both necessary and sufficient to support robust arthritis development. IDO2 function in B cells was contingent on a cognate, Ag-specific interaction to exert its immunomodulatory effects on arthritis development. We confirmed a similar requirement in an established model of contact hypersensitivity, in which IDO2-expressing B cells are required for a robust inflammatory response. Mechanistic investigations showed that IDO2-deficient B cells lacked the ability to upregulate the costimulatory marker CD40, suggesting IDO2 acts at the T-B cell interface to modulate the potency of T cell help needed to promote autoantibody production. Overall, our findings revealed that IDO2 expression by B cells modulates autoimmune responses by supporting the cross talk between autoreactive T and B cells.

  7. An interaction between a neuropeptide Y gene polymorphism and early adversity modulates endocrine stress responses.

    PubMed

    Witt, Stephanie H; Buchmann, Arlette F; Blomeyer, Dorothea; Nieratschker, Vanessa; Treutlein, Jens; Esser, Günter; Schmidt, Martin H; Bidlingmaier, Martin; Wiedemann, Klaus; Rietschel, Marcella; Laucht, Manfred; Wüst, Stefan; Zimmermann, Ulrich S

    2011-08-01

    Interindividual variability in the regulation of the human stress system accounts for a part of the individual's liability to stress-related diseases. These differences are influenced by environmental and genetic factors. Early childhood adversity is a well-studied environmental factor affecting an individual's stress response which has been shown to be modulated by gene-environment interaction (GxE). Neuropeptide Y (NPY) plays a role in stress regulation and genetic variation in NPY may influence stress responses. In this study, we analyzed the association of a common variant in the NPY gene promoter, rs16147, with cortisol and ACTH responses to acute psychosocial stress in young adults from the Mannheim Study of Children at Risk (MARS), an ongoing epidemiological cohort study following the outcome of early adversity from birth into adulthood. We found evidence of a GxE interaction between rs16147 and early adversity significantly affecting HPA axis responses to acute psychosocial stress. These findings suggest that the neurobiological mechanisms linking early adverse experience and later neuroendocrine stress regulation are modulated by a gene variant whose functional relevance is documented by increasing convergent evidence from in vitro, animal and human studies.

  8. Nitric oxide modulates salt and sugar responses via different signaling pathways.

    PubMed

    Newland, Philip L; Yates, Paul

    2008-04-01

    Locusts lay their eggs by digging into a substrate using rhythmic opening and closing movements of ovipositor valves at the end of the abdomen. The digging rhythm is inhibited by chemosensory stimulation of chemoreceptors on the valves. Nitric oxide (NO) modulated the effects of chemosensory stimulation on the rhythm. Stimulation with either sucrose or sodium chloride (NaCl) stopped the digging rhythm, whereas simultaneous bath application of the NO inhibitor, N-nitro-L-arginine methyl ester (L-NAME), increased the duration for which the digging rhythm stopped. Increasing NO levels caused a significant reduction in the cessation of the rhythm in response to the same 2 chemicals. Bath applying cyclic guanosine monophosphate (cGMP), the soluble guanylate inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and the generic protein kinase inhibitor H-7 had no effect on the duration for which the rhythm stopped in response to NaCl stimulation. Conversely, bath application of cGMP and ODQ resulted in a significant decrease and increase, respectively, in the duration for which the digging rhythm stopped when stimulated with sucrose. Moreover, bath application of the selective protein kinase G (PKG) inhibitor KT-5823 also resulted in a significant increase in the duration of cessation of the rhythm when stimulated with sucrose. Results suggest that NO modulates the behavioral responses to NaCl via a cGMP/PKG-independent pathway while modulating the responses to sucrose via a NO-cGMP/PKG-dependent pathway.

  9. Modulation of the in vitro immune response by lead, nickel and zinc

    SciTech Connect

    Warner, G.L.

    1986-01-01

    The ability of Pb, Ni and Zn to modulate the in vitro murine immune response was examined. 100 ..mu..M Pb and Ni were shown to enhance the in vitro PFC response to SRBC while 100 ..mu..M Zn had inhibitory effects. Each of the cations stimulated splenocyte proliferation as determined by (/sup 3/H) thymidine incorporation, autoradiography and flow cytometric cell cycle analysis (acridine orange staining). Media selection was an important factor in the ability of these cations to modulate the immune response. Cation induced lymphoproliferation occurred late in culture (day 5 or later), was dependent on cell density (cells/ml) and required the presence of both T cells and la/sup +/ cells. Treatment of splenocytes with anti-Thyl. 2, anti-Lytl or anti-L3T4 completely abrogated the ability of these metals to induce proliferation, indicating that helper T cells (Lytl/sup +/ + 2/sup -/, L3T4/sup +/) are required at the initiation of culture. Pb, Ni or Zn preferentially enhanced the recovery of Thy/sup +/ cells as determined by flow cytometry of 7 day cation stimulated splenocytes. Zn preferentially enhanced the entry of T suppressor cells (Lyt2/sup +/) into the cell cycle. Pb, Ni and Zn induced the production/secretion of IL2, the expression of IL2 receptor (IL2R), and monoclonal anti-IL2, anti-IL2R and anti(gamma)IFN inhibited the induction of lymphoproliferation. These results are consistent with the hypothesis that Pb, Ni, and Zn modulate the immune response by activating T cells specific for altered self la or by altering immunoregulation associated with the autologous MLR.

  10. DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs.

    PubMed

    Rossiello, Francesca; Aguado, Julio; Sepe, Sara; Iannelli, Fabio; Nguyen, Quan; Pitchiaya, Sethuramasundaram; Carninci, Piero; d'Adda di Fagagna, Fabrizio

    2017-02-27

    The DNA damage response (DDR) is a set of cellular events that follows the generation of DNA damage. Recently, site-specific small non-coding RNAs, also termed DNA damage response RNAs (DDRNAs), have been shown to play a role in DDR signalling and DNA repair. Dysfunctional telomeres activate DDR in ageing, cancer and an increasing number of identified pathological conditions. Here we show that, in mammals, telomere dysfunction induces the transcription of telomeric DDRNAs (tDDRNAs) and their longer precursors from both DNA strands. DDR activation and maintenance at telomeres depend on the biogenesis and functions of tDDRNAs. Their functional inhibition by sequence-specific antisense oligonucleotides allows the unprecedented telomere-specific DDR inactivation in cultured cells and in vivo in mouse tissues. In summary, these results demonstrate that tDDRNAs are induced at dysfunctional telomeres and are necessary for DDR activation and they validate the viability of locus-specific DDR inhibition by targeting DDRNAs.

  11. Death, dying, and domination.

    PubMed

    Spindelman, Marc

    2008-06-01

    This Article critiques conventional liberal arguments for the right to die on liberal grounds. It contends that these arguments do not go far enough to recognize and address private, and in particular structural, forms of domination. It presents an alternative that does, which is thus more respectful of true freedom in the context of death and dying, and also more consistent with liberalism. After discussing obstacles to the achievement of a right to die that encompasses freedom from both public and private domination, the Article closes with a significant reform project within bioethics that might help bring it about.

  12. Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network

    PubMed Central

    Nwachukwu, Jerome C; Srinivasan, Sathish; Bruno, Nelson E; Parent, Alexander A; Hughes, Travis S; Pollock, Julie A; Gjyshi, Olsi; Cavett, Valerie; Nowak, Jason; Garcia-Ordonez, Ruben D; Houtman, René; Griffin, Patrick R; Kojetin, Douglas J; Katzenellenbogen, John A; Conkright, Michael D; Nettles, Kendall W

    2014-01-01

    Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. In this study, we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERα ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFα genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERα and several ERα coregulators, suggesting that ERα functions as a primary conduit for resveratrol activity. DOI: http://dx.doi.org/10.7554/eLife.02057.001 PMID:24771768

  13. Modulated ferromagnetic ordering and the magnetocaloric response of Eu{sub 4}PdMg

    SciTech Connect

    Ryan, D. H. Legros, Anaëlle; Niehaus, Oliver; Pöttgen, Rainer; Cadogan, J. M.; Flacau, R.

    2015-05-07

    Neutron powder diffraction confirms that the primary ordering mode in Eu{sub 4}PdMg is ferromagnetic with a europium moment of 6.5(2) μ{sub B}. {sup 151}Eu Mössbauer spectroscopy shows that the unusual linear temperature dependence of the magnetisation reported for this system is an intrinsic property and not an artefact of the applied field. The form and temperature evolution of the {sup 151}Eu Mössbauer spectra strongly suggest that there is an incommensurate modulation to the magnetic structure that modifies the basic ferromagnetic order. This modulated structure may be the origin of the broad magnetocaloric response previously observed in Eu{sub 4}PdMg.

  14. Glucose administration does not modulate prolactin response to exercise, TRH or haloperidol injection.

    PubMed

    Vigas, M; Jezová, D

    1994-01-01

    Glucose was found to exert an In vitro regulatory effect on prolactin secretion. Its role in the modulation of stimulated secretion of prolactin in man is, however, not clear. To evaluate the effect of hyperglycaemia on prolactin release, three stimulatory tests with different mechanisms of stimulation were employed. Healthy male subjects served as volunteers during submaximal exercise, TRH test (0.2 mg i.v.) and administration of haloperidol (2 mg i.v.). Glucose (100 g in 400 ml) or an equal volume of water was given 30 min before the tests. Blood for glucose and prolactin analysis was taken via an indwelling catheter. The plasma prolactin concentration increased in response to each of the stimuli applied. However, the prolactin increase during hyperglycaemia did not differ from values obtained in tests performed in normoglycaemia after water administration. These results indicate that prolactin release in healthy man is not modulated by hyperglycaemia.

  15. Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

    PubMed

    Perros, Alexis J; Christensen, Anne-Marie; Flower, Robert L; Dean, Melinda M

    2015-10-01

    The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

  16. Is Baseline Cardiac Autonomic Modulation Related to Performance and Physiological Responses Following a Supramaximal Judo Test?

    PubMed Central

    Blasco-Lafarga, Cristina; Martínez-Navarro, Ignacio; Mateo-March, Manuel

    2013-01-01

    Little research exists concerning Heart Rate (HR) Variability (HRV) following supramaximal efforts focused on upper-body explosive strength-endurance. Since they may be very demanding, it seems of interest to analyse the relationship among performance, lactate and HR dynamics (i.e. HR, HRV and complexity) following them; as well as to know how baseline cardiac autonomic modulation mediates these relationships. The present study aimed to analyse associations between baseline and post-exercise HR dynamics following a supramaximal Judo test, and their relationship with lactate, in a sample of 22 highly-trained male judoists (20.70±4.56 years). A large association between the increase in HR from resting to exercise condition and performance suggests that individuals exerted a greater sympathetic response to achieve a better performance (Rating of Perceived Exertion: 20; post-exercise peak lactate: 11.57±2.24 mmol/L; 95.76±4.13 % of age-predicted HRmax). Athletes with higher vagal modulation and lower sympathetic modulation at rest achieved both a significant larger ∆HR and a faster post-exercise lactate removal. A enhanced resting parasympathetic modulation might be therefore related to a further usage of autonomic resources and a better immediate metabolic recovery during supramaximal exertions. Furthermore, analyses of variance displayed a persistent increase in α1 and a decrease in lnRMSSD along the 15 min of recovery, which are indicative of a diminished vagal modulation together with a sympathovagal balance leaning to sympathetic domination. Eventually, time-domain indices (lnRMSSD) showed no lactate correlations, while nonlinear indices (α1 and lnSaEn) appeared to be moderate to strongly correlated with it, thus pointing to shared mechanisms between neuroautonomic and metabolic regulation. PMID:24205273

  17. Response of cardiac autonomic modulation after a single exposure to musical auditory stimulation

    PubMed Central

    Ferreira, Lucas L.; Vanderlei, Luiz Carlos M.; Guida, Heraldo L.; de Abreu, Luiz Carlos; Garner, David M.; Vanderlei, Franciele M.; Ferreira, Celso; Valenti, Vitor E.

    2015-01-01

    The acute effects after exposure to different styles of music on cardiac autonomic modulation assessed through heart rate variability (HRV) analysis have not yet been well elucidated. We aimed to investigate the recovery response of cardiac autonomic modulation in women after exposure to musical auditory stimulation of different styles. The study was conducted on 30 healthy women aged between 18 years and 30 years. We did not include subjects having previous experience with musical instruments and those who had an affinity for music styles. The volunteers remained at rest for 10 min and were exposed to classical baroque (64-84 dB) and heavy metal (75-84 dB) music for 10 min, and their HRV was evaluated for 30 min after music cessation. We analyzed the following HRV indices: Standard deviation of normal-to-normal (SDNN) intervals, root mean square of successive differences (RMSSD), percentage of normal-to-normal 50 (pNN50), low frequency (LF), high frequency (HF), and LF/HF ratio. SDNN, LF in absolute units (ms2) and normalized (nu), and LF/HF ratio increased while HF index (nu) decreased after exposure to classical baroque music. Regarding the heavy metal music style, it was observed that there were increases in SDNN, RMSSD, pNN50, and LF (ms2) after the musical stimulation. In conclusion, the recovery response of cardiac autonomic modulation after exposure to auditory stimulation with music featured an increased global activity of both systems for the two musical styles, with a cardiac sympathetic modulation for classical baroque music and a cardiac vagal tone for the heavy metal style. PMID:25774614

  18. Response of cardiac autonomic modulation after a single exposure to musical auditory stimulation.

    PubMed

    Ferreira, Lucas L; Vanderlei, Luiz Carlos M; Guida, Heraldo L; de Abreu, Luiz Carlos; Garner, David M; Vanderlei, Franciele M; Ferreira, Celso; Valenti, Vitor E

    2015-01-01

    The acute effects after exposure to different styles of music on cardiac autonomic modulation assessed through heart rate variability (HRV) analysis have not yet been well elucidated. We aimed to investigate the recovery response of cardiac autonomic modulation in women after exposure to musical auditory stimulation of different styles. The study was conducted on 30 healthy women aged between 18 years and 30 years. We did not include subjects having previous experience with musical instruments and those who had an affinity for music styles. The volunteers remained at rest for 10 min and were exposed to classical baroque (64-84 dB) and heavy metal (75-84 dB) music for 10 min, and their HRV was evaluated for 30 min after music cessation. We analyzed the following HRV indices: Standard deviation of normal-to-normal (SDNN) intervals, root mean square of successive differences (RMSSD), percentage of normal-to-normal 50 (pNN50), low frequency (LF), high frequency (HF), and LF/HF ratio. SDNN, LF in absolute units (ms 2 ) and normalized (nu), and LF/HF ratio increased while HF index (nu) decreased after exposure to classical baroque music. Regarding the heavy metal music style, it was observed that there were increases in SDNN, RMSSD, pNN50, and LF (ms 2 ) after the musical stimulation. In conclusion, the recovery response of cardiac autonomic modulation after exposure to auditory stimulation with music featured an increased global activity of both systems for the two musical styles, with a cardiac sympathetic modulation for classical baroque music and a cardiac vagal tone for the heavy metal style.

  19. A network-based phenotype mapping approach to identify genes that modulate drug response phenotypes

    PubMed Central

    Cairns, Junmei; Ung, Choong Yong; da Rocha, Edroaldo Lummertz; Zhang, Cheng; Correia, Cristina; Weinshilboum, Richard; Wang, Liewei; Li, Hu

    2016-01-01

    To better address the problem of drug resistance during cancer chemotherapy and explore the possibility of manipulating drug response phenotypes, we developed a network-based phenotype mapping approach (P-Map) to identify gene candidates that upon perturbed can alter sensitivity to drugs. We used basal transcriptomics data from a panel of human lymphoblastoid cell lines (LCL) to infer drug response networks (DRNs) that are responsible for conferring response phenotypes for anthracycline and taxane, two common anticancer agents use in clinics. We further tested selected gene candidates that interact with phenotypic differentially expressed genes (PDEGs), which are up-regulated genes in LCL for a given class of drug response phenotype in triple-negative breast cancer (TNBC) cells. Our results indicate that it is possible to manipulate a drug response phenotype, from resistant to sensitive or vice versa, by perturbing gene candidates in DRNs and suggest plausible mechanisms regulating directionality of drug response sensitivity. More important, the current work highlights a new way to formulate systems-based therapeutic design: supplementing therapeutics that aim to target disease culprits with phenotypic modulators capable of altering DRN properties with the goal to re-sensitize resistant phenotypes. PMID:27841317

  20. Antidromic potential spread modulates the receptor responses in the stretch receptor neurons of the crayfish.

    PubMed

    Purali, Nuhan

    2011-12-01

    The effects of antidromic potential spread were investigated in the stretch receptor neurons of the crayfish. Current and potential responses to conductance changes were recorded in the dynamic clamp condition and compared to those obtained by using some conventional clamp methods and a compartmental neuron model. An analogue circuit was used for dynamic calculation of the injected receptor current as a function of the membrane potential and the given conductance change. Alternatively, receptor current responses to a mechanical stimulus were recorded and compared when the cell was voltage clamped to a previously recorded impulse wave form and the resting potential, respectively. Under dynamic clamp, the receptor current had an oscillating waveform which contrasts with the conventional recordings. Frequency, amplitude and sign of the oscillations were dependent on the applied conductance level, reversal potential and electrotonic attenuation. Mean current amplitude and frequency of the evoked impulse responses were smaller under dynamic clamp, especially for large conductance increases. However, firing frequency was larger if plotted against the mean current response. Recorded responses were similar to those calculated in the model. It was not possible to evoke any adaptation in the slowly adapting neuron by using the dynamic clamp. Evoked potential change served as a self limiting response, preventing the depolarization block. However, impulse duration was significantly shorter in the rapidly adapting neuron when the dynamic clamp was used. It was concluded that, in the stretch receptor neurons during a conductance increase, antidromic potential spread modulates the receptor responses and contributes to adaptation.

  1. HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition.

    PubMed

    Prentice, Heather A; Tomaras, Georgia D; Geraghty, Daniel E; Apps, Richard; Fong, Youyi; Ehrenberg, Philip K; Rolland, Morgane; Kijak, Gustavo H; Krebs, Shelly J; Nelson, Wyatt; DeCamp, Allan; Shen, Xiaoying; Yates, Nicole L; Zolla-Pazner, Susan; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Kaewkungwal, Jaranit; Pitisuttithum, Punnee; Ferrari, Guido; McElrath, M Juliana; Montefiori, David C; Bailer, Robert T; Koup, Richard A; O'Connell, Robert J; Robb, Merlin L; Michael, Nelson L; Gilbert, Peter B; Kim, Jerome H; Thomas, Rasmi

    2015-07-15

    In the RV144 vaccine trial, two antibody responses were found to correlate with HIV-1 acquisition. Because human leukocyte antigen (HLA) class II-restricted CD4(+) T cells are involved in antibody production, we tested whether HLA class II genotypes affected HIV-1-specific antibody levels and HIV-1 acquisition in 760 individuals. Indeed, antibody responses correlated with acquisition only in the presence of single host HLA alleles. Envelope (Env)-specific immunoglobulin A (IgA) antibodies were associated with increased risk of acquisition specifically in individuals with DQB1*06. IgG antibody responses to Env amino acid positions 120 to 204 were higher and were associated with decreased risk of acquisition and increased vaccine efficacy only in the presence of DPB1*13. Screening IgG responses to overlapping peptides spanning Env 120-204 and viral sequence analysis of infected individuals defined differences in vaccine response that were associated with the presence of DPB1*13 and could be responsible for the protection observed. Overall, the underlying genetic findings indicate that HLA class II modulated the quantity, quality, and efficacy of antibody responses in the RV144 trial.

  2. HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition

    PubMed Central

    Prentice, Heather A.; Tomaras, Georgia D.; Geraghty, Daniel E.; Apps, Richard; Fong, Youyi; Ehrenberg, Philip K.; Rolland, Morgane; Kijak, Gustavo H.; Krebs, Shelly J.; Nelson, Wyatt; DeCamp, Allan; Shen, Xiaoying; Yates, Nicole L.; Zolla-Pazner, Susan; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Kaewkungwal, Jaranit; Pitisuttithum, Punnee; Ferrari, Guido; Juliana McElrath, M.; Montefiori, David C.; Bailer, Robert T.; Koup, Richard A.; O’Connell, Robert J.; Robb, Merlin L.; Michael, Nelson L.; Gilbert, Peter B.; Kim, Jerome H.; Thomas, Rasmi

    2016-01-01

    In the RV144 vaccine trial, two antibody responses were found to correlate with HIV-1 acquisition. Because human leukocyte antigen (HLA) class II–restricted CD4+ T cells are involved in antibody production, we tested whether HLA class II genotypes affected HIV-1–specific antibody levels and HIV-1 acquisition in 760 individuals. Indeed, antibody responses correlated with acquisition only in the presence of single host HLA alleles. Envelope (Env)–specific immunoglobulin A (IgA) antibodies were associated with increased risk of acquisition specifically in individuals with DQB1*06. IgG antibody responses to Env amino acid positions 120 to 204 were higher and were associated with decreased risk of acquisition and increased vaccine efficacy only in the presence of DPB1*13. Screening IgG responses to overlapping peptides spanning Env 120–204 and viral sequence analysis of infected individuals defined differences in vaccine response that were associated with the presence of DPB1*13 and could be responsible for the protection observed. Overall, the underlying genetic findings indicate that HLA class II modulated the quantity, quality, and efficacy of antibody responses in the RV144 trial. PMID:26180102

  3. Reward-Modulated Response Inhibition, Cognitive Shifting, and the Orbital Frontal Cortex in Early Adolescence

    PubMed Central

    Zhai, Zu Wei; Pajtek, Stefan; Luna, Beatriz; Geier, Charles F.; Ridenour, Ty A.; Clark, Duncan B.

    2014-01-01

    Immaturities in cognitive shifting are associated with adolescent risk behaviors. The orbital frontal cortex (OFC) regulates reward processing and response inhibition. This study tested the relationship between cognitive shifting, OFC activity, and reward-modulated response inhibition in young adolescents. An fMRI antisaccade (AS) paradigm examined the effects of reward conditions on inhibitory response and OFC processing. A validated self-report inventory assessed cognitive shifting. Compared to neutral, reward trials showed better AS performance and increased OFC activation. Cognitive shifting positively associated with AS performance in reward and neutral trials. Poorer cognitive shifting predicted greater OFC activation. Results indicate lower OFC efficiency, as greater activation to achieve correct performance, underlies cognitive shifting problems. These neurocognitive impairments are relevant for understanding adolescent risk behaviors. PMID:26755891

  4. Interactions between Starch, Lipids, and Proteins in Foods: Microstructure Control for Glycemic Response Modulation.

    PubMed

    Parada, Javier; Santos, Jose L

    2016-10-25

    In real food, starch is usually forming part of a matrix with lipids and proteins. However, research on this ternary system and interactions between such food components has been scarce so far. The control of food microstructure is crucial to determine the product properties, including sensorial and nutritionals ones. This paper reviews the microstructural principles of interactions between starch, lipids, and proteins in foods as well as their effect on postprandial glycemic response, considering human intrinsic differences on postprandial glycemic responses. Several lines of research support the hypothesis that foods without rapidly digestible starch will not mandatorily generate the lowest postprandial glycemic response, highlighting that the full understanding of food microstructure, which modulates starch digestion, plays a key role on food design from a nutritional viewpoint.

  5. Leptin modulates the late fever response to LPS in diet-induced obese animals.

    PubMed

    Pohl, Joanna; Woodside, Barbara; Luheshi, Giamal N

    2014-11-01

    Leptin is an important modulator of both inflammation and energy homeostasis, making it a key interface between the inflammatory response to pathogenic stimuli and the energy status of the host. In previous studies we demonstrated that sickness responses to systemic immune challenge, including fever, are significantly exacerbated in diet induced obese animals. To investigate whether this exacerbation is functionally linked to the obesity associated increase in circulating levels of leptin, a species-specific leptin antiserum (LAS) was used to neutralize endogenous leptin in diet-induced obese adult male Wistar rats treated with a single intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) (100μg/kg). LAS significantly reduced the magnitude of the later phases of the fever response, and attenuated the circulating levels of IL-6, IL-1ra and bioactivity of leptin in the obese animals. In addition, the antiserum significantly attenuated the hypothalamic expression of IL-1ß, IκBα, COX2, SOCS3 and IL-6 in both lean and obese rats 10h after the LPS injection and NF-IL6 in the hypothalamus of obese rats only. The relatively late rise in brain IL-6 suggested a role in mediating the extended fever response in obese animals and we tested this by neutralizing brain IL-6 using an IL6-AS injected intracerebroventricularly (4μl, icv). The IL6-AS significantly but transiently (between 9h and 12h post LPS) reduced the late fever response of obese rats. These results demonstrate that leptin plays an important part in modulating the late portion of the fever response to LPS, likely through the induction of hypothalamic IL-6 in obese animals.

  6. Predicting invasive species impacts: a community module functional response approach reveals context dependencies.

    PubMed

    Paterson, Rachel A; Dick, Jaimie T A; Pritchard, Daniel W; Ennis, Marilyn; Hatcher, Melanie J; Dunn, Alison M

    2015-03-01

    Predatory functional responses play integral roles in predator-prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species. Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator-prey interactions and thus the predictive capability of the comparative functional response approach. We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses. Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator. Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator. This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies.

  7. Predicting invasive species impacts: a community module functional response approach reveals context dependencies

    PubMed Central

    Paterson, Rachel A; Dick, Jaimie T A; Pritchard, Daniel W; Ennis, Marilyn; Hatcher, Melanie J; Dunn, Alison M

    2015-01-01

    Summary Predatory functional responses play integral roles in predator–prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species. Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator–prey interactions and thus the predictive capability of the comparative functional response approach. We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses. Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator. Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator. This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies. PMID:25265905

  8. Histamine in the posterodorsal medial amygdala modulates cardiovascular reflex responses in awake rats.

    PubMed

    Quagliotto, E; Neckel, H; Riveiro, D F; Casali, K R; Mostarda, C; Irigoyen, M C; Dall'ago, P; Rasia-Filho, A A

    2008-12-10

    Centrally injected histamine (HA) affects heart rate (HR), arterial blood pressure (BP), and sympathetic activity in rats. The posterodorsal medial amygdala (MePD) has high levels of histidine decarboxylase, connections with brain areas involved with the modulation of cardiovascular responses, and is relevant for the pathogenesis of hypertension. However, there is no report demonstrating the role of the MePD histaminergic activity on the cardiovascular function in awake rats. The aims of the present work were: 1) to study the effects of two doses (10-100 nM) of HA microinjected in the MePD on basal cardiovascular recordings and on baroreflex- and chemoreflex-mediated responses; 2) to reveal whether cardiovascular reflex responses could be affected by MePD microinjections of (R)-alpha-methylhistamine (AH3), an agonist of the inhibitory autoreceptor H3; and, 3) to carry out a power spectral analysis to evaluate the contribution of the sympathetic and parasympathetic components in the variability of the HR and BP recordings. When compared with the control group (microinjected with saline, 0.3 microl), HA (10 nM) promoted an increase in the MAP50, i.e. the mean value of BP at half of the HR range evoked by the baroreflex response. Histamine (100 nM) did not affect the baroreflex activity, but significantly decreased the parasympathetic component of the HR variability, increased the sympathetic/parasympathetic balance at basal conditions (these two latter evaluated by the power spectral analysis), and promoted an impairment in the chemoreflex bradycardic response. Microinjection of AH3 (10 microM) led to mixed results, which resembled the effects of both doses of HA employed here. Present data suggest that cardiovascular changes induced by baroreceptors and chemoreceptors involve the histaminergic activity in the MePD. This neural regulation of reflex cardiovascular responses can have important implications for homeostatic and allostatic conditions and possibly for the

  9. Modulation of Neuronal Responses by Exogenous Attention in Macaque Primary Visual Cortex.

    PubMed

    Wang, Feng; Chen, Minggui; Yan, Yin; Zhaoping, Li; Li, Wu

    2015-09-30

    Visual perception is influenced by attention deployed voluntarily or triggered involuntarily by salient stimuli. Modulation of visual cortical processing by voluntary or endogenous attention has been extensively studied, but much less is known about how involuntary or exogenous attention affects responses of visual cortical neurons. Using implanted microelectrode arrays, we examined the effects of exogenous attention on neuronal responses in the primary visual cortex (V1) of awake monkeys. A bright annular cue was flashed either around the receptive fields of recorded neurons or in the opposite visual field to capture attention. A subsequent grating stimulus probed the cue-induced effects. In a fixation task, when the cue-to-probe stimulus onset asynchrony (SOA) was <240 ms, the cue induced a transient increase of neuronal responses to the probe at the cued location during 40-100 ms after the onset of neuronal responses to the probe. This facilitation diminished and disappeared after repeated presentations of the same cue but recurred for a new cue of a different color. In another task to detect the probe, relative shortening of monkey's reaction times for the validly cued probe depended on the SOA in a way similar to the cue-induced V1 facilitation, and the behavioral and physiological cueing effects remained after repeated practice. Flashing two cues simultaneously in the two opposite visual fields weakened or diminished both the physiological and behavioral cueing effects. Our findings indicate that exogenous attention significantly modulates V1 responses and that the modulation strength depends on both novelty and task relevance of the stimulus. Significance statement: Visual attention can be involuntarily captured by a sudden appearance of a conspicuous object, allowing rapid reactions to unexpected events of significance. The current study discovered a correlate of this effect in monkey primary visual cortex. An abrupt, salient, flash enhanced neuronal

  10. Nitrite is a positive modulator of the Frank-Starling response in the vertebrate heart.

    PubMed

    Angelone, Tommaso; Gattuso, Alfonsina; Imbrogno, Sandra; Mazza, Rosa; Tota, Bruno

    2012-06-01

    Evidence from both mammalian and nonmammalian vertebrates indicates that intracardiac nitric oxide (NO) facilitates myocardial relaxation, ventricular diastolic distensibility, and, consequently, the Frank-Starling response, i.e., the preload-induced increase of cardiac output. Since nitrite ion (NO(2)(-)), the major storage pool of bioactive NO, recently emerged as a cardioprotective endogenous modulator, we explored its influence on the Frank-Starling response in eel, frog, and rat hearts, used as paradigms of fish, amphibians, and mammals, respectively. We demonstrated that, like NO, exogenous nitrite improves the Frank-Starling response in all species, as indicated by an increase of stroke volume and stroke work (eel and frog) and of left ventricular (LV) pressure and LVdP/dt max (rat), used as indexes of inotropism. Unlike in frog and rat, in eel, the positive influence of nitrite appeared to be dependent on NO synthase inhibition. In all species, the effect was sensitive to NO scavengers, independent on nitroxyl anion, and mediated by a cGMP/PKG-dependent pathway. Moreover, the nitrite treatment increased S-nitrosylation of lower-molecular-weight proteins in cytosolic and membrane fractions. These results suggest that nitrite acts as a physiological source of NO, modulating through different species-specific mechanisms, the stretch-induced intrinsic regulation of the vertebrate heart.

  11. GABAergic and glycinergic inhibition modulate monaural auditory response properties in the avian superior olivary nucleus

    PubMed Central

    Coleman, W. L.; Fischl, M. J.; Weimann, S. R.

    2011-01-01

    The superior olivary nucleus (SON) is the primary source of inhibition in the avian auditory brainstem. While much is known about the role of inhibition at the SON's target nuclei, little is known about how the SON itself processes auditory information or how inhibition modulates these properties. Additionally, the synaptic physiology of inhibitory inputs within the SON has not been described. We investigated these questions using in vivo and in vitro electrophysiological techniques in combination with immunohistochemistry in the chicken, an organism for which the auditory brainstem has otherwise been well characterized. We provide a thorough characterization of monaural response properties in the SON and the influence of inhibitory input in shaping these features. We found that the SON contains a heterogeneous mixture of response patterns to acoustic stimulation and that in most neurons these responses are modulated by both GABAergic and glycinergic inhibitory inputs. Interestingly, many SON neurons tuned to low frequencies have robust phase-locking capability and the precision of this phase locking is enhanced by inhibitory inputs. On the synaptic level, we found that evoked and spontaneous inhibitory postsynaptic currents (IPSCs) within the SON are also mediated by both GABAergic and glycinergic inhibition in all neurons tested. Analysis of spontaneous IPSCs suggests that most SON cells receive a mixture of both purely GABAergic terminals, as well as terminals from which GABA and glycine are coreleased. Evidence for glycinergic signaling within the SON is a novel result that has important implications for understanding inhibitory function in the auditory brainstem. PMID:21368002

  12. Temporal and spectral dynamics underlying cognitive control modulated by task-irrelevant stimulus-response learning.

    PubMed

    Cao, Yanan; Cao, Xiangyi; Yue, Zhenzhu; Wang, Ling

    2017-02-01

    Behavioral and recent neuroimaging findings have shown reversal of interference effects due to manipulating proportion congruency (PC), which suggests that task-irrelevant stimulus-response (S-R) associations are strengthened and applied to predict responses. However, it is unclear how the strengthened S-R associations are represented and applied in the brain. We investigated with a between-subjects PC paradigm of the Hedge and Marsh task using electroencephalography (EEG). The behavioral results showed the reversal of the conflict effects, suggesting that task-irrelevant S-R associations were strengthened and used to prepare responses. The EEG results revealed the PC-related reversal of the conflict effects in the frontocentral N2 and parietal P3b amplitudes. Time-frequency analyses showed more pronounced PC-related reversal of the conflict effects in theta band (4-8 Hz) activity in frontocentral sites. These results suggest that the strengthened S-R associations due to PC manipulation modulated cognitive control. Importantly, the amplitude of lateralized readiness potential was higher in the high-PC condition than in the low-PC condition, suggesting that the strengthened short-term-memory spatial S-R associations that modulated cognitive control were applied similarly to long-term-memory spatial S-R associations.

  13. Modulation of Temporal Precision in Thalamic Population Responses to Natural Visual Stimuli

    PubMed Central

    Desbordes, Gaëlle; Jin, Jianzhong; Alonso, Jose-Manuel; Stanley, Garrett B.

    2010-01-01

    Natural visual stimuli have highly structured spatial and temporal properties which influence the way visual information is encoded in the visual pathway. In response to natural scene stimuli, neurons in the lateral geniculate nucleus (LGN) are temporally precise – on a time scale of 10–25 ms – both within single cells and across cells within a population. This time scale, established by non stimulus-driven elements of neuronal firing, is significantly shorter than that of natural scenes, yet is critical for the neural representation of the spatial and temporal structure of the scene. Here, a generalized linear model (GLM) that combines stimulus-driven elements with spike-history dependence associated with intrinsic cellular dynamics is shown to predict the fine timing precision of LGN responses to natural scene stimuli, the corresponding correlation structure across nearby neurons in the population, and the continuous modulation of spike timing precision and latency across neurons. A single model captured the experimentally observed neural response, across different levels of contrasts and different classes of visual stimuli, through interactions between the stimulus correlation structure and the nonlinearity in spike generation and spike history dependence. Given the sensitivity of the thalamocortical synapse to closely timed spikes and the importance of fine timing precision for the faithful representation of natural scenes, the modulation of thalamic population timing over these time scales is likely important for cortical representations of the dynamic natural visual environment. PMID:21151356

  14. Cognitive modulation of psychophysical, respiratory and autonomic responses to cold pressor test.

    PubMed

    Santarcangelo, Enrica L; Paoletti, Giulia; Chiavacci, Iacopo; Palombo, Carlo; Carli, Giancarlo; Varanini, Maurizio

    2013-01-01

    In healthy subjects with high hypnotisability (highs) under hypnosis, subjectively effective suggestions for analgesia abolish the increases in blood pressure associated with cold pressor test (cpt) by reducing the peripheral vascular resistance. The aim of the present study was to investigate the effects of the suggestions of analgesia on the responses to cpt in healthy highs (n = 22) and in low hypnotisable participants (lows, n = 22) out of hypnosis. Cpt was administered without (CPT) and with suggestions for analgesia (CPT+AN). Psychophysical (pain intensity, pain threshold, cpt duration (time of immersion) and pain tolerance, defined as the difference between cpt duration and pain threshold), respiratory (amplitude and frequency) and autonomic variables (tonic skin conductance, mean RR interval (RR = 1/heart rate), blood pressure, skin blood flow) were studied. The suggestions for analgesia increased cpt duration and RR in both groups, but decreased pain intensity and enhanced pain threshold only in highs; in both groups they did not modulate systolic blood pressure, tonic skin conductance and skin blood flow; thus, increased parasympathetic activity appears responsible for the heart rate reduction induced by suggestions in both groups. In conclusion, our findings show that suggestions modulate pain experience differentially in highs and lows, and are partially effective also in lows. We hypothesize that the mechanisms responsible for the efficacy of suggestions in healthy lows may be involved also in their efficacy in chronic pain patients with low hypnotisability.

  15. Cognitive Modulation of Psychophysical, Respiratory and Autonomic Responses to Cold Pressor Test

    PubMed Central

    Santarcangelo, Enrica L.; Paoletti, Giulia; Chiavacci, Iacopo; Palombo, Carlo; Carli, Giancarlo; Varanini, Maurizio

    2013-01-01

    In healthy subjects with high hypnotisability (highs) under hypnosis, subjectively effective suggestions for analgesia abolish the increases in blood pressure associated with cold pressor test (cpt) by reducing the peripheral vascular resistance. The aim of the present study was to investigate the effects of the suggestions of analgesia on the responses to cpt in healthy highs (n = 22) and in low hypnotisable participants (lows, n = 22) out of hypnosis. Cpt was administered without (CPT) and with suggestions for analgesia (CPT+AN). Psychophysical (pain intensity, pain threshold, cpt duration (time of immersion) and pain tolerance, defined as the difference between cpt duration and pain threshold), respiratory (amplitude and frequency) and autonomic variables (tonic skin conductance, mean RR interval (RR = 1/heart rate), blood pressure, skin blood flow) were studied. The suggestions for analgesia increased cpt duration and RR in both groups, but decreased pain intensity and enhanced pain threshold only in highs; in both groups they did not modulate systolic blood pressure, tonic skin conductance and skin blood flow; thus, increased parasympathetic activity appears responsible for the heart rate reduction induced by suggestions in both groups. In conclusion, our findings show that suggestions modulate pain experience differentially in highs and lows, and are partially effective also in lows. We hypothesize that the mechanisms responsible for the efficacy of suggestions in healthy lows may be involved also in their efficacy in chronic pain patients with low hypnotisability. PMID:24130680

  16. GABAergic and glycinergic inhibition modulate monaural auditory response properties in the avian superior olivary nucleus.

    PubMed

    Coleman, W L; Fischl, M J; Weimann, S R; Burger, R M

    2011-05-01

    The superior olivary nucleus (SON) is the primary source of inhibition in the avian auditory brainstem. While much is known about the role of inhibition at the SON's target nuclei, little is known about how the SON itself processes auditory information or how inhibition modulates these properties. Additionally, the synaptic physiology of inhibitory inputs within the SON has not been described. We investigated these questions using in vivo and in vitro electrophysiological techniques in combination with immunohistochemistry in the chicken, an organism for which the auditory brainstem has otherwise been well characterized. We provide a thorough characterization of monaural response properties in the SON and the influence of inhibitory input in shaping these features. We found that the SON contains a heterogeneous mixture of response patterns to acoustic stimulation and that in most neurons these responses are modulated by both GABAergic and glycinergic inhibitory inputs. Interestingly, many SON neurons tuned to low frequencies have robust phase-locking capability and the precision of this phase locking is enhanced by inhibitory inputs. On the synaptic level, we found that evoked and spontaneous inhibitory postsynaptic currents (IPSCs) within the SON are also mediated by both GABAergic and glycinergic inhibition in all neurons tested. Analysis of spontaneous IPSCs suggests that most SON cells receive a mixture of both purely GABAergic terminals, as well as terminals from which GABA and glycine are coreleased. Evidence for glycinergic signaling within the SON is a novel result that has important implications for understanding inhibitory function in the auditory brainstem.

  17. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function

    PubMed Central

    Reunanen, Justus; Meijerink, Marjolein; Pietilä, Taija E.; Kainulainen, Veera; Klievink, Judith; Huuskonen, Laura; Aalvink, Steven; Skurnik, Mikael; Boeren, Sjef; Satokari, Reetta; Mercenier, Annick; Palva, Airi; Smidt, Hauke; de Vos, Willem M.; Belzer, Clara

    2017-01-01

    Gut barrier function is key in maintaining a balanced response between the host and its microbiome. The microbiota can modulate changes in gut barrier as well as metabolic and inflammatory responses. This highly complex system involves numerous microbiota-derived factors. The gut symbiont Akkermansia muciniphila is positively correlated with a lean phenotype, reduced body weight gain, amelioration of metabolic responses and restoration of gut barrier function by modulation of mucus layer thickness. However, the molecular mechanisms behind its metabolic and immunological regulatory properties are unexplored. Herein, we identify a highly abundant outer membrane pili-like protein of A. muciniphila MucT that is directly involved in immune regulation and enhancement of trans-epithelial resistance. The purified Amuc_1100 protein and enrichments containing all its associated proteins induced production of specific cytokines through activation of Toll-like receptor (TLR) 2 and TLR4. This mainly leads to high levels of IL-10 similar to those induced by the other beneficial immune suppressive microorganisms such as Faecalibacterium prausnitzii A2-165 and Lactobacillus plantarum WCFS1. Together these results indicate that outer membrane protein composition and particularly the newly identified highly abundant pili-like protein Amuc_1100 of A. muciniphila are involved in host immunological homeostasis at the gut mucosa, and improvement of gut barrier function. PMID:28249045

  18. Thalidomide modulates Mycobacterium leprae-induced NF-κB pathway and lower cytokine response.

    PubMed

    Hernandez, Maristela de Oliveira; Fulco, Tatiana de Oliveira; Pinheiro, Roberta Olmo; Pereira, Renata de Meirelles Santos; Redner, Paulo; Sarno, Euzenir Nunes; Lopes, Ulisses Gazos; Sampaio, Elizabeth Pereira

    2011-11-16

    It is widely accepted that tumor necrosis factor alpha (TNF-α) plays a critical role in the development of tissue and nerve damage in leprosy and during the reactional episodes of acute inflammation. Thalidomide (N-α-phthalimidoglutarimide), a drug used to treat leprosy reaction, modulates immune response, inhibits inflammation and NF-κB activity. Here we investigated whether thalidomide inhibits NF-κB activation induced by Mycobacterium leprae, p38 and ERK1/2 MAPK activation. EMSA and supershift assays were performed to investigate NF-κB activation in response to M. leprae and its modulation following in vitro treatment with thalidomide. Luciferase assay was assayed in transfected THP-1 cells to determine NF-κB transcriptional activity. Flow cytometry and immunofluorescence were used to investigate p65 accumulation in the nucleus. Immunoblotting was used to investigate p38 and ERK1/2 phosphorylation. Following activation of PBMC and monocytes with M. leprae, the formation and nuclear localization of NF-κB complexes composed mainly of p65/p50 and p50/p50 dimers was observed. Induction of NF-κB activation and DNA binding activity was inhibited by thalidomide. The drug also reduced M. leprae-induced TNF-α production and inhibited p38 and ERK1/2 activation. Definition of the activation mechanisms in cells stimulated with M. leprae can lead to the development of new therapy applications to modulate NF-κB activation and to control the inflammatory manifestations due to enhanced TNF-α response as observed in leprosy and in leprosy reactions.

  19. Cyclin-Dependent Kinase Inhibitor 1a (p21) Modulates Response to Cocaine and Motivated Behaviors.

    PubMed

    Scholpa, Natalie E; Briggs, Sherri B; Wagner, John J; Cummings, Brian S

    2016-04-01

    This study investigated the functional role of cyclin-dependent kinase inhibitor 1a (Cdkn1a or p21) in cocaine-induced responses using a knockout mouse model. Acute locomotor activity after cocaine administration (15 mg/kg, i.p.) was decreased in p21(-/-) mice, whereas cocaine-induced place preference was enhanced. Interestingly, κ-opioid-induced place aversion was also significantly enhanced. Concentration-dependent analysis of locomotor activity in response to cocaine demonstrated a rightward shift in the p21(-/-) mice. Pretreatment with a 5-hydroxytryptamine receptor antagonist did not alter the enhancement of cocaine-induced conditioned place preference in p21(-/-) mice, indicating a lack of involvement of serotonergic signaling in this response. Cocaine exposure increased p21 expression exclusively in the ventral sector of the hippocampus of rodents after either contingent or noncontingent drug administration. Increased p21 expression was accompanied by increased histone acetylation of the p21 promoter region in rats. Finally, increased neurogenesis in the dorsal hippocampus of p21(-/-) mice was also observed. These results show that functional loss of p21 altered the acute locomotor response to cocaine and the conditioned responses to either rewarding or aversive stimuli. Collectively, these findings demonstrate a previously unreported involvement of p21 in modulating responses to cocaine and in motivated behaviors.

  20. Sharks modulate their escape behavior in response to predator size, speed and approach orientation.

    PubMed

    Seamone, Scott; Blaine, Tristan; Higham, Timothy E

    2014-12-01

    Escape responses are often critical for surviving predator-prey interactions. Nevertheless, little is known about how predator size, speed and approach orientation impact escape performance, especially in larger prey that are primarily viewed as predators. We used realistic shark models to examine how altering predatory behavior and morphology (size, speed and approach orientation) influences escape behavior and performance in Squalus acanthias, a shark that is preyed upon by apex marine predators. Predator models induced C-start escape responses, and increasing the size and speed of the models triggered a more intense response (increased escape turning rate and acceleration). In addition, increased predator size resulted in greater responsiveness from the sharks. Among the responses, predator approach orientation had the most significant impact on escapes, such that the head-on approach, as compared to the tail-on approach, induced greater reaction distances and increased escape turning rate, speed and acceleration. Thus, the anterior binocular vision in sharks renders them less effective at detecting predators approaching from behind. However, it appears that sharks compensate by performing high-intensity escapes, likely induced by the lateral line system, or by a sudden visual flash of the predator entering their field of view. Our study reveals key aspects of escape behavior in sharks, highlighting the modulation of performance in response to predator approach.

  1. Blunted Opiate Modulation of Prolactin Response in Smoking Men and Women

    PubMed Central

    Shaw, Darcy; al’Absi, Mustafa

    2010-01-01

    Endogenous opioids are integral in modulating drug reward, but it is believed these may act through several mechanisms including hypothalamic-pituitary-adrenocortical (HPA) and dopamine pathways. This study was developed to examine how nicotine dependence alters endogenous opioid regulation of prolactin response, a peripheral marker of dopaminergic activity. Smokers and nonsmokers completed two sessions during which placebo or 50 mg of naltrexone was administered, using a double-blind, counterbalanced design. Blood samples and mood measures were obtained during a resting absorption period, after exposure to two noxious stimuli (cold pressor and thermal pain), and during an extended recovery period. Opioid blockade increased prolactin response, indicating an inhibitory effect of the endogenous opioid system on prolactin, possibly mediated by reduced stimulatory effects of dopamine on this hormone. These responses were attenuated in smokers relative to nonsmokers. There was also gender disparity in prolactin response, with women showing a stronger response to endogenous opioid modification than men regardless of smoking status. The attenuated effects of opioid blockade may reflect dysregulated opiodergic and dopaminergic effects. Results extend previous reports showing blunted opioid regulation of the HPA response in dependent smokers. PMID:19969014

  2. Cyclin-Dependent Kinase Inhibitor 1a (p21) Modulates Response to Cocaine and Motivated Behaviors

    PubMed Central

    Scholpa, Natalie E.; Briggs, Sherri B.; Wagner, John J.

    2016-01-01

    This study investigated the functional role of cyclin-dependent kinase inhibitor 1a (Cdkn1a or p21) in cocaine-induced responses using a knockout mouse model. Acute locomotor activity after cocaine administration (15 mg/kg, i.p.) was decreased in p21−/− mice, whereas cocaine-induced place preference was enhanced. Interestingly, κ-opioid–induced place aversion was also significantly enhanced. Concentration-dependent analysis of locomotor activity in response to cocaine demonstrated a rightward shift in the p21−/− mice. Pretreatment with a 5-hydroxytryptamine receptor antagonist did not alter the enhancement of cocaine-induced conditioned place preference in p21−/− mice, indicating a lack of involvement of serotonergic signaling in this response. Cocaine exposure increased p21 expression exclusively in the ventral sector of the hippocampus of rodents after either contingent or noncontingent drug administration. Increased p21 expression was accompanied by increased histone acetylation of the p21 promoter region in rats. Finally, increased neurogenesis in the dorsal hippocampus of p21−/− mice was also observed. These results show that functional loss of p21 altered the acute locomotor response to cocaine and the conditioned responses to either rewarding or aversive stimuli. Collectively, these findings demonstrate a previously unreported involvement of p21 in modulating responses to cocaine and in motivated behaviors. PMID:26791604

  3. Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells.

    PubMed

    Wang, Guo-Yong; Liets, Lauren C; Chalupa, Leo M

    2003-08-01

    Several lines of evidence suggest that nitric oxide (NO) can regulate diverse retinal functions, but whether this gas is capable of modulating the visual responses of retinal output neurons has not been established. In the present study the effects of NO on rod-driven responses of retinal ganglion cells were tested by making whole cell patch-clamp recordings from morphologically identified ganglion cells in the isolated ferret retina. Bath application of L-arginine, the substrate of nitric oxide synthase, and S-nitroso-N-acetylpenicillamine, the NO donor, was found to differentially affect on and off discharge patterns. The introduction of these drugs significantly decreased visual responses of retinal ganglion cells, but the effects were more pronounced on off than on on discharges. The peak discharge rates of on responses were usually reduced by about 40%, but not completely blocked. In contrast, off responses were completely blocked in most cells. These differential effects were observed in on-off cells as well as in cells that yielded just on or off discharges. The off responses that were blocked by NO were also blocked by DL-2-amino-phosphonobutyric acid (APB) and strychnine, suggesting the involvement of the APB-sensitive rod pathway.

  4. Immunobiotic Bifidobacteria Strains Modulate Rotavirus Immune Response in Porcine Intestinal Epitheliocytes via Pattern Recognition Receptor Signaling

    PubMed Central

    Miyazaki, Ayako; Soma, Junichi; Suda, Yoshihito; Aso, Hisashi; Nochi, Tomonori; Iwabuchi, Noriyuki; Xiao, Jin-zhong; Saito, Tadao; Villena, Julio; Kitazawa, Haruki

    2016-01-01

    In this work, we aimed to characterize the antiviral response of an originally established porcine intestinal epithelial cell line (PIE cells) by evaluating the molecular innate immune response to rotavirus (RVs). In addition, we aimed to select immunomodulatory bacteria with antiviral capabilities. PIE cells were inoculated with RVs isolated from different host species and the infective titers and the molecular innate immune response were evaluated. In addition, the protection against RVs infection and the modulation of immune response by different lactic acid bacteria (LAB) strains was studied. The RVs strains OSU (porcine) and UK (bovine) effectively infected PIE cells. Our results also showed that RVs infection in PIE cells triggered TLR3-, RIG-I- and MDA-5-mediated immune responses with activation of IRF3 and NF-κB, induction of IFN-β and up-regulation of the interferon stimulated genes MxA and RNase L. Among the LAB strains tested, Bifidobacterium infantis MCC12 and B. breve MCC1274 significantly reduced RVs titers in infected PIE cells. The beneficial effects of both bifidobacteria were associated with reduction of A20 expression, and improvements of IRF-3 activation, IFN-β production, and MxA and RNase L expressions. These results indicate the value of PIE cells for studying RVs molecular innate immune response in pigs and for the selection of beneficial bacteria with antiviral capabilities. PMID:27023883

  5. Immunobiotic Bifidobacteria Strains Modulate Rotavirus Immune Response in Porcine Intestinal Epitheliocytes via Pattern Recognition Receptor Signaling.

    PubMed

    Ishizuka, Takamasa; Kanmani, Paulraj; Kobayashi, Hisakazu; Miyazaki, Ayako; Soma, Junichi; Suda, Yoshihito; Aso, Hisashi; Nochi, Tomonori; Iwabuchi, Noriyuki; Xiao, Jin-zhong; Saito, Tadao; Villena, Julio; Kitazawa, Haruki

    2016-01-01

    In this work, we aimed to characterize the antiviral response of an originally established porcine intestinal epithelial cell line (PIE cells) by evaluating the molecular innate immune response to rotavirus (RVs). In addition, we aimed to select immunomodulatory bacteria with antiviral capabilities. PIE cells were inoculated with RVs isolated from different host species and the infective titers and the molecular innate immune response were evaluated. In addition, the protection against RVs infection and the modulation of immune response by different lactic acid bacteria (LAB) strains was studied. The RVs strains OSU (porcine) and UK (bovine) effectively infected PIE cells. Our results also showed that RVs infection in PIE cells triggered TLR3-, RIG-I- and MDA-5-mediated immune responses with activation of IRF3 and NF-κB, induction of IFN-β and up-regulation of the interferon stimulated genes MxA and RNase L. Among the LAB strains tested, Bifidobacterium infantis MCC12 and B. breve MCC1274 significantly reduced RVs titers in infected PIE cells. The beneficial effects of both bifidobacteria were associated with reduction of A20 expression, and improvements of IRF-3 activation, IFN-β production, and MxA and RNase L expressions. These results indicate the value of PIE cells for studying RVs molecular innate immune response in pigs and for the selection of beneficial bacteria with antiviral capabilities.

  6. Hypothalamic neuronal histamine modulates febrile response but not anorexia induced by lipopolysaccharide.

    PubMed

    Chiba, Seiichi; Itateyama, Emi; Oka, Kyoko; Masaki, Takayuki; Sakata, Toshiie; Yoshimatsu, Hironobu

    2005-05-01

    This study examined the contribution of hypothalamic neuronal histamine (HA) to the anorectic and febrile responses induced by lipopolysaccharide (LPS), an exogenous pyrogen, and the endogenous pyrogens interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Intraperitoneal (ip) injection of LPS, IL-1beta, or TNF-alpha suppressed 24-hr cumulative food intake and increased rectal temperature in rats. To analyze the histaminergic contribution, rats were pretreated with intracerebroventricular (icv) injection of 2.44 mmol/kg or ip injection of 244 mmol/kg of alpha-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase (HDC), to deplete neural HA. The depletion of neural HA augmented the febrile response to ip injection of LPS and IL-1beta and alleviated the anorectic response to ip injection of IL-1beta. However, the depletion of neural HA did not modify the LPS-induced anorectic response or TNF-alpha-induced febrile and anorectic responses. Consistent with these results, the rate of hypothalamic HA turnover, assessed by the accumulation of tele-methylhistamine (t-MH), was elevated with ip injections of LPS and IL-1beta, but unaffected by TNF-alpha at equivalent doses. This suggests that (i) LPS and IL-1beta activate hypothalamic neural HA turnover; (ii) hypothalamic neural HA suppresses the LPS- and IL-1beta-induced febrile responses and accelerates the IL-1beta-induced anorectic response; and (iii) TNF-alpha modulates the febrile and anorectic responses via a neural HA-independent pathway. Therefore, hypothalamic neural HA is involved in the IL-1beta-dominant pathway, rather than the TNF-alpha-dominant pathway, preceding the systemic inflammatory response induced by exogenous pyrogens, such as LPS. Further research on this is needed.

  7. Polarisation response of delay dependent absorption modulation in strong field dressed helium atoms probed near threshold

    NASA Astrophysics Data System (ADS)

    Simpson, E. R.; Sanchez-Gonzalez, A.; Austin, D. R.; Diveki, Z.; Hutchinson, S. E. E.; Siegel, T.; Ruberti, M.; Averbukh, V.; Miseikis, L.; Strüber, C. S.; Chipperfield, L.; Marangos, J. P.

    2016-08-01

    We present the first measurement of the vectorial response of strongly dressed helium atoms probed by an attosecond pulse train (APT) polarised either parallel or perpendicular to the dressing field polarisation. The transient absorption is probed as a function of delay between the APT and the linearly polarised 800 nm field of peak intensity 1.3× {10}14 {{W}} {{cm}}-2. The APT spans the photon energy range 16-42 eV, covering the first ionisation energy of helium (24.59 eV). With parallel polarised dressing and probing fields, we observe modulations with periods of one half and one quarter of the dressing field period. When the polarisation of the dressing field is altered from parallel to perpendicular with respect to the APT polarisation we observe a large suppression in the modulation depth of the above ionisation threshold absorption. In addition to this we present the intensity dependence of the harmonic modulation depth as a function of delay between the dressing and probe fields, with dressing field peak intensities ranging from 2 × 1012 to 2 × 1014 {{W}} {{cm}}-2. We compare our experimental results with a full-dimensional solution of the single-atom time-dependent (TD) Schrödinger equation obtained using the recently developed abinitio TD B-spline ADC method and find good qualitative agreement for the above threshold harmonics.

  8. Interactions Between Odorant Functional Group and Hydrocarbon Structure Influence Activity in Glomerular Response Modules in the Rat Olfactory Bulb

    PubMed Central

    Johnson, Brett A.; Farahbod, Haleh; Leon, Michael

    2008-01-01

    To investigate the effect of odorant hydrocarbon structure on spatial representations in the olfactory bulb systematically, we exposed rats to odorant chemicals possessing one of four different oxygen-containing functional groups on one of five different hydrocarbon backbones. We also used several hydrocarbon odorants lacking other functional groups. Hydrocarbon structural categories included straight-chained, branched, double-bonded, alicyclic, and aromatic features. Activity throughout the entire glomerular layer was measured as uptake of [14C]2-deoxyglucose and was mapped into anatomically standardized data matrices for statistical comparisons across different animals. Patterns evoked by straight-chained aliphatic odorants confirmed an association of activity in particular glomerular response modules with particular functional groups. However, the amount of activity in these same modules also was affected significantly by differences in hydrocarbon structure. Thus, the molecular features recognized by receptors projecting to these response modules appear to involve both functional group and hydrocarbon structural elements. In addition, particular benzyl and cyclohexyl odorants evoked activity in dorsal modules previously associated with the ketone functional group, which represents an exception to the rule of one feature per response module that had emerged from our previous studies. These dorsal modules also responded to nitrogen-containing aromatic compounds involving pyridine and pyrazine rings. The unexpected overlap in modular responses to ketones and odorants seemingly unrelated to ketones may reflect some covert shared molecular feature, the existence of odorant sensory neurons with multiple specificities, or a mosaic of sensory neuron projections to these particular modules. PMID:15678471

  9. Dying autologous cells as instructors of the immune system.

    PubMed

    Munoz, L E; Herrmann, M; Berens, C

    2015-01-01

    In an organism, cell death occurs at many different sites and in many different forms. It is frequently part of normal development or serves to maintain cell homeostasis. In other cases, cell death not only occurs due to injury, disease or infection, but also as a consequence of various therapeutic interventions. However, in all of these scenarios, the immune system has to react to the dying and dead cells and decide whether to mount an immune response, to remain quiet or to initiate healing and repopulation. This is essential for the organism, testified by many diseases that are associated with malfunctioning in the cell death process, the corpse removal, or the ensuing immune responsiveness. Therefore, dying cells generally have to be considered as instructors of the immune system. How this happens and which signals and pathways contribute to modulate or shape the immune response is still elusive in many conditions. The articles presented in this Special Issue address such open questions. They highlight that the context in which cell death occurs will not only influence the cell death process itself, but also affect the surrounding cellular milieu, how the generation and presence of 'eat me' signals can have an impact on cell clearance, and that the exact nature of the residual 'debris' and how it is processed are fundamental to determining the immunological consequences. Hopefully, these articles initiate new approaches and new experiments to complete our understanding of how cell death and the immune system interact with each other.

  10. BT cationic peptides: small peptides that modulate innate immune responses of chicken heterophils and monocytes.

    PubMed

    Kogut, Michael H; Genovese, Kenneth J; He, Haiqi; Swaggerty, Christina L; Jiang, Yi Wei

    2012-01-15

    Neonatal poultry exhibit a transient susceptibility to infectious diseases during the first week of life that stems from inefficient host defense mechanisms. Yet, the initial host immune response to pathogens is a critical determinant of disease resistance and susceptibility. With this context in mind, novel ways to stimulate or modulate the hosts' natural immune response is emerging as an important area of interest for food animal producers including the poultry industry. Specifically, we have been investigating new modulation strategies tailored around the selective stimulation of the host's immune system, and particularly rapid acting innate immunity, as an alternative to direct targeting of microbial pathogens. One such approach that we have been investigating is the use of a group of cationic peptides produced by a Gram-positive soil bacterium, Brevibacillus texasporus (BT peptides). We have previously shown that, provided as a feed additive, BT peptides significantly induced a concentration-dependent protection against cecal colonization and extraintestinal colonization by Salmonella enterica serovar Enteritidis (SE). This protection is not the result of direct antibacterial activity of the BT peptides on the SE since the concentrations used were below the minimum inhibitory concentration for SE. We also found that BT are not absorbed in the intestine, but still induce a significant up-regulation in the functional efficiency of peripheral blood heterophils and monocytes. The mechanisms of this immune modulation are unknown. Here, using in vitro models for measuring: (1) leukocyte oxidative burst, (2) changes in leukocyte cytokine and chemokines gene expression profiles, and (3) phosphorylation of the mitogen activated protein kinases (MAPKs) in leukocytes, we evaluated the role of BT peptides as priming mediators for heterophil and monocyte responses at the level of cell function, gene transcription/expression, and cell phosphorylation following stimulation

  11. An evaluation of the response modulation hypothesis in relation to attention-deficit/hyperactivity disorder.

    PubMed

    Farmer, Richard F; Rucklidge, Julia J

    2006-08-01

    Several hypotheses related to Newman's (e.g., Patterson & Newman, 1993) response modulation hypothesis were examined among adolescents with attention-deficit/hyperactivity disorder (ADHD; n=18) and normal controls (n=23). Consistent with predictions, youth with ADHD committed more passive avoidance errors (PAEs) than controls during the latter trials of a computerized go/no go task with mixed incentives, and this effect remained significant or marginally significant even after common variance associated with variables that covary with ADHD (i.e., IQ, oppositional-defiant/conduct disorder [ODD/CD] symptoms, anxious/depressed mood) was removed. While a moderate inverse association was observed between PAE frequency and the amount of time spent viewing response feedback following punishment, both categorical (diagnostic) and dimensional analyses of ADHD symptomatology indicated that ADHD and reflection on punishment feedback are uniquely associated with PAE commission. Findings from this study are discussed in relation to models of disinhibition applicable to youth with ADHD.

  12. Modulations of muscle modes in automatic postural responses induced by external surface translations.

    PubMed

    Asaka, Tadayoshi; Yahata, Kentaro; Mani, Hiroki; Wang, Yun

    2011-01-01

    The authors applied principal component analysis to investigate muscle activation patterns (M-modes) involved in the automatic postural responses induced by external surface perturbations. They focused on M-mode modulations as responses to the effects of practice, stability of the conditions and perturbed directions. While peak center of mass velocity reduced with practice, M-modes were similar with practice and across stability conditions. In contrast, atypical sway mode coactivations that combined proximal trunk muscles with distal muscles of the opposite lower extremity of the ventral-dorsal side were observed under the unstable conditions in both forward and backward perturbations after practice. In addition, M-modes in the forward translations were characterized by increased cocontraction patterns. Results suggest that compositions of the underlying M-modes show minor differences in each perturbed direction, but practice enhances coactivation patterns combining proximal muscles with distal muscles, and with accompanying cocontraction patterns, under more challenging conditions.

  13. Modulation of heat shock protein response in SH-SY5Y by mobile phone microwaves

    PubMed Central

    Calabrò, Emanuele; Condello, Salvatore; Currò, Monica; Ferlazzo, Nadia; Caccamo, Daniela; Magazù, Salvatore; Ientile, Riccardo

    2012-01-01

    AIM: To investigate putative biological damage caused by GSM mobile phone frequencies by assessing electromagnetic fields during mobile phone working. METHODS: Neuron-like cells, obtained by retinoic-acid-induced differentiation of human neuroblastoma SH-SY5Y cells, were exposed for 2 h and 4 h to microwaves at 1800 MHz frequency bands. RESULTS: Cell stress response was evaluated by MTT assay as well as changes in the heat shock protein expression (Hsp20, Hsp27 and Hsp70) and caspase-3 activity levels, as biomarkers of apoptotic pathway. Under our experimental conditions, neither cell viability nor Hsp27 expression nor caspase-3 activity was significantly changed. Interestingly, a significant decrease in Hsp20 expression was observed at both times of exposure, whereas Hsp70 levels were significantly increased only after 4 h exposure. CONCLUSION: The modulation of the expression of Hsps in neuronal cells can be an early response to radiofrequency microwaves. PMID:22371824

  14. Mechanisms of Cholera Toxin in the Modulation of TH17 Responses.

    PubMed

    Tsai, Hsing-Chuan; Wu, Reen

    2015-01-01

    Numerous studies have shown that TH17 cells and their signature cytokine IL-17A are critical to host defense against various bacterial and fungal infections. The protective responses mediated by TH17 cells and IL-17A include the recruitment of neutrophils, release of antimicrobial peptides and chemokines, and enhanced tight junction of epithelial cells. Due to the importance of TH17 cells in infections, efforts have been made to develop TH17-based vaccines. The goal of vaccination is to establish a protective immunological memory. Most currently approved vaccines are antibody-based and have limited protection against stereotypically different strains. Studies show that T-cell-based vaccines may overcome this limitation and protect hosts against infection of different strains. Two main strategies are used to develop TH17 vaccines: identification of TH17-specific antigens and TH17-skewing adjuvants. Studies have revealed that cholera toxin (CT) induces a potent Th17 response following vaccination. Antigen vaccination along with CT induces a robust TH17 response, which is sometimes accompanied by TH1 responses. Due to the toxicity of CT, it is hard to apply CT in a clinical setting. Thus, understanding how CT modulates TH17 responses may lead to the development of successful TH17-based vaccines.

  15. Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

    PubMed Central

    EL-SAGHIRE, HOUSSEIN; VANDEVOORDE, CHARLOT; OST, PIET; MONSIEURS, PIETER; MICHAUX, ARLETTE; DE MEERLEER, GERT; BAATOUT, SARAH; THIERENS, HUBERT

    2014-01-01

    Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18–24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation. PMID:24435511

  16. Modulation of. beta. -adrenergic response in rat brain astrocytes by serum and hormones

    SciTech Connect

    Wu, D.K.; Morrison, R.S.; de Vellis, J.

    1985-01-01

    Purified astrocyte cultures from neonatal rat cerebrum respond to isoproterenol, a ..beta..-adrenergic agonist, with a transient rise in cAMP production. This astroglial property was regulated by serum, a chemically defined medium (serum-free medium plus hydrocortisone, putrescine, prostaglandin F/sub 2/, insulin, and fibroblast growth factor) and epidermal growth factor. Compared to astrocytes grown in serum-supplemented medium, astrocytes grown in the chemically defined medium were nonresponsive to isoproterenol stimulation, and this difference did not appear to be due to selection of a subpopulation of cells by either medium. The data suggest that a decreased ..beta..-adrenergic receptor number and an increased degradation of cAMP may account for the reduced response to ..beta..-adrenergic stimulation. The nonresponsive state of astrocytes in the defined medium was reversible when the medium was replaced with serum-supplemented medium. An active substance(s) in serum was responsible for restoring the responsiveness of astrocytes. Each of the five components of the defined medium had little effect by itself; however, together they acted synergistically to desensitize astrocytes to ..beta..-adrenergic stimulation. On the other hand, epidermal growth factor, a potent mitogen for astrocytes, was very competent by itself in reducing the cAMP response of astrocytes to ..beta..-adrenergic stimulation. Thus purified astrocytes grown in the chemically defined medium appear to be a good model for the study of hormonal interactions and of serum factors which may modulate the ..beta..-adrenergic response.

  17. Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation

    NASA Technical Reports Server (NTRS)

    Ryder, K. D.; Duncan, R. L.

    2000-01-01

    Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.

  18. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis.

    PubMed

    Dekkers, Johanna F; Berkers, Gitte; Kruisselbrink, Evelien; Vonk, Annelotte; de Jonge, Hugo R; Janssens, Hettie M; Bronsveld, Inez; van de Graaf, Eduard A; Nieuwenhuis, Edward E S; Houwen, Roderick H J; Vleggaar, Frank P; Escher, Johanna C; de Rijke, Yolanda B; Majoor, Christof J; Heijerman, Harry G M; de Winter-de Groot, Karin M; Clevers, Hans; van der Ent, Cornelis K; Beekman, Jeffrey M

    2016-06-22

    Identifying subjects with cystic fibrosis (CF) who may benefit from cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs is time-consuming, costly, and especially challenging for individuals with rare uncharacterized CFTR mutations. We studied CFTR function and responses to two drugs-the prototypical CFTR potentiator VX-770 (ivacaftor/KALYDECO) and the CFTR corrector VX-809 (lumacaftor)-in organoid cultures derived from the rectal epithelia of subjects with CF, who expressed a broad range of CFTR mutations. We observed that CFTR residual function and responses to drug therapy depended on both the CFTR mutation and the genetic background of the subjects. In vitro drug responses in rectal organoids positively correlated with published outcome data from clinical trials with VX-809 and VX-770, allowing us to predict from preclinical data the potential for CF patients carrying rare CFTR mutations to respond to drug therapy. We demonstrated proof of principle by selecting two subjects expressing an uncharacterized rare CFTR genotype (G1249R/F508del) who showed clinical responses to treatment with ivacaftor and one subject (F508del/R347P) who showed a limited response to drug therapy both in vitro and in vivo. These data suggest that in vitro measurements of CFTR function in patient-derived rectal organoids may be useful for identifying subjects who would benefit from CFTR-correcting treatment, independent of their CFTR mutation.

  19. Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection.

    PubMed

    Sharma, Vivek; Mishra, Mamata; Ghosh, Soumya; Tewari, Richa; Basu, Anirban; Seth, Pankaj; Sen, Ellora

    2007-06-15

    The proinflammatory cytokine interleukin-1beta (IL-1beta) contributes to inflammation and neuronal death in CNS injuries and neurodegenerative pathologies, and astrocytes have been implicated as the primary mediators of IL-1beta induced neuronal death. As astrocytes play an important role in supporting the survival and functions of neurons, we investigated the effect of plant flavonoids quercetin and luteolin, with known anti-inflammatory properties in modulating the response of human astrocytes to IL-1beta for therapeutic intervention. Flavonoids significantly decreased the release of reactive oxygen species (ROS) from astrocytes stimulated with IL-1beta. This decrease was accompanied by an increase in expression of superoxide dismutase (SOD-1) and thioredoxin (TRX1)-mediators associated with protection against oxidative stress. Flavonoids not only modulated the expression of astrocytes specific molecules such as glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and ceruloplasmin (CP) both in the presence and absence of IL-1beta but also decreased the elevated levels of proinflammatory cytokine interleukin-6 (IL-6) and chemokines interleukin-8 (IL-8), interferon-inducible protein (IP-10), monocyte-chemoattractant protein-1 (MCP-1), and RANTES from IL-1beta activated astrocytes. Significant decrease in neuronal apoptosis was observed in neurons cultured in conditioned medium obtained from astrocytes treated with a combination of IL-1beta and flavonoids as compared to that treated with IL-1beta alone. Our result suggests that by (i) enhancing the potential of activated astrocytes to detoxify free radical, (ii) reducing the expression of proinflammatory cytokines and chemokines, and (iii) modulating expression of mediators associated with enhanced physiological activity of astrocyte in response to injury, flavonoids confer (iv) protection against IL-1beta induced astrocyte mediated neuronal damage.

  20. Modulation of virulence factors in Francisella tularensis determines human macrophage responses

    PubMed Central

    Carlson, Paul E.; Carroll, James A.; O’Dee, Dawn M.; Nau, Gerard J.

    2009-01-01

    Francisella tularensis, the causative agent of tularemia and Category A biodefense agent, is known to replicate within host macrophages, though the pathogenesis of this organism is incompletely understood. We have isolated a variant of F. tularensis Live Vaccine Strain (LVS) based on colony morphology and its effect on macrophages. Human monocyte-derived macrophages produced more tumor necrosis factor α (TNFα), interleukin (IL)-1β, IL-6, and IL-12 p40 following exposure to the variant, designated the activating variant (ACV). The immunoreactivity of the lipopolysaccharide (LPS) from both LVS and ACV was comparable to the previously described blue variant and was distinct from the gray variant of LVS. We found, however, the soluble protein fractions of LVS and ACV differed. Further investigation using two-dimensional gel electrophoresis demonstrated higher levels of several proteins in the parental LVS isolate. The differentially-expressed proteins featured several associated with virulence in F. tularensis and other pathogens, including intracellular growth locus C (IglC), a σ54 modulation protein family member (YhbH), and aconitase. ACV reverted to the LVS phenotype, indicated by low cytokine induction and high IglC expression, after growth in a chemically-defined media. These data provide evidence that the levels of virulence factors in F. tularensis are modulated based on culture conditions and that this modulation impacts host responses. This work provides a basis for investigation of Francisella virulence factor regulation and the identification of additional factors, co-regulated with IglC, that affect macrophage responses. PMID:17369012

  1. Biotic context and soil properties modulate native plant responses to enhanced rainfall

    PubMed Central

    Eskelinen, Anu; Harrison, Susan

    2015-01-01

    Background and Aims The environmental and biotic context within which plants grow have a great potential to modify responses to climatic changes, yet few studies have addressed both the direct effects of climate and the modulating roles played by variation in the biotic (e.g. competitors) and abiotic (e.g. soils) environment. Methods In a grassland with highly heterogeneous soils and community composition, small seedlings of two native plants, Lasthenia californica and Calycadenia pauciflora, were transplanted into factorially watered and fertilized plots. Measurements were made to test how the effect of climatic variability (mimicked by the watering treatment) on the survival, growth and seed production of these species was modulated by above-ground competition and by edaphic variables. Key Results Increased competition outweighed the direct positive impacts of enhanced rainfall on most fitness measures for both species, resulting in no net effect of enhanced rainfall. Both species benefitted from enhanced rainfall when the absence of competitors was accompanied by high soil water retention capacity. Fertilization did not amplify the watering effects; rather, plants benefitted from enhanced rainfall or competitor removal only in ambient nutrient conditions with high soil water retention capacity. Conclusions The findings show that the direct effects of climatic variability on plant fitness may be reversed or neutralized by competition and, in addition, may be strongly modulated by soil variation. Specifically, coarse soil texture was identified as a factor that may limit plant responsiveness to altered water availability. These results highlight the importance of considering the abiotic as well as biotic context when making future climate change forecasts. PMID:26159934

  2. Dimerization Controls Marburg Virus VP24-dependent Modulation of Host Antioxidative Stress Responses.

    PubMed

    Johnson, Britney; Li, Jing; Adhikari, Jagat; Edwards, Megan R; Zhang, Hao; Schwarz, Toni; Leung, Daisy W; Basler, Christopher F; Gross, Michael L; Amarasinghe, Gaya K

    2016-08-28

    Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola virus (EBOV), causes lethal hemorrhagic fever with case fatality rates that have exceeded 50% in some outbreaks. Within an infected cell, there are numerous host-viral interactions that contribute to the outcome of infection. Recent studies identified MARV protein 24 (mVP24) as a modulator of the host antioxidative responses, but the molecular mechanism remains unclear. Using a combination of biochemical and mass spectrometry studies, we show that mVP24 is a dimer in solution that directly binds to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to regulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). This interaction between Keap1 and mVP24 occurs through the Kelch interaction loop (K-Loop) of mVP24 leading to upregulation of antioxidant response element transcription, which is distinct from other Kelch binders that regulate Nrf2 activity. N-terminal truncations disrupt mVP24 dimerization, allowing monomeric mVP24 to bind Kelch with higher affinity and stimulate higher antioxidative stress response element (ARE) reporter activity. Mass spectrometry-based mapping of the interface revealed overlapping binding sites on Kelch for mVP24 and the Nrf2 proteins. Substitution of conserved cysteines, C209 and C210, to alanine in the mVP24 K-Loop abrogates Kelch binding and ARE activation. Our studies identify a shift in the monomer-dimer equilibrium of MARV VP24, driven by its interaction with Keap1 Kelch domain, as a critical determinant that modulates host responses to pathogenic Marburg viral infections.

  3. Cortical influences on brainstem circuitry responsible for conditioned pain modulation in humans.

    PubMed

    Youssef, Andrew M; Macefield, Vaughan G; Henderson, Luke A

    2016-07-01

    Conditioned pain modulation (CPM) is a powerful endogenous analgesic mechanism which can completely inhibit incoming nociceptor signals at the primary synapse. The circuitry responsible for CPM lies within the brainstem and involves the subnucleus reticularis dorsalis (SRD). While the brainstem is critical for CPM, the cortex can significantly modulate its expression, likely via the brainstem circuitry critical for CPM. Since higher cortical regions such as the anterior, mid-cingulate, and dorsolateral prefrontal cortices are activated by noxious stimuli and show reduced activations during other analgesic responses, we hypothesized that these regions would display reduced responses during CPM analgesia. Furthermore, we hypothesized that functional connectivity strength between these cortical regions and the SRD would be stronger in those that express CPM analgesia compared with those that do not. We used functional magnetic resonance imaging to determine sites recruited during CPM expression and their influence on the SRD. A lack of CPM analgesia was associated with greater signal intensity increases during each test stimulus in the presence of the conditioning stimulus compared to test stimuli alone in the mid-cingulate and dorsolateral prefrontal cortices and increased functional connectivity with the SRD. In contrast, those subjects exhibiting CPM analgesia showed no change in the magnitude of signal intensity increases in these cortical regions or strength of functional connectivity with the SRD. These data suggest that during multiple or widespread painful stimuli, engagement of the prefrontal and cingulate cortices prevents the generation of CPM analgesia, raising the possibility altered responsiveness in these cortical regions underlie the reduced CPM observed in individuals with chronic pain. Hum Brain Mapp 37:2630-2644, 2016. © 2016 Wiley Periodicals, Inc.

  4. Real-time quantification of endothelial response to shear stress and vascular modulators.

    PubMed

    DeStefano, Jackson G; Williams, Ashley; Wnorowski, Alexa; Yimam, Nahom; Searson, Peter C; Wong, Andrew D

    2017-03-27

    Quiescence is commonly used to describe the inactive state of endothelial cells (ECs) in monolayers that have reached homeostasis. Experimentally quiescence is usually described in terms of the relative change in cell activity (e.g. turnover, speed, etc.) in response to a perturbation (e.g. solute, shear stress, etc.). The objective of this study is to provide new insight into EC quiescence by quantitatively defining the morphology and activity of confluent cell monolayers in response to shear stress and vascular modulators. Confluent monolayers of human umbilical vein ECs (HUVECs) were subjected to a range of shear stresses (4-16 dyne cm(-2)) under steady flow. Using phase contrast, time-lapse microscopy and image analysis, we quantified EC morphology, speed, proliferation, and apoptosis rates over time and detected differences in monolayer responses under various media conditions: basal media supplemented with growth factors, interleukin-8, or cyclic AMP. In all conditions, we observed a transition from cobblestone to spindle-like morphology in a dose-dependent manner due to shear stress. Cyclic AMP enhanced the elongation and alignment of HUVECs due to shear stress and reduced steady state cell speed. We observed the lowest proliferation rates below 8 dyne cm(-2) and found that growth factors and cyclic AMP reduced proliferation and apoptosis; interleukin-8 similarly decreased proliferation, but increased apoptosis. We have quantified the response of ECs in confluent monolayers to shear stress and vascular modulators in terms of morphology, speed, proliferation and apoptosis and have established quantifiable metrics of cell activity to define vascular quiescence under shear stress.

  5. Targeting microRNAs as key modulators of tumor immune response.

    PubMed

    Paladini, Laura; Fabris, Linda; Bottai, Giulia; Raschioni, Carlotta; Calin, George A; Santarpia, Libero

    2016-06-27

    The role of immune response is emerging as a key factor in the complex multistep process of cancer. Tumor microenvironment contains different types of immune cells, which contribute to regulate the fine balance between anti and protumor signals. In this context, mechanisms of crosstalk between cancer and immune cells remain to be extensively elucidated. Interestingly, microRNAs (miRNAs) have been demonstrated to function as crucial regulators of immune response in both physiological and pathological conditions. Specifically, different miRNAs have been reported to have a role in controlling the development and the functions of tumor-associated immune cells. This review aims to describe the most important miRNAs acting as critical modulators of immune response in the context of different solid tumors. In particular, we discuss recent studies that have demonstrated the existence of miRNA-mediated mechanisms regulating the recruitment and the activation status of specific tumor-associated immune cells in the tumor microenvironment. Moreover, various miRNAs have been found to target key cancer-related immune pathways, which concur to mediate the secretion of immunosuppressive or immunostimulating factors by cancer or immune cells. Modalities of miRNA exchange and miRNA-based delivery strategies are also discussed. Based on these findings, the modulation of individual or multiple miRNAs has the potential to enhance or inhibit specific immune subpopulations supporting antitumor immune responses, thus contributing to negatively affect tumorigenesis. New miRNA-based strategies can be developed for more effective immunotherapeutic interventions in cancer.

  6. Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice.

    PubMed

    Jiang, Shu-Hua; Ping, Li-Feng; Sun, Feng-Yan; Wang, Xiao-Lei; Sun, Zhi-Juan

    2016-12-01

    Taraxasterol is an effective component of dandelion that has anti-inflammatory effects in vivo and in vitro. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. Eight-week-old CCR9-deficient mice were injected with a collagen II monoclonal antibody cocktail to create a rheumatoid arthritis model. In the experimental group, arthritic model mice were treated with 10 mg/kg taraxasterol once per day for 5 days. Treatment with taraxasterol significantly increased the pain thresholds and reduced the clinical arthritic scores of the mice in the experimental group compared with those of the model group. Furthermore, treatment with taraxasterol significantly suppressed tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and nuclear factor-κB protein expression levels compared with those in the rheumatoid arthritis model mice. Taraxasterol treatment also significantly reduced nitric oxide, prostaglandin E2 and cyclooxygenase-2 levels compared with those in the rheumatoid arthritis model group. These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice.

  7. Shear response of a frictional interface to a normal load modulation

    NASA Astrophysics Data System (ADS)

    Bureau, L.; Baumberger, T.; Caroli, C.

    2000-11-01

    We study the shear response of a sliding multicontact interface submitted to a harmonically modulated normal load, without loss of contact. We measure, at low velocities (V<100 μm s-1), the average value F¯ of the friction force and the amplitude of its first and second harmonic components. The excitation frequency (f=120 Hz) is chosen much larger than the natural one, associated with the dynamical aging of the interface. We show the following: (i) In agreement with the engineering thumb rule, even a modest modulation induces a substantial decrease of F¯. (ii) The Rice-Ruina state and rate model, though appropriate to describe the slow frictional dynamics, must be extended when dealing with our ``high'' frequency regime. That is, the rheology which controls the shear strength must explicitly account not only for the plastic response of the adhesive junctions between load-bearing asperities, but also for the elastic contribution of the asperities bodies. This ``elastoplastic'' friction model leads to predictions in excellent quantitative agreement with all our experimental data.

  8. Dynamic Modulation of Innate Immune Response by Varying Dosages of Lipopolysaccharide (LPS) in Human Monocytic Cells*

    PubMed Central

    Morris, Matthew C.; Gilliam, Elizabeth A.; Button, Julia; Li, Liwu

    2014-01-01

    Innate monocytes and macrophages can be dynamically programmed into distinct states depending upon the strength of external stimuli. Innate programming may bear significant relevance to the pathogenesis and resolution of human inflammatory diseases. However, systems analyses with regard to the dynamic programming of innate leukocytes are lacking. In this study, we focused on the dynamic responses of human promonocytic THP-1 cells to lipopolysaccharide (LPS). We observed that varying dosages of LPS differentially modulate the expression of selected pro- and anti- inflammatory mediators such as IL-6 and IL-33. Super-low dosages of LPS preferentially induced the pro-inflammatory mediator IL-6, while higher dosages of LPS induced both IL-6 and IL-33. Mechanistically, we demonstrated that super-low and high doses of LPS cause differential activation of GSK3 and Akt, as well as the transcription factors FoxO1 and CREB. Inhibition of GSK3 enabled THP-1 cells to express IL-33 when challenged with super-low dose LPS. On the other hand, activation of CREB with adenosine suppressed IL-6 expression. Taken together, our study reveals a dynamic modulation of monocytic cells in response to varying dosages of endotoxin, and may shed light on our understanding of the dynamic balance that controls pathogenesis and resolution of inflammatory diseases. PMID:24970893

  9. The properties of electromagnetic responses and optical modulation in terahertz metamaterials

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Shi, Yulei; Wang, Wei; Zhou, Qingli; Zhang, Cunlin

    2016-11-01

    Metamaterials with subwavelength structural features show unique electromagnetic responses that are unattainable with natural materials. Recently, the research on these artificial materials has been pushed forward to the terahertz (THz) region because of potential applications in biological fingerprinting, security imaging, and high frequency magnetic and electric resonant devices. Furthermore, active control of their properties could further facilitate and open up new applications in terms of modulation and switching. In our work, we will first present our studies of dipole arrays at terahertz frequencies. Then in experimental and theoretical studies of terahertz subwavelength L-shaped structure, we proposed an unusual-mode current resonance responsible for low-frequency characteristic dip in transmission spectra. Comparing spectral properties of our designed simplified structures with that of split-ring resonators, we attribute this unusual mode to the resonance coupling and splitting under the broken symmetry of the structure. Finally, we use optical pump-terahertz probe method to investigate the spectral and dynamic behaviour of optical modulation in the split-ring resonators. We have observed the blue-shift and band broadening in the spectral changes of transmission under optical excitation at different delay times. The calculated surface currents using finite difference time domain simulation are presented to characterize these resonances, and the blue-shift can be explained by the changed refractive index and conductivity in the photoexcited semiconductor substrate.

  10. Methanothermobacter thermautotrophicus modulates its membrane lipids in response to hydrogen and nutrient availability

    PubMed Central

    Yoshinaga, Marcos Y.; Gagen, Emma J.; Wörmer, Lars; Broda, Nadine K.; Meador, Travis B.; Wendt, Jenny; Thomm, Michael; Hinrichs, Kai-Uwe

    2015-01-01

    Methanothermobacter thermautotrophicus strain ΔH is a model hydrogenotrophic methanogen, for which extensive biochemical information, including the complete genome sequence, is available. Nevertheless, at the cell membrane lipid level, little is known about the responses of this archaeon to environmental stimuli. In this study, the lipid composition of M. thermautotrophicus was characterized to verify how this archaeon modulates its cell membrane components during growth phases and in response to hydrogen depletion and nutrient limitation (potassium and phosphate). As opposed to the higher abundance of phospholipids in the stationary phase of control experiments, cell membranes under nutrient, and energy stress were dominated by glycolipids that likely provided a more effective barrier against ion leakage. We also identified particular lipid regulatory mechanisms in M. thermautotrophicus, which included the accumulation of polyprenols under hydrogen-limited conditions and an increased content of sodiated adducts of lipids in nutrient-limited cells. These findings suggest that M. thermautotrophicus intensely modulates its cell membrane lipid composition to cope with energy and nutrient availability in dynamic environments. PMID:25657645

  11. Participation of purines in the modulation of inflammatory response in rats experimentally infected by Cryptococcus neoformans.

    PubMed

    de Azevedo, Maria Isabel; Ferreiro, Laerte; Da Silva, Aleksandro S; Tonin, Alexandre A; Monteiro, Danieli Urach; Casali, Emerson A; Moritz, Cesar E J; Schirmbeck, Gabriel H; Cardoso, Valesca V; Flores, Mariana M; Fighera, Rafael; Stefani, Lenita M; Santurio, Janio M

    2016-10-01

    The present study was carried out to assess the participation of purines in the activation and modulation of inflammatory response of rats experimentally infected by Cryptococcus neoformans. Twenty four Wistar rats were divided into two groups of 12 animals each: Group A - uninfected control group and Group B - infected by C. neoformans. Blood was collected 20 and 50 days post-infection (PI) from six animals of each group in order to verify purine levels (adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine (ADO), inosine (INO), hypoxanthine (HYPO), xanthine (XAN) and uric acid (URIC)). ATP levels were significantly increased (P < 0.05) in serum from infected animals on days 20 and 50 PI, as well as adenosine levels after 20 days PI on rats. On day 50 PI, levels of adenosine and uric acid were also reduced, but the levels of inosine and xanthine increased in animals infected by the fungus (P < 0.05). Therefore, it was possible to conclude that the purine levels in serum were altered and that these changes may be able to influence the pathogenesis of the disease caused by C. neoformans due the participation of purines (ATP and adenosine main) in the activation and modulation of inflammatory response.

  12. Prestimulus EEG alpha oscillations modulate task-related fMRI BOLD responses to auditory stimuli.

    PubMed

    Walz, Jennifer M; Goldman, Robin I; Carapezza, Michael; Muraskin, Jordan; Brown, Truman R; Sajda, Paul

    2015-06-01

    EEG alpha-band activity is generally thought to represent an inhibitory state related to decreased attention and play a role in suppression of task-irrelevant stimulus processing, but a competing hypothesis suggests an active role in processing task-relevant information - one in which phase dynamics are involved. Here we used simultaneous EEG-fMRI and a whole-brain analysis to investigate the effects of prestimulus alpha activity on the event-related BOLD response during an auditory oddball task. We separately investigated the effects of the posterior alpha rhythm's power and phase on activity related to task-relevant stimulus processing and also investigated higher-level decision-related processing. We found stronger decision-related BOLD activity in areas late in the processing stream when subjects were in the high alpha power state prior to stimulus onset, but did not detect any effect in primary sensory regions. Our phase analysis revealed correlates in the bilateral thalamus, providing support for a thalamo-cortical loop in attentional modulations and suggesting that the cortical alpha rhythm acts as a cyclic modulator of task-related responses very early in the processing stream. Our results help to reconcile the competing inhibition and active-processing hypotheses for ongoing alpha oscillations and begin to tease apart the distinct roles and mechanisms underlying their power and phase.

  13. [Growth responses of belowground modules of Carex lasiocarpa to different water regimes and water experiences].

    PubMed

    Wang, Li; Song, Chang-Chun; Hu, Jin-Ming; Yang, Tao

    2008-10-01

    With seedling's transplanting experiment under different water levels, this paper studied the growth responses of belowground modules of Carex lasiocarpa to various water regimes and water experiences in Sanjiang Plain. The results showed that the belowground modules of C. lasiocarpa had significantly different responses to water regimes. At thriving stage, the length of rhizome and adventitious root decreased with increasing water level, and until later growth stage, the maximal value still appeared under drought condition. However, under dry-wet alternate condition, the length of rhizome and adventitious root increased most from thriving stage to the end, indicating that stable and lower water level could improve the growth of rhizome and adventitious root. The biomass of rhizome, adventitious root, and belowground part were maximal under dry-wet alternate condition at both growth stages. For those with different water experiences, the ones undergoing alternate condition in early growth season and then drought had maximal rhizome biomass, and the others under sustained alternate condition had maximal adventitious root and belowground biomass. More biomass was distributed to rhizome in the later growth season under various water regimes. The percentage of rhizome in total biomass was significantly higher under drought condition than under other water conditions through the growth season. Besides, C. lasiocarpa grew slowly when submerged, but could recover through rhizomatic reproduction after the stress disappeared.

  14. Nephrilin peptide modulates a neuroimmune stress response in rodent models of burn trauma and sepsis

    PubMed Central

    Mascarenhas, Desmond D; ElAyadi, Amina; Singh, Baljit K; Prasai, Anesh; Hegde, Sachin D; Herndon, David N; Finnerty, Celeste C

    2013-01-01

    Sepsis occurs three times more often in burns than in other types of trauma, suggesting an overlap or synergy between underlying immune mechanisms in burn trauma and sepsis. Nephrilin peptide, a designed inhibitor of mTORC2, has previously been shown to modulate a neuroimmune stress response in rodent models of xenobiotic and metabolic stress. Here we investigate the effect of nephrilin peptide administration in different rodent models of burn trauma and sepsis. In a rat scald burn model, daily subcutaneous bolus injection of 4 mg/kg nephrilin significantly reduced the elevation of kidney tissue substance P, S100A9 gene expression, PMN infiltration and plasma inflammatory markers in the acute phase, while suppressing plasma CCL2 and insulin C-peptide, kidney p66shc-S36 phosphorylation and PKC-beta and CGRP in dorsal root ganglia at 14 days (chronic phase). In the mouse cecal ligation and puncture model of sepsis, nephrilin fully protected mice from mortality between surgery and day 7, compared to 67% mortality in saline-treated animals, while significantly reducing elevated CCL2 in plasma. mTORC2 may modulate important neuroimmune responses in both burn trauma and sepsis. PMID:24273694

  15. Modulation of the cytokine response in human monocytes by mycobacterium leprae phenolic glycolipid-1.

    PubMed

    Manca, Claudia; Peixoto, Blas; Malaga, Wladimir; Guilhot, Christophe; Kaplan, Gilla

    2012-01-01

    Leprosy is a chronic but treatable infectious disease caused by the intracellular pathogen Mycobacterium leprae. M. leprae cell wall is characterized by a unique phenolic glycolipid-1 (PGL-1) reported to have several immune functions. We have examined the role of PGL-1 in the modulation of monocyte cytokine/chemokine production in naive human monocytes. PGL-1 in its purified form or expressed in a recombinant Mycobacterium bovis Bacillus Colmette-Guérin (BCG) background (rBCG-PGL-1) was tested. We found that PGL-1 selectively modulated the induction of specific monocyte cytokines and chemokines and, when used as prestimulus, exerted priming and/or inhibitory effects on the induction of selected cytokines/chemokines in response to a second stimulus. Taken together, the results of this study support a modulatory role for PGL-1 in the innate immune response to M. leprae. Thus, PGL-1 may play an important role in the development of the anergic clinical forms of disease and in tissue damage seen in lepromatous patients and during the reactional states of leprosy.

  16. Self-esteem modulates amygdala-ventrolateral prefrontal cortex connectivity in response to mortality threats.

    PubMed

    Yanagisawa, Kuniaki; Abe, Nobuhito; Kashima, Emiko S; Nomura, Michio

    2016-03-01

    Reminders of death often elicit defensive responses in individuals, especially among those with low self-esteem. Although empirical evidence indicates that self-esteem serves as a buffer against mortality threats, the precise neural mechanism underlying this effect remains unknown. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that self-esteem modulates neural responses to death-related stimuli, especially functional connectivity within the limbic-frontal circuitry, thereby affecting subsequent defensive reactions. As predicted, individuals with high self-esteem subjected to a mortality threat exhibited increased amygdala-ventrolateral prefrontal cortex (VLPFC) connectivity during the processing of death-related stimuli compared with individuals who have low self-esteem. Further analysis revealed that stronger functional connectivity between the amygdala and the VLPFC predicted a subsequent decline in responding defensively to those who threaten one's beliefs. These results suggest that the amygdala-VLPFC interaction, which is modulated by self-esteem, can reduce the defensiveness caused by death-related stimuli, thereby providing a neural explanation for why individuals with high self-esteem exhibit less defensive reactions to mortality threats.

  17. Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice

    PubMed Central

    Jiang, Shu-Hua; Ping, Li-Feng; Sun, Feng-Yan; Wang, Xiao-Lei; Sun, Zhi-Juan

    2016-01-01

    Taraxasterol is an effective component of dandelion that has anti-inflammatory effects in vivo and in vitro. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. Eight-week-old CCR9-deficient mice were injected with a collagen II monoclonal antibody cocktail to create a rheumatoid arthritis model. In the experimental group, arthritic model mice were treated with 10 mg/kg taraxasterol once per day for 5 days. Treatment with taraxasterol significantly increased the pain thresholds and reduced the clinical arthritic scores of the mice in the experimental group compared with those of the model group. Furthermore, treatment with taraxasterol significantly suppressed tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and nuclear factor-κB protein expression levels compared with those in the rheumatoid arthritis model mice. Taraxasterol treatment also significantly reduced nitric oxide, prostaglandin E2 and cyclooxygenase-2 levels compared with those in the rheumatoid arthritis model group. These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice. PMID:28101182

  18. Modeling the Regulatory Mechanisms by Which NLRX1 Modulates Innate Immune Responses to Helicobacter pylori Infection

    PubMed Central

    Philipson, Casandra W.; Bassaganya-Riera, Josep; Viladomiu, Monica; Kronsteiner, Barbara; Abedi, Vida; Hoops, Stefan; Michalak, Pawel; Kang, Lin; Girardin, Stephen E.; Hontecillas, Raquel

    2015-01-01

    Helicobacter pylori colonizes half of the world’s population as the dominant member of the gastric microbiota resulting in a lifelong chronic infection. Host responses toward the bacterium can result in asymptomatic, pathogenic or even favorable health outcomes; however, mechanisms underlying the dual role of H. pylori as a commensal versus pathogenic organism are not well characterized. Recent evidence suggests mononuclear phagocytes are largely involved in shaping dominant immunity during infection mediating the balance between host tolerance and succumbing to overt disease. We combined computational modeling, bioinformatics and experimental validation in order to investigate interactions between macrophages and intracellular H. pylori. Global transcriptomic analysis on bone marrow-derived macrophages (BMDM) in a gentamycin protection assay at six time points unveiled the presence of three sequential host response waves: an early transient regulatory gene module followed by sustained and late effector responses. Kinetic behaviors of pattern recognition receptors (PRRs) are linked to differential expression of spatiotemporal response waves and function to induce effector immunity through extracellular and intracellular detection of H. pylori. We report that bacterial interaction with the host intracellular environment caused significant suppression of regulatory NLRC3 and NLRX1 in a pattern inverse to early regulatory responses. To further delineate complex immune responses and pathway crosstalk between effector and regulatory PRRs, we built a computational model calibrated using time-series RNAseq data. Our validated computational hypotheses are that: 1) NLRX1 expression regulates bacterial burden in macrophages; and 2) early host response cytokines down-regulate NLRX1 expression through a negative feedback circuit. This paper applies modeling approaches to characterize the regulatory role of NLRX1 in mechanisms of host tolerance employed by macrophages to

  19. Repeatedly administered antidepressant drugs modulate humoral and cellular immune response in mice through action on macrophages

    PubMed Central

    Kozlowski, Michael; Bryniarski, Pawel; Strobel, Spencer; Bryk, Agata; Myszka, Michal; Tyszka, Anna; Kuszmiersz, Piotr; Nowakowski, Jaroslaw; Filipczak-Bryniarska, Iwona

    2016-01-01

    Depression is associated with an altered immune response, which could be normalized by antidepressant drugs. However, little is known about the influence of antidepressants on the peripheral immune response and function of macrophages in individuals not suffering from depression. Our studies were aimed at determining the influence of antidepressant drugs on the humoral and cellular immune response in mice. Mice were treated intraperitoneally with imipramine, fluoxetine, venlafaxine, or moclobemide and contact immunized with trinitrophenyl hapten followed by elicitation and measurement of contact sensitivity by ear swelling response. Peritoneal macrophages from drug-treated mice were either pulsed with sheep erythrocytes or conjugated with trinitrophenyl and transferred into naive recipients to induce humoral or contact sensitivity response, respectively. Secretion of reactive oxygen intermediates, nitric oxide, and cytokines by macrophages from drug-treated mice was assessed, respectively, in chemiluminometry, Griess-based colorimetry and enzyme-linked immunosorbent assay, and the expression of macrophage surface markers was analyzed cytometrically. Treatment of mice with fluoxetine, venlafaxine, and moclobemide results in suppression of humoral and cell-mediated immunity with a reduction of the release of macrophage proinflammatory mediators and the expression of antigen-presentation markers. In contrast, treatment with imipramine enhanced the humoral immune response and macrophage secretory activity but slightly suppressed active contact sensitivity. Our studies demonstrated that systemically delivered antidepressant drugs modulate the peripheral humoral and cell-mediated immune responses, mostly through their action on macrophages. Imipramine was rather proinflammatory, whereas other tested drugs expressed immunosuppressive potential. Current observations may be applied to new therapeutic strategies dedicated to various disorders associated with excessive

  20. DELLA proteins modulate Arabidopsis defences induced in response to caterpillar herbivory

    PubMed Central

    Bede, Jacqueline C.

    2014-01-01

    Upon insect herbivory, many plant species change the direction of metabolic flux from growth into defence. Two key pathways modulating these processes are the gibberellin (GA)/DELLA pathway and the jasmonate pathway. In this study, the effect of caterpillar herbivory on plant-induced responses was compared between wild-type Arabidopsis thaliana (L.) Heynh. and quad-della mutants that have constitutively elevated GA responses. The labial saliva (LS) of caterpillars of the beet armyworm, Spodoptera exigua, is known to influence induced plant defence responses. To determine the role of this herbivore cue in determining metabolic shifts, plants were subject to herbivory by caterpillars with intact or impaired LS secretions. In both wild-type and quad-della plants, a jasmonate burst is an early response to caterpillar herbivory. Negative growth regulator DELLA proteins are required for the LS-mediated suppression of hormone levels. Jasmonate-dependent marker genes are induced in response to herbivory independently of LS, with the exception of AtPDF1.2 that showed LS-dependent expression in the quad-della mutant. Early expression of the salicylic acid (SA)-marker gene, AtPR1, was not affected by herbivory which also reflected SA hormone levels; however, this gene showed LS-dependent expression in the quad-della mutant. DELLA proteins may positively regulate glucosinolate levels and suppress laccase-like multicopper oxidase activity in response to herbivory. The present results show a link between DELLA proteins and early, induced plant defences in response to insect herbivory; in particular, these proteins are necessary for caterpillar LS-associated attenuation of defence hormones. PMID:24399173

  1. Postnatal development of neuronal responses to frequency-modulated tones in chinchilla auditory cortex.

    PubMed

    Brown, Trecia A; Harrison, Robert V

    2010-01-14

    Responses to cortical neurons to frequency-modulated (FM) stimuli have been described in various adult animal models. Here, we ask whether FM coding at the cortical level is innate or if it is influenced by postnatal environmental experience. We report on the FM response properties of neurons in core auditory cortex of newborn (P3), 1-month-old (P28) and adult (>1-year-old) anesthetized chinchillas (Chinchilla laniger). Upward and downward linear FM sweeps spanning frequencies from 0.1 to 20 kHz were presented monaurally at speeds of 0.05 to 0.82 kHz/ms. Results indicated that neurons in neonatal pups were responsive to FM stimulation. While we observed a developmental increase in the selectivity of units for FM sweep direction (p<0.01, one-way ANOVA), selectivity for sweep speed appeared to be established early in development. Chinchilla pup neurons also demonstrated single-peak (single dominant response during FM sweep presentation) and multi-peak (multiple distinct responses during FM sweep) temporal response patterns to FM stimuli similar to those observed in adults. A developmental increase in the proportion of multi-peak units closely paralleled a previously reported increase in the complexity of pure tone receptive fields. We suggest that units in core auditory cortex of the chinchilla are not uniquely activated by FM sounds but that FM responses are largely predictable based on how changing frequency stimuli interact with the tonal receptive fields of neurons in the auditory cortex.

  2. Spatiotemporal reconstruction of auditory steady-state responses to acoustic amplitude modulations: Potential sources beyond the auditory pathway.

    PubMed

    Farahani, Ehsan Darestani; Goossens, Tine; Wouters, Jan; van Wieringen, Astrid

    2017-03-01

    Investigating the neural generators of auditory steady-state responses (ASSRs), i.e., auditory evoked brain responses, with a wide range of screening and diagnostic applications, has been the focus of various studies for many years. Most of these studies employed a priori assumptions regarding the number and location of neural generators. The aim of this study is to reconstruct ASSR sources with minimal assumptions in order to gain in-depth insight into the number and location of brain regions that are activated in response to low- as well as high-frequency acoustically amplitude modulated signals. In order to reconstruct ASSR sources, we applied independent component analysis with subsequent equivalent dipole modeling to single-subject EEG data (young adults, 20-30 years of age). These data were based on white noise stimuli, amplitude modulated at 4, 20, 40, or 80Hz. The independent components that exhibited a significant ASSR were clustered among all participants by means of a probabilistic clustering method based on a Gaussian mixture model. Results suggest that a widely distributed network of sources, located in cortical as well as subcortical regions, is active in response to 4, 20, 40, and 80Hz amplitude modulated noises. Some of these sources are located beyond the central auditory pathway. Comparison of brain sources in response to different modulation frequencies suggested that the identified brain sources in the brainstem, the left and the right auditory cortex show a higher responsiveness to 40Hz than to the other modulation frequencies.

  3. The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis.

    PubMed

    van Driel, Boaz; Wang, Guoxing; Liao, Gongxian; Halibozek, Peter J; Keszei, Marton; O'Keeffe, Michael S; Bhan, Atul K; Wang, Ninghai; Terhorst, Cox

    2015-09-01

    The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria. Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate responses to bacteria and regulates peripheral inflammation by assessing the outcome of C. rodentium infections in Rag(-/-) mice. Surprisingly, the pathology and immune responses in the lamina propria of C. rodentium-infected Slamf6(-/-) Rag(-/-) mice were markedly reduced as compared with those of Rag(-/-) mice. Infiltration of inflammatory phagocytes into the lamina propria was consistently lower in Slamf6(-/-) Rag(-/-) mice than in Rag(-/-) animals. Concomitant with the reduced systemic translocation of the bacteria was an enhanced production of IL-22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore, administering a mAb (330) that inhibits bacterial interactions with Slamf6 to Rag(-/-) mice ameliorated the infection compared with a control antibody. We conclude that Slamf6-mediated interactions of colonic innate immune cells with specific Gram(-) bacteria reduce mucosal protection and enhance inflammation, contributing to lethal colitis that is caused by C. rodentium infections in Rag(-/-) mice.

  4. FILAMENTOUS FLOWER Is a Direct Target of JAZ3 and Modulates Responses to Jasmonate

    PubMed Central

    Giménez-Ibañez, Selena; Fernandez-Barbero, Gemma; Solano, Roberto

    2015-01-01

    The plant hormone jasmonate (JA) plays an important role in regulating growth, development, and immunity. Activation of the JA-signaling pathway is based on the hormone-triggered ubiquitination and removal of transcriptional repressors (JASMONATE-ZIM DOMAIN [JAZ] proteins) by an SCF receptor complex (SCFCOI1/JAZ). This removal allows the rapid activation of transcription factors (TFs) triggering a multitude of downstream responses. Identification of TFs bound by the JAZ proteins is essential to better understand how the JA-signaling pathway modulates and integrates different responses. In this study, we found that the JAZ3 repressor physically interacts with the YABBY (YAB) family transcription factor FILAMENTOUS FLOWER (FIL)/YAB1. In Arabidopsis thaliana, FIL regulates developmental processes such as axial patterning and growth of lateral organs, shoot apical meristem activity, and inflorescence phyllotaxy. Phenotypic analysis of JA-regulated responses in loss- and gain-of-function FIL lines suggested that YABs function as transcriptional activators of JA-triggered responses. Moreover, we show that MYB75, a component of the WD-repeat/bHLH/MYB complex regulating anthocyanin production, is a direct transcriptional target of FIL. We propose that JAZ3 interacts with YABs to attenuate their transcriptional function. Upon perception of JA signal, degradation of JAZ3 by the SCFCOI1 complex releases YABs to activate a subset of JA-regulated genes in leaves leading to anthocyanin accumulation, chlorophyll loss, and reduced bacterial defense. PMID:26530088

  5. BAS-drive trait modulates dorsomedial striatum activity during reward response-outcome associations.

    PubMed

    Costumero, Víctor; Barrós-Loscertales, Alfonso; Fuentes, Paola; Rosell-Negre, Patricia; Bustamante, Juan Carlos; Ávila, César

    2016-09-01

    According to the Reinforcement Sensitivity Theory, behavioral studies have found that individuals with stronger reward sensitivity easily detect cues of reward and establish faster associations between instrumental responses and reward. Neuroimaging studies have shown that processing anticipatory cues of reward is accompanied by stronger ventral striatum activity in individuals with stronger reward sensitivity. Even though establishing response-outcome contingencies has been consistently associated with dorsal striatum, individual differences in this process are poorly understood. Here, we aimed to study the relation between reward sensitivity and brain activity while processing response-reward contingencies. Forty-five participants completed the BIS/BAS questionnaire and performed a gambling task paradigm in which they received monetary rewards or punishments. Overall, our task replicated previous results that have related processing high reward outcomes with activation of striatum and medial frontal areas, whereas processing high punishment outcomes was associated with stronger activity in insula and middle cingulate. As expected, the individual differences in the activity of dorsomedial striatum correlated positively with BAS-Drive. Our results agree with previous studies that have related the dorsomedial striatum with instrumental performance, and suggest that the individual differences in this area may form part of the neural substrate responsible for modulating instrumental conditioning by reward sensitivity.

  6. Diet-induced obesity modulates epigenetic responses to ionizing radiation in mice.

    PubMed

    Vares, Guillaume; Wang, Bing; Ishii-Ohba, Hiroko; Nenoi, Mitsuru; Nakajima, Tetsuo

    2014-01-01

    Both exposure to ionizing radiation and obesity have been associated with various pathologies including cancer. There is a crucial need in better understanding the interactions between ionizing radiation effects (especially at low doses) and other risk factors, such as obesity. In order to evaluate radiation responses in obese animals, C3H and C57BL/6J mice fed a control normal fat or a high fat (HF) diet were exposed to fractionated doses of X-rays (0.75 Gy ×4). Bone marrow micronucleus assays did not suggest a modulation of radiation-induced genotoxicity by HF diet. Using MSP, we observed that the promoters of p16 and Dapk genes were methylated in the livers of C57BL/6J mice fed a HF diet (irradiated and non-irradiated); Mgmt promoter was methylated in irradiated and/or HF diet-fed mice. In addition, methylation PCR arrays identified Ep300 and Socs1 (whose promoters exhibited higher methylation levels in non-irradiated HF diet-fed mice) as potential targets for further studies. We then compared microRNA regulations after radiation exposure in the livers of C57BL/6J mice fed a normal or an HF diet, using microRNA arrays. Interestingly, radiation-triggered microRNA regulations observed in normal mice were not observed in obese mice. miR-466e was upregulated in non-irradiated obese mice. In vitro free fatty acid (palmitic acid, oleic acid) administration sensitized AML12 mouse liver cells to ionizing radiation, but the inhibition of miR-466e counteracted this radio-sensitization, suggesting that the modulation of radiation responses by diet-induced obesity might involve miR-466e expression. All together, our results suggested the existence of dietary effects on radiation responses (especially epigenetic regulations) in mice, possibly in relationship with obesity-induced chronic oxidative stress.

  7. Prior probabilities modulate cortical surprise responses: A study of event-related potentials.

    PubMed

    Seer, Caroline; Lange, Florian; Boos, Moritz; Dengler, Reinhard; Kopp, Bruno

    2016-07-01

    The human brain predicts events in its environment based on expectations, and unexpected events are surprising. When probabilistic contingencies in the environment are precisely instructed, the individual can form expectations based on quantitative probabilistic information ('inference-based learning'). In contrast, when probabilistic contingencies are imprecisely instructed, expectations are formed based on the individual's cumulative experience ('experience-based learning'). Here, we used the urn-ball paradigm to investigate how variations in prior probabilities and in the precision of information about these priors modulate choice behavior and event-related potential (ERP) correlates of surprise. In the urn-ball paradigm, participants are repeatedly forced to infer hidden states responsible for generating observable events, given small samples of factual observations. We manipulated prior probabilities of the states, and we rendered the priors calculable or incalculable, respectively. The analysis of choice behavior revealed that the tendency to consider prior probabilities when making decisions about hidden states was stronger when prior probabilities were calculable, at least in some of our participants. Surprise-related P3b amplitudes were observed in both the calculable and the incalculable prior probability condition. In contrast, calculability of prior probabilities modulated anteriorly distributed ERP amplitudes: when prior probabilities were calculable, surprising events elicited enhanced P3a amplitudes. However, when prior probabilities were incalculable, surprise was associated with enhanced N2 amplitudes. Furthermore, interindividual variability in reliance on prior probabilities was associated with attenuated P3b surprise responses under calculable in comparison to incalculable prior probabilities. Our results suggest two distinct neural systems for probabilistic learning that are recruited depending on contextual cues such as the precision of

  8. Grapevine Plasticity in Response to an Altered Microclimate: Sauvignon Blanc Modulates Specific Metabolites in Response to Increased Berry Exposure1

    PubMed Central

    du Plessis, Kari; Jacobson, Dan A.

    2016-01-01

    In this study, the metabolic and physiological impacts of an altered microclimate on quality-associated primary and secondary metabolites in grape (Vitis vinifera) ‘Sauvignon Blanc’ berries was determined in a high-altitude vineyard. The leaf and lateral shoot removal in the bunch zones altered the microclimate by increasing the exposure of the berries. The physical parameters (berry diameter and weight), primary metabolites (sugars and organic acids), as well as bunch temperature and leaf water potential were predominantly not affected by the treatment. The increased exposure led to higher levels of specific carotenoids and volatile terpenoids in the exposed berries, with earlier berry stages reacting distinctly from the later developmental stages. Plastic/nonplastic metabolite responses could be further classified to identify metabolites that were developmentally controlled and/or responded to the treatment in a predictable fashion (assessed over two consecutive vintages). The study demonstrates that grapevine berries exhibit a degree of plasticity within their secondary metabolites and respond physiologically to the increased exposure by increasing metabolites with potential antioxidant activity. Taken together, the data provide evidence that the underlying physiological responses relate to the maintenance of stress pathways by modulating antioxidant molecules in the berries. PMID:26628747

  9. Cycle training modulates satellite cell and transcriptional responses to a bout of resistance exercise.

    PubMed

    Murach, Kevin A; Walton, R Grace; Fry, Christopher S; Michaelis, Sami L; Groshong, Jason S; Finlin, Brian S; Kern, Philip A; Peterson, Charlotte A

    2016-09-01

    This investigation evaluated whether moderate-intensity cycle ergometer training affects satellite cell and molecular responses to acute maximal concentric/eccentric resistance exercise in middle-aged women. Baseline and 72 h postresistance exercise vastus lateralis biopsies were obtained from seven healthy middle-aged women (56 ± 5 years, BMI 26 ± 1, VO2max 27 ± 4) before and after 12 weeks of cycle training. Myosin heavy chain (MyHC) I- and II-associated satellite cell density and cross-sectional area was determined via immunohistochemistry. Expression of 93 genes representative of the muscle-remodeling environment was also measured via NanoString. Overall fiber size increased ~20% with cycle training (P = 0.052). MyHC I satellite cell density increased 29% in response to acute resistance exercise before endurance training and 50% with endurance training (P < 0.05). Following endurance training, MyHC I satellite cell density decreased by 13% in response to acute resistance exercise (acute resistance × training interaction, P < 0.05). Genes with an interaction effect tracked with satellite cell behavior, increasing in the untrained state and decreasing in the endurance trained state in response to resistance exercise. Similar satellite cell and gene expression response patterns indicate coordinated regulation of the muscle environment to promote adaptation. Moderate-intensity endurance cycle training modulates the response to acute resistance exercise, potentially conditioning the muscle for more intense concentric/eccentric activity. These results suggest that cycle training is an effective endurance exercise modality for promoting growth in middle-aged women, who are susceptible to muscle mass loss with progressing age.

  10. Anticipatory modulation of neck muscle reflex responses induced by mechanical perturbations of the human forehead.

    PubMed

    Kuramochi, Rieko; Kimura, Toshitaka; Nakazawa, Kimitaka; Akai, Masami; Torii, Suguru; Suzuki, Shuji

    2004-08-12

    The aim of this study was to test whether anticipation of upcoming head blow stimuli, which elicit reflex responses in the neck muscle, makes the reflex responses greater or not. In nine healthy subjects the reflex responses were elicited in the sternocleidomastoid (SCM) muscle in the eyes-open (EO) and eyes-closed (EC) conditions, which corresponded to the predictable and unpredictable conditions, respectively. The subjects were instructed not to resist the perturbations after the impact. The results demonstrated that the reflex response of the SCM muscle was significantly smaller in the predictable EO condition than in the unpredictable EC condition (P < 0.05), although no significant differences were observed in either the background EMG activities or the head accelerations. Further, this effect of anticipation was observed only in the later reflex EMG component, which most probably mediated the stretch reflex pathway. In contrast, no significant difference was observed in the early component, which was presumed to be the vestibular-collic reflex. The reduced stretch reflex response was suggested to be functionally relevant to the task requirement, i.e., to let the neck extension movement occur, and not to resist after the impact of the head blow. It was concluded that the anticipation has an effect on reducing the stretch reflex responses in the neck muscle, but does not have any effect on the presumed vestibular-collic reflex under the present experimental paradigm. It is suggested that the gain of the stretch reflex pathway is modulated by anticipatory information of upcoming mechanical event.

  11. Coinfection with Streptococcus pneumoniae modulates the B cell response to influenza virus.

    PubMed

    Wolf, Amaya I; Strauman, Maura C; Mozdzanowska, Krystyna; Whittle, James R R; Williams, Katie L; Sharpe, Arlene H; Weiser, Jeffrey N; Caton, Andrew J; Hensley, Scott E; Erikson, Jan

    2014-10-01

    Pathogen-specific antibodies (Abs) protect against respiratory infection with influenza A virus (IAV) and Streptococcus pneumoniae and are the basis of effective vaccines. Sequential or overlapping coinfections with both pathogens are common, yet the impact of coinfection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in mice coinfected with IAV and S. pneumoniae and that this response differs, depending on the order of pathogen exposure. In mice exposed to S. pneumoniae prior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4(+) T follicular helper (TFH) cell numbers. In contrast, secondary S. pneumoniae infection exaggerates early antiviral antibody-secreting cell formation, and at later times, levels of GCs, TFH cells, and antiviral serum IgG are elevated. Mice exposed to S. pneumoniae prior to IAV do not maintain the initially robust GC response in secondary lymphoid organs and exhibit reduced antiviral serum IgG with diminished virus neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective antiviral Abs and may partially explain the differential susceptibility to and disease outcomes from IAV infection in humans. Importance: Respiratory tract coinfections, specifically those involving influenza A viruses and Streptococcus pneumoniae, remain a top global health burden. We sought to determine how S. pneumoniae coinfection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection.

  12. Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

    PubMed Central

    Brown, Aisling F.; Leech, John M.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2014-01-01

    In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20–80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune “priming” or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity. PMID:24409186

  13. The role of ozone feedback in modulating the atmospheric response to the solar cycle forcing

    NASA Astrophysics Data System (ADS)

    Bednarz, Ewa; Maycock, Amanda; Braesicke, Peter; Telford, Paul; Abraham, Luke; Pyle, John

    2016-04-01

    in the seasonality of the dynamical response in the Northern Hemisphere high latitudes. All in all, our results highlight the importance of the solar-ozone feedback in modulating the atmospheric response to the solar cycle forcing and the importance of properly representing this for future model studies of the impact of the solar cycle forcing on climate.

  14. Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

    PubMed Central

    Hussain, Salik; Al-Nsour, Faris; Rice, Annette B; Marshburn, Jamie; Ji, Zhaoxia; Zink, Jeffery I; Yingling, Brenda; Walker, Nigel J; Garantziotis, Stavros

    2012-01-01

    Background Cerium dioxide (CeO2) nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO2 nanoparticles. We investigated the inflammation-modulating effects of CeO2 nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes. Methods CD14+ cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 μg/mL of CeO2 nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL) prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10. Results CeO2 nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter), zeta potential analysis (−14 mV), and transmission electron microscopy (irregular-shaped particles). Transmission electron microscopy of CD14+ cells exposed to CeO2 nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO2 nanoparticle-treated cells and control cells at noncytotoxic doses. No significant effects of CeO2 nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO2 nanoparticles followed by lipopolysaccharide exposure. Conclusion CeO2 nanoparticles at noncytotoxic concentrations neither

  15. Emotional Distraction and Bodily Reaction: Modulation of Autonomous Responses by Anodal tDCS to the Prefrontal Cortex.

    PubMed

    Schroeder, Philipp A; Ehlis, Ann-Christine; Wolkenstein, Larissa; Fallgatter, Andreas J; Plewnia, Christian

    2015-01-01

    Prefrontal electric stimulation has been demonstrated to effectively modulate cognitive processing. Specifically, the amelioration of cognitive control (CC) over emotional distraction by transcranial direct current stimulation (tDCS) points toward targeted therapeutic applications in various psychiatric disorders. In addition to behavioral measures, autonomous nervous system (ANS) responses are fundamental bodily signatures of emotional information processing. However, interactions between the modulation of CC by tDCS and ANS responses have received limited attention. We here report on ANS data gathered in healthy subjects that performed an emotional CC task parallel to the modulation of left prefrontal cortical activity by 1 mA anodal or sham tDCS. Skin conductance responses (SCRs) to negative and neutral pictures of human scenes were reduced by anodal as compared to sham tDCS. Individual SCR amplitude variations were associated with the amount of distraction. Moreover, the stimulation-driven performance- and SCR-modulations were related in form of a quadratic, inverse-U function. Thus, our results indicate that non-invasive brain stimulation (i.e., anodal tDCS) can modulate autonomous responses synchronous to behavioral improvements, but the range of possible concurrent improvements from prefrontal stimulation is limited. Interactions between cognitive, affective, neurophysiological, and vegetative responses to emotional content can shape brain stimulation effectiveness and require theory-driven integration in potential treatment protocols.

  16. Modulation of Visually Evoked Postural Responses by Contextual Visual, Haptic and Auditory Information: A ‘Virtual Reality Check’

    PubMed Central

    Meyer, Georg F.; Shao, Fei; White, Mark D.; Hopkins, Carl; Robotham, Antony J.

    2013-01-01

    Externally generated visual motion signals can cause the illusion of self-motion in space (vection) and corresponding visually evoked postural responses (VEPR). These VEPRs are not simple responses to optokinetic stimulation, but are modulated by the configuration of the environment. The aim of this paper is to explore what factors modulate VEPRs in a high quality virtual reality (VR) environment where real and virtual foreground objects served as static visual, auditory and haptic reference points. Data from four experiments on visually evoked postural responses show that: 1) visually evoked postural sway in the lateral direction is modulated by the presence of static anchor points that can be haptic, visual and auditory reference signals; 2) real objects and their matching virtual reality representations as visual anchors have different effects on postural sway; 3) visual motion in the anterior-posterior plane induces robust postural responses that are not modulated by the presence of reference signals or the reality of objects that can serve as visual anchors in the scene. We conclude that automatic postural responses for laterally moving visual stimuli are strongly influenced by the configuration and interpretation of the environment and draw on multisensory representations. Different postural responses were observed for real and virtual visual reference objects. On the basis that automatic visually evoked postural responses in high fidelity virtual environments should mimic those seen in real situations we propose to use the observed effect as a robust objective test for presence and fidelity in VR. PMID:23840760

  17. Co-expression network analyses identify functional modules associated with development and stress response in Gossypium arboreum

    PubMed Central

    You, Qi; Zhang, Liwei; Yi, Xin; Zhang, Kang; Yao, Dongxia; Zhang, Xueyan; Wang, Qianhua; Zhao, Xinhua; Ling, Yi; Xu, Wenying; Li, Fuguang; Su, Zhen

    2016-01-01

    Cotton is an economically important crop, essential for the agriculture and textile industries. Through integrating transcriptomic data, we discovered that multi-dimensional co-expression network analysis was powerful for predicting cotton gene functions and functional modules. Here, the recently available transcriptomic data on Gossypium arboreum, including data on multiple growth stages of tissues and stress treatment samples were applied to construct a co-expression network exploring multi-dimensional expression (development and stress) through multi-layered approaches. Based on differential gene expression and network analysis, a fibre development regulatory module of the gene GaKNL1 was found to regulate the second cell wall through repressing the activity of REVOLUTA, and a tissue-selective module of GaJAZ1a was examined in response to water stress. Moreover, comparative genomics analysis of the JAZ1-related regulatory module revealed high conservation across plant species. In addition, 1155 functional modules were identified through integrating the co-expression network, module classification and function enrichment tools, which cover functions such as metabolism, stress responses, and transcriptional regulation. In the end, an online platform was built for network analysis (http://structuralbiology.cau.edu.cn/arboreum), which could help to refine the annotation of cotton gene function and establish a data mining system to identify functional genes or modules with important agronomic traits. PMID:27922095

  18. When a Baby Dies.

    ERIC Educational Resources Information Center

    Church, Martha Jo; And Others

    Written especially for grieving mothers whose babies have died, this booklet offers an overview of stages and experiences through which bereaved parents commonly pass. Specifically, the text is intended to give comfort to bereaved parents, offer insight into the grieving process, and provide thoughts on leave-taking ceremonies. The first section…

  19. When Somebody Dies

    MedlinePlus

    ... to have fun with. That absence leaves a big hole in our lives. Maybe you had a pet that died . Remember the first few times you walked into the house after your dog or cat was gone? It was strange not to have ...

  20. Die Kosmologie der Griechen.

    NASA Astrophysics Data System (ADS)

    Mittelstraß, J.

    Contents: 1. Mythische Eier. 2. Thales-Welten. 3. "Alles ist voller Götter". 4. Griechische Astronomie. 5. "Rettung der Phänomene". 6. Aristotelische Kosmololgie. 7. Aristoteles-Welt und Platon-Welt. 8. Noch einmal: die Göttlichkeit der Welt. 9. Griechischer Idealismus.

  1. When Somebody Dies

    MedlinePlus

    ... A A What's in this article? When — and How — Does It Happen? Where Do Dead People Go? What Does Grieving Mean? What About Me? If I'm Going to Die Someday, What Should I Do Now? en español ...

  2. Viewing photos and reading nouns of natural graspable objects similarly modulate motor responses.

    PubMed

    Marino, Barbara F M; Sirianni, Miriam; Volta, Riccardo Dalla; Magliocco, Fabio; Silipo, Francesco; Quattrone, Aldo; Buccino, Giovanni

    2014-01-01

    It is well known that the observation of graspable objects recruits the same motor representations involved in their actual manipulation. Recent evidence suggests that the presentation of nouns referring to graspable objects may exert similar effects. So far, however, it is not clear to what extent the modulation of the motor system during object observation overlaps with that related to noun processing. To address this issue, 2 behavioral experiments were carried out using a go-no go paradigm. Healthy participants were presented with photos and nouns of graspable and non-graspable natural objects. Also scrambled images and pseudowords obtained from the original stimuli were used. At a go-signal onset (150 ms after stimulus presentation) participants had to press a key when the stimulus referred to a real object, using their right (Experiment 1) or left (Experiment 2) hand, and refrain from responding when a scrambled image or a pseudoword was presented. Slower responses were found for both photos and nouns of graspable objects as compared to non-graspable objects, independent of the responding hand. These findings suggest that processing seen graspable objects and written nouns referring to graspable objects similarly modulates the motor system.

  3. Ubc9 acetylation modulates distinct SUMO target modification and hypoxia response

    PubMed Central

    Hsieh, Yung-Lin; Kuo, Hong-Yi; Chang, Che-Chang; Naik, Mandar T; Liao, Pei-Hsin; Ho, Chun-Chen; Huang, Tien-Chi; Jeng, Jen-Chong; Hsu, Pang-Hung; Tsai, Ming-Daw; Huang, Tai-Huang; Shih, Hsiu-Ming

    2013-01-01

    While numerous small ubiquitin-like modifier (SUMO) conjugated substrates have been identified, very little is known about the cellular signalling mechanisms that differentially regulate substrate sumoylation. Here, we show that acetylation of SUMO E2 conjugase Ubc9 selectively downregulates the sumoylation of substrates with negatively charged amino acid-dependent sumoylation motif (NDSM) consisting of clustered acidic residues located downstream from the core ψ-K-X-E/D consensus motif, such as CBP and Elk-1, but not substrates with core ψ-K-X-E/D motif alone or SUMO-interacting motif. Ubc9 is acetylated at residue K65 and K65 acetylation attenuates Ubc9 binding to NDSM substrates, causing a reduction in NDSM substrate sumoylation. Furthermore, Ubc9 K65 acetylation can be downregulated by hypoxia via SIRT1, and is correlated with hypoxia-elicited modulation of sumoylation and target gene expression of CBP and Elk-1 and cell survival. Our data suggest that Ubc9 acetylation/deacetylation serves as a dynamic switch for NDSM substrate sumoylation and we report a previously undescribed SIRT1/Ubc9 regulatory axis in the modulation of protein sumoylation and the hypoxia response. PMID:23395904

  4. Viewing photos and reading nouns of natural graspable objects similarly modulate motor responses

    PubMed Central

    Marino, Barbara F. M.; Sirianni, Miriam; Volta, Riccardo Dalla; Magliocco, Fabio; Silipo, Francesco; Quattrone, Aldo; Buccino, Giovanni

    2014-01-01

    It is well known that the observation of graspable objects recruits the same motor representations involved in their actual manipulation. Recent evidence suggests that the presentation of nouns referring to graspable objects may exert similar effects. So far, however, it is not clear to what extent the modulation of the motor system during object observation overlaps with that related to noun processing. To address this issue, 2 behavioral experiments were carried out using a go-no go paradigm. Healthy participants were presented with photos and nouns of graspable and non-graspable natural objects. Also scrambled images and pseudowords obtained from the original stimuli were used. At a go-signal onset (150 ms after stimulus presentation) participants had to press a key when the stimulus referred to a real object, using their right (Experiment 1) or left (Experiment 2) hand, and refrain from responding when a scrambled image or a pseudoword was presented. Slower responses were found for both photos and nouns of graspable objects as compared to non-graspable objects, independent of the responding hand. These findings suggest that processing seen graspable objects and written nouns referring to graspable objects similarly modulates the motor system. PMID:25538596

  5. Modulation of Caenorhabditis elegans immune response and modification of Shigella endotoxin upon interaction.

    PubMed

    Kesika, Periyanaina; Prasanth, Mani Iyer; Balamurugan, Krishnaswamy

    2015-04-01

    To analyze the pathogenesis at both physiological and molecular level using the model organism, Caenorhabditis elegans at different developmental stages in response to Shigella spp. and its pathogen associated molecular patterns such as lipopolysaccharide. The solid plate and liquid culture-based infection assays revealed that Shigella spp. infects C. elegans and had an impact on the brood size and pharyngeal pumping rate. LPS of Shigella spp. was toxic to C. elegans. qPCR analysis revealed that host innate immune genes have been modulated upon Shigella spp. infections and its LPS challenges. Non-destructive analysis was performed to kinetically assess the alterations in LPS during interaction of Shigella spp. with C. elegans. The modulation of innate immune genes attributed the surrendering of host immune system to Shigella spp. by favoring the infection. LPS appeared to have a major role in Shigella-mediated pathogenesis and Shigella employs a tactic behavior of modifying its LPS content to escape from the recognition of host immune system.

  6. Transcriptional Modulation of Enterotoxigenic Escherichia coli Virulence Genes in Response to Epithelial Cell Interactions

    PubMed Central

    Kansal, Rita; Rasko, David A.; Sahl, Jason W.; Munson, George P.; Roy, Koushik; Luo, Qingwei; Sheikh, Alaullah; Kuhne, Kurt J.

    2013-01-01

    Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of morbidity and mortality due to diarrheal illness in developing countries. There is currently no effective vaccine against these important pathogens. Because genes modulated by pathogen-host interactions potentially encode putative vaccine targets, we investigated changes in gene expression and surface morphology of ETEC upon interaction with intestinal epithelial cells in vitro. Pan-genome microarrays, quantitative reverse transcriptase PCR (qRT-PCR), and transcriptional reporter fusions of selected promoters were used to study changes in ETEC transcriptomes. Flow cytometry, immunofluorescence microscopy, and scanning electron microscopy were used to investigate alterations in surface antigen expression and morphology following pathogen-host interactions. Following host cell contact, genes for motility, adhesion, toxin production, immunodominant peptides, and key regulatory molecules, including cyclic AMP (cAMP) receptor protein (CRP) and c-di-GMP, were substantially modulated. These changes were accompanied by visible changes in both ETEC architecture and the expression of surface antigens, including a novel highly conserved adhesin molecule, EaeH. The studies reported here suggest that pathogen-host interactions are finely orchestrated by ETEC and are characterized by coordinated responses involving the sequential deployment of multiple virulence molecules. Elucidation of the molecular details of these interactions could highlight novel strategies for development of vaccines for these important pathogens. PMID:23115039

  7. Water flow modulates the response of coral reef communities to ocean acidification.

    PubMed

    Comeau, S; Edmunds, P J; Lantz, C A; Carpenter, R C

    2014-10-20

    By the end of the century coral reefs likely will be affected negatively by ocean acidification (OA), but both the effects of OA on coral communities and the crossed effects of OA with other physical environmental variables are lacking. One of the least considered physical parameters is water flow, which is surprising considering its strong role in modulating the physiology of reef organisms and communities. In the present study, the effects of flow were tested on coral reef communities maintained in outdoor flumes under ambient pCO2 and high pCO2 (1300 μatm). Net calcification of coral communities, including sediments, was affected by both flow and pCO2 with calcification correlated positively with flow under both pCO2 treatments. The effect of flow was less evident for sediments where dissolution exceeded precipitation of calcium carbonate under all flow speeds at high pCO2. For corals and calcifying algae there was a strong flow effect, particularly at high pCO2 where positive net calcification was maintained at night in the high flow treatment. Our results demonstrate the importance of water flow in modulating the coral reef community response to OA and highlight the need to consider this parameter when assessing the effects of OA on coral reefs.

  8. Correlation of neural responses in the cochlear nucleus with low-frequency noise amplitude modulation of a tonal signal

    NASA Astrophysics Data System (ADS)

    Bibikov, N. G.

    2014-09-01

    The responses of single neurons of the cochlear nucleus of a grass frog to long tonal signals amplitude-modulated by repeat intervals of low-frequency noise have been studied. The carrier frequency always corresponded to the characteristic frequency of the studied cell (a range of 0.2 kHz-2 kHz); the modulated signal was noise in the ranges 0-15 Hz, 0-50 Hz, or 0-150 Hz. We obtained the correlation functions of the cyclic histogram reflecting the change in probability of a neuron pulse discharge (spike) during the modulation period with the shape of the signal envelope in the same period. The form of the obtained correlation functions usually does not change qualitatively with a change in carrier level or modulation depth; however, this could essentially depend of the frequency component of the modulating function. In the majority of cases, comparison of the cyclic histogram of the reaction with only the current amplitude value does not adequately reveal the signal's time features that determine the reaction of a neuron. The response is also determined by the other sound features, primarily by the rate of the change in amplitude. The studied neurons differed among themselves, both in preference toward a certain range of modulated frequencies and in the features of the envelope that caused the cell's response.

  9. Event-related potential responses to perceptual reversals are modulated by working memory load.

    PubMed

    Intaitė, Monika; Koivisto, Mika; Castelo-Branco, Miguel

    2014-04-01

    While viewing ambiguous figures, such as the Necker cube, the available perceptual interpretations alternate with one another. The role of higher level mechanisms in such reversals remains unclear. We tested whether perceptual reversals of discontinuously presented Necker cube pairs depend on working memory resources by manipulating cognitive load while recording event-related potentials (ERPs). The ERPs showed early enhancements of negativity, which were obtained in response to the first cube approximately 500 ms before perceived reversals. We found that working memory load influenced reversal-related brain responses in response to the second cube over occipital areas at the 150-300 ms post-stimulus and over central areas at P3 time window (300-500 ms), suggesting that it modulates intermediate visual processes. Interestingly, reversal rates remained unchanged by the working memory load. We propose that perceptual reversals in discontinuous presentation of ambiguous stimuli are governed by an early (well preceding pending reversals) mechanism, while the effects of load on the reversal related ERPs may reflect general top-down influences on visual processing, possibly mediated by the prefrontal cortex.

  10. Ethylene positively regulates cold tolerance in grapevine by modulating the expression of ETHYLENE RESPONSE FACTOR 057

    PubMed Central

    Sun, Xiaoming; Zhao, Tingting; Gan, Shuheng; Ren, Xiaodie; Fang, Linchuan; Karungo, Sospeter Karanja; Wang, Yi; Chen, Liang; Li, Shaohua; Xin, Haiping

    2016-01-01

    Ethylene (ET) is a gaseous plant hormone that plays essential roles in biotic and abiotic stress responses in plants. However, the role of ET in cold tolerance varies in different species. This study revealed that low temperature promotes the release of ET in grapevine. The treatment of exogenous 1-aminocyclopropane-1-carboxylate increased the cold tolerance of grapevine. By contrast, the application of the ET biosynthesis inhibitor aminoethoxyvinylglycine reduced the cold tolerance of grapevine. This finding suggested that ET positively affected cold stress responses in grapevine. The expression of VaERF057, an ET signaling downstream gene, was strongly induced by low temperature. The overexpression of VaERF057 also enhanced the cold tolerance of Arabidopsis. Under cold treatment, malondialdehyde content was lower and superoxide dismutase, peroxidase, and catalase activities were higher in transgenic lines than in wild-type plants. RNA-Seq results showed that 32 stress-related genes, such as CBF1-3, were upregulated in VaERF057-overexpressing transgenic line. Yeast one-hybrid results further demonstrated that VaERF057 specifically binds to GCC-box and DRE motifs. Thus, VaERF057 may directly regulate the expression of its target stress-responsive genes by interacting with a GCC-box or a DRE element. Our work confirmed that ET positively regulates cold tolerance in grapevine by modulating the expression of VaERF057. PMID:27039848

  11. GSK3β Mediates Renal Response to Vasopressin by Modulating Adenylate Cyclase Activity

    PubMed Central

    Patel, Satish; Hao, ChuanMing; Woodgett, James; Harris, Raymond

    2010-01-01

    Glycogen synthase kinase 3β (GSK3β), a serine/threonine protein kinase, is a key target of drug discovery in several diseases, including diabetes and Alzheimer disease. Because lithium, a potent inhibitor of GSK3β, causes nephrogenic diabetes insipidus, GSK3β may play a crucial role in regulating water homeostasis. We developed renal collecting duct-specific GSK3β knockout mice to determine whether deletion of GSK3β affects arginine vasopressin-dependent renal water reabsorption. Although only mildly polyuric under normal conditions, knockout mice exhibited an impaired urinary concentrating ability in response to water deprivation or treatment with a vasopressin analogue. The knockout mice had reduced levels of mRNA, protein, and membrane localization of the vasopressin-responsive water channel aquaporin 2 compared with wild-type mice. The knockout mice also expressed lower levels of pS256-AQP2, a phosphorylated form crucial for membrane trafficking. Levels of cAMP, a major regulator of aquaporin 2 expression and trafficking, were also lower in the knockout mice. Both GSK3β gene deletion and pharmacologic inhibition of GSK3β reduced adenylate cyclase activity. In summary, GSK3β inactivation or deletion reduces aquaporin 2 expression by modulating adenylate cyclase activity and cAMP generation, thereby impairing responses to vasopressin in the renal collecting duct. PMID:20056751

  12. Endogenous μ-opioid peptides modulate immune response towards malignant melanoma.

    PubMed

    Boehncke, Sandra; Hardt, Katja; Schadendorf, Dirk; Henschler, Reinhard; Boehncke, Wolf-Henning; Duthey, Beatrice

    2011-01-01

    Opioids exert major effects not only in the central nervous system but also in immune responses. We investigated the effects of μ-opioid peptides, secreted by tumor cells, on anti-tumor immune responses. For this purpose, tumor growth was studied in wild-type and μ-opioid receptor-deficient (MOR-/-) mice injected with B16 melanoma cells. The ability of these cells to produce opioids was studied by Western blots in vitro. Finally, biopsy material from human melanomas was investigated by immunohistochemistry for ß endorphin expression. Injection of B16 melanoma cells, producing endogenous ß endorphin, in the flank of MOR-/- mice revealed a profound reduction in tumor growth, paralleled by a significantly higher infiltration of immune cells into the tumors, when compared to tumor growth after injection of B16 melanoma cells into wild-type mice. Opioids present in B16 cell supernatant significantly reduced the proliferation of normal but not MOR-/- leucocytes. Immunohistochemical analyses of biopsies from human melanoma tissues showed a positive correlation between expression of ß endorphin and tumor progression. Our data provide evidence that μ-opioid peptides may play a major role in cancer progression by modulating immune response. This finding may have implications for the future optimization of immunointerventions for cancer.

  13. Focal adhesion kinase knockdown modulates the response of human corneal epithelial cells to topographic cues.

    PubMed

    Dreier, Britta; Raghunathan, Vijaya Krishna; Russell, Paul; Murphy, Christopher J

    2012-12-01

    A rapidly expanding literature broadly documents the impact of biophysical cues on cellular behaviors. In spite of increasing research efforts in this field, the underlying signaling processes are poorly understood. One of the candidate molecules for being involved in mechanotransduction is focal adhesion kinase (FAK). To examine the role of FAK in the response of immortalized human corneal epithelial (hTCEpi) cells to topographic cues, FAK was depleted by siRNA transfection. Contrary to expectations, FAK knockdown resulted in an enhanced response with a greater number of hTCEpi cells aligned to the long axis of anisotropically ordered surface ridges and grooves. Both underlying topographic features and FAK depletion modulated the migration of corneal epithelial cells. The impact of FAK knockdown on both migration and alignment varied depending on the topographic cues to which the cells were exposed, with the most significant change observed on the biologically relevant size scale (400nm). Additionally, a change in expression of genes encoding perinuclear Nesprins 1 and 2 (SYNE1, 2) was observed in response to topographic cues. SYNE1/2 expression was also altered by FAK depletion, suggesting that these proteins might represent a link between cytosolic and nuclear signaling processes. The data presented here have relevance to our understanding of the fundamental processes involved in corneal cell behavior to topographic cues. These results highlight the importance of incorporating biophysical cues in the conduction of in vitro studies and into the design and fabrication of implantable prosthetics.

  14. Analysis and modulation of the immune response of mice to acetylcholine receptor by anti-idiotypes.

    PubMed

    Souroujon, M C; Barchan, D; Fuchs, S

    1985-01-01

    Anti-idiotypes were raised in mice against three well-characterized anti-acetylcholine receptor (AChR) monoclonal antibodies (mcAbs), as well as against polyclonal mouse anti-AChR antibodies. In binding experiments, the anti-idiotypic antibodies inhibited the binding of AChR only to the immunizing idiotype. However, a less restricted specificity was found in in vivo experiments. Mice producing anti-idiotypes were challenged with AChR and the idiotypic composition of their anti-AChR response was analysed using specific rabbit anti-idiotypic antibodies. It was found that preimmunization with a certain idiotype leads to the preferential suppression of this particular idiotype in the polyclonal response to AChR. However, preimmunization with either polyclonal or monoclonal anti-AChR antibodies resulted in a reduction of the overall anti-Torpedo AChR and anti-muscle AChR titers. This reduction was greater than would be expected from the representation of each of the respective idiotypes in the polyclonal anti-AChR serum, and may imply that in addition to the immunizing idiotype other anti-AChR idiotypes are also suppressed. Our results suggest that anti-idiotypes may have a potential for the modulation of the autoimmune response directed against AChR in myasthenia.

  15. Habituation of Auditory Steady State Responses Evoked by Amplitude-Modulated Acoustic Signals in Rats

    PubMed Central

    Prado-Gutierrez, Pavel; Castro-Fariñas, Anisleidy; Morgado-Rodriguez, Lisbet; Velarde-Reyes, Ernesto; Martínez, Agustín D.; Martínez-Montes, Eduardo

    2015-01-01

    Generation of the auditory steady state responses (ASSR) is commonly explained by the linear combination of random background noise activity and the stationary response. Based on this model, the decrease of amplitude that occurs over the sequential averaging of epochs of the raw data has been exclusively linked to the cancelation of noise. Nevertheless, this behavior might also reflect the non-stationary response of the ASSR generators. We tested this hypothesis by characterizing the ASSR time course in rats with different auditory maturational stages. ASSR were evoked by 8-kHz tones of different supra-threshold intensities, modulated in amplitude at 115 Hz. Results show that the ASSR amplitude habituated to the sustained stimulation and that dishabituation occurred when deviant stimuli were presented. ASSR habituation increased as animals became adults, suggesting that the ability to filter acoustic stimuli with no-relevant temporal information increased with age. Results are discussed in terms of the current model of the ASSR generation and analysis procedures. They might have implications for audiometric tests designed to assess hearing in subjects who cannot provide reliable results in the psychophysical trials. PMID:26557360

  16. Three dimensional patient-specific collagen architecture modulates cartilage responses in the knee joint during gait.

    PubMed

    Räsänen, Lasse P; Mononen, Mika E; Lammentausta, Eveliina; Nieminen, Miika T; Jurvelin, Jukka S; Korhonen, Rami K

    2016-01-01

    Site-specific variation of collagen fibril orientations can affect cartilage stresses in knee joints. However, this has not been confirmed by 3-D analyses. Therefore, we present a novel method for evaluation of the effect of patient-specific collagen architecture on time-dependent mechanical responses of knee joint cartilage during gait. 3-D finite element (FE) models of a human knee joint were created with the collagen architectures obtained from T2 mapped MRI (patient-specific model) and from literature (literature model). The effect of accuracy of the implementation of collagen fibril architecture into the model was examined by using a submodel with denser FE mesh. Compared to the literature model, fibril strains and maximum principal stresses were reduced especially in the superficial/middle regions of medial tibial cartilage in the patient-specific model after the loading response of gait (up to -413 and -26%, respectively). Compared to the more coarsely meshed joint model, the patient-specific submodel demonstrated similar strain and stress distributions but increased values particularly in the superficial cartilage regions (especially stresses increased >60%). The results demonstrate that implementation of subject-specific collagen architecture of cartilage in 3-D modulates location- and time-dependent mechanical responses of human knee joint cartilage. Submodeling with more accurate implementation of collagen fibril architecture alters cartilage stresses particularly in the superficial/middle tissue.

  17. Modulation of spatial and stimulus-response learning strategies by exogenous cortisol in healthy young women.

    PubMed

    Schwabe, Lars; Oitzl, Melly S; Richter, Steffen; Schächinger, Hartmut

    2009-04-01

    Glucocorticoids (GCs) are known to influence learning and memory processes. While most studies focus on the effects of GCs on the performance within a single memory system, we asked whether GCs modulate also the transition between hippocampus-dependent spatial and caudate nucleus-dependent stimulus-response memory systems. Eighty-four young healthy women received a placebo, 5 or 30 mg hydrocortisone orally. One hour later, participants were asked to locate a win-card in a 3D model of a room. The card could be located via two strategies: spatial (multiple distal cues) and stimulus-response (a single proximal cue). Relocation of the proximal cue after 12 trials revealed the strategy, number of trials to learning criterion the performance. As expected, more trials were needed to acquire the task with hydrocortisone. Remarkably, hydrocortisone switched the use of learning strategies towards more spatial learning (dose-dependently: placebo 4% < 5 mg 21%< 30 mg 32%), independent of autonomic and subjective arousal. The learning curves of spatial and stimulus-response learners were comparable. Our results demonstrate that exogenous GCs prior to learning affect the performance within a memory system and also coordinate the use of multiple memory systems. Taking into account this dual action of GCs will contribute to a better understanding of stress (hormone) effects on learning and memory.

  18. Transient Response Dynamic Module Modifications to Include Static and Kinetic Friction Effects

    NASA Technical Reports Server (NTRS)

    Misel, J. E.; Nenno, S. B.; Takahashi, D.

    1984-01-01

    A methodology that supports forced transient response dynamic solutions when both static and kinetic friction effects are included in a structural system model is described. Modifications that support this type of nonlinear transient response solution are summarized for the transient response dynamics (TRD) NASTRAN module. An overview of specific modifications for the NASTRAN processing subroutines, INITL, TRD1C, and TRD1D, are described with further details regarding inspection of nonlinear input definitions to define the type of nonlinear solution required, along with additional initialization requirements and specific calculation subroutines to successfully solve the transient response problem. The extension of the basic NASTRAN nonlinear methodology is presented through several stages of development to the point where constraint equations and residual flexibility effects are introduced into the finite difference Newmark-Beta recurrsion formulas. Particular emphasis is placed on cost effective solutions for large finite element models such as the Space Shuttle with friction degrees of freedom between the orbiter and payloads mounted in the cargo bay. An alteration to the dynamic finite difference equations of motion is discussed, which allows one to include friction effects at reasonable cost for large structural systems such as the Space Shuttle. Data are presented to indicate the possible impact of transient friction loads to the payload designer for the Space Shuttle. Transient response solution data are also included, which compare solutions without friction forces and those with friction forces for payloads mounted in the Space Shuttle cargo bay. These data indicate that payload components can be sensitive to friction induced loads.

  19. Selective estrogen receptor modulators differentially alter the immune response of gilthead seabream juveniles.

    PubMed

    Rodenas, M C; Cabas, I; García-Alcázar, A; Meseguer, J; Mulero, V; García-Ayala, A

    2016-05-01

    17α-ethynylestradiol (EE2), a synthetic estrogen used in oral contraceptives and hormone replacement therapy, tamoxifen (Tmx), a selective estrogen-receptor modulator used in hormone replacement therapy, and G1, a G protein-coupled estrogen receptor (GPER) selective agonist, differentially increased the hepatic vitellogenin (vtg) gene expression and altered the immune response in adult gilthead seabream (Sparus aurata L.) males. However, no information exists on the effects of these compounds on the immune response of juveniles. This study aims, for the first time, to investigate the effects of the dietary intake of EE2, Tmx or G1 on the immune response of gilthead seabream juveniles and the capacity of the immune system of the specimens to recover its functionality after ceasing exposures (recovery period). The specimens were immunized with hemocyanin in the presence of aluminium adjuvant 1 (group A) or 120 (group B) days after the treatments ceased (dpt). The results indicate that EE2 and Tmx, but not G1, differentially promoted a transient alteration in hepatic vtg gene expression. Although all three compounds did not affect the production of reactive oxygen intermediates, they inhibited the induction of interleukin-1β (il1b) gene expression after priming. Interestingly, although Tmx increased the percentage of IgM-positive cells in both head kidney and spleen during the recovery period, the antibody response of vaccinated fish varied depending on the compound used and when the immunization was administered. Taken together, our results suggest that these compounds differentially alter the capacity of fish to respond to infection during ontogeny and, more interestingly, that the adaptive immune response remained altered to an extent that depends on the compound.

  20. Oral inflammation, a role for antimicrobial peptide modulation of cytokine and chemokine responses.

    PubMed

    Brogden, Kim A; Johnson, Georgia K; Vincent, Steven D; Abbasi, Taher; Vali, Shireen

    2013-10-01

    Acute and chronic inflammation commonly occurs throughout the oral cavity. The most common causes are physical damage and microbial infections, and less frequently immune reactions and malignant changes. All of these processes result in the induction of antimicrobial peptides, chemokines and cytokines that lead to cellular infiltrates, a vascular response, tissue destruction and cellular proliferation. A fascinating concept developing in the current literature suggests that antimicrobial peptides modulate the production of chemokines, cytokines and other cellular mediators and that this may have a larger ramification as an underlying mechanism mediating inflammation. Here, we propose that the ability of antimicrobial peptides to induce chemokines and anti-inflammatory or proinflammatory cytokines plays an important role in the early events of oral inflammation and may be a target for the prevention or treatment of oral inflammatory conditions.

  1. The biliprotein C-phycocyanin modulates the early radiation response: a pilot study.

    PubMed

    Ivanova, Katia G; Stankova, Katia G; Nikolov, Vladimir N; Georgieva, Radostina T; Minkova, Kaledona M; Gigova, Lili G; Rupova, Ivanka T; Boteva, Rayna N

    2010-01-01

    This study analyzed the effects of biliprotein C-phycocyanin (C-PC) on the enzymatic antioxidant defence system in lymphocytes of nuclear power-plant workers and non-exposed controls. Changes in the protein levels of manganese super oxide dismutase (MnSOD), catalase and glutathione-S-transferase (GST) were used as markers for early biological effects of a single in vitro exposure of cells to: (i) 2Gy gamma rays; (ii) 5muM C-PC; and (iii) a combination of C-PC plus irradiation with 2Gy. The results showed that C-PC selectively stimulated the lymphocyte antioxidant defence system of occupationally exposed subjects. The activation of the antioxidant protective mechanisms as part of the early radiation response was probably related to the chronic low-dose occupational exposure. The modulating capacity of C-PC at the molecular level may be of interest for the protection of occupationally exposed persons.

  2. 'I love Rock 'n' Roll'--music genre preference modulates brain responses to music.

    PubMed

    Istók, Eva; Brattico, Elvira; Jacobsen, Thomas; Ritter, Aileen; Tervaniemi, M

    2013-02-01

    The present study examined the effect of participants' music genre preference on the neural processes underlying evaluative and cognitive judgements of music using the event-related potential technique. To this aim, two participant groups differing in their preference for Latin American and Heavy Metal music performed a liking judgement and a genre classification task on a variety of excerpts of either music genre. A late positive potential (LPP) was elicited in all conditions between 600 and 900 ms after stimulus onset. During the genre classification task, an early negativity was elicited by the preferred compared to the non-preferred music at around 230-370 ms whereas the non-preferred genre was characterized by a larger LPP. The findings suggest that evaluative and cognitive judgements of music are accompanied by affective responses and that the valence of music may spontaneously modulate early processes of music categorization even when no overt liking judgement is required.

  3. Carbon monoxide and mitochondria—modulation of cell metabolism, redox response and cell death

    PubMed Central

    Almeida, Ana S.; Figueiredo-Pereira, Cláudia; Vieira, Helena L. A.

    2015-01-01

    Carbon monoxide (CO) is an endogenously produced gasotransmitter, which is associated with cytoprotection and cellular homeostasis in several distinct cell types and tissues. CO mainly targets mitochondria because: (i) mitochondrial heme-proteins are the main potential candidates for CO to bind, (ii) many CO's biological actions are dependent on mitochondrial ROS signaling and (iii) heme is generated in the mitochondrial compartment. Mitochondria are the key cell energy factory, producing ATP through oxidative phosphorylation and regulating cell metabolism. These organelles are also implicated in many cell signaling pathways and the production of reactive oxygen species (ROS). Finally, mitochondria contain several factors activating programmed cell death pathways, which are released from the mitochondrial inter-membrane space upon mitochondrial membrane permeabilization. Therefore, disclosing CO mode of action at mitochondria opens avenues for deeper understanding CO's biological properties. Herein, it is discussed how CO affects the three main aspects of mitochondrial modulation of cell function: metabolism, redox response and cell death. PMID:25709582

  4. Electroporation modulates the embryogenic responses of asparagus (Asparagus officinalis L.) microspores.

    PubMed

    Delaitre, C; Ochatt, S; Deleury, E

    2001-01-01

    Microspores of three genotypes of Asparagus officinalis L. were mechanically isolated without affecting their viability and were submitted to electric fields in order to modulate their competence for embryogenesis. When a constant pulse length and various field strengths (250, 500, 750, 1000, 1500, and 2000 V/cm) were tested, the viability of electro-treated microspores decreased as the field strength increased, for all genotypes. Conversely, the embryogenic competence was genotype dependent and was enhanced by low voltages for two clones when microspores were cultured in the presence of auxin. When the effect of pulse duration was studied, despite a strong genotype effect on responses, a short pulse coupled with a low voltage appeared to improve the competence for proembryo formation compared with nonelectroporated microspores, while longer pulses significantly improved microspore division.

  5. Experience Modulates the Reproductive Response to Heat Stress in C. elegans via Multiple Physiological Processes

    PubMed Central

    Gouvêa, Devin Y.; Aprison, Erin Z.; Ruvinsky, Ilya

    2015-01-01

    Natural environments are considerably more variable than laboratory settings and often involve transient exposure to stressful conditions. To fully understand how organisms have evolved to respond to any given stress, prior experience must therefore be considered. We investigated the effects of individual and ancestral experience on C. elegans reproduction. We documented ways in which cultivation at 15°C or 25°C affects developmental time, lifetime fecundity, and reproductive performance after severe heat stress that exceeds the fertile range of the organism but is compatible with survival and future fecundity. We found that experience modulates multiple aspects of reproductive physiology, including the male and female germ lines and the interaction between them. These responses vary in their environmental sensitivity, suggesting the existence of complex mechanisms for coping with unpredictable and stressful environments. PMID:26713620

  6. Extension of long wavelength response by modulation doping in extrinsic germanium infrared detectors

    NASA Technical Reports Server (NTRS)

    Hadek, V.; Farhoomand, J.; Beichman, C. A.; Watson, D. M.; Jack, M. D.

    1985-01-01

    A new concept for infrared detectors based on multilayer epitaxy and modulation doping has been investigated. This permits a high doping concentration and lower excitation energy in the photodetecting layer as is necessary for longer wavelength response, without incurring the detrimental effects of increased dark current and noise as would be the case with conventional detector designs. Germanium photodetectors using conventional materials and designs have a long wavelength cutoff in the infrared at 138 microns, which can only be extended through the inconvenient application of mechanical stress or magnetic fields. As a result of this approach which was arrived at from theoretical considerations and subsequently demonstrated experimentally, the long wavelength cutoff for germanium extrinsic detectors was extended beyond 200 microns, as determined by direct infrared optical measurements.

  7. The Role of Environmental Factors in Modulating Immune Responses in Early Life

    PubMed Central

    MacGillivray, Duncan M.; Kollmann, Tobias R.

    2014-01-01

    The concept of immunological memory stipulates that past exposures shape present immune function. These exposures include not only specific antigens impacting adaptive immune memory but also conserved pathogen or danger associated molecular patterns that mold innate immune responses for prolonged periods of time. It should thus not come as a surprise that there is a vast range of external or environmental factors that impact immunity. The importance of environmental factors modulating immunity is most readily recognized in early life, a period of rapidly changing environments. We here summarize available data on the role of environment shaping immune development and from it derive an overarching hypothesis relating the underlying molecular mechanisms and evolutionary principles involved. PMID:25309535

  8. The velocity of light intensity increase modulates the photoprotective response in coastal diatoms.

    PubMed

    Giovagnetti, Vasco; Flori, Serena; Tramontano, Ferdinando; Lavaud, Johann; Brunet, Christophe

    2014-01-01

    In aquatic ecosystems, the superimposition of mixing events to the light diel cycle exposes phytoplankton to changes in the velocity of light intensity increase, from diurnal variations to faster mixing-related ones. This is particularly true in coastal waters, where diatoms are dominant. This study aims to investigate if coastal diatoms differently activate the photoprotective responses, xanthophyll cycle (XC) and non-photochemical fluorescence quenching (NPQ), to cope with predictable light diel cycle and unpredictable mixing-related light variations. We compared the effect of two fast light intensity increases (simulating mixing events) with that of a slower increase (corresponding to the light diel cycle) on the modulation of XC and NPQ in the planktonic coastal diatom Pseudo-nitzschia multistriata. During each light treatment, the photon flux density (PFD) progressively increased from darkness to five peaks, ranging from 100 to 650 µmol photons m-2 s-1. Our results show that the diel cycle-related PFD increase strongly activates XC through the enhancement of the carotenoid biosynthesis and induces a moderate and gradual NPQ formation over the light gradient. In contrast, during mixing-related PFD increases, XC is less activated, while higher NPQ rapidly develops at moderate PFD. We observe that together with the light intensity and its increase velocity, the saturation light for photosynthesis (Ek) is a key parameter in modulating photoprotection. We propose that the capacity to adequately regulate and actuate alternative photoprotective 'safety valves' in response to changing velocity of light intensity increase further enhances the photophysiological flexibility of diatoms. This might be an evolutionary outcome of diatom adaptation to turbulent marine ecosystems characterized by unpredictable mixing-related light changes over the light diel cycle.

  9. Modulations of the Chicken Cecal Microbiome and Metagenome in Response to Anticoccidial and Growth Promoter Treatment

    PubMed Central

    Danzeisen, Jessica L.; Kim, Hyeun Bum; Isaacson, Richard E.; Tu, Zheng Jin; Johnson, Timothy J.

    2011-01-01

    With increasing pressures to reduce or eliminate the use of antimicrobials for growth promotion purposes in production animals, there is a growing need to better understand the effects elicited by these agents in order to identify alternative approaches that might be used to maintain animal health. Antibiotic usage at subtherapeutic levels is postulated to confer a number of modulations in the microbes within the gut that ultimately result in growth promotion and reduced occurrence of disease. This study examined the effects of the coccidiostat monensin and the growth promoters virginiamycin and tylosin on the broiler chicken cecal microbiome and metagenome. Using a longitudinal design, cecal contents of commercial chickens were extracted and examined using 16S rRNA and total DNA shotgun metagenomic pyrosequencing. A number of genus-level enrichments and depletions were observed in response to monensin alone, or monensin in combination with virginiamycin or tylosin. Of note, monensin effects included depletions of Roseburia, Lactobacillus and Enterococcus, and enrichments in Coprococcus and Anaerofilum. The most notable effect observed in the monensin/virginiamycin and monensin/tylosin treatments, but not in the monensin-alone treatments, was enrichments in Escherichia coli. Analysis of the metagenomic dataset identified enrichments in transport system genes, type I fimbrial genes, and type IV conjugative secretion system genes. No significant differences were observed with regard to antimicrobial resistance gene counts. Overall, this study provides a more comprehensive glimpse of the chicken cecum microbial community, the modulations of this community in response to growth promoters, and targets for future efforts to mimic these effects using alternative approaches. PMID:22114729

  10. Detector level ABI spectral response function: FM4 analysis and comparison for different ABI modules

    NASA Astrophysics Data System (ADS)

    Efremova, Boryana; Pearlman, Aaron J.; Padula, Frank; Wu, Xiangqian

    2016-09-01

    A new generation of imaging instruments Advanced Baseline Imager (ABI) is to be launched aboard the Geostationary Operational Environmental Satellites - R Series (GOES-R). Four ABI flight modules (FM) are planned to be launched on GOES-R,S,T,U, the first one in the fall of 2016. Pre-launch testing is on-going for FM3 and FM4. ABI has 16 spectral channels, six in the visible/near infrared (VNIR 0.47 - 2.25 μm), and ten in the thermal infrared (TIR 3.9 - 13.3 μm) spectral regions, to be calibrated on-orbit by observing respectively a solar diffuser and a blackbody. Each channel has hundreds of detectors arranged in columns. Operationally one Analytic Generation of Spectral Response (ANGEN) function will be used to represent the spectral response function (SRF) of all detectors in a band. The Vendor conducted prelaunch end-to-end SRF testing to compare to ANGEN; detector specific SRF data was taken for: i) best detector selected (BDS) mode - for FM 2,3, and 4; and ii) all detectors (column mode) - for four spectral bands in FM3 and FM4. The GOES-R calibration working group (CWG) has independently used the SRF test data for FM2 and FM3 to study the potential impact of detector-to-detector SRF differences on the ABI detected Earth view radiances. In this paper we expand the CWG analysis to include the FM4 SRF test data - the results are in agreement with the Vendor analysis, and show excellent instrument performance and compare the detector-to-detector SRF differences and their potential impact on the detected Earth view radiances for all of the tested ABI modules.

  11. Modulations of the chicken cecal microbiome and metagenome in response to anticoccidial and growth promoter treatment.

    PubMed

    Danzeisen, Jessica L; Kim, Hyeun Bum; Isaacson, Richard E; Tu, Zheng Jin; Johnson, Timothy J

    2011-01-01

    With increasing pressures to reduce or eliminate the use of antimicrobials for growth promotion purposes in production animals, there is a growing need to better understand the effects elicited by these agents in order to identify alternative approaches that might be used to maintain animal health. Antibiotic usage at subtherapeutic levels is postulated to confer a number of modulations in the microbes within the gut that ultimately result in growth promotion and reduced occurrence of disease. This study examined the effects of the coccidiostat monensin and the growth promoters virginiamycin and tylosin on the broiler chicken cecal microbiome and metagenome. Using a longitudinal design, cecal contents of commercial chickens were extracted and examined using 16S rRNA and total DNA shotgun metagenomic pyrosequencing. A number of genus-level enrichments and depletions were observed in response to monensin alone, or monensin in combination with virginiamycin or tylosin. Of note, monensin effects included depletions of Roseburia, Lactobacillus and Enterococcus, and enrichments in Coprococcus and Anaerofilum. The most notable effect observed in the monensin/virginiamycin and monensin/tylosin treatments, but not in the monensin-alone treatments, was enrichments in Escherichia coli. Analysis of the metagenomic dataset identified enrichments in transport system genes, type I fimbrial genes, and type IV conjugative secretion system genes. No significant differences were observed with regard to antimicrobial resistance gene counts. Overall, this study provides a more comprehensive glimpse of the chicken cecum microbial community, the modulations of this community in response to growth promoters, and targets for future efforts to mimic these effects using alternative approaches.

  12. Human amnion epithelial cells modulate the inflammatory response to ventilation in preterm lambs

    PubMed Central

    Melville, Jacqueline M.; McDonald, Courtney A.; Bischof, Robert J.; Polglase, Graeme R.; Lim, Rebecca; Wallace, Euan M.; Jenkin, Graham; Moss, Timothy J.

    2017-01-01

    Ventilation of preterm neonates causes pulmonary inflammation that can contribute to lung injury, propagate systemically and result in long-term disease. Modulation of this initial response may reduce lung injury and its sequelae. We aimed to determine the effect of human amnion epithelial cells (hAECs) on immune activation and lung injury in preterm neonatal lambs. Preterm lambs received intratracheal hAECs (90x106) or vehicle, prior to 2 h of mechanical ventilation. Within 5 min of ventilation onset, lambs also received intravenous hAECs (90x106) or vehicle. Lung histology, bronchoalveolar lavage (BAL) cell phenotypes, and cytokine profiles were examined after 2 h of ventilation, and in unventilated controls. Histological indices of lung injury were higher than control, in vehicle-treated ventilated lambs but not in hAEC-treated ventilated lambs. Ventilation-induced pulmonary leukocyte recruitment was greater in hAEC-treated lambs than in vehicle-treated lambs. Lung IL-1β and IL-6 mRNA expression was higher in vehicle- and hAEC-treated ventilated lambs than in controls but IL-8 mRNA levels were greater than control only in vehicle-treated ventilated lambs. Numbers of CD44+ and CD21+ lymphocytes and macrophages from the lungs were altered in vehicle- and hAEC-treated ventilated lambs. Numbers of CD8+ macrophages were lower in hAEC-treated ventilated lambs than in vehicle-treated ventilated lambs. Indices of systemic inflammation were not different between vehicle- and hAEC-treated lambs. Human amnion epithelial cells modulate the pulmonary inflammatory response to ventilation in preterm lambs, and reduce acute lung injury. Immunomodulatory effects of hAECs reduce lung injury in preterm neonates and may protect against longer-term respiratory disease. PMID:28346529

  13. Human amnion epithelial cells modulate the inflammatory response to ventilation in preterm lambs.

    PubMed

    Melville, Jacqueline M; McDonald, Courtney A; Bischof, Robert J; Polglase, Graeme R; Lim, Rebecca; Wallace, Euan M; Jenkin, Graham; Moss, Timothy J

    2017-01-01

    Ventilation of preterm neonates causes pulmonary inflammation that can contribute to lung injury, propagate systemically and result in long-term disease. Modulation of this initial response may reduce lung injury and its sequelae. We aimed to determine the effect of human amnion epithelial cells (hAECs) on immune activation and lung injury in preterm neonatal lambs. Preterm lambs received intratracheal hAECs (90x106) or vehicle, prior to 2 h of mechanical ventilation. Within 5 min of ventilation onset, lambs also received intravenous hAECs (90x106) or vehicle. Lung histology, bronchoalveolar lavage (BAL) cell phenotypes, and cytokine profiles were examined after 2 h of ventilation, and in unventilated controls. Histological indices of lung injury were higher than control, in vehicle-treated ventilated lambs but not in hAEC-treated ventilated lambs. Ventilation-induced pulmonary leukocyte recruitment was greater in hAEC-treated lambs than in vehicle-treated lambs. Lung IL-1β and IL-6 mRNA expression was higher in vehicle- and hAEC-treated ventilated lambs than in controls but IL-8 mRNA levels were greater than control only in vehicle-treated ventilated lambs. Numbers of CD44+ and CD21+ lymphocytes and macrophages from the lungs were altered in vehicle- and hAEC-treated ventilated lambs. Numbers of CD8+ macrophages were lower in hAEC-treated ventilated lambs than in vehicle-treated ventilated lambs. Indices of systemic inflammation were not different between vehicle- and hAEC-treated lambs. Human amnion epithelial cells modulate the pulmonary inflammatory response to ventilation in preterm lambs, and reduce acute lung injury. Immunomodulatory effects of hAECs reduce lung injury in preterm neonates and may protect against longer-term respiratory disease.

  14. Modulating protein behaviors on responsive surface by external electric fields: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Xie, Yun; Pan, Yufang; Zhang, Rong; Liang, Ying; Li, Zhanchao

    2015-01-01

    Molecular dynamics simulations were employed to investigate the modulation of protein behaviors on the electrically responsive zwitterionic phosphorylcholine self-assembled monolayers (PC-SAMs). Results show that PC-SAMs could sensitively respond to the applied electric fields and exhibit three states with different charge distributions, namely both the negatively charged phosphate groups and the positively charged choline groups are exposed to the solution in the absence of electric fields (state 1), phosphate groups exposed in the presence of positive electric fields (state 2), and choline groups exposed in the presence of negative electric fields (state 3). Under state 1, the adsorption of Cyt c on the PC-SAM is reversible and the orientations of Cyt c are randomly distributed. Under state 2, the adsorption of Cyt c is enhanced due to the electrostatic attractions between the exposed phosphate groups and the positively charged protein; when adsorbed on the PC-SAMs, Cyt c tends to adopt the orientation with the heme plane perpendicular to the surface plane, and the percentage of this orientation increases as the field strength rises up. Under state 3, the adsorption of Cyt c is retarded because of the electrostatic repulsions between the exposed choline groups and the protein; however, if the gaps between PC chains are large enough, Cyt c could insert into the PC-SAM and access the phosphate groups after overcoming a slight energy barrier. Under three states, the basic backbone structures of Cyt c are well kept within the simulation time since the conformation of Cyt c is mainly affected by the surface-generated electric fields, whose strengths are modulated by the external electric fields and are not strong enough to deform protein. The results indicate the possibility of regulating protein behaviors, including promoting or retarding protein adsorption and regulating protein orientations, on responsive surfaces by applying electric fields on the surfaces without

  15. Osmotic modulation of stimulus-evoked responses in the rat supraoptic nucleus.

    PubMed

    Bhumbra, G S; Orlans, H O; Dyball, R E J

    2008-04-01

    Neural information is conveyed by action potentials along axons to downstream synaptic targets. Synapses permit functionally relevant modulation of the information transmitted by converging inputs. Previous studies have measured the amount of information associated with a given stimulus based either on spike counts or on the relative frequencies of spike sequences represented as binary strings. Here we apply information theory to the phase-interval stimulus histogram (PhISH) to measure the extent of the stimulus-evoked response using the statistical relationship between each interspike interval and its phase within the stimulus cycle. We used the PhISH as a novel approach to investigate how different osmotic states affect the flow of information through the osmoreceptor complex of the hypothalamus. The amount of information conveyed from one (afferent) element of the complex, the anteroventral region of the third ventricle (AV3V), to another (an efferent element), the supraoptic nucleus, was increased by hypertonic stimulation (intravenous mannitol, z = 4.39, P < 0.001) and decreased by hypotonic stimulation (intragastric water, z = -3.37, P < 0.001). Supraoptic responses to AV3V stimulation differed from those that follow stimulation of a hypothalamic element outside the osmoreceptor complex, the suprachiasmatic nucleus (SCN), which also projects to the supraoptic nucleus. Thus osmosensitive gain control mechanisms differentially modulate osmotically dependent and osmotically independent inputs, and enhance the osmoresponsiveness of supraoptic cells within a physiological range. The value of the novel approach is that its use is not limited to the osmoreceptor ensemble but it can be used to investigate the flow of information throughout the central nervous system.

  16. Suprachiasmatic astrocytes modulate the circadian clock in response to TNF-α1

    PubMed Central

    Duhart, José M.; Leone, María Juliana; Paladino, Natalia; Evans, Jennifer A.; Castanon-Cervantes, Oscar; Davidson, Alec J.; Golombek, Diego A.

    2013-01-01

    The immune and the circadian systems interact in a bidirectional fashion. The master circadian oscillator, located in the suprachiasmatic nuclei of the hypothalamus (SCN), responds to peripheral and local immune stimuli, such as proinflammatory cytokines and bacterial endotoxin. Astrocytes exert several immune functions in the central nervous system and there is growing evidence that points towards a role of these cells in the regulation of circadian rhythms. The aim of this work was to assess the response of SCN astrocytes to immune stimuli, particularly to the proinflammatory cytokine TNF-α. TNF-α applied to cultures of SCN astrocytes from Per2luc knock in mice altered both the phase and amplitude of PER2 expression rhythms, in a phase dependent manner. Furthermore, conditioned media from SCN astrocytes cultures transiently challenged with TNF-α induced an increase in Per1 expression in NIH 3T3 cells, that was blocked by TNF-α antagonism. In addition, these conditioned media could induce phase shifts in SCN PER2 rhythms and, when administered intracerebroventricularly, induced phase delays in behavioral circadian rhythms and SCN activation in control mice, but not in TNF-Receptor-1 mutants. In summary, our results show that TNF-α modulates the molecular clock of SCN astrocytes in vitro and also that, in response to this molecule, SCN astrocytes can modulate clock gene expression in other cells and tissues, and induce phase shifts in a circadian behavioral output in vivo. These findings suggest a role for astroglial cells in the alteration of circadian timing by immune activation. PMID:24062487

  17. α-Fetoprotein as a modulator of the pro-inflammatory response of human keratinocytes

    PubMed Central

    Potapovich, AI; Pastore, S; Kostyuk, VA; Lulli, D; Mariani, V; De Luca, C; Dudich, EI; Korkina, LG

    2009-01-01

    Background and purpose: The immunomodulatory effects of α-fetoprotein (AFP) on lymphocytes and macrophages have been described in vitro and in vivo. Recombinant forms of human AFP have been proposed as potential therapeutic entities for the treatment of autoimmune diseases. We examined the effects of embryonic and recombinant human AFP on the spontaneous, UVA- and cytokine-induced pro-inflammatory responses of human keratinocytes. Experimental approach: Cultures of primary and immortalized human keratinocytes (HaCaT) and human blood T lymphocytes were used. The effects of AFP on cytokine expression were studied by bioplexed elisa and quantitative reverse transcriptase polymerase chain reaction assay. Kinase and nuclear factor kappa B (NFκB) phosphorylation were quantified by intracellular elisa. Nuclear activator protein 1 and NFκB DNA binding activity was measured by specific assays. Nitric oxide and H2O2 production and redox status were assessed by fluorescent probe and biochemical methods. Key results: All forms of AFP enhanced baseline expression of cytokines, chemokines and growth factors. AFP dose-dependently increased tumour necrosis factor alpha-stimulated granulocyte macrophage colony stimulating factor and interleukin 8 expression and decreased tumour necrosis factor alpha-induced monocyte chemotactic protein 1 and IP-10 (interferon gamma-produced protein of 10 kDa) expression. AFP induced a marked activator protein 1 activation in human keratinocytes. AFP also increased H2O2 and modulated nitrite/nitrate levels in non-stimulated keratinocytes whereas it did not affect these parameters or cytokine release from UVA-stimulated cells. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Akt1 but not NFκB was activated by AFP alone or by its combination with UVA. Conclusions and implications: Exogenous AFP induces activation of human keratinocytes, with de novo expression of a number of pro-inflammatory mediators and modulation of their

  18. Responses of respiratory modulated and tonic units in the retrotrapezoid nucleus to CO2.

    PubMed

    Nattie, E E; Fung, M L; Li, A; St John, W M

    1993-10-01

    We hypothesized that the retrotrapezoid nucleus (RTN) contains both respiratory modulated (RM) and non-respiratory modulated (NRM) neurons which participate in the ventilatory response to increased CO2. We made extracellular recordings of the activity of 46 single units in the RTN of 9 decerebrate, paralyzed, ventilated cats (5 intact; 4 with carotid body and sinus ablation) under eucapnic (PCO2 = 34.2 +/- 3.5 mmHg; mean +/- SD) and hypercapnic (PCO2 = 47.4 +/- 3.4 conditions. To define a RM unit, we used the eta 2 statistic which is the ratio of the variance of the unit firing rate within respiratory cycles to that across respiratory cycles. We classified the units as RM (N = 17) if the eta 2 values in eucapnia or hypercapnia were > or = 0.25 and as NRM (N = 29) if the values were < 0.25. Overall, 19/46 units (41%) increased their firing rate with increased CO2, 5 decreased their firing rate, and 22 had no significant change in firing rate. Of 17 RM units, 8 (47%) increased their mean firing rate with hypercapnia from 7.6 +/- 3.9 to 23.2 +/- 6.8 spikes/sec. These included 5 inspiratory units, 2 inspiratory units that had an onset of firing in late expiration (Pre-I/I), and 1 expiratory unit. Seven of these also changed their discharge pattern (eucapnic eta 2 = 0.02 to 0.12; hypercapnic eta 2 = 0.34 to 0.79) Of 29 NRM units, 11 (38%) showed a significant increase in mean firing rate with CO2 stimulation from 19.8 +/- 7.2 to 31.3 +/- 8.2 spikes/sec. The RTN has RM units which change their discharge pattern and firing rate in response to increased CO2, as do units within the medulla and pons, and it has NRM units which are also responsive to increased CO2. These data indicate that some neurons of the RTN are involved in the central chemoreceptor response but they provide no direct evidence that chemoreception resides within the RTN.

  19. Crustacean hyperglycemic hormones directly modulate the immune response of hemocytes in shrimp Litopenaeus vannamei.

    PubMed

    Wang, Lin; Chen, Hao; Xu, Jianchao; Xu, Qingsong; Wang, Mengqiang; Zhao, Depeng; Wang, Lingling; Song, Linsheng

    2017-03-01

    A robust immune response against invading pathogens is crucial for host to survive, which depends greatly on the well balance of metabolism. Increasing evidence has indicated that some metabolic hormones, such as insulin, could modulate immune responses directly. Crustacean hyperglycemic hormone (CHH) family is a group of ecdysozoans-specific peptide hormone involved in glucose metabolism and other biological events. In the present study, two members of CHH family (designated as LvCHH I and LvCHH II) in shrimp Litopenaeus vannamei with one and two crustacean neurohormone domains respectively were chosen to investigate their putative modulatory roles in both glucose metabolism and immune response. LvCHH I and LvCHH II were both expressed in the sinus gland and lamina ganglionalis of eyestalks and were significantly induced after white spot syndrome virus (WSSV) infection. Meanwhile, significant increases of hemolymph glucose levels were observed in shrimp at 12 and 24 h after WSSV infection while the glucose inside the hemocytes decreased at 6 h and then increased at 12 h. Gain-of-function of rLvCHHs was subsequently conducted in vivo by injecting the recombinant proteins (rLvCHH I and rLvCHH II). The hemolymph glucose increased significantly from 0.5 h to 3 h after the shrimps received an injection of rLvCHH I, while it decreased at 0.5 h and increased afterward at 3 h post rLvCHH II injection. At the meantime, significant decreases of reactive oxygen species level in hemocytes were observed at 3 h and 6 h post rLvCHH I injection, while it remained unchanged in rLvCHH II injection group. rLvCHH I and rLvCHH II could bind to the cytomembrane of primary shrimp hemocytes in vitro, and the expressions of superoxide dismutase and LvRelish increased when the hemocytes were incubated with rLvCHH I for 3 h. Meanwhile, the expression of antimicrobial peptides, crustin and penaeidin-4, were also induced by rLvCHH I and rLvCHH II. These results demonstrated that

  20. Modulation of reflex responses in hand muscles during rhythmical finger tasks in a subject with writer's cramp.

    PubMed

    Xia, Ruiping; Bush, Brian M H

    2007-03-01

    The objective of this study was to examine phase- and task-dependent modulation of stretch reflexes during repetitive finger movements in writer's cramp, and compare them with normal controls from our previous study. A subject with writer's cramp conducted two rhythmic tasks, index finger abduction (RFA) and a pen-squeezing (RPS) task akin to handwriting. Stretch reflexes were evoked by mechanical perturbations at random phases of each task. Surface electromyograms (EMG) were recorded from two hand muscles, first dorsal interosseous (FDI) and flexor digitorum superficialis (FDS). The reflex response and background EMG activity of each muscle were modulated in a phase-dependent manner in both tasks. However, they varied largely in phase during the RFA task, but in approximately inverse phase-relationship during RPS. Reflex sensitivity, as represented by the slope of the linear regression between response and background, was much lower for both muscles in the 'writing' task (RPS) than in the RFA task with its positively correlated responses. These phase- and task-related modulation patterns differed dramatically from those observed in our control subjects, where reflex responses were modulated largely in phase with background activity and reflex sensitivity was much higher, particularly in FDI during RFA and FDS during RPS. The altered reflex modulation patterns in writer's cramp may reflect deficiencies of integration of proprioceptive afferent inputs and reduced inhibition at cortical and spinal levels during writing performance. Results from this case study support clinically identified task-specific feature of focal hand dystonia.

  1. Herausforderungen durch die deutsche Wiedervereinigung

    NASA Astrophysics Data System (ADS)

    Stäglin, Reiner

    Die Wiedervereinigung stellte auch die Statistik vor große Aufgaben. Die als Organ der staatlichen Planung staatsnah orientierte Statistik der DDR musste auf das zur Neutralität und wissenschaftlichen Unabhängigkeit verpflichtete System der Bundesrepublik umgestellt werden. Ebenso verlangten die Universitäten eine Neuorientierung. Die Deutsche Statistische Gesellschaft hat sich vor allem dreier Aufgaben mit großem Engagement, aber auch mit Bedachtsamkeit angenommen: Aufnahme und Integration der Statistiker aus den neuen Bundesländern in die Gesellschaft, Begleitung der Neuausrichtung des Faches Statistik an deren Hochschulen und Sicherung sowie Nutzung von Datenbeständen der ehemaligen DDR.

  2. Housing environment modulates physiological and behavioral responses to anxiogenic stimuli in trait anxiety male rats.

    PubMed

    Ravenelle, R; Santolucito, H B; Byrnes, E M; Byrnes, J J; Donaldson, S T

    2014-06-13

    Environmental enrichment can modulate mild and chronic stress, responses to anxiogenic stimuli as well as drug vulnerability in a number of animal models. The current study was designed to examine the impact of postnatal environmental enrichment on selectively bred 4th generation high- (HAn) and low-anxiety (LAn) male rats. After weaning, animals were placed in isolated (IE), social (SE) and enriched environments (EE) (e.g., toys, wheels, ropes, changed weekly). We measured anxiety-like behavior (ALB) on the elevated plus maze (EPM; trial 1 at postnatal day (PND) 46, trial 2 at PND 63), amphetamine (AMPH) (0.5mg/kg, IP)-induced locomotor behavior, basal and post anxiogenic stimuli changes in (1) plasma corticosterone, (2) blood pressure and (3) core body temperature. Initially, animals showed consistent trait differences on EPM with HAn showing more ALB but after 40 days in select housing, HAn rats reared in an EE showed less ALB and diminished AMPH-induced activity compared to HAn animals housed in IE and SE. In the physiological tests, animals housed in EE showed elevated adrenocortical responses to forced novel object exposure but decreased body temperature and blood pressure changes after an air puff stressor. All animals reared in EE and SE had elevated brain-derived neurotrophic factor (BDNF)-positive cells in the central amygdala (CeA), CA1 and CA2 hippocampal regions and the caudate putamen, but these differences were most pronounced in HAn rats for CeA, CA1 and CA2. Overall, these findings suggest that environmental enrichment offers benefits for trait anxiety rats including a reduction in behavioral and physiological responses to anxiogenic stimuli and AMPH sensitivity, and these responses correlate with changes in BDNF expression in the central amygdala, hippocampus and the caudate putamen.

  3. Post-error action control is neurobehaviorally modulated under conditions of constant speeded response

    PubMed Central

    Soshi, Takahiro; Ando, Kumiko; Noda, Takamasa; Nakazawa, Kanako; Tsumura, Hideki; Okada, Takayuki

    2015-01-01

    Post-error slowing (PES) is an error recovery strategy that contributes to action control, and occurs after errors in order to prevent future behavioral flaws. Error recovery often malfunctions in clinical populations, but the relationship between behavioral traits and recovery from error is unclear in healthy populations. The present study investigated the relationship between impulsivity and error recovery by simulating a speeded response situation using a Go/No-go paradigm that forced the participants to constantly make accelerated responses prior to stimuli disappearance (stimulus duration: 250 ms). Neural correlates of post-error processing were examined using event-related potentials (ERPs). Impulsivity traits were measured with self-report questionnaires (BIS-11, BIS/BAS). Behavioral results demonstrated that the commission error for No-go trials was 15%, but PES did not take place immediately. Delayed PES was negatively correlated with error rates and impulsivity traits, showing that response slowing was associated with reduced error rates and changed with impulsivity. Response-locked error ERPs were clearly observed for the error trials. Contrary to previous studies, error ERPs were not significantly related to PES. Stimulus-locked N2 was negatively correlated with PES and positively correlated with impulsivity traits at the second post-error Go trial: larger N2 activity was associated with greater PES and less impulsivity. In summary, under constant speeded conditions, error monitoring was dissociated from post-error action control, and PES did not occur quickly. Furthermore, PES and its neural correlate (N2) were modulated by impulsivity traits. These findings suggest that there may be clinical and practical efficacy of maintaining cognitive control of actions during error recovery under common daily environments that frequently evoke impulsive behaviors. PMID:25674058

  4. The endogenous immune response modulates the course of IgA-immune complex mediated nephropathy.

    PubMed

    Chao, T-K; Rifai, A; Ka, S-M; Yang, S-M; Shui, H-A; Lin, Y-F; Sytwu, H-K; Lee, W-H; Kung, J T; Chen, A

    2006-07-01

    In animal models of IgA nephropathy, the inevitable endogenous immune response to passively administered antigens alone or in complex with specific IgA mask the exact role each might play in pathogenesis. To delineate the role the immune response might play, we have developed a passive model with exclusive IgA-immune complex-mediated nephropathy in B-cell-deficient (BCD) mice. Glomerular IgA immune deposits were induced by administration of purified IgA antiphosphorylcholine and the specific pneumococcal C-polysaccharide (PnC) antigen daily for 2 weeks into BCD and wild-type (WT) mice. In BCD mice IgA+PnC deposits induced severe glomerular injury and renal dysfunction. In contrast, WT mice developed intense glomerular IgG and IgM and C3 co-deposits of the IgA+PnC with significantly less renal injury. Cytofluorometric analysis revealed that PnC induced in BCD, but not in WT, a rapid and dramatic increase in number of activated CD3(+)/CD69(+) T-cell population. The nuclear factor-kappa B (NF-kappaB) transcription factor was activated early and progressively increased in response to glomerular IgA+PnC deposits. These results suggest that nephritogenic IgA+PnC immune deposits induce glomerular and renal dysfunction through activation of the NF-kappaB. This inflammatory pathway is modulated by the endogenous cellular and antibody response to the antigen affecting the course of IgA nephropathy progression.

  5. Gaze Direction Modulates the Relation between Neural Responses to Faces and Visual Awareness.

    PubMed

    Madipakkam, Apoorva Rajiv; Rothkirch, Marcus; Guggenmos, Matthias; Heinz, Andreas; Sterzer, Philipp

    2015-09-30

    Gaze direction and especially direct gaze is a powerful nonverbal cue that plays an important role in social interactions. Here we studied the neural mechanisms underlying the privileged access of direct gaze to visual awareness. We performed functional magnetic resonance imaging in healthy human volunteers who were exposed to faces with direct or averted gaze under continuous flash suppression, thereby manipulating their awareness of the faces. A gaze processing network comprising fusiform face area (FFA), superior temporal sulcus, amygdala, and intraparietal sulcus showed overall reduced neural responses when participants reported to be unaware of the faces. Interestingly, direct gaze elicited greater responses than averted gaze when participants were aware of the faces, but smaller responses when they were unaware. Additional between-subject correlation and single-trial analyses indicated that this pattern of results was due to a modulation of the relationship between neural responses and awareness by gaze direction: with increasing neural activation in the FFA, direct-gaze faces entered awareness more readily than averted-gaze faces. These findings suggest that for direct gaze, lower levels of neural activity are sufficient to give rise to awareness than for averted gaze, thus providing a neural basis for privileged access of direct gaze to awareness. Significance statement: Another person's eye gaze directed at oneself is a powerful social signal acting as a catalyst for further communication. Here, we studied the neural mechanisms underlying the prioritized access of direct gaze to visual awareness in healthy human volunteers and show that with increasing neural activation, direct-gaze faces enter awareness more readily than averted-gaze faces. This suggests that for a socially highly relevant cue like direct gaze, lower levels of neural activity are sufficient to give rise to awareness compared with averted gaze, possibly because the human brain is attuned

  6. Gadd45 modulation of intrinsic and extrinsic stress responses in myeloid cells.

    PubMed

    Hoffman, Barbara; Liebermann, Dan A

    2009-01-01

    Gadd45 proteins modulate signaling in response to physiological and environmental stressors. Expression of gadd45 genes is rapidly induced by different stressors, including differentiation-inducing cytokines and genotoxic stress. Induction of gadd45 genes at the onset of myeloid differentiation suggested that Gadd45 protein(s) play a role in hematopoiesis, yet no apparent abnormalities were observed in either the bone marrow (BM) or peripheral blood compartments of mice deficient for either gadd45a or gadd45b. However, under conditions of hematological stress, including acute stimulation with cytokines, myelo-ablation and inflammation, both gadd45a-deficient and gadd45b-deficient mice exhibited deficiencies. This is discussed within the context of what is known about Gadd45 proteins in stress signaling, hematopoietic development and the innate immune response. Furthermore, myeloid enriched BM cells from gadd45a and gadd45b deficient mice were observed to be more sensitive to ultraviolet radiation (UVC), VP-16 and daunorubicin (DNR) induced apoptosis compared to wild-type (WT) cells, displaying defective G2/M arrest following exposure to UVC and VP-16, but not to DNR. Novel mechanisms that mediate the pro-survival functions of Gadd45 in hematopoietic cells following UV irradiation were demonstrated, involving activation of the Gadd45a-p38-NF-kappaB survival pathway and Gadd45b mediated inhibition of the stress response MKK4-JNK apoptotic pathway. The ramifications regarding the pathogenesis of different leukemias and the response of normal and malignant hematopoietic cells to chemo- and radiation-therapy, as well as other challenges to the hematopoietic compartment, are discussed.

  7. Identification of Lactobacillus plantarum genes modulating the cytokine response of human peripheral blood mononuclear cells

    PubMed Central

    2010-01-01

    Background Modulation of the immune system is one of the most plausible mechanisms underlying the beneficial effects of probiotic bacteria on human health. Presently, the specific probiotic cell products responsible for immunomodulation are largely unknown. In this study, the genetic and phenotypic diversity of strains of the Lactobacillus plantarum species were investigated to identify genes of L. plantarum with the potential to influence the amounts of cytokines interleukin 10 (IL-10) and IL-12 and the ratio of IL-10/IL-12 produced by peripheral blood mononuclear cells (PBMCs). Results A total of 42 Lactobacillus plantarum strains isolated from diverse environmental and human sources were evaluated for their capacity to stimulate cytokine production in PBMCs. The L. plantarum strains induced the secretion of the anti-inflammatory cytokine IL-10 over an average 14-fold range and secretion of the pro-inflammatory cytokine IL-12 over an average 16-fold range. Comparisons of the strain-specific cytokine responses of PBMCs to comparative genome hybridization profiles obtained with L. plantarum WCFS1 DNA microarrays (also termed gene-trait matching) resulted in the identification of 6 candidate genetic loci with immunomodulatory capacities. These loci included genes encoding an N-acetyl-glucosamine/galactosamine phosphotransferase system, the LamBDCA quorum sensing system, and components of the plantaricin (bacteriocin) biosynthesis and transport pathway. Deletion of these genes in L. plantarum WCFS1 resulted in growth phase-dependent changes in the PBMC IL-10 and IL-12 cytokine profiles compared with wild-type cells. Conclusions The altered PBMC cytokine profiles obtained with the L. plantarum WCFS1 mutants were in good agreement with the predictions made by gene-trait matching for the 42 L. plantarum strains. This study therefore resulted in the identification of genes present in certain strains of L. plantarum which might be responsible for the stimulation of anti

  8. Responses of neurons in chinchilla auditory cortex to frequency-modulated tones.

    PubMed

    Brown, Trecia A; Harrison, Robert V

    2009-04-01

    Frequency-modulated (FM) stimuli have been used to explore the behavior of neurons in the auditory cortex of several animal models; however, the properties of FM-sensitive auditory cortical neurons in the chinchilla are still unknown. Single-unit responses to FM stimulation were obtained from the auditory cortex of anesthetized adult chinchillas (Chinchilla laniger). Upward and downward linear FM sweeps spanning frequencies from 0.1 to 20 kHz were presented at speeds of 0.05 to 0.82 kHz/ms. Results indicated that >90% of sampled neurons were responsive to FM sweeps. The population preference was for upward FM sweeps and for medium to fast speeds (> or =0.3 kHz/ms). Few units (3%) were selective for downward FM sweeps, whereas <22% of units preferred slow speeds (< or =0.1 kHz/ms). Velocity preference and direction sensitivity were positively correlated for upward sweeps only (r = 0.40, P = 0.0021, t-test). Three types of firing rate patterns were observed in the FM response peristimulus time histograms: a single peak at sweep onset/offset ("onset") and a single peak ("late") or multiple peaks ("burst") during the sweep. "Late" units expressed the highest mean values for direction sensitivity and speed selectivity; "onset" units were selective only for direction and "burst" units were not selective for either direction or speed. The robust responsiveness of these neurons to FM sweeps suggests a functional role for FM detection such as the identification of FM sweeps present in vocalizations of other organisms within the chinchilla's natural environment.

  9. Modeling the Mechanical Performance of Die Casting Dies

    SciTech Connect

    R. Allen Miller

    2004-02-27

    The following report covers work performed at Ohio State on modeling the mechanical performance of dies. The focus of the project was development and particularly verification of finite element techniques used to model and predict displacements and stresses in die casting dies. The work entails a major case study performed with and industrial partner on a production die and laboratory experiments performed at Ohio State.

  10. Response variability of frontal eye field neurons modulates with sensory input and saccade preparation but not visual search salience

    PubMed Central

    Purcell, Braden A.; Heitz, Richard P.; Cohen, Jeremiah Y.

    2012-01-01

    Discharge rate modulation of frontal eye field (FEF) neurons has been identified with a representation of visual search salience (physical conspicuity and behavioral relevance) and saccade preparation. We tested whether salience or saccade preparation are evident in the trial-to-trial variability of discharge rate. We quantified response variability via the Fano factor in FEF neurons recorded in monkeys performing efficient and inefficient visual search tasks. Response variability declined following stimulus presentation in most neurons, but despite clear discharge rate modulation, variability did not change with target salience. Instead, we found that response variability was modulated by stimulus luminance and the number of items in the visual field independently of attentional demands. Response variability declined to a minimum before saccade initiation, and presaccadic response variability was directionally tuned. In addition, response variability was correlated with the response time of memory-guided saccades. These results indicate that the trial-by-trial response variability of FEF neurons reflects saccade preparation and the strength of sensory input, but not visual search salience or attentional allocation. PMID:22956785

  11. A Novel Approach to Identify Genes that Modulate Response of Human Ovarian Cancer Cells to Chemotherapeutic Agents Using High-Throughput RNA Interference

    DTIC Science & Technology

    2008-12-01

    sensitizing targets of cisplatin and paclitaxel in SKOV-3 cells. • Performed a kinase siRNA library screening for modulators of cisplatin response...Performed a kinase siRNA library screening for modulators of paclitaxel response. • Identified kinase genes whose silencing enhanced the response

  12. A disease module in the interactome explains disease heterogeneity, drug response and captures novel pathways and genes in asthma.

    PubMed

    Sharma, Amitabh; Menche, Jörg; Huang, C Chris; Ort, Tatiana; Zhou, Xiaobo; Kitsak, Maksim; Sahni, Nidhi; Thibault, Derek; Voung, Linh; Guo, Feng; Ghiassian, Susan Dina; Gulbahce, Natali; Baribaud, Frédéric; Tocker, Joel; Dobrin, Radu; Barnathan, Elliot; Liu, Hao; Panettieri, Reynold A; Tantisira, Kelan G; Qiu, Weiliang; Raby, Benjamin A; Silverman, Edwin K; Vidal, Marc; Weiss, Scott T; Barabási, Albert-László

    2015-06-01

    Recent advances in genetics have spurred rapid progress towards the systematic identification of genes involved in complex diseases. Still, the detailed understanding of the molecular and physiological mechanisms through which these genes affect disease phenotypes remains a major challenge. Here, we identify the asthma disease module, i.e. the local neighborhood of the interactome whose perturbation is associated with asthma, and validate it for functional and pathophysiological relevance, using both computational and experimental approaches. We find that the asthma disease module is enriched with modest GWAS P-values against the background of random variation, and with differentially expressed genes from normal and asthmatic fibroblast cells treated with an asthma-specific drug. The asthma module also contains immune response mechanisms that are shared with other immune-related disease modules. Further, using diverse omics (genomics, gene-expression, drug response) data, we identify the GAB1 signaling pathway as an important novel modulator in asthma. The wiring diagram of the uncovered asthma module suggests a relatively close link between GAB1 and glucocorticoids (GCs), which we experimentally validate, observing an increase in the level of GAB1 after GC treatment in BEAS-2B bronchial epithelial cells. The siRNA knockdown of GAB1 in the BEAS-2B cell line resulted in a decrease in the NFkB level, suggesting a novel regulatory path of the pro-inflammatory factor NFkB by GAB1 in asthma.

  13. Modulation of TCR responsiveness by the Grb2-family adaptor, Gads.

    PubMed

    Lugassy, Jennie; Corso, Jasmin; Beach, Dvora; Petrik, Thomas; Oellerich, Thomas; Urlaub, Henning; Yablonski, Deborah

    2015-01-01

    T cell antigen receptor (TCR) signaling depends on three interacting adaptor proteins: SLP-76, Gads, and LAT. Their mechanisms of signaling have been extensively explored, with the aid of fortuitously isolated LAT- and SLP-76-deficient T cell lines, but no such tools were available for Gads, a Grb2-family adaptor that bridges the TCR-inducible interaction between SLP-76 and LAT. TALEN-directed genome editing was applied to disrupt the first coding exon of human Gads in the Jurkat T cell line. Gads was dispensable for TCR-induced phosphorylation of SLP-76, but was a dose-dependent amplifier of TCR-induced CD69 expression. Gads conferred responsiveness to weak TCR stimuli, leading to PLC-γ1 phosphorylation and calcium flux. TALEN-derived, Gads-deficient T cell lines provide a uniquely tractable genetic platform for exploring its regulatory features, such as Gads phosphorylation at T262, which we observed by mass spectrometry. Upon mutation of this site, TCR responsiveness and sensitivity to weak TCR stimuli were increased. This study demonstrates the feasibility of TALEN-based reverse genetics in Jurkat T cells, while enriching our understanding of Gads as a regulated modulator of TCR sensitivity.

  14. Modulation of the immune response by infection with Cryptosporidium spp. in children with allergic diseases.

    PubMed

    Guangorena-Gómez, J O; Maravilla-Domínguez, A; García-Arenas, G; Cervantes-Flores, M; Meza-Velázquez, R; Rivera-Guillén, M; Acosta-Saavedra, L C; Goytia-Acevedo, R C

    2016-08-01

    It has been demonstrated that the allergic response can be ameliorated by the administration of pathogen derivatives that activate Toll-like receptors and induce a Th1-type immune response (IR). Cryptosporidium is a parasite that promotes an IR via Toll-like receptors and elicits the production of Th1-type cytokines, which limit cryptosporidiosis. The aim of this study was to investigate allergy-related immune markers in children naturally infected with Cryptosporidium. In a cross-sectional study, 49 children with or without clinical diagnosis of allergies, oocysts of Cryptosporidium spp. in the faeces were screened microscopically. We microscopically screened for leucocytes, examined T and B cells for allergy-related activation markers using flow cytometry and evaluated serum for total IgE using chemiluminescence. Children with allergies and Cryptosporidium in the faeces had significantly lower levels of total IgE, B cells, CD19(+) CD23(+) and CD19(+) CD124(+) cells as well as a greater percentage of interferon-gamma (IFN-γ(+) ) and IL-4(+) CD4(+) cells than children with allergies without Cryptosporidium. This is the first description of the modulation of the IR in children with allergic diseases in the setting of natural Cryptosporidium infection. Our findings suggest the involvement of CD4(+) cells producing IL-4 and IFN-γ in the IR to Cryptosporidium in naturally infected children.

  15. Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

    PubMed

    Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E

    2014-03-01

    Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

  16. Emotion processing fails to modulate putative mirror neuron response to trained visuomotor associations.

    PubMed

    Fitzgibbon, Bernadette M; Kirkovski, Melissa; Fornito, Alex; Paton, Bryan; Fitzgerald, Paul B; Enticott, Peter G

    2016-04-01

    Recent neuroimaging studies have demonstrated that activation of the putative human mirror neuron system (MNS) can be elicited via visuomotor training. This is generally interpreted as supporting an associative learning account of the mirror neuron system (MNS) that argues against the ontogeny of the MNS to be an evolutionary adaptation for social cognition. The current study assessed whether a central component of social cognition, emotion processing, would influence the MNS activity to trained visuomotor associations, which could support a broader role of the MNS in social cognition. Using functional magnetic resonance imaging (fMRI), we assessed repetition suppression to the presentation of stimulus pairs involving a simple hand action and a geometric shape that was either congruent or incongruent with earlier association training. Each pair was preceded by an image of positive, negative, or neutral emotionality. In support of an associative learning account of the MNS, repetition suppression was greater for trained pairs compared with untrained pairs in several regions, primarily supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). This response, however, was not modulated by the valence of the emotional images. These findings argue against a fundamental role of emotion processing in the mirror neuron response, and are inconsistent with theoretical accounts linking mirror neurons to social cognition.

  17. The shopping brain: math anxiety modulates brain responses to buying decisions.

    PubMed

    Jones, William J; Childers, Terry L; Jiang, Yang

    2012-01-01

    Metacognitive theories propose that consumers track fluency feelings when buying, which may have biological underpinnings. We explored this using event-related potential (ERP) measures as twenty high-math anxiety (High MA) and nineteen low-math anxiety (Low MA) consumers made buying decisions for promoted (e.g., 15% discount) and non-promoted products. When evaluating prices, ERP correlates of higher perceptual and conceptual fluency were associated with buys, however only for High MA females under no promotions. In contrast, High MA females and Low MA males demonstrated greater FN400 amplitude, associated with enhanced conceptual processing, to prices of buys relative to non-buys under promotions. Concurrent late positive component (LPC) differences under no promotions suggest discrepant retrieval processes during price evaluations between consumer groups. When making decisions to buy or not, larger (smaller) P3, sensitive to outcome responses in the brain, was associated with buying for High MA females (Low MA females) under promotions, an effect also present for males under no promotions. Thus, P3 indexed decisions to buy differently between anxiety groups, but only for promoted items among females and for no promotions among males. Our findings indicate that perceptual and conceptual processes interact with anxiety and gender to modulate brain responses during consumer choices.

  18. Calpain A modulates Toll responses by limited Cactus/IκB proteolysis

    PubMed Central

    Fontenele, Marcio; Lim, Bomyi; Oliveira, Danielle; Buffolo, Márcio; Perlman, David H.; Schupbach, Trudi; Araujo, Helena

    2013-01-01

    Calcium-dependent cysteine proteases of the calpain family are modulatory proteases that cleave their substrates in a limited manner. Among their substrates, calpains target vertebrate and invertebrate IκB proteins. Because proteolysis by calpains potentially generates novel protein functions, it is important to understand how this affects NFκB activity. We investigate the action of Calpain A (CalpA) on the Drosophila melanogaster IκB homologue Cactus in vivo. CalpA alters the absolute amounts of Cactus protein. Our data indicate, however, that CalpA uses additional mechanisms to regulate NFκB function. We provide evidence that CalpA interacts physically with Cactus, recognizing a Cactus pool that is not bound to Dorsal, a fly NFκB/Rel homologue. We show that proteolytic cleavage by CalpA generates Cactus fragments lacking an N-terminal region required for Toll responsiveness. These fragments are generated in vivo and display properties distinct from those of full-length Cactus. We propose that CalpA targets free Cactus, which is incorporated into and modulates Toll-responsive complexes in the embryo and immune system. PMID:23864715

  19. Alarmin’ Immunologists: IL-33 as a Putative Target for Modulating T Cell-Dependent Responses

    PubMed Central

    Gajardo Carrasco, Tania; Morales, Rodrigo A.; Pérez, Francisco; Terraza, Claudia; Yáñez, Luz; Campos-Mora, Mauricio; Pino-Lagos, Karina

    2015-01-01

    IL-33 is a known member of the IL-1 cytokine superfamily classically named “atypical” due to its diverse functions. The receptor for this cytokine is the ST2 chain (or IL-1RL1), part of the IL-1R family, and the accessory chain IL-1R. ST2 can be found as both soluble and membrane-bound forms, property that explains, at least in part, its wide range of functions. IL-33 has increasingly gained our attention as a potential target to modulate immune responses. At the beginning, it was known as one of the participants during the development of allergic states and other Th2-mediated responses and it is now accepted that IL-33 contributes to Th1-driven pathologies as demonstrated in animal models of experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis, and trinitrobenzene sulfonic acid-induced experimental colitis, among others. Interestingly, current data are placing IL-33 as a novel regulator of immune tolerance by affecting regulatory T cells (Tregs); although the mechanism is not fully understood, it seems that dendritic cells and myeloid suppressor-derived cells may be cooperating in the generation and/or establishment of IL-33-mediated tolerance. Here, we review the most updated literature on IL-33, its role on T cell biology, and its impact in immune tolerance. PMID:26082774

  20. Lanthionine Synthetase C-Like 2 Modulates Immune Responses to Influenza Virus Infection

    PubMed Central

    Leber, Andrew; Bassaganya-Riera, Josep; Tubau-Juni, Nuria; Zoccoli-Rodriguez, Victoria; Lu, Pinyi; Godfrey, Victoria; Kale, Shiv; Hontecillas, Raquel

    2017-01-01

    Broad-based, host-targeted therapeutics have the potential to ameliorate viral infections without inducing antiviral resistance. We identified lanthionine synthetase C-like 2 (LANCL2) as a new therapeutic target for immunoinflammatory diseases. To examine the therapeutic efficacy of oral NSC61610 administration on influenza, we infected C57BL/6 mice with influenza A H1N1pdm virus and evaluated influenza-related mortality, lung inflammatory profiles, and pulmonary histopathology. Oral treatment with NSC61610 ameliorates influenza virus infection by down-modulating pulmonary inflammation through the downregulation of TNF-α and MCP-1 and reduction in the infiltration of neutrophils. NSC61610 treatment increases IL10-producing CD8+ T cells and macrophages in the lungs during the resolution phase of disease. The loss of LANCL2 or neutralization of IL-10 in mice infected with influenza virus abrogates the ability of NSC61610 to accelerate recovery and induce IL-10-mediated regulatory responses. These studies validate that oral treatment with NSC61610 ameliorates morbidity and mortality and accelerates recovery during influenza virus infection through a mechanism mediated by activation of LANCL2 and subsequent induction of IL-10 responses by CD8+ T cells and macrophages in the lungs. PMID:28270815

  1. Capuchin monkeys (Cebus apella) modulate their use of an uncertainty response depending on risk.

    PubMed

    Beran, Michael J; Perdue, Bonnie M; Church, Barbara A; Smith, J David

    2016-01-01

    Metacognition refers to thinking about thinking, and there has been a great deal of interest in how this ability manifests across primates. Based on much of the work to date, a tentative division has been drawn with New World monkeys on 1 side and Old World monkeys and apes on the other. Specifically, Old World monkeys, apes, and humans often show patterns reflecting metacognition, but New World monkeys typically do not, or show less convincing behavioral patterns. However, recent data suggest that this difference may relate to other aspects of some experimental tasks. For example, 1 possibility is that risk tolerance affects how capuchin monkeys, a New World primate species, tend to perform. Specifically, it has recently been argued that on tasks in which there are 2 or 3 options, the "risk" of guessing is tolerable for capuchins because there is a high probability of being correct even if they "know they do not know" or feel something akin to uncertainty. The current study investigated this possibility by manipulating the degree of risk (2-choices vs. 6-choices) and found that capuchin monkeys used the uncertainty response more on 6-choice trials than on 2-choice trials. We also found that rate of reward does not appear to underlie these patterns of performance, and propose that the degree of risk is modulating capuchin monkeys' use of the uncertainty response. Thus, the apparent differences between New and Old World monkeys in metacognition may reflect differences in risk tolerance rather than access to metacognitive states.

  2. Binding Dynamics of Targeted Microbubbles in Response to Modulated Acoustic Radiation Force

    PubMed Central

    Wang, Shiying; Hossack, John A; Klibanov, Alexander L; Mauldin, F William

    2014-01-01

    Detection of molecular targeted microbubbles plays a foundational role in ultrasound-based molecular imaging and targeted gene or drug delivery. In this paper, an empirical model describing the binding dynamics of targeted microbubbles in response to modulated acoustic radiation forces in large vessels is presented and experimentally verified using tissue-mimicking flow phantoms. Higher flow velocity and microbubble concentration led to faster detaching rates for specifically bound microbubbles (p < 0.001). Higher time-averaged acoustic radiation force intensity led to faster attaching rates and a higher saturation level of specifically bound microbubbles (p < 0.05). The level of residual microbubble signal in targeted experiments after cessation of radiation forces was the only response parameter that was reliably different between targeted and control experiments (p < 0.05). A related parameter, the ratio of residual-to-saturated microbubble signal (Rresid), is proposed as a measurement that is independent of absolute acoustic signal magnitude and therefore able to reliably detect targeted adhesion independently of control measurements (p < 0.01). These findings suggest the possibility of enhanced detection of specifically bound microbubbles in real-time, using relatively short imaging protocols (approximately 3 min), without waiting for free microbubble clearance. PMID:24374866

  3. Modulation of Dendritic-Epithelial Cell Responses against Sphingomonas Paucimobilis by Dietary Fibers

    PubMed Central

    Bermudez-Brito, Miriam; Faas, Marijke M; de Vos, Paul

    2016-01-01

    Non-fermenting Gram-negative bacilli, such as Sphingomonas paucimobilis (S.paucimobilis), are among the most widespread causes of nosocomial infections. Up to now, no definitive guidelines exist for antimicrobial therapy for S. paucimobilis infections. As we have shown that some dietary fibers exhibit pronounced immune-regulatory properties, we hypothesized that specific immune active dietary fibers might modulate the responses against S. paucimobilis. We studied the immunomodulatory effects of dietary fibers against S. paucimobilis on cytokine release and maturation of human dendritic cells (DCs) in co-cultures of DCs and intestinal epithelial cells (IECs). S. paucimobilis infection resulted in increased release of pro-inflammatory cytokines and chemokines by DCs/IECs; these effects were strongly attenuated by specific dietary fibers. Chicory inulin, sugar beet pectin, and both starches had the strongest regulatory effects. IL-12 and TNF-α were drastically diminished upon exposure to chicory inulin and sugar beet pectin, or both starches. High-maize 260, was more effective in the reduction of chemokine release than the others fibers tested. In summary, chicory inulin, sugar beet pectin, High-maize 260, and Novelose 330 attenuate S. paucimobilis-induced cytokines. These results demonstrate that dietary fibers with a specific chemical composition can be used to manage immune responses against pathogens such as S. paucimobilis. PMID:27452116

  4. Octopamine and tyramine modulate the thermoregulatory fanning response in honey bees (Apis mellifera L.).

    PubMed

    Cook, Chelsea N; Brent, Colin S; Breed, Michael D

    2017-03-17

    Biogenic amines regulate the proximate mechanisms underlying most behavior, including those that contribute to the overall success of complex societies. For honey bees, one critical set of behaviors contributing to the welfare of a colony is involved with nest thermoregulation. Worker honeybees cool the colony by performing a fanning behavior, the expression of which is largely influenced by response thresholds modulated by the social environment. Here, we examined how changes in biogenic amines affect this group-performed thermoregulatory fanning behavior in honeybees. Concentrations of two biogenic amines, octopamine and tyramine, are significantly lower in active fanners than in non-fanners, but there is no difference in dopamine and serotonin. Direct feeding of octopamine and tyramine induced a decrease in fanning responses, but only when both amines were included in the treatment. This is the first evidence that fanning behavior is influenced by these two biogenic amines, and this result is consistent with the typical role of these neurotransmitters in regulating locomotor activity in other insects. Individual variation in amine expression also provides a mechanistic link that helps to explain how this group behavior might be coordinated within a colony.

  5. Sialylation of Helicobacter bizzozeronii lipopolysaccharides modulates Toll-like receptor (TLR) 2 mediated response.

    PubMed

    Kondadi, Pradeep Kumar; Revez, Joana; Hänninen, Marja-Liisa; Rossi, Mirko

    2015-01-21

    Sialic acid in lipopolysaccharides (LPS) of mucosal pathogens is known to be an important virulence factor. Few strains of Helicobacter pylori express sialyl-Lewis-X and we have reported that human and canine Helicobacter bizzozeronii strains express sialyl-lactoseamine in their LPS. However, the role of sialyation of Helicobacter LPS in the interaction with the host cells is still unknown. In this study H. bizzozeronii LPS is shown to activate the TLR2 in a dose and strain dependent manner in the in vitro HEK-293 cells model expressing TLR2, but not the cells expressing TLR4. These results indicate that TLR2 is the specific receptor for H. bizzozzeronii LPS, as previously described for H. pylori. To further explore the role of sialylation of H. bizzozeronii LPS on TLR2 response, H. bizzozeronii Δhbs2 mutant strains deficient in sialyltransferase activity were constructed by homologous recombination. LPS from H. bizzozeronii Δhbs2 strains enhanced the NF-ĸB induction via TLR2 compared to the respective wild types, leading to the conclusion that the sialylation of H. bizzozeronii LPS in wild-type strains may modulate host immune response.

  6. HIV-1 Tat modulates T-bet expression and induces Th1 type of immune response

    SciTech Connect

    Kulkarni, Asavari; Ravi, Dyavar S.; Singh, Kamini; Rampalli, Shravanti; Parekh, Vrajesh; Mitra, Debashis; Chattopadhyay, Samit . E-mail: samit@nccs.res.in

    2005-04-08

    The HIV-1 transactivator Tat performs various viral and cellular functions. Primarily, it induces processive transcription from the HIV-1 LTR promoter. However, Tat secreted from infected cells is known to activate uninfected lymphocytes through receptors. To further delineate the specific target genes, extracellular Tat was expressed on the cell membrane of stimulator cells and co-cultured with human PBMCs. Along with induced CD4{sup +} T cell proliferation and IFN-{gamma} secretion, there was strong upregulation of T-bet expression which is majorly implicated in generating T{sub H}1 type of immune response. To further delineate the effect of extracellular Tat on HIV replication, both p24 analysis and in vivo GFP expression were performed. There was a significant inhibition of HIV-1 replication in human CEM-GFP cell line and hPBMCs. Thus, for the first time we report that apart from its transactivation activity, extracellular Tat acts as a costimulatory molecule that affects viral replication by modulating host immune response through induction of T-bet expression and IFN-{gamma} secretion.

  7. Like or dislike? Affective preference modulates neural response to others' gains and losses.

    PubMed

    Wang, Yang; Qu, Chen; Luo, Qiuling; Qu, Lulu; Li, Xuebing

    2014-01-01

    Previous studies have demonstrated that the brain responds differentially to others' gains and losses relative to one's own, moderated by social context factors such as competition and interpersonal relationships. In the current study, we tested the hypothesis that the neural response to others' outcomes could be modulated by a short-term induced affective preference. We engaged 17 men and 18 women in a social-exchange game, in which two confederates played fairly or unfairly. Both men and women rated the fair player as likable and the unfair players as unlikable. Afterwards, ERPs were recorded while participants observed each confederates playing a gambling game individually. This study examines feedback related negativity (FRN), an ERP component sensitive to negative feedback. ANOVA showed a significant interaction in which females but not males displayed stronger FRNs when observing likable players' outcomes compared to unlikable ones'. However, males did not respond differently under either circumstance. These findings suggest that, at least in females, the neural response is influenced by a short-term induced affective preference.

  8. (Still) longing for food: insulin reactivity modulates response to food pictures.

    PubMed

    Kroemer, Nils B; Krebs, Lena; Kobiella, Andrea; Grimm, Oliver; Vollstädt-Klein, Sabine; Wolfensteller, Uta; Kling, Ricarda; Bidlingmaier, Martin; Zimmermann, Ulrich S; Smolka, Michael N

    2013-10-01

    Overweight and obesity pose serious challenges to public health and are promoted by our food-rich environment. We used functional magnetic resonance imaging (fMRI) to investigate reactivity to food cues after overnight fasting and following a standardized caloric intake (i.e., a 75 g oral glucose tolerance test, OGTT) in 26 participants (body mass index, BMI between 18.5 and 24.9 kg m(-2)). They viewed pictures of palatable food and low-level control stimuli in a block design and rated their current appetite after each block. Compared to control pictures, food pictures activated a large bilateral network typically involved in homeostatically and hedonically motivated food processing. Glucose ingestion was followed by decreased activation in the basal ganglia and paralimbic regions and increased activation in parietal and occipital regions. Plasma level increases in insulin correlated with cue-induced appetite at the neural and behavioral level. High insulin increases were associated with reduced activation in various bilateral regions including the fusiform gyrus, the superior temporal gyrus, the medial frontal gyrus, and the limbic system in the right hemisphere. In addition, they were accompanied by lower subjective appetite ratings following food pictures and modulated the neural response associated with it (e.g., in the fusiform gyrus). We conclude that individual insulin reactivity is critical to reduce food-cue responsivity after an initial energy intake and thereby may help to counteract overeating.

  9. Psychopathic traits modulate brain responses to drug cues in incarcerated offenders

    PubMed Central

    Cope, Lora M.; Vincent, Gina M.; Jobelius, Justin L.; Nyalakanti, Prashanth K.; Calhoun, Vince D.; Kiehl, Kent A.

    2014-01-01

    Recent neuroscientific evidence indicates that psychopathy is associated with abnormal function and structure in limbic and paralimbic areas. Psychopathy and substance use disorders are highly comorbid, but clinical experience suggests that psychopaths abuse drugs for different reasons than non-psychopaths, and that psychopaths do not typically experience withdrawal and craving upon becoming incarcerated. These neurobiological abnormalities may be related to psychopaths' different motivations for—and symptoms of—drug use. This study examined the modulatory effect of psychopathic traits on the neurobiological craving response to pictorial drug stimuli. Drug-related pictures and neutral pictures were presented and rated by participants while hemodynamic activity was monitored using functional magnetic resonance imaging. These data were collected at two correctional facilities in New Mexico using the Mind Research Network mobile magnetic resonance imaging system. The sample comprised 137 incarcerated adult males and females (93 females) with histories of substance dependence. The outcome of interest was the relation between psychopathy scores (using the Hare Psychopathy Checklist-Revised) and hemodynamic activity associated with viewing drug-related pictures vs. neutral pictures. There was a negative association between psychopathy scores and hemodynamic activity for viewing drug-related cues in the anterior cingulate, posterior cingulate, hippocampus, amygdala, caudate, globus pallidus, and parts of the prefrontal cortex. Psychopathic traits modulate the neurobiological craving response and suggest that individual differences are important for understanding and treating substance abuse. PMID:24605095

  10. Rapid Curtailing of the Stringent Response by Toxin-Antitoxin Module-Encoded mRNases

    PubMed Central

    Tian, Chengzhe; Roghanian, Mohammad; Jørgensen, Mikkel Girke; Sneppen, Kim; Sørensen, Michael Askvad; Gerdes, Kenn

    2016-01-01

    ABSTRACT Escherichia coli regulates its metabolism to adapt to changes in the environment, in particular to stressful downshifts in nutrient quality. Such shifts elicit the so-called stringent response, coordinated by the alarmone guanosine tetra- and pentaphosphate [(p)ppGpp]. On sudden amino acid (aa) starvation, RelA [(p)ppGpp synthetase I] activity is stimulated by binding of uncharged tRNAs to a vacant ribosomal site; the (p)ppGpp level increases dramatically and peaks within the time scale of a few minutes. The decrease of the (p)ppGpp level after the peak is mediated by the decreased production of mRNA by (p)ppGpp-associated transcriptional regulation, which reduces the vacant ribosomal A site and thus constitutes negative feedback to the RelA-dependent (p)ppGpp synthesis. Here we showed that on sudden isoleucine starvation, this peak was higher in an E. coli strain that lacks the 10 known mRNase-encoding toxin-antitoxin (TA) modules present in the wild-type (wt) strain. This observation suggested that toxins are part of the negative-feedback mechanism to control the (p)ppGpp level during the early stringent response. We built a ribosome trafficking model to evaluate the fold increase in RelA activity just after the onset of aa starvation. Combining this with a feedback model between the (p)ppGpp level and the mRNA level, we obtained reasonable fits to the experimental data for both strains. The analysis revealed that toxins are activated rapidly, within a minute after the onset of starvation, reducing the mRNA half-life by ∼30%. IMPORTANCE The early stringent response elicited by amino acid starvation is controlled by a sharp increase of the cellular (p)ppGpp level. Toxin-antitoxin module-encoded mRNases are activated by (p)ppGpp through enhanced degradation of antitoxins. The present work shows that this activation happens over a very short time scale and that the activated mRNases negatively affect the (p)ppGpp level. The proposed mathematical model of

  11. The presence of primary cilia in cancer cells does not predict responsiveness to modulation of smoothened activity.

    PubMed

    Spann, Ashley L; Yuan, Kun; Goliwas, Kayla F; Steg, Adam D; Kaushik, Devanshu D; Kwon, Yeon-Jin; Frost, Andra R

    2015-07-01

    Primary cilia are microtubule-based organelles that regulate smoothened-dependent activation of the GLI transcription factors in canonical hedgehog signaling. In many cancers, primary cilia are markedly decreased or absent. The lack of primary cilia may inhibit or alter canonical hedgehog signaling and, thereby, interfere in the cellular responsiveness to modulators of smoothened activity. Clinical trials of smoothened antagonists for cancer treatment have shown the best response in basal cell carcinomas, with limited response in other solid tumors. To determine whether the presence or absence of primary cilia in cancer cells will predict their responsiveness to modulation of smoothened activity, we compared the ability of an agonist and/or inhibitor of smoothened (SAG and SANT1, respectively) to modulate GLI-mediated transcription, as measured by GLI1 mRNA level or GLI-luciferase reporter activity, in non-cancer cells with primary cilia (ovarian surface epithelial cells and breast fibroblasts), in cancer cells that cannot assemble primary cilia (MCF7, MDA-MB-231 cell lines), and in cancer cells with primary cilia (SKOV3, PANC1 cell lines). As expected, SAG and SANT1 resulted in appropriate modulation of GLI transcriptional activity in ciliated non-cancer cells, and failed to modulate GLI transcriptional activity in cancer cells without primary cilia. However, there was also no modulation of GLI transcriptional activity in either ciliated cancer cell line. SAG treatment of SKOV3 induced localization of smoothened to primary cilia, as assessed by immunofluorescence, even though there was no increase in GLI transcriptional activity, suggesting a defect in activation of SMO in the primary cilia or in steps later in the hedgehog pathway. In contrast to SKOV3, SAG treatment of PANC1 did not cause the localization of smoothened to primary cilia. Our data demonstrate that the presence of primary cilia in the cancer epithelial cells lines tested does not indicate their

  12. Die kalte Zunge

    NASA Astrophysics Data System (ADS)

    Bartels, Sören; Müller, Rüdiger

    Gefühlte Temperaturen. Ist ein Null Grad Celsius kalter Metallstab eigentlich kälter als ein Holzstab mit der selben Temperatur? Rein physikalisch gesehen natürlich nicht, aber wenn wir beide Stäbe anfassen, kommt uns der Metallstab deutlich kälter vor. Und wer kennt nicht die Szene aus dem Film Dumm und Dümmer in der Harry mit seiner Zunge am Metallrahmen des Skilifts hängen bleibt.Würde das auch passieren, wenn man an einem eiskalten Stück Holz lecken würde? Wohl kaum, doch woran liegt das eigentlich? Unterschiedliche Materialien haben verschiedene Fähigkeiten, Wärme zu übertragen und zu leiten. So transportiert Metall die von der Zunge ausgehende Wärme sehr schnell weiter und verändert seine Temperatur kaum, während die Zunge abkühlt. Holz hingegen leitet Wärme fast gar nicht und daher wird der Teil, der von der Zunge berührt wird, aufgewärmt.

  13. Lactobacillus acidophilus and L. reuteri modulate cytokine responses in gnotobiotic pigs infected with human rotavirus

    PubMed Central

    Azevedo, M. S. P.; Zhang, W.; Wen, K.; Gonzalez, A. M.; Saif, L. J.; Yousef, A. E.; Yuan, L.

    2012-01-01

    Probiotic lactic acid bacteria (LAB) have been shown to alleviate inflammation, enhance the immunogenicity of rotavirus vaccines, or reduce the severity of rotavirus diarrhoea. Although the mechanisms are not clear, the differential Th1/Th2/Th3-driving capacities and modulating effects on cytokine production of different LAB strains may be the key. Our goal was to delineate the influence of combining two probiotic strains L. acidophilus and L. reuteri on the development of cytokine responses in neonatal gnotobiotic pigs infected with human rotavirus (HRV). We demonstrated that HRV alone, or HRV plus LAB, but not LAB alone, initiated serum cytokine responses, as indicated by significantly higher concentrations of IFN-α, IFN-γ, IL-12, and IL-10 at post-inoculation day (PID) 2 in the HRV only and LAB+HRV+ pigs compared to LAB only and LAB-HRV- pigs. Peak cytokine responses coincided with the peak of HRV replication. LAB further enhanced the Th1 and Th2 cytokine responses to HRV infection as indicated by significantly higher concentrations of IL-12, IFN-γ, IL-4 and IL-10 in the LAB+HRV+ pigs compared to the LAB-HRV+ pigs. The LAB+HRV+ pigs maintained relatively constant concentrations of TGF-β compared to the HRV only group which had a significant increase at PID 2 and decrease at PID 7, suggesting a regulatory role of LAB in maintaining gut homeostasis. At PID 28, cytokine secreting cell (CSC) responses, measured by ELISpot, showed increased Th1 (IL-12, IFN-γ) CSC numbers in the LAB+HRV+ and LAB-HRV+ groups compared to LAB only and LAB-HRV- pigs, with significantly increased IL-12 CSCs in spleen and PBMCs and IFN-γ CSCs in spleen of the LAB+HRV+ group. Thus, HRV infection alone, but not LAB alone was effective in inducing cytokine responses but LAB significantly enhanced both Th1 and Th2 cytokines in HRV-infected pigs. LAB may also help to maintain immunological homeostasis during HRV infection by regulating TGF-β production. PMID:22348907

  14. Heated die facilitates tungsten forming

    NASA Technical Reports Server (NTRS)

    Chattin, J. H.; Haystrick, J. E.; Laughlin, J. C.; Leidy, R. A.

    1966-01-01

    Tungsten forming in a press brake employs a bottom die assembly with a heating manifold between two water-cooled die sections. The manifold has hydrogen-oxygen burners spaced along its length for even heat during forming.

  15. Dynamic Modulation of Myelination in Response to Visual Stimuli Alters Optic Nerve Conduction Velocity

    PubMed Central

    Etxeberria, Ainhoa; Hokanson, Kenton C.; Dao, Dang Q.; Mayoral, Sonia R.; Mei, Feng; Redmond, Stephanie A.; Ullian, Erik M.

    2016-01-01

    Myelin controls the time required for an action potential to travel from the neuronal soma to the axon terminal, defining the temporal manner in which information is processed within the CNS. The presence of myelin, the internodal length, and the thickness of the myelin sheath are powerful structural factors that control the velocity and fidelity of action potential transmission. Emerging evidence indicates that myelination is sensitive to environmental experience and neuronal activity. Activity-dependent modulation of myelination can dynamically alter action potential conduction properties but direct functional in vivo evidence and characterization of the underlying myelin changes is lacking. We demonstrate that in mice long-term monocular deprivation increases oligodendrogenesis in the retinogeniculate pathway but shortens myelin internode lengths without affecting other structural properties of myelinated fibers. We also demonstrate that genetically attenuating synaptic glutamate neurotransmission from retinal ganglion cells phenocopies the changes observed after monocular deprivation, suggesting that glutamate may constitute a signal for myelin length regulation. Importantly, we demonstrate that visual deprivation and shortened internodes are associated with a significant reduction in nerve conduction velocity in the optic nerve. Our results reveal the importance of sensory input in the building of myelinated fibers and suggest that this activity-dependent alteration of myelination is important for modifying the conductive properties of brain circuits in response to environmental experience. SIGNIFICANCE STATEMENT Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are capable of ensheathing axons with myelin without molecular cues from neurons. However, this default myelination process can be modulated by changes in neuronal activity. Here, we show, for the first time, that experience-dependent activity modifies the length of myelin

  16. Effects of herbal medicinal formulas on suppressing viral replication and modulating immune responses.

    PubMed

    Liao, Hui-Fen; Lu, Min-Chi; Chang, Hon-Chou; Wei, Cheng-Chung; Kao, Chih-Hsiung; Chen, Zong-Huei; Huang, Chin-Chin; Li, Ching

    2010-01-01

    The Chinese medicinal herbs Radix Isatidis and Viola yedoensis Makino have been suggested to possess antiviral activity. This study tests whether these and other Chinese and Western herbal medicinal formulas can modulate the immune functions involving virus-suppression in BALB/c mouse. We first confirmed the extract from Viola yedoensis Makino, but not from Radix Isatidis, the traditional Chinese medicine (TCM) formula Chui-Uren-Chien (CUC), or a Western homeopathic medicinal drink Método Canova, could inhibit the replications of herpes simplex virus-1 and enterovirus 71 in the human neuroblastoma SK-N-SH cell line. Subsequently, the same herbal extracts and drink underwent toxicity and immunomodulatory tests on mice of 5-7 weeks old. After 8 weeks of feeding different herbal medicinal formulas, no hepatic or renal toxicity was noted in any tested animal; whereas among the immune function evaluations, only the mice treated with CUC extract were found to be associated with significant increases (p < 0.05) in both the level of plasma IgG and the percentage of monocyte in blood mononuclear cells as well as the activation of macrophage Raw264.7 cells for nitric oxide production, suggesting its role in modulating the non-specific immune response. Analyses using protein arrays showed CUC was the most potent herbal medicinal formula eliciting fluctuations in plasma cytokine and chemokine concentrations. Taking all experimental data together, we conclude Chui-Uren-Chien possesses immunomodulatory capability in mouse, but none of the herbal medicinal formulas tested here are involved in strengthening antiviral immunity.

  17. Neuroticism modulates the effects of intranasal vasopressin treatment on the neural response to positive and negative social interactions.

    PubMed

    Feng, Chunliang; DeMarco, Ashley C; Haroon, Ebrahim; Rilling, James K

    2015-07-01

    Neuroticism is a fundamental personality trait associated with proneness to feel negative affect. Here we ask how Neuroticism influences the neural response to positive and negative social interactions and how Neuroticism modulates the effect of intranasal oxytocin (OT) and vasopressin (AVP) on the neural response to social interactions. In a double-blind, placebo-controlled study, 153 male participants were randomized to receive 24 IU intranasal OT, 20 IU AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner's Dilemma Game. On a different day, subjects completed the NEO personality inventory to measure Neuroticism. Neuroticism was positively correlated with the neural response to negative social interactions in the anterior cingulate cortex/medial prefrontal cortex and with the neural response to positive social interactions in the insula, indicating that Neuroticism modulates neuropsychological processing of both negative and positive social interactions. Neuroticism did not modulate the effect of intranasal OT treatment on the neural response to either positive or negative social interactions. On the other hand, AVP treatment significantly interacted with Neuroticism to modulate the BOLD response to both positive and negative social interactions. Specifically, AVP increased anterior cingulate cortex/medial prefrontal cortex and lateral temporal lobe responses to negative social interactions to a greater extent in participants scoring high rather than low on Neuroticism. AVP also increased the insula response to positive social interactions to a greater extent in participants scoring high rather than low on Neuroticism. These results imply that AVP may increase emotion regulation in response to negative social interactions and the salience of positive social interactions to a greater extent in individuals high compared to low in Neuroticism. The current findings urge caution against uniform clinical application of nonapeptides

  18. Designing a Die for Hydroforming

    NASA Astrophysics Data System (ADS)

    Vasile, Radu

    2016-12-01

    Designing a die is in every application field an intensive process of bringing together know how from design, testing and every-day use from previous dies with the new application requirements. Contribution deals with a knowledge oriented, modular and feature integrated computer aided design system for die development. This paper describes the concepts behind designing a hydroforming die for sheet metal forming, with easy application-use in small workshops for testing hydroforming capabilities of different materials.

  19. Only signaling modules that discriminate sharply between stimulatory and nonstimulatory inputs require basal signaling for fast cellular responses

    NASA Astrophysics Data System (ADS)

    Artomov, Mykyta; Kardar, Mehran; Chakraborty, Arup K.

    2010-09-01

    In many types of cells, binding of molecules to their receptors enables cascades of intracellular chemical reactions to take place (signaling). However, a low level of signaling also occurs in most unstimulated cells. Such basal signaling in resting cells can have many functions, one of which is that it is thought to be required for fast cellular responses to external stimuli. A mechanistic understanding of why this is true and which features of cellular signaling networks make basal signaling necessary for fast responses is unknown. We address this issue by obtaining the time required for activation of common types of cell signaling modules with and without basal signaling. Our results show that the absence of basal signaling does not have any dramatic effects on the response time for signaling modules that exhibit a graded response to increasing stimulus levels. In sharp contrast, signaling modules that exhibit sharp dose-response curves which discriminate sensitively between stimuli to which the cell needs to respond and low-grade inputs (or stochastic noise) require basal signaling for fast cellular responses. In such cases, we find that an optimal level of basal signaling balances the requirements for fast cellular responses while minimizing spurious activation without appropriate stimulation.

  20. Soluble guanylate cyclase modulators blunt hyperoxia effects on calcium responses of developing human airway smooth muscle.

    PubMed

    Britt, Rodney D; Thompson, Michael A; Kuipers, Ine; Stewart, Alecia; Vogel, Elizabeth R; Thu, James; Martin, Richard J; Pabelick, Christina M; Prakash, Y S

    2015-09-15

    Exposure to moderate hyperoxia in prematurity contributes to subsequent airway dysfunction and increases the risk of developing recurrent wheeze and asthma. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic GMP (cGMP) axis modulates airway tone by regulating airway smooth muscle (ASM) intracellular Ca(2+) ([Ca(2+)]i) and contractility. However, the effects of hyperoxia on this axis in the context of Ca(2+)/contractility are not known. In developing human ASM, we explored the effects of novel drugs that activate sGC independent of NO on alleviating hyperoxia (50% oxygen)-induced enhancement of Ca(2+) responses to bronchoconstrictor agonists. Treatment with BAY 41-2272 (sGC stimulator) and BAY 60-2770 (sGC activator) increased cGMP levels during exposure to 50% O2. Although 50% O2 did not alter sGCα1 or sGCβ1 expression, BAY 60-2770 did increase sGCβ1 expression. BAY 41-2272 and BAY 60-2770 blunted Ca(2+) responses to histamine in cells exposed to 50% O2. The effects of BAY 41-2272 and BAY 60-2770 were reversed by protein kinase G inhibition. These novel data demonstrate that BAY 41-2272 and BAY 60-2770 stimulate production of cGMP and blunt hyperoxia-induced increases in Ca(2+) responses in developing ASM. Accordingly, sGC stimulators/activators may be a useful therapeutic strategy in improving bronchodilation in preterm infants.

  1. Enhancing Perception of Contaminated Food through Acid-Mediated Modulation of Taste Neuron Responses

    PubMed Central

    Chen, Yan; Amrein, Hubert

    2015-01-01

    SUMMARY Background Natural foods not only contain nutrients, but also non-nutritious and potentially harmful chemicals. Thus, animals need to evaluate food content in order to make adequate feeding decisions. Results Here, we investigate the effects of acids on the taste neuron responses and on taste behavior of desirable, nutritious sugars and sugar/bitter compound mixtures in Drosophila melanogaster. Using Ca2+ imaging, we show that acids neither activate sweet nor bitter taste neurons in tarsal taste sensilla. However, they suppress responses to bitter compounds in bitter-sensing neurons. Moreover, acids reverse suppression of bitter compounds exerted on sweet-sensing neurons. Consistent with these observations, behavioral analyses show that bitter compound-mediated inhibition on feeding behavior is alleviated by acids. To investigate the cellular mechanism by which acids modulate these effects, we silenced bitter sensing gustatory neurons. Surprisingly, this intervention had little effect on acid-mediated de-repression of sweet neuron or feeding responses to either sugar/bitter compound mixtures, or sugar/bitter compound/acid mixtures, suggesting two independent pathways by which bitter compounds are sensed. Conclusions Our investigations reveal that acids, when presented in dietary relevant concentrations, enhance the perception of sugar/bitter compound mixtures. Drosophila’s natural food sources - fruits and cohabitating yeast - are rich in sugars and acids, but are rapidly colonized by microorganisms, such as fungi, protozoan parasites and bacteria, many of which produce bitter compounds. We propose that acids present in most fruits counteract the inhibitory effects of these bitter compounds during feeding. PMID:25131671

  2. Modulation of porcine intestinal epitheliocytes immunetranscriptome response by Lactobacillus jensenii TL2937.

    PubMed

    Kobayashi, H; Albarracin, L; Sato, N; Kanmani, P; Kober, A K M H; Ikeda-Ohtsubo, W; Suda, Y; Nochi, T; Aso, H; Makino, S; Kano, H; Ohkawara, S; Saito, T; Villena, J; Kitazawa, H

    2016-11-30

    In order to evaluate probiotic strains applicable for the beneficial immunomodulation of the porcine gut (immunobiotics), we previously developed a porcine intestinal epitheliocyte cell line (PIE cells). Here, transcriptomic studies using PIE cells were performed considering that this information would be valuable for understanding the mechanisms involved in the protective activity of the immunobiotic strain Lactobacillus jensenii TL2937 against intestinal inflammatory damage in pigs. In addition, those studies would provide criteria for selecting biomarkers for the screening of new immunobiotic strains. We performed microarray analysis to investigate the transcriptomic response of PIE cells to the challenge with heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs) and, the changes induced by L. jensenii TL2937 in that response. The approach allowed us to obtain a global overview of the immune genes involved in the response of PIE cells to heat-stable ETEC PAMPs. We observed that L. jensenii TL2937 differently modulated gene expression in ETEC PAMPs-challenged PIE cells. Microarray and RT-PCR analysis indicated that the most remarkable changes in PIE cells transcriptomic profile after heat-stable ETEC PAMPs challenge were observed in chemokines, adhesion molecules, complement and coagulation cascades factors. In addition, an anti-inflammatory effect triggered by TL2937 strain in PIE cells was clearly demonstrated. The decrease in the expression of chemokines (CCL8, CXCL5, CXCL9, CXCL10, and CXCL11), complement (C1R, C1S, C3, and CFB), and coagulation factors (F3) by L. jensenii TL2937 supports our previous reports on the immunoregulatory effect of this strain. These results provided clues for the better understanding of the mechanism underlying host-immunobiotic interaction in the porcine host. The comprehensive transcriptomic profiles of PIE cells provided by our analyses successfully identified a group of genes, which

  3. Social stress modulates the cortisol response to an acute stressor in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Jeffrey, J D; Gollock, M J; Gilmour, K M

    2014-01-15

    In rainbow trout (Oncorhynchus mykiss) of subordinate social status, circulating cortisol concentrations were elevated under resting conditions but the plasma cortisol and glucose responses to an acute stressor (confinement in a net) were attenuated relative to those of dominant trout. An in vitro head kidney preparation, and analysis of the expression of key genes in the stress axis prior to and following confinement in a net were then used to examine the mechanisms underlying suppression of the acute cortisol stress response in trout experiencing chronic social stress. With porcine adrenocorticotropic hormone (ACTH) as the secretagogue, ACTH-stimulated cortisol production was significantly lower for head kidney preparations from subordinate trout than for those from dominant trout. Dominant and subordinate fish did not, however, differ in the relative mRNA abundance of melanocortin-2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) or cytochrome P450 side chain cleavage enzyme (P450scc) within the head kidney, although the relative mRNA abundance of these genes was significantly higher in both dominant and subordinate fish than in sham trout (trout that did not experience social interactions but were otherwise treated identically to the dominant and subordinate fish). The relative mRNA abundance of all three genes was significantly higher in trout exposed to an acute net stressor than under control conditions. Upstream of cortisol production in the stress axis, plasma ACTH concentrations were not affected by social stress, nor was the relative mRNA abundance of the binding protein for corticotropin releasing factor (CRF-BP). The relative mRNA abundance of CRF in the pre-optic area of subordinate fish was significantly higher than that of dominant or sham fish 1h after exposure to the stressor. Collectively, the results indicate that chronic social stress modulates cortisol production at the level of the interrenal cells, resulting in an attenuated

  4. Auxin and Ethylene Response Interactions during Arabidopsis Root Hair Development Dissected by Auxin Influx Modulators

    PubMed Central

    Rahman, Abidur; Hosokawa, Satoko; Oono, Yutaka; Amakawa, Taisaku; Goto, Nobuharu; Tsurumi, Seiji

    2002-01-01

    The plant hormones auxin and ethylene have been shown to play important roles during root hair development. However, cross talk between auxin and ethylene makes it difficult to understand the independent role of either hormone. To dissect their respective roles, we examined the effects of two compounds, chromosaponin I (CSI) and 1-naphthoxyacetic acid (1-NOA), on the root hair developmental process in wild-type Arabidopsis, ethylene-insensitive mutant ein2-1, and auxin influx mutants aux1-7, aux1-22, and double mutant aux1-7 ein2. β-Glucuronidase (GUS) expression analysis in the BA-GUS transgenic line, consisting of auxin-responsive domains of PS-IAA4/5 promoter and GUS reporter, revealed that 1-NOA and CSI act as auxin uptake inhibitors in Arabidopsis roots. The frequency of root hairs in ein2-1 roots was greatly reduced in the presence of CSI or 1-NOA, suggesting that endogenous auxin plays a critical role for the root hair initiation in the absence of an ethylene response. All of these mutants showed a reduction in root hair length, however, the root hair length could be restored with a variable concentration of 1-naphthaleneacetic acid (NAA). NAA (10 nm) restored the root hair length of aux1 mutants to wild-type level, whereas 100 nm NAA was needed for ein2-1 and aux1-7 ein2 mutants. Our results suggest that insensitivity in ethylene response affects the auxin-driven root hair elongation. CSI exhibited a similar effect to 1-NOA, reducing root hair growth and the number of root hair-bearing cells in wild-type and ein2-1 roots, while stimulating these traits in aux1-7and aux1-7ein2 roots, confirming that CSI is a unique modulator of AUX1. PMID:12481073

  5. Auxin and ethylene response interactions during Arabidopsis root hair development dissected by auxin influx modulators.

    PubMed

    Rahman, Abidur; Hosokawa, Satoko; Oono, Yutaka; Amakawa, Taisaku; Goto, Nobuharu; Tsurumi, Seiji

    2002-12-01

    The plant hormones auxin and ethylene have been shown to play important roles during root hair development. However, cross talk between auxin and ethylene makes it difficult to understand the independent role of either hormone. To dissect their respective roles, we examined the effects of two compounds, chromosaponin I (CSI) and 1-naphthoxyacetic acid (1-NOA), on the root hair developmental process in wild-type Arabidopsis, ethylene-insensitive mutant ein2-1, and auxin influx mutants aux1-7, aux1-22, and double mutant aux1-7 ein2. Beta-glucuronidase (GUS) expression analysis in the BA-GUS transgenic line, consisting of auxin-responsive domains of PS-IAA4/5 promoter and GUS reporter, revealed that 1-NOA and CSI act as auxin uptake inhibitors in Arabidopsis roots. The frequency of root hairs in ein2-1 roots was greatly reduced in the presence of CSI or 1-NOA, suggesting that endogenous auxin plays a critical role for the root hair initiation in the absence of an ethylene response. All of these mutants showed a reduction in root hair length, however, the root hair length could be restored with a variable concentration of 1-naphthaleneacetic acid (NAA). NAA (10 nM) restored the root hair length of aux1 mutants to wild-type level, whereas 100 nM NAA was needed for ein2-1 and aux1-7 ein2 mutants. Our results suggest that insensitivity in ethylene response affects the auxin-driven root hair elongation. CSI exhibited a similar effect to 1-NOA, reducing root hair growth and the number of root hair-bearing cells in wild-type and ein2-1 roots, while stimulating these traits in aux1-7and aux1-7ein2 roots, confirming that CSI is a unique modulator of AUX1.

  6. Membrane-associated HB-EGF modulates HGF-induced cellular responses in MDCK cells.

    PubMed

    Singh, Amar B; Tsukada, Toshiaki; Zent, Roy; Harris, Raymond C

    2004-03-15

    In MDCK cells, hepatocyte growth factor/scatter factor (HGF/SF) induces epithelial cell dissociation, scattering, migration, growth and formation of branched tubular structures. By contrast, these cells neither scatter nor form tubular structures in response to the epidermal growth factor (EGF) family of growth factors. Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors and is synthesized as a membrane-associated precursor molecule (proHB-EGF). ProHB-EGF is proteolytically cleaved to release a soluble ligand (sHB-EGF) that activates the EGF receptor. Although recent studies suggest possible physiological functions, the role of proHB-EGF remains largely undefined. Using MDCK cells stably expressing proHB-EGF, a noncleavable deletion mutant of proHB-EGF or soluble HB-EGF, we show that epithelial cell functions differ depending on the form of HB-EGF being expressed. Expression of noncleavable membrane-anchored HB-EGF promoted cell-matrix and cell-cell interactions and decreased cell migration, HGF/SF-induced cell scattering and formation of tubular structures. By contrast, expression of soluble HB-EGF induced increased cell migration, decreased cell-matrix and cell-cell interactions and promoted the development of long unbranched tubular structures in response to HGF/SF. These findings suggest that HB-EGF can not only modulate HGF/SF-induced cellular responses in MDCK cells but also that membrane-bound HB-EGF and soluble HB-EGF give rise to distinctly different effects on cell-cell and cell-extracellular matrix interactions.

  7. Glucocorticoids and protein kinase A coordinately modulate transcription factor recruitment at a glucocorticoid-responsive unit.

    PubMed Central

    Espinás, M L; Roux, J; Pictet, R; Grange, T

    1995-01-01

    The rat tyrosine aminotransferase gene is a model system to study transcriptional regulation by glucocorticoid hormones. We analyzed transcription factor binding to the tyrosine aminotransferase gene glucocorticoid-responsive unit (GRU) at kb -2.5, using in vivo footprinting studies with both dimethyl sulfate and DNase I. At this GRU, glucocorticoid activation triggers a disruption of the nucleosomal structure. We show here that various regulatory pathways affect transcription factor binding to this GRU. The binding differs in two closely related glucocorticoid-responsive hepatoma cell lines. In line H4II, glucocorticoid induction promotes the recruitment of hepatocyte nuclear factor 3 (HNF3), presumably through the nucleosomal disruption. However, the footprint of the glucocorticoid receptor (GR) is not visible, even though a regular but transient interaction of the GR is necessary to maintain HNF3 binding. In contrast, in line FTO2B, HNF3 binds to the GRU in the absence of glucocorticoids and nucleosomal disruption, showing that a "closed" chromatin conformation does not repress the binding of certain transcription factors in a uniform manner. In FTO2B cells, the footprint of the GR is detectable, but this requires the activation of protein kinase A. In addition, protein kinase A stimulation also improves the recruitment of HNF3 independently of glucocorticoids and enhances the glucocorticoid response mediated by this GRU in an HNF3-dependent manner. In conclusion, the differences in the behavior of this regulatory sequence in the two cell lines show that various regulatory pathways are integrated at this GRU through modulation of interrelated events: transcription factor binding to DNA and nucleosomal disruption. PMID:7565684

  8. Clinical response of advanced cancer patients to cellular immunotherapy and intensity-modulated radiation therapy

    PubMed Central

    Hasumi, Kenichiro; Aoki, Yukimasa; Wantanabe, Ryuko; Mann, Dean L

    2013-01-01

    Patients afflicted with advanced cancers were treated with the intratumoral injection of autologous immature dendritic cells (iDCs) followed by activated T-cell infusion and intensity-modulated radiation therapy (IMRT). A second round of iDCs and activated T cells was then administered to patients after the last radiation cycle. This complete regimen was repeated for new and recurring lesions after 6 weeks of follow-up. One year post therapy, outcome analyses were performed to evaluate treatment efficacy. Patients were grouped according to both the number and size of tumors and clinical parameters at treatment initiation, including recurrent disease after standard cancer therapy, Stage IV disease, and no prior therapy. Irrespective of prior treatment status, 23/37 patients with ≤ 5 neoplastic lesions that were ≤ 3 cm in diameter achieved complete responses (CRs), and 5/37 exhibited partial responses (PRs). Among 130 individuals harboring larger and more numerous lesions, CRs were observed in 7/74 patients that had received prior SCT and in 2/56 previously untreated patients. Some patients manifested immune responses including an increase in CD8+CD56+ lymphocytes among circulating mononuclear cells in the course of treatment. To prospectively explore the therapeutic use of these cells, CD8+ cells were isolated from patients that had been treated with cellular immunotherapy and IMRT, expanded in vitro, and injected into recurrent metastatic sites in 13 individuals who underwent the same immunoradiotherapeutic regimens but failed to respond. CRs were achieved in 34 of 58 of such recurrent lesions while PRs in 17 of 58. These data support the expanded use of immunoradiotherapy in advanced cancer patients exhibiting progressive disease. PMID:24349874

  9. Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550)

    PubMed Central

    Ghoreschi, Kamran; Jesson, Michael I.; Li, Xiong; Lee, Jamie L.; Ghosh, Sarbani; Alsup, Jason W.; Warner, James D.; Tanaka, Masao; Steward-Tharp, Scott M.; Gadina, Massimo; Thomas, Craig; Minnerly, John C.; Storer, Chad E.; LaBranche, Timothy P.; Radi, Zaher A.; Dowty, Martin E.; Head, Richard D.; Meyer, Debra M.; Kishore, Nandini; O'Shea, John J.

    2011-01-01

    Inhibitors of the JAK family of non-receptor tyrosine kinases have demonstrated clinical efficacy in rheumatoid arthritis and other inflammatory disorders; however, the precise mechanisms by which JAK inhibition improves inflammatory immune responses remain unclear. Here we examined the mode of action of tofacitinib (CP-690,550) on JAK/STAT signaling pathways involved in adaptive and innate immune responses. To determine the extent of inhibition of specific JAK/STAT-dependent pathways, we analyzed cytokine stimulation of mouse and human T cells in vitro. We also investigated the consequences of CP-690,550 treatment on Th cell differentiation of naïve murine CD4+ T cells. CP-690,550 inhibited IL-4-dependent Th2 cell differentiation, and interestingly also interfered with Th17 cell differentiation. Expression of IL-23 receptor and of the Th17 cytokines IL-17A, IL-17F and IL-22 were blocked when naïve Th cells were stimulated with IL-6 and IL-23. In contrast, IL-17A-production was enhanced when Th17 cells were differentiated in the presence of TGF-β. Moreover, CP-690,550 also prevented activation of STAT1, induction of T-bet and subsequent generation of Th1 cells. In a model of established arthritis, CP-690,550 rapidly improved disease by inhibiting production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. Furthermore, efficacy in this disease model correlated with inhibition of both JAK1 and JAK3 signaling pathways. CP-690,550 also modulated innate responses to LPS in vivo through a mechanism likely involving inhibition of STAT1 signaling. Thus, CP-690,550 may improve autoimmune diseases and prevent transplant rejection by suppressing the differentiation of pathogenic Th1 and Th17 cells, as well as innate immune cell signaling. PMID:21383241

  10. Entorhinal cortex stimulation modulates amygdala and piriform cortex responses to olfactory bulb inputs in the rat.

    PubMed

    Mouly, A-M; Di Scala, G

    2006-01-01

    The rodent olfactory bulb sends direct projections to the piriform cortex and to two structures intimately implicated in memory processes, the entorhinal cortex and the amygdala. The piriform cortex has monosynaptic projections with the amygdala and the piriform cortex and is therefore in a position to modulate olfactory input either directly in the piriform cortex, or via the amygdala. In order to investigate this hypothesis, field potential signals induced in anesthetized rats by electrical stimulation of the olfactory bulb or the entorhinal cortex were recorded simultaneously in the piriform cortex (anterior part and posterior part) and the amygdala (basolateral nucleus and cortical nucleus). Single-site paired-pulse stimulation was used to assess the time courses of short-term inhibition and facilitation in each recording site in response to electrical stimulation of the olfactory bulb and entorhinal cortex. Paired-pulse stimulation of the olfactory bulb induced homosynaptic inhibition for short interpulse interpulse intervals (20-30 ms) in all the recording sites, with a significantly lower degree of inhibition in the anterior piriform cortex than in the other structures. At longer intervals (40-80 ms), paired-pulse facilitation was observed in all the structures. Paired-pulse stimulation of the entorhinal cortex mainly resulted in inhibition for the shortest interval duration (20 ms) in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. Double-site paired-pulse stimulation was then applied to determine if stimulation of the entorhinal cortex can modulate responses to olfactory bulb stimulation. For short interpulse intervals (20 ms) heterosynaptic inhibition was observed in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. The level of inhibition was greater in the basolateral nucleus than in the other structures. Taken together these data suggest that the

  11. 7alpha,11beta-Dimethyl-19-nortestosterone: a potent and selective androgen response modulator with prostate-sparing properties.

    PubMed

    Cook, C Edgar; Kepler, John A

    2005-02-15

    7alpha,11beta-Dimethyl-19-nortestosterone, made by 1,6-methyl addition to 17beta-acetoxy-11beta-methylestra-4,6-dien-3-one, was a highly potent and selective androgen response modulator, with enhanced androgen receptor binding, androgenic activity and anabolic:androgenic ratio over its two monomethyl homologs.

  12. Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional responses of neutrophils of neonatal foals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neutrophils play an important role in protecting against infection. Foals have age-dependent deficiencies in neutrophil function that may contribute to their predisposition to infection. Thus, we investigated the ability of a CpG-ODN formulated with Emulsigen® to modulate functional responses of ne...

  13. TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

    EPA Science Inventory

    TITLE:
    TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

  14. The arabidopsis polyamine transporter LHRI/AtPUT3 modulates heat responsive gene expression by regulating mRNA stability

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyamines (PA) involve in the gene regulation by interacting with various anionic macromolecules such as DNA, RNA and proteins and modulating their structure and function. Previous studies have showed that changing in polyamine biosynthesis alters plant response to different abiotic stresses. Here,...

  15. Proteasome modulator 9 gene SNPs, responsible for anti-depressant response, are in linkage with generalized anxiety disorder.

    PubMed

    Gragnoli, Claudia

    2014-09-01

    Proteasome modulator 9 (PSMD9) gene single nucleotide polymorphism (SNP) rs1043307/rs2514259 (E197G) is associated with significant clinical response to the anti-depressant desipramine. PSMD9 SNP rs74421874 [intervening sequence (IVS) 3 + nt460 G>A], rs3825172 (IVS3 + nt437 C>T) and rs1043307/rs2514259 (E197G A>G) are all linked to type 2 diabetes (T2D), maturity-onset-diabetes-of the young 3 (MODY3), obesity and waist circumference, hypertension, hypercholesterolemia, T2D-macrovascular and T2D-microvascular disease, T2D-neuropathy, T2D-carpal tunnel syndrome, T2D-nephropathy, T2D-retinopathy, non-diabetic retinopathy and depression. PSMD9 rs149556654 rare SNP (N166S A>G) and the variant S143G A>G also contribute to T2D. PSMD9 is located in the chromosome 12q24 locus, which per se is in linkage with depression, bipolar disorder and anxiety. In the present study, we wanted to determine whether PSMD9 is linked to general anxiety disorder in Italian T2D families. Two-hundred Italian T2D families were phenotyped for generalized anxiety disorder, using the diagnostic criteria of DSM-IV. When the diagnosis was unavailable or unclear, the trait was reported as unknown. The 200 Italians families were tested for the PSMD9 T2D risk SNPs rs74421874 (IVS3 + nt460 G>A), rs3825172 (IVS3 +nt437 T>C) and for the T2D risk and anti-depressant response SNP rs1043307/rs2514259 (E197G A>G) for evidence of linkage with generalized anxiety disorder. Non-parametric linkage analysis was executed via Merlin software. One-thousand simulation tests were performed to exclude results due to random chance. In our study, the PSMD9 gene SNPs rs74421874, rs3825172, and rs1043307/rs2514259 result in linkage to generalized anxiety disorder. This is the first report describing PSMD9 gene SNPs in linkage to generalized anxiety disorder in T2D families.

  16. Dying with dignity.

    PubMed

    Madan, T N

    1992-08-01

    Death is a theme of central importance in all cultures, but the manner in which it is interpreted varies from society to society. Even so, traditional cultures, including Christian, Hindu and Jain religious traditions, exhibited a positive attitude to death and did not look upon it in a dualistic framework of good vs bad, or desirable vs undesirable. Nor was pessimism the dominant mood in their thinking about death itself. A fundamental paradigm shift occurred in the West in the eighteenth century when death was desacralized and transformed into a secular event amenable to human manipulation. From those early beginnings, dying and death have been thoroughly medicalized and brought under the purview of high technology in the twentieth century. Once death is seen as a problem for professional management, the hospital displaces the home, and specialists with different kinds and degrees of expertise take over from the family. Everyday speech and the religious idiom yield place to medical jargon. The subject (an ageing, sick or dying person) becomes the object of this make-believe yet real world. As the object of others' professional control, he or she loses the freedom of self-assessment, expression and choice. Or, he or she may be expected to choose when no longer able to do so. Thus, not only freedom but dignity also is lost, and lawyers join doctors in crisis manipulation and perpetuation. Although the modern medical culture has originated in the West, it has gradually spread to all parts of the world, subjugating other kinds of medical knowledge and other attitudes to dying and death.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes

    PubMed Central

    Grosse, Susann; Stenvik, Jørgen; Nilsen, Asbjørn M

    2016-01-01

    Co-stimulation of the immune system to more than one agent concomitantly is very common in real life, and considering the increasing use of engineered nanoparticles and nanomaterials, it is highly relevant to assess the ability of these materials to modulate key innate immune responses, which has not yet been studied in detail. We investigated the immunomodulatory effects of 10 nm and 30 nm iron oxide nanoparticles (IONPs) on primary human monocytes in the presence and absence of Toll-like receptor 4 agonist lipopolysaccharide (LPS). Prior to the cell studies, we characterized the physicochemical properties of the nanoparticles in cell culture medium and ensured that the nanoparticles were free from biological contamination. Cellular uptake of the IONPs in monocytes was assessed using transmission electron microscopy. Using enzyme-linked immunosorbent assay, we found that the IONPs per se did not induce the production of proinflammatory cytokines tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, the IONPs had the ability to suppress LPS-induced nuclear factor kappa B activation and production of proinflammatory cytokines in primary human monocytes in an LPS and a particle dose-dependent manner. Using confocal microscopy and fluorescently labeled LPS, we showed that the effects correlated with impaired LPS internalization by monocytes in the presence of IONPs, which could be partly explained by LPS adsorption onto the nanoparticle surface. Additionally, the results from particle pretreatment experiments indicate that other cellular mechanisms might also play a role in the observed effects, which warrants further studies to elucidate the additional mechanisms underlying the capacity of IONPs to alter the reactivity of monocytes to LPS and to mount an appropriate cellular response. PMID:27695322

  18. In vivo modulation of Campylobacter jejuni virulence in response to environmental stress.

    PubMed

    Klančnik, Anja; Vučković, Darinka; Plankl, Mojca; Abram, Maja; Smole Možina, Sonja

    2013-06-01

    Campylobacters have developed a number of mechanisms for responding to environmental conditions, although the different virulence properties of these cells following exposure to stress are still poorly understood. We analyzed in vitro stress responses and the consequent in vivo modulation of Campylobacter jejuni pathogenicity in BALB/c mice, as a result of the exposure of the C. jejuni to environmental stress (starvation, oxidative stress, heat shock). In vitro, the influence of starvation and oxidative stress was milder than that of heat shock, although the majority of the stress conditions influenced the survival of C. jejuni. During starvation, C. jejuni viability was maintained longer than its culturability. Additionally, starvation elicited transformation of stressed bacteria to coccoid forms. In contrast, bacteria exposed to oxygen remained culturable, but their viability decreased. Pre-starvation did not contribute to improved survival of C. jejuni cells during oxygen exposure. Changes in bacteria numbers and the levels of several cytokines (interleukins 6 and 10, tumor necrosis factor-α, interferon-γ) were followed in vivo, in liver homogenates from the mice intravenously infected with either control (untreated) or stressed C. jejuni. The systemic infection with the control or stressed C. jejuni occurred with different production dynamics of the cytokines investigated. Starvation was the most powerful stress factor, which significantly decreased infectious potential of C. jejuni during the first 3 days postinfection. The most pronounced differences in cytokine production were found in interferon-γ and interleukin-10 production, which indicates that these have roles in the immune response to C. jejuni infection. These in vivo studies of environmental impact on bacterial virulence reveal that microbial adaptation during stress challenge is crucial not just for pathogen survival out of the host, but also during host-pathogen interactions, and thus for the

  19. Exogenous daytime melatonin modulates response of adolescent mice in a repeated unpredictable stress paradigm.

    PubMed

    Onaolapo, Adejoke Yetunde; Adebayo, Ajibola Nurudeen; Onaolapo, Olakunle James

    2017-02-01

    The immediate and short-term behavioural and physiological implications of exposure to stressful scenarios in the adolescent period are largely unknown; however, increases in occurrence of stress-related physiological and psychological disorders during puberty highlight the need to study substances that may modulate stress reactivity during a crucial stage of maturation. Seven groups of mice (12-15 g each) were administered distilled water (DW) (non-stressed and stressed controls), sertraline (10 mg/kg), diazepam (2 mg/kg) or one of three doses of melatonin (5, 10 and 15 mg/kg). Mice were exposed to 30 min of chronic mild stress (25 min of cage shaking, cage tilting, handling and 5 min of forced swimming in tepid warm water at 25 °C, in a random order) after administration of DW or drugs, daily for 21 days. Behavioural assessments were conducted on day 1 and day 21 (after which mice were sacrificed, blood taken for estimation of corticosterone levels and brain homogenates used for estimation of antioxidant activities). Administration of melatonin resulted in an increase in horizontal locomotion and self-grooming, while rearing showed a time-dependent increase, compared to non-stress and stress controls. Working memory improved with increasing doses of melatonin (compared to controls and diazepam); in comparison to setraline however, working memory decreased. A dose-related anxiolytic effect is seen when melatonin is compared to non-stressed and stressed controls. Melatonin administration reduced the systemic/oxidant response to repeated stress. Administration of melatonin in repeatedly stressed adolescent mice was associated with improved central excitation, enhancement of working memory, anxiolysis and reduced systemic response to stress.

  20. Adaptations in responsiveness of brainstem pain-modulating neurons in acute compared with chronic inflammation.

    PubMed

    Cleary, Daniel R; Heinricher, Mary M

    2013-06-01

    Despite similar behavioral hypersensitivity, acute and chronic pain have distinct neural bases. We used intraplantar injection of complete Freund's adjuvant to directly compare activity of pain-modulating neurons in the rostral ventromedial medulla (RVM) in acute vs chronic inflammation. Heat-evoked and von Frey-evoked withdrawal reflexes and corresponding RVM neuronal activity were recorded in lightly anesthetized animals either during the first hour after complete Freund's adjuvant injection (acute) or 3 to 10 days later (chronic). Thermal and modest mechanical hyperalgesia during acute inflammation were associated with increases in the spontaneous activity of pain-facilitating ON-cells and suppression of pain-inhibiting OFF-cells. Acute hyperalgesia was reversed by RVM block, showing that the increased activity of RVM ON-cells is necessary for acute behavioral hypersensitivity. In chronic inflammation, thermal hyperalgesia had resolved but mechanical hyperalgesia had become pronounced. The spontaneous discharges of ON- and OFF-cells were not different from those in control subjects, but the mechanical response thresholds for both cell classes were reduced into the innocuous range. RVM block in the chronic condition worsened mechanical hyperalgesia. These studies identify distinct contributions of RVM ON- and OFF-cells to acute and chronic inflammatory hyperalgesia. During early immune-mediated inflammation, ON-cell spontaneous activity promotes hyperalgesia. After inflammation is established, the antinociceptive influence of OFF-cells is dominant, yet the lowered threshold for the OFF-cell pause allows behavioral responses to stimuli that would normally be considered innocuous. The efficacy of OFF-cells in counteracting sensitization of ascending transmission pathways could therefore be an important determining factor in development of chronic inflammatory pain.

  1. Capuchin Monkeys (Cebus apella) Modulate Their Use of an Uncertainty Response Depending on Risk

    PubMed Central

    Beran, Michael J.; Perdue, Bonnie M.; Church, Barbara A.; Smith, J. David

    2015-01-01

    Metacognition refers to thinking about thinking, and there has been a great deal of interest in how this ability manifests across primates. Based on much of the work to date, a tentative division has been drawn with New World monkeys on one side and Old World monkeys and apes on the other. Specifically, Old World monkeys, apes and humans often show patterns reflecting metacognition, but New World monkeys typically fail to do so, or show less convincing behavioral patterns. However, recent data suggests that this difference may relate to other aspects of some experimental tasks. For example, one possibility is that risk tolerance affects how capuchin monkeys, a New World primate species, tend to perform. Specifically, it has recently been argued that on tasks in which there are two or three options, the ‘risk’ of guessing is tolerable for capuchins since there is a high probability of being correct even if they ‘know they do not know’ or feel something akin to uncertainty. The current study investigated this possibility by manipulating the degree of risk (2-choices versus 6-choices) and found that capuchin monkeys used the uncertainty response more on 6-choice trials than on 2-choice trials. We also found that rate of reward does not appear to underlie these patterns of performance, and propose that the degree of risk is modulating the use of the uncertainty response in capuchin monkeys. Thus, the apparent differences between New and Old world monkeys in metacognition may reflect differences in risk tolerance rather than access to metacognitive states. PMID:26551351

  2. Uropathogenic Escherichia coli modulates innate immunity to suppress Th1-mediated inflammatory responses during infectious epididymitis.

    PubMed

    Lang, Tali; Hudemann, Christoph; Tchatalbachev, Svetlin; Stammler, Angelika; Michel, Vera; Aslani, Ferial; Bhushan, Sudhanshu; Chakraborty, Trinad; Renz, Harald; Meinhardt, Andreas

    2014-03-01

    Infectious epididymitis in men, a frequent entity in urological outpatient settings, is commonly caused by bacteria originating from the anal region ascending the genitourinary tract. One of the most prevalent pathogens associated with epididymitis is Escherichia coli. In our previous study, we showed that semen quality is compromised in men following epididymitis associated with specific E. coli pathovars. Thus, our aim was to investigate possible differences in immune responses elicited during epididymitis following infection with the uropathogenic E. coli (UPEC) strain CFT073 and the nonpathogenic enteric E. coli (NPEC) strain 470. Employing an in vivo experimental epididymitis model, C57BL/6 mice were infected with UPEC CFT073, NPEC 470, or phosphate-buffered saline (PBS) as a sham control for up to 7 days. After infection with NPEC 470, the expression of proinflammatory cytokines interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha in the epididymis was significantly increased. Conversely, UPEC CFT073-challenged mice displayed inflammatory gene expression at levels comparable to sham PBS-treated animals. Moreover, by day 7 only NPEC-infected animals showed activation of adaptive immunity evident by a substantial influx of CD3+ and F4/80+ cells in the epididymal interstitium. This correlated with enhanced production of Th1-associated cytokines IL-2 and gamma interferon (IFN-γ). Furthermore, splenocytes isolated from UPEC-infected mice exhibited diminished T-cell responses with significantly reduced secretion of IL-2 and IFN-γ in contrast to NPEC-infected animals. Overall, these findings provide new insights into understanding pathogen-specific modulation of host immunity during acute phases of epididymitis, which may influence severity of disease and clinical outcomes.

  3. Somatostatin modulates mast cell-induced responses in murine spinal neurons and satellite cells.

    PubMed

    Van Op den bosch, Joeri; Van Nassauw, Luc; Van Marck, Eric; Timmermans, Jean-Pierre

    2009-08-01

    The course of intestinal inflammatory responses is tightly coordinated by the extensive communication between the immune system and the enteric nervous system, among which the bidirectional mast cell-neuron interaction within the intestinal wall plays a prominent role. Recent research suggests that somatostatin (SOM) is able to inhibit this self-reinforcing network by simultaneously suppressing the inflammatory activities of both neurons and mast cells. Therefore, we assessed the modulatory effects of SOM on both the short-term and long-term effects induced by the main mast cell mediators histamine (HIS) and 5-HT on spinal sensory neurons. Short-term incubation of dorsal root ganglion cultures with HIS and 5-HT induced neuronal CGRP-release and calcium-mediated activation of both neurons and nonneuronal cells, both of which effects were significantly reduced by SOM. In addition, SOM was also able to suppress the increased neuronal expression of pro- and anti-inflammatory peptides induced by long-term exposure to HIS and 5-HT. Immunocytochemical and molecular-biological experiments revealed the possible involvement of somatostatin receptor 1 (SSTR1) and SSTR2A in these profound SOM-dependent effects. These data, combined with the increased expression of pro- and anti-inflammatory peptides and several SSTRs in murine dorsal root ganglia following intestinal inflammation, reveal that intestinal inflammation not only induces the onset of proinflammatory cascades but simultaneously triggers endogenous systems destined to prevent excessive tissue damage. Moreover, these data provide for the first time functional evidence that SOM is able to directly modulate intestinal inflammatory responses by interference with the coordinating mast cell-neuron communication.

  4. Taurine protects cisplatin induced cardiotoxicity by modulating inflammatory and endoplasmic reticulum stress responses.

    PubMed

    Chowdhury, Sayantani; Sinha, Krishnendu; Banerjee, Sharmistha; Sil, Parames C

    2016-11-12

    Oxidative stress, ER stress, inflammation, and apoptosis results in the pathogenesis of cisplatin-induced cardiotoxicity. The present study was designed to investigate the signaling mechanisms involved in the ameliorating effect of taurine, a conditionally essential amino acid, against cisplatin-mediated cardiac ER stress dependent apoptotic death and inflammation. Mice were simultaneously treated with taurine (150 mg kg(-1) body wt, i.p.) and cisplatin (10 mg kg(-1) body wt, i.p.) for a week. Cisplatin exposure significantly altered serum creatine kinase and troponin T levels. In addition, histological studies revealed disintegration in the normal radiation pattern of cardiac muscle fibers. However, taurine administration could abate such adverse effects of cisplatin. Taurine administration significantly mitigated the reactive oxygen species production, alleviated the overexpression of nuclear factor-κB (NF-κB), and inhibited the elevation of proinflammatoy cytokines, adhesion molecules, and chemokines. Cisplatin exposure resulted in the unfolded protein response (UPR)-regulated CCAAT/enhancer binding protein (CHOP) up-regulation, induction of GRP78: a marker of ER stress and eIF2α signaling. Increase in calpain-1 expression level, activation of caspase-12 and caspase-3, cleavage of the PARP protein as well as the inhibition of antiapoptotic protein Bcl-2 were reflected on cisplatin-triggered apoptosis. Taurine could, however, combat against such cisplatin induced cardiac-abnormalities. The above mentioned findings suggest that taurine plays a beneficial role in providing protection against cisplatin-induced cardiac damage by modulating inflammatory responses and ER stress. © 2016 BioFactors, 42(6):647-664, 2016.

  5. BAP1 inhibits the ER stress gene regulatory network and modulates metabolic stress response.

    PubMed

    Dai, Fangyan; Lee, Hyemin; Zhang, Yilei; Zhuang, Li; Yao, Hui; Xi, Yuanxin; Xiao, Zhen-Dong; You, M James; Li, Wei; Su, Xiaoping; Gan, Boyi

    2017-03-21

    The endoplasmic reticulum (ER) is classically linked to metabolic homeostasis via the activation of unfolded protein response (UPR), which is instructed by multiple transcriptional regulatory cascades. BRCA1 associated protein 1 (BAP1) is a tumor suppressor with de-ubiquitinating enzyme activity and has been implicated in chromatin regulation of gene expression. Here we show that BAP1 inhibits cell death induced by unresolved metabolic stress. This prosurvival role of BAP1 depends on its de-ubiquitinating activity and correlates with its ability to dampen the metabolic stress-induced UPR transcriptional network. BAP1 inhibits glucose deprivation-induced reactive oxygen species and ATP depletion, two cellular events contributing to the ER stress-induced cell death. In line with this, Bap1 KO mice are more sensitive to tunicamycin-induced renal damage. Mechanically, we show that BAP1 represses metabolic stress-induced UPR and cell death through activating transcription factor 3 (ATF3) and C/EBP homologous protein (CHOP), and reveal that BAP1 binds to ATF3 and CHOP promoters and inhibits their transcription. Taken together, our results establish a previously unappreciated role of BAP1 in modulating the cellular adaptability to metabolic stress and uncover a pivotal function of BAP1 in the regulation of the ER stress gene-regulatory network. Our study may also provide new conceptual framework for further understanding BAP1 function in cancer.

  6. Moderate consumption of red wine can modulate human intestinal inflammatory response.

    PubMed

    Muñoz-González, Irene; Espinosa-Martos, Irene; Rodríguez, Juan M; Jiménez-Girón, Ana; Martín-Álvarez, Pedro J; Bartolomé, Begoña; Moreno-Arribas, M Victoria

    2014-10-29

    In this study, 24 immune markers were analyzed in feces from healthy volunteers (n = 34) before and after consumption of a red wine (12% ethanol, 1758 mg/L total polyphenols) for 4 weeks. Analysis of the data permitted the differentiation of a six-volunteer subgroup showing unusually high basal values of cytokines. For this subgroup, consumption of wine significantly (P < 0.05) reduced the content of 16 markers to usual values, especially noticeable for those cytokines that promote initial inflammation (TNF-α, IL-6, and IFN-γ). On the contrary, no significant differences in the concentration of any immune marker were observed after wine consumption for the rest of the volunteers. Additionally, significant and negative correlations among cytokines IFN-γ, IL-8, and IL-6 and the total fecal content of phenolic metabolites were found for the high-cytokines-values subgroup, before wine intake. This study shows, for the first time, that moderate consumption of red wine could modulate inflammatory intestinal response in vivo.

  7. Cinnamaldehyde modulates LPS-induced systemic inflammatory response syndrome through TRPA1-dependent and independent mechanisms.

    PubMed

    Mendes, Saulo J F; Sousa, Fernanda I A B; Pereira, Domingos M S; Ferro, Thiago A F; Pereira, Ione C P; Silva, Bruna L R; Pinheiro, Aruanã J M C R; Mouchrek, Adriana Q S; Monteiro-Neto, Valério; Costa, Soraia K P; Nascimento, José L M; Grisotto, Marcos A G; da Costa, Robson; Fernandes, Elizabeth S

    2016-05-01

    Cinnamaldehyde is a natural essential oil suggested to possess anti-bacterial and anti-inflammatory properties; and to activate transient receptor potential ankyrin 1 (TRPA1) channels expressed on neuronal and non-neuronal cells. Here, we investigated the immunomodulatory effects of cinnamaldehyde in an in vivo model of systemic inflammatory response syndrome (SIRS) induced by lipopolysaccharide. Swiss mice received a single oral treatment with cinnamaldehyde 1 h before LPS injection. To investigate whether cinnamaldehyde effects are dependent on TRPA1 activation, animals were treated subcutaneously with the selective TRPA1 antagonist HC-030031 5 min prior to cinnamaldehyde administration. Vehicle-treated mice were used as controls. Cinnamaldehyde ameliorated SIRS severity in LPS-injected animals. Diminished numbers of circulating mononuclear cells and increased numbers of peritoneal mononuclear and polymorphonuclear cell numbers were also observed. Cinnamaldehyde augmented the number of peritoneal Ly6C(high) and Ly6C(low) monocyte/macrophage cells in LPS-injected mice. Reduced levels of nitric oxide, plasma TNFα and plasma and peritoneal IL-10 were also detected. Additionally, IL-1β levels were increased in the same animals. TRPA1 antagonism by HC-030031 reversed the changes in the number of circulating and peritoneal leukocytes in cinnamaldehyde-treated animals, whilst increasing the levels of peritoneal IL-10 and reducing peritoneal IL-1β. Overall, cinnamaldehyde modulates SIRS through TRPA1-dependent and independent mechanisms.

  8. Cigarette Smoke-Exposed Candida albicans Increased Chitin Production and Modulated Human Fibroblast Cell Responses

    PubMed Central

    Alanazi, Humidah; Semlali, Abdelhabib; Perraud, Laura; Chmielewski, Witold; Zakrzewski, Andrew

    2014-01-01

    The predisposition of cigarette smokers for development of respiratory and oral bacterial infections is well documented. Cigarette smoke can also contribute to yeast infection. The aim of this study was to investigate the effect of cigarette smoke condensate (CSC) on C. albicans transition, chitin content, and response to environmental stress and to examine the interaction between CSC-pretreated C. albicans and normal human gingival fibroblasts. Following exposure to CSC, C. albicans transition from blastospore to hyphal form increased. CSC-pretreated yeast cells became significantly (P < 0.01) sensitive to oxidation but significantly (P < 0.01) resistant to both osmotic and heat stress. CSC-pretreated C. albicans expressed high levels of chitin, with 2- to 8-fold recorded under hyphal conditions. CSC-pretreated C. albicans adhered better to the gingival fibroblasts, proliferated almost three times more and adapted into hyphae, while the gingival fibroblasts recorded a significantly (P < 0.01) slow growth rate but a significantly higher level of IL-1β when in contact with CSC-pretreated C. albicans. CSC was thus able to modulate both C. albicans transition through the cell wall chitin content and the interaction between C. albicans and normal human gingival fibroblasts. These findings may be relevant to fungal infections in the oral cavity in smokers. PMID:25302312

  9. Cigarette smoke-exposed Candida albicans increased chitin production and modulated human fibroblast cell responses.

    PubMed

    Alanazi, Humidah; Semlali, Abdelhabib; Perraud, Laura; Chmielewski, Witold; Zakrzewski, Andrew; Rouabhia, Mahmoud

    2014-01-01

    The predisposition of cigarette smokers for development of respiratory and oral bacterial infections is well documented. Cigarette smoke can also contribute to yeast infection. The aim of this study was to investigate the effect of cigarette smoke condensate (CSC) on C. albicans transition, chitin content, and response to environmental stress and to examine the interaction between CSC-pretreated C. albicans and normal human gingival fibroblasts. Following exposure to CSC, C. albicans transition from blastospore to hyphal form increased. CSC-pretreated yeast cells became significantly (P < 0.01) sensitive to oxidation but significantly (P < 0.01) resistant to both osmotic and heat stress. CSC-pretreated C. albicans expressed high levels of chitin, with 2- to 8-fold recorded under hyphal conditions. CSC-pretreated C. albicans adhered better to the gingival fibroblasts, proliferated almost three times more and adapted into hyphae, while the gingival fibroblasts recorded a significantly (P < 0.01) slow growth rate but a significantly higher level of IL-1β when in contact with CSC-pretreated C. albicans. CSC was thus able to modulate both C. albicans transition through the cell wall chitin content and the interaction between C. albicans and normal human gingival fibroblasts. These findings may be relevant to fungal infections in the oral cavity in smokers.

  10. PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway.

    PubMed

    Bi, Guanghui; Yan, Jingfeng; Sun, Shuzhen; Qu, Xinhua

    2017-02-10

    Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p. Overexpression of PRRT2 strongly impaired the cell viability and promoted cell apoptosis and these anti-tumor effects could be largely reversed by microRNA-30a-5p. Mechanistically, PRRT2 expression was closely correlated genes involved in unfolded protein response (UPR) pathway and introduction of PRRT2 inhibited gene expression in the three branches of UPR, including PERK axis, IRE1 axis and ATF6 axis. Taken together, our findings identify PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention.

  11. Pre-attentive modulation of brain responses to tones in coloured-hearing synesthetes

    PubMed Central

    2012-01-01

    Background Coloured-hearing (CH) synesthesia is a perceptual phenomenon in which an acoustic stimulus (the inducer) initiates a concurrent colour perception (the concurrent). Individuals with CH synesthesia "see" colours when hearing tones, words, or music; this specific phenomenon suggesting a close relationship between auditory and visual representations. To date, it is still unknown whether the perception of colours is associated with a modulation of brain functions in the inducing brain area, namely in the auditory-related cortex and associated brain areas. In addition, there is an on-going debate as to whether attention to the inducer is necessarily required for eliciting a visual concurrent, or whether the latter can emerge in a pre-attentive fashion. Results By using the EEG technique in the context of a pre-attentive mismatch negativity (MMN) paradigm, we show that the binding of tones and colours in CH synesthetes is associated with increased MMN amplitudes in response to deviant tones supposed to induce novel concurrent colour perceptions. Most notably, the increased MMN amplitudes we revealed in the CH synesthetes were associated with stronger intracerebral current densities originating from the auditory cortex, parietal cortex, and ventral visual areas. Conclusions The automatic binding of tones and colours in CH synesthetes is accompanied by an early pre-attentive process recruiting the auditory cortex, inferior and superior parietal lobules, as well as ventral occipital areas. PMID:23241212

  12. Auditory steady-state responses reveal amplitude modulation gap detection thresholds

    NASA Astrophysics Data System (ADS)

    Ross, Bernhard; Pantev, Christo

    2004-05-01

    Auditory evoked magnetic fields were recorded from the left hemisphere of healthy subjects using a 37-channel magnetometer while stimulating the right ear with 40-Hz amplitude modulated (AM) tone-bursts with 500-Hz carrier frequency in order to study the time-courses of amplitude and phase of auditory steady-state responses (ASSRs). The stimulus duration of 300 ms and the duration of the silent periods (3-300 ms) between succeeding stimuli were chosen to address the question whether the time-course of the ASSR can reflect both temporal integration and temporal resolution in the central auditory processing. Long lasting perturbations of the ASSR were found after gaps in the AM sound, even for gaps of short duration. These were interpreted as evidences for an auditory reset mechanism. Concomitant psycho-acoustical tests corroborated that gap durations perturbing the ASSR were in the same range as the threshold for AM gap detection. Magnetic source localizations estimated the ASSR sources in the primary auditory cortex, suggesting that the processing of temporal structures in the sound is performed at or below the cortical level.

  13. BAP1 inhibits the ER stress gene regulatory network and modulates metabolic stress response

    PubMed Central

    Dai, Fangyan; Lee, Hyemin; Zhang, Yilei; Zhuang, Li; Yao, Hui; Xi, Yuanxin; Xiao, Zhen-Dong; You, M. James; Li, Wei; Su, Xiaoping; Gan, Boyi

    2017-01-01

    The endoplasmic reticulum (ER) is classically linked to metabolic homeostasis via the activation of unfolded protein response (UPR), which is instructed by multiple transcriptional regulatory cascades. BRCA1 associated protein 1 (BAP1) is a tumor suppressor with de-ubiquitinating enzyme activity and has been implicated in chromatin regulation of gene expression. Here we show that BAP1 inhibits cell death induced by unresolved metabolic stress. This prosurvival role of BAP1 depends on its de-ubiquitinating activity and correlates with its ability to dampen the metabolic stress-induced UPR transcriptional network. BAP1 inhibits glucose deprivation-induced reactive oxygen species and ATP depletion, two cellular events contributing to the ER stress-induced cell death. In line with this, Bap1 KO mice are more sensitive to tunicamycin-induced renal damage. Mechanically, we show that BAP1 represses metabolic stress-induced UPR and cell death through activating transcription factor 3 (ATF3) and C/EBP homologous protein (CHOP), and reveal that BAP1 binds to ATF3 and CHOP promoters and inhibits their transcription. Taken together, our results establish a previously unappreciated role of BAP1 in modulating the cellular adaptability to metabolic stress and uncover a pivotal function of BAP1 in the regulation of the ER stress gene-regulatory network. Our study may also provide new conceptual framework for further understanding BAP1 function in cancer. PMID:28275095

  14. Light and dark modulation of chlorophyll biosynthetic genes in response to temperature.

    PubMed

    Mohanty, Sasmita; Grimm, Bernhard; Tripathy, Baishnab C

    2006-08-01

    Temperature and light significantly influence chloroplast development and chlorophyll biosynthesis. To understand the mechanism of the modulation of chlorophyll biosynthesis, the levels of transcripts and proteins of many enzymatic steps of tetrapyrrole biosynthesis in wheat and cucumber were simultaneously examined. The effect of low (chill-stress) as well as high (heat-stress) temperatures on dark- and light-grown seedlings was monitored. The protochlorophyllide oxidoreductase (POR) content was greatly reduced in response to light in control and heat-stressed seedlings. However, the POR level was not reduced in light-exposed chill-stressed seedlings. The genes for glutamate semialdehyde aminotransferase (gsa; cucumber), glutamyl-tRNA reductase (GluTR; cucumber), 5-aminolevulinic acid dehydratase (Ala D; cucumber and wheat) and for a subunit of Mg-chelatase (Chl I; wheat) showed a reduced expression in cold stress compared to controls and heat-stress conditions. Although expression of the ferrochelatase gene (Fch) and geranylgeranyl reductase gene (Chl P) was upregulated in light, they were downregulated by both chill- and heat-stress. Interestingly, gsa and uroporphyrinogen decarboxylase gene (UroD) and gene product abundance was stimulated by light and heat-stress implying the presence of both light and heat-inducible elements in their promoters. This observation corroborates with the previous report of increased enzymatic activity of UroD in heat-stressed cucumber seedlings. The gsa and Uro D may play an important role in tolerance of the greening process of plants to heat-stress.

  15. Tactile stimulation and hemispheric asymmetries modulate auditory perception and neural responses in primary auditory cortex.

    PubMed

    Hoefer, M; Tyll, S; Kanowski, M; Brosch, M; Schoenfeld, M A; Heinze, H-J; Noesselt, T

    2013-10-01

    Although multisensory integration has been an important area of recent research, most studies focused on audiovisual integration. Importantly, however, the combination of audition and touch can guide our behavior as effectively which we studied here using psychophysics and functional magnetic resonance imaging (fMRI). We tested whether task-irrelevant tactile stimuli would enhance auditory detection, and whether hemispheric asymmetries would modulate these audiotactile benefits using lateralized sounds. Spatially aligned task-irrelevant tactile stimuli could occur either synchronously or asynchronously with the sounds. Auditory detection was enhanced by non-informative synchronous and asynchronous tactile stimuli, if presented on the left side. Elevated fMRI-signals to left-sided synchronous bimodal stimulation were found in primary auditory cortex (A1). Adjacent regions (planum temporale, PT) expressed enhanced BOLD-responses for synchronous and asynchronous left-sided bimodal conditions. Additional connectivity analyses seeded in right-hemispheric A1 and PT for both bimodal conditions showed enhanced connectivity with right-hemispheric thalamic, somatosensory and multisensory areas that scaled with subjects' performance. Our results indicate that functional asymmetries interact with audiotactile interplay which can be observed for left-lateralized stimulation in the right hemisphere. There, audiotactile interplay recruits a functional network of unisensory cortices, and the strength of these functional network connections is directly related to subjects' perceptual sensitivity.

  16. Dbo/Henji Modulates Synaptic dPAK to Gate Glutamate Receptor Abundance and Postsynaptic Response

    PubMed Central

    Wang, Manyu; Chen, Pei-Yi; Wang, Chien-Hsiang; Lai, Tzu-Ting; Tsai, Pei-I; Cheng, Ying-Ju; Kao, Hsiu-Hua; Chien, Cheng-Ting

    2016-01-01

    In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ). In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD) houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties. In henji mutants, GluRIIA abundance is upregulated but that of GluRIIB is not. Electrophysiological results also support a GluR compositional shift towards a higher IIA/IIB ratio at henji NMJs. Strikingly, dPAK, a positive regulator for GluRIIA synaptic localization, accumulates at the henji PSD. Reducing the dpak gene dosage suppresses satellite boutons and GluRIIA accumulation at henji NMJs. In addition, dPAK associated with Henji through the Kelch repeats which is the domain essential for Henji localization and function at postsynapses. We propose that Henji acts at postsynapses to restrict both presynaptic bouton growth and postsynaptic GluRIIA abundance by modulating dPAK. PMID:27736876

  17. An alternative telomerase RNA in Arabidopsis modulates enzyme activity in response to DNA damage

    PubMed Central

    Cifuentes-Rojas, Catherine; Nelson, Andrew D.L.; Boltz, Kara A.; Kannan, Kalpana; She, Xintao; Shippen, Dorothy E.

    2012-01-01

    Telomerase replenishes telomere tracts by reiteratively copying its RNA template, TER. Unlike other model organisms, Arabidopsis thaliana harbors two divergent TER genes. However, only TER1 is required for telomere maintenance. Here we examine the function of TER2. We show that TER2 is spliced and its 3′ end is truncated in vivo to generate a third TER isoform, TER2S. TERT preferentially associates with TER2 > TER1 > TER2S. Moreover, TER2 and TER2S assemble with Ku and POT1b (protection of telomeres), forming RNP (ribonucleoprotein) complexes distinct from TER1 RNP. Plants null for TER2 display increased telomerase enzyme activity, while TER2 overexpression inhibits telomere synthesis from TER1 and leads to telomere shortening. These findings argue that TER2 negatively regulates telomerase by sequestering TERT in a nonproductive RNP complex. Introduction of DNA double-strand breaks by zeocin leads to an immediate and specific spike in TER2 and a concomitant decrease in telomerase enzyme activity. This response is not triggered by replication stress or telomere dysfunction and is abrogated in ter2 mutants. We conclude that Arabidopsis telomerase is modulated by TER2, a novel DNA damage-induced noncoding RNA that works in concert with the canonical TER to promote genome integrity. PMID:23109676

  18. Recombinant human lactoferrin modulates human PBMC derived macrophage responses to BCG and LPS.

    PubMed

    Hwang, Shen-An; Kruzel, Marian L; Actor, Jeffrey K

    2016-12-01

    Lactoferrin, an iron-binding glycoprotein found in mammalian mucosal secretions and granules of neutrophils, possesses several immune modulatory properties. Published reports indicate that lactoferrin enhances the efficacy of the tuberculosis vaccine, BCG (Bacillus Calmette Guerin), both by increasing macrophage and dendritic cell ability to stimulate receptive T cells and by modulating the inflammatory response. This report is the first to demonstrate the effects of a recombinant human lactoferrin (10 μg/mL) on human PBMC derived CD14(+) and CD16(+) macrophages stimulated with a strong (LPS, 10 ng/mL) or weaker (BCG, MOI 1:1) stimulator of inflammation. After 3 days culture, LPS and human lactoferrin treated CD14(+) cells significantly increased production of IL-10, IL-6, and MCP-1 compared to the LPS only group. In contrast, similarly treated CD16(+) macrophages increased production of IL-12p40 and IL-10 and decreased TNF-α. Limited changes were observed in BCG stimulated CD14(+) and CD16(+) macrophages with and without lactoferrin. Analysis of surface expression of antigen presentation and co-stimulatory molecules demonstrated that CD14(+) macrophages, when stimulated with BCG or LPS and cultured with lactoferrin, increased expression of CD86. CD16(+) macrophages treated with lactoferrin showed a similar trend of increase in CD86 expression, but only when stimulated with BCG.

  19. Breast cancer cell-associated endopeptidase EC 24.11 modulates proliferative response to bombesin

    PubMed Central

    Burns, D M; Walker, B; Gray, J; Nelson, J

    1999-01-01

    We have investigated the production, growth and inactivation of gastrin-releasing peptide (GRP)-like peptides in human breast cancer cell lines. Radioimmunoassay detected GRP-like immunoreactivity (GRP-LI) in T47D breast cancer cells but not in the conditioned medium, indicating rapid clearance. No GRP-LI was found in the ZR-75-1 or MDA-MB-436 cells or their conditioned medium. High-performance liquid chromatography (HPLC) analysis of the GRP-LI in the T47D cells revealed a major peak, which co-eluted with GRP18–27, and a minor more hydrophilic peak. In vitro stimulation of T47D cell growth by bombesin (BN) was enhanced to 138% of control levels (bombesin alone) by the addition of the selective endopeptidase EC 3.4.24.11 inhibitor phosphoramidon (0.1 ng ml−;1). Fluorogenic analysis using whole cells confirmed low levels of this phosphoramidon-sensitive enzyme on the T47D cells. This enzyme, previously unreported in human breast cancer cells, significantly modulates both T47D growth and its response to BN-induced growth. © 1999 Cancer Research Campaign PMID:9888460

  20. Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells

    PubMed Central

    Miraucourt, Loïs S; Tsui, Jennifer; Gobert, Delphine; Desjardins, Jean-François; Schohl, Anne; Sild, Mari; Spratt, Perry; Castonguay, Annie; De Koninck, Yves; Marsh-Armstrong, Nicholas; Wiseman, Paul W; Ruthazer, Edward S

    2016-01-01

    Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate retina, but the role of endocannabinoids in vision is not fully understood. Here, we identified a novel mechanism underlying a CB1R-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of NKCC1 activity. Clomeleon imaging and patch clamp recordings revealed that inhibition of NKCC1 downstream of CB1R activation reduces intracellular Cl− levels in RGCs, hyperpolarizing the resting membrane potential. We confirmed that such hyperpolarization enhances RGC action potential firing in response to subsequent depolarization, consistent with the increased intrinsic excitability of RGCs observed with CB1R activation. Using a dot avoidance assay in freely swimming Xenopus tadpoles, we demonstrate that CB1R activation markedly improves visual contrast sensitivity under low-light conditions. These results highlight a role for endocannabinoids in vision and present a novel mechanism for cannabinoid modulation of neuronal activity through Cl− regulation. DOI: http://dx.doi.org/10.7554/eLife.15932.001 PMID:27501334

  1. Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism

    PubMed Central

    Yang, Wei; Bai, Yibing; Xiong, Ying; Zhang, Jin; Chen, Shuokai; Zheng, Xiaojun; Meng, Xiangbo; Li, Lunyi; Wang, Jing; Xu, Chenguang; Yan, Chengsong; Wang, Lijuan; Chang, Catharine C. Y.; Chang, Ta-Yuan; Zhang, Ti; Zhou, Penghui; Song, Bao-Liang; Liu, Wanli; Sun, Shao-cong; Liu, Xiaolong; Li, Bo-liang; Xu, Chenqi

    2016-01-01

    CD8+ T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment1–4. Reactivating the cytotoxicity of CD8+ T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8+ T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme5, led to potentiated effector function and enhanced proliferation of CD8+ but not CD4+ T cells. This is due to the increase in the plasma membrane cholesterol level of CD8+ T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8+ T cells were better than wild-type CD8+ T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile6,7, to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy. PMID:26982734

  2. c-Myc modulation: a key role in melanoma drug response

    PubMed Central

    Fico, Annalisa; Alfano, Daniela; Valentino, Anna; Vasta, Valeria; Cavalcanti, Ernesta; Travali, Salvatore; Patriarca, Eduardo J; Caputo, Emilia

    2015-01-01

    Understanding molecular mechanisms involved in melanoma resistance to drugs is a big challenge. Experimental evidences suggested a correlation between mutational status in B-RAF and melanoma cell susceptibility to drugs, such as paclitaxel, doxorubicin and temozolomide, which generate an accumulation of hydrogen peroxide (H2O2) in the cells. We investigated the survival phenotype and the protein level of c-myc, a B-RAF target molecule, in melanoma cells, carrying a different mutational status in B-RAF, upon paclitaxel, doxorubicin and H2O2 treatment. For the first time, we reported c-myc modulation is critical for melanoma drug response. It appeared drug-specific and post-transcriptionally driven through PP2A; in correlation, cell pre-treatment with okadaic acid (OA), a specific PP2A inhibitor, as well as PP2A silencing of melanoma cells, was able to increase melanoma cell drug-sensitivity and c-myc protein level. This is relevant for designing efficacious therapeutic strategies in melanoma. PMID:25835050

  3. Response of a Fabry-Perot cavity to phase modulated light

    NASA Technical Reports Server (NTRS)

    Hils, Dieter; Hall, J. L.

    1987-01-01

    A solution to the lock-in detection method, which is valid for arbitrary values of the modulation frequency, is described. The theory for determining frequency modulation of a single frequency laser is presented. The theoretical predictions for the optimum modulation index are compared to experimental solutions for the quasi-static regime. Signal line shapes for first, second, and third harmonic generations are derived and examined. It is noted that there is good correlation between experimental and quasi-static theory data for the relation between small modulation frequency and resonance linewidth.

  4. Concurrent modulation of neuronal and behavioural olfactory responses to sex and host plant cues in a male moth

    PubMed Central

    Kromann, Sophie H.; Saveer, Ahmed M.; Binyameen, Muhammad; Bengtsson, Marie; Birgersson, Göran; Hansson, Bill S.; Schlyter, Fredrik; Witzgall, Peter; Ignell, Rickard; Becher, Paul G.

    2015-01-01

    Mating has profound effects on animal physiology and behaviour, not only in females but also in males, which we show here for olfactory responses. In cotton leafworm moths, Spodoptera littoralis, odour-mediated attraction to sex pheromone and plant volatiles are modulated after mating, producing a behavioural response that matches the physiological condition of the male insect. Unmated males are attracted by upwind flight to sex pheromone released by calling females, as well as to volatiles of lilac flowers and green leaves of the host plant cotton, signalling adult food and mating sites, respectively. Mating temporarily abolishes male attraction to females and host plant odour, but does not diminish attraction to flowers. This behavioural modulation is correlated with a response modulation in the olfactory system, as shown by electro-physiological recordings from antennae and by functional imaging of the antennal lobe, using natural odours and synthetic compounds. An effect of mating on the olfactory responses to pheromone and cotton plant volatiles but not to lilac flowers indicates the presence of functionally independent neural circuits within the olfactory system. Our results indicate that these circuits interconnect and weigh perception of social and habitat odour signals to generate appropriate behavioural responses according to mating state. PMID:25621329

  5. A Dual-Responsive Nanocomposite toward Climate-Adaptable Solar Modulation for Energy-Saving Smart Windows.

    PubMed

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

    2017-02-22

    In this work, a novel fully autonomous photothermotropic material made by hybridization of the poly(N-isopropylacrylamide) (PNIPAM) hydrogel and antimony-tin oxide (ATO) is presented. In this photothermotropic system, the near-infrared (NIR)-absorbing ATO acts as nanoheater to induce the optical switching of the hydrogel. Such a new passive smart window is characterized by excellent NIR shielding, a photothermally activated switching mechanism, enhanced response speed, and solar modulation ability. Systems with 0, 5, 10, and 15 atom % Sb-doped ATO in PNIPAM were investigated, and it was found that a PNIPAM/ATO nanocomposite is able to be photothermally activated. The 10 atom % Sb-doped PNIPAM/ATO exhibits the best response speed and solar modulation ability. Different film thicknesses and ATO contents will affect the response rate and solar modulation ability. Structural stability tests at 15 cycles under continuous exposure to solar irradiation at 1 sun intensity demonstrated the performance stability of such a photothermotropic system. We conclude that such a novel photothermotropic hybrid can be used as a new generation of autonomous passive smart windows for climate-adaptable solar modulation.

  6. Characterization of submillisecond response optical addressing phase modulator based on low light scattering polymer network liquid crystal

    SciTech Connect

    Xiangjie, Zhao E-mail: zxjdouble@gmail.com; Cangli, Liu; Jiazhu, Duan; Dayong, Zhang; Yongquan, Luo

    2015-01-07

    Optically addressed conventional nematic liquid crystal spatial light modulator has attracted wide research interests. But the slow response speed limited its further application. In this paper, polymer network liquid crystal (PNLC) was proposed to replace the conventional nematic liquid crystal to enhance the response time to the order of submillisecond. The maximum light scattering of the employed PNLC was suppressed to be less than 2% at 1.064 μm by optimizing polymerization conditions and selecting large viscosity liquid crystal as solvent. The occurrence of phase ripple phenomenon due to electron diffusion and drift in photoconductor was found to deteriorate the phase modulation effect of the optical addressed PNLC phase modulator. The wavelength effect and AC voltage frequency effect on the on state dynamic response of phase change was investigated by experimental methods. These effects were interpreted by electron diffusion and drift theory based on the assumption that free electron was inhomogeneously distributed in accordance with the writing beam intensity distribution along the incident direction. The experimental results indicated that the phase ripple could be suppressed by optimizing the wavelength of the writing beam and the driving AC voltage frequency when varying the writing beam intensity to generate phase change in 2π range. The modulation transfer function was also measured.

  7. α-Adrenoceptor constrictor responses and their modulation in slow-twitch and fast-twitch mouse skeletal muscle

    PubMed Central

    Lambert, David G; Thomas, Gail D

    2005-01-01

    Vasoconstrictor responses to sympathetic nerve stimulation and their sensitivity to metabolic modulation reportedly differ in fast-twitch and slow-twitch muscles, but the underlying mechanisms are not known. Both α1- and α2-adrenoceptors mediate these vascular responses in fast-twitch muscle, while their roles in slow-twitch muscle are less well defined. In this study, the phosphorylation of smooth muscle myosin regulatory light chain (smRLC) was measured as an index of vasoconstriction in slow-twitch soleus muscles and fast-twitch extensor digitorum longus (EDL) muscles isolated from C57BL/6J mice. In soleus muscles, incubation with phenylephrine (PE) or UK 14,304 to selectively activate α1- or α2-adrenoceptors resulted in concentration-dependent increases in smRLC phosphorylation. To evaluate metabolic modulation of these responses, vasodilator pathways previously implicated in such modulation in fast-twitch muscle were activated in soleus muscles by treatment with the nitric oxide (NO) donor nitroprusside or the ATP-sensitive potassium (KATP) channel opener cromakalim. Both drugs inhibited responses to UK 14,304, but not to PE. The effect of nitroprusside to antagonize UK 14,304 responses was prevented by inhibition of guanylyl cyclase or by blockade of KATP channels, but not by blockade of other potassium channels. Results were similar in EDL muscles. These data provide the first evidence for α2-adrenoceptor-mediated constriction in slow-twitch muscle, and show that it is sensitive to modulation by NO via a cGMP-dependent mechanism that requires KATP channel activation. Based on the similar findings in soleus and EDL muscles, fibre type does not appear to determine the innate vascular response to α1- or α2-adrenoceptor activation. PMID:15618269

  8. Retrospectively and prospectively modulated hippocampal place responses are differentially distributed along a common path in a continuous T-maze.

    PubMed

    Catanese, Julien; Viggiano, Alessandro; Cerasti, Erika; Zugaro, Michaël B; Wiener, Sidney I

    2014-09-24

    Hippocampal place responses can be prospectively or retrospectively modulated by the animal's future or prior trajectory. Two main hypotheses explain this. The "multiple-map hypothesis" switches between different maps for different trajectories (rate remapping). In contrast, in the "buffer hypothesis," the hippocampus encodes an ongoing representation that includes the recent past and/or the impending future choice. This study examines the distribution of prospective and retrospective responses distributed along a common path in a continuous T-maze (providing all four combinations of provenance and destination) during a visual discrimination task. The multiple-map hypothesis predicts either uniform distributions or concerted shifts about a task-decision relevant point, whereas the buffer hypothesis predicts a time-limited overexpression around choice points (with retrospective responses after the central arm entry point and prospective responses nearer its exit). Here bilateral recordings in the dorsal CA1 region of the rat hippocampus show that retrospective responses were twice as prevalent as prospective responses. Furthermore, retrospective and prospective modulations have distinct spatial distributions, with retrospective primarily in the first two-thirds of the central arm and prospective restricted to the last third. To test for possible trial-by-trial remapping in relation to the two-thirds transition point, data from the first and second halves of the sessions were compared. Backward drift of path-modulated activity was significant only for retrospective, but not prospective, fields. Thus, these data are more consistent with the buffer hypothesis. Retrospective and prospective modulation would then participate in a single hippocampal representation of spatial and behavioral context.

  9. Nitrate-responsive miR393/AFB3 regulatory module controls root system architecture in Arabidopsis thaliana.

    PubMed

    Vidal, Elena A; Araus, Viviana; Lu, Cheng; Parry, Geraint; Green, Pamela J; Coruzzi, Gloria M; Gutiérrez, Rodrigo A

    2010-03-02

    One of the most striking examples of plant developmental plasticity to changing environmental conditions is the modulation of root system architecture (RSA) in response to nitrate supply. Despite the fundamental and applied significance of understanding this process, the molecular mechanisms behind nitrate-regulated changes in developmental programs are still largely unknown. Small RNAs (sRNAs) have emerged as master regulators of gene expression in plants and other organisms. To evaluate the role of sRNAs in the nitrate response, we sequenced sRNAs from control and nitrate-treated Arabidopsis seedlings using the 454 sequencing technology. miR393 was induced by nitrate in these experiments. miR393 targets transcripts that code for a basic helix-loop-helix (bHLH) transcription factor and for the auxin receptors TIR1, AFB1, AFB2, and AFB3. However, only AFB3 was regulated by nitrate in roots under our experimental conditions. Analysis of the expression of this miR393/AFB3 module, revealed an incoherent feed-forward mechanism that is induced by nitrate and repressed by N metabolites generated by nitrate reduction and assimilation. To understand the functional role of this N-regulatory module for plant development, we analyzed the RSA response to nitrate in AFB3 insertional mutant plants and in miR393 overexpressors. RSA analysis in these plants revealed that both primary and lateral root growth responses to nitrate were altered. Interestingly, regulation of RSA by nitrate was specifically mediated by AFB3, indicating that miR393/AFB3 is a unique N-responsive module that controls root system architecture in response to external and internal N availability in Arabidopsis.

  10. Acetylbritannilactone Modulates MicroRNA-155-Mediated Inflammatory Response in Ischemic Cerebral Tissues

    PubMed Central

    Wen, Ya; Zhang, Xiangjian; Dong, Lipeng; Zhao, Jingru; Zhang, Cong; Zhu, Chunhua

    2015-01-01

    Inflammatory responses play a critical role in ischemic brain injury. MicroRNA-155 (miR-155) induces the expression of inflammatory cytokines, and acetylbritannilactone (ABL) exerts potent antiinflammatory actions by inhibiting expression of inflammation-related genes. However, the functions of miR-155 and the actual relationship between ABL and miR-155 in ischemia-induced cerebral inflammation remain unclear. In this study, cerebral ischemia of wild-type (WT) and miR-155−/− mice was induced by permanent middle cerebral artery occlusion (MCAO). pAd-miR-155 was injected into the lateral cerebral ventricle 24 h before MCAO to induce miR-155 overexpression. MCAO mice and oxygen-glucose deprivation (OGD)-treated BV2 cells were used to examine the effects of ABL and miR-155 overexpression or deletion on the expression of proinflammatory cytokines. We demonstrated that ABL treatment significantly reduced neurological deficits and cerebral infarct volume by inhibiting tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression in ischemic cerebral tissue and OGD-treated BV2 cells. Mechanistic studies suggested that the observed decrease in TNF-α and IL-1β expression was attributable to the ABL-induced suppression of the expression of nuclear factor-kappa B (NF-κB) and Toll-like receptor 4 (TLR4). We further found that miR-155 promoted TNF-α and IL-1β expression by upregulating TLR4 and downregulating the expression of suppressor of cytokine signaling 1 (SOCS1) and myeloid differentiation primary response gene 88 (MyD88), while ABL exerted an inhibitory effect on miR-155-mediated gene expression. In conclusion, miR-155 mediates inflammatory responses in ischemic cerebral tissue by modulating TLR4/MyD88 and SOCS1 expression, and ABL exerts its antiinflammatory action by suppressing miR-155 expression, suggesting a novel miR-155-based therapy for ischemic stroke. PMID:25811992

  11. Suppressor of cytokine signaling 2 modulates the immune response profile and development of experimental cerebral malaria.

    PubMed

    Brant, Fatima; Miranda, Aline S; Esper, Lisia; Gualdrón-López, Melisa; Cisalpino, Daniel; de Souza, Danielle da Gloria; Rachid, Milene Alvarenga; Tanowitz, Herbert B; Teixeira, Mauro Martins; Teixeira, Antônio Lucio; Machado, Fabiana Simão

    2016-05-01

    Plasmodium falciparum infection results in severe malaria in humans, affecting various organs, including the liver, spleen and brain, and resulting in high morbidity and mortality. The Plasmodium berghei ANKA (PbA) infection in mice closely recapitulates many aspects of human cerebral malaria (CM); thus, this model has been used to investigate the pathogenesis of CM. Suppressor of cytokine signaling 2 (SOCS2), an intracellular protein induced by cytokines and hormones, modulates the immune response, neural development, neurogenesis and neurotrophic pathways. However, the role of SOCS2 during CM remains unknown. SOCS2 knockout (SOCS2(-/-)) mice infected with PbA show an initial resistance to infection with reduced parasitemia and production of TNF, TGF-β, IL-12 and IL-17 in the brain. Interestingly, in the late phase of infection, SOCS2(-/-) mice display increased parasitemia and reduced Treg cell infiltration, associated with enhanced levels of Th1 and Th17 cells and related cytokines IL-17, IL-6, and TGF-β in the brain. A significant reduction in protective neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), was also observed. Moreover, the molecular alterations in the brain of infected SOCS2(-/-) mice were associated with anxiety-related behaviors and cognition impairment. Mechanistically, these results revealed enhanced nitric oxide (NO) production in PbA-infected SOCS2(-/-) mice, and the inhibition of NO synthesis through l-NAME led to a marked decrease in survival, the disruption of parasitemia control and more pronounced anxiety-like behavior. Treatment with l-NAME also shifted the levels of Th1, Th7 and Treg cells in the brains of infected SOCS2(-/-) mice to the background levels observed in infected WT, with remarkable exception of increased CD8(+)IFN(+) T cells and inflammatory monocytes. These results indicate that SOCS2 plays a dual role during PbA infection, being detrimental

  12. Lactobacillus crispatus Modulates Vaginal Epithelial Cell Innate Response to Candida albicans

    PubMed Central

    Niu, Xiao-Xi; Li, Ting; Zhang, Xu; Wang, Su-Xia; Liu, Zhao-Hui

    2017-01-01

    Background: Vulvovaginal candidiasis is caused by Candida albicans. The vaginal epithelium, as the first site of the initial stage of infection by pathogens, plays an important role in resisting genital tract infections. Moreover, lactobacilli are predominant members of the vaginal microbiota that help to maintain a normal vaginal microenvironment. Therefore, Lactobacillus crispatus was explored for its capacity to intervene in the immune response of vaginal epithelial cells VK2/E6E7 to C. albicans. Methods: We examined the interleukin-2 (IL-2), 4, 6, 8, and 17 produced by VK2/E6E7 cells infected with C. albicans and treated with L. crispatus in vitro. The capacity of L. crispatus to adhere to VK2/E6E7 and inhibit C. albicans growth was also tested by scanning electron microscopy (SEM) and adhesion experiments. Results: Compared with group VK2/E6E7 with C. albicans, when treated with L. crispatus, the adhesion of C. albicans to VK2/E6E7 cells decreased significantly by 52.87 ± 1.22%, 47.03 ± 1.35%, and 42.20 ± 1.55% under competition, exclusion, and displacement conditions, respectively. SEM revealed that the invasion of C. albicans into VK2/E6E7 cells was caused by induced endocytosis and active penetration. L. crispatus could effectively protect the cells from the virulence of hyphae and spores of C. albicans and enhance the local immune function of the VK2/E6E7 cells. The concentrations of IL-2, 6, and 17 were upregulated significantly (P < 0.01) and that of IL-8 were downregulated significantly (P < 0.01) in infected VK2/E6E7 cells treated with L. crispatus. The concentration of IL-4 was similar to that of the group VK2/E6E7 with C. albicans (24.10 ± 0.97 vs. 23.12 ± 0.76 pg/ml, P = 0.221). Conclusions: L. crispatus can attenuate the virulence of C. albicans, modulate the secretion of cytokines and chemokines, and enhance the immune response of VK2/E6E7 cells in vitro. The vaginal mucosa has a potential function in the local immune responses against

  13. ERP responses to processing prosodic phrasing of sentences in amplitude modulated noise.

    PubMed

    Carroll, Rebecca; Ruigendijk, Esther

    2016-02-01

    Intonation phrase boundaries (IPBs) were hypothesized to be especially difficult to process in the presence of an amplitude modulated noise masker because of a potential rhythmic competition. In an event-related potential study, IPBs were presented in silence, stationary, and amplitude modulated noise. We elicited centro-parietal Closure Positive Shifts (CPS) in 23 young adults with normal hearing at IPBs in all acoustic conditions, albeit with some differences. CPS peak amplitudes were highest in stationary noise, followed by modulated noise, and lowest in silence. Both noise types elicited CPS delays, slightly more so in stationary compared to amplitude modulated noise. These data suggest that amplitude modulation is not tantamount to a rhythmic competitor for prosodic phrasing but rather supports an assumed speech perception benefit due to local release from masking. The duration of CPS time windows was, however, not only longer in noise compared to silence, but also longer for amplitude modulated compared to stationary noise. This is interpreted as support for additional processing load associated with amplitude modulation for the CPS component. Taken together, processing prosodic phrasing of sentences in amplitude modulated noise seems to involve the same issues that have been observed for the perception and processing of segmental information that are related to lexical items presented in noise: a benefit from local release from masking, even for prosodic cues, and a detrimental additional processing load that is associated with either stream segregation or signal reconstruction.

  14. Accurate defect die placement and nuisance defect reduction for reticle die-to-die inspections

    NASA Astrophysics Data System (ADS)

    Wen, Vincent; Huang, L. R.; Lin, C. J.; Tseng, Y. N.; Huang, W. H.; Tuo, Laurent C.; Wylie, Mark; Chen, Ellison; Wang, Elvik; Glasser, Joshua; Kelkar, Amrish; Wu, David

    2015-10-01

    Die-to-die reticle inspections are among the simplest and most sensitive reticle inspections because of the use of an identical-design neighboring-die for the reference image. However, this inspection mode can have two key disadvantages: (1) The location of the defect is indeterminate because it is unclear to the inspector whether the test or reference image is defective; and (2) nuisance and false defects from mask manufacturing noise and tool optical variation can limit the usable sensitivity. The use of a new sequencing approach for a die-to-die inspection can resolve these issues without any additional scan time, without sacrifice in sensitivity requirement, and with a manageable increase in computation load. In this paper we explore another approach for die-to-die inspections using a new method of defect processing and sequencing. Utilizing die-to-die double arbitration during defect detection has been proven through extensive testing to generate accurate placement of the defect in the correct die to ensure efficient defect disposition at the AIMS step. The use of this method maintained the re