665 research outputs found
Evidence for impaired extinction learning in humans after distal stress exposure
Stressful or traumatic events can be risk factors for anxiety or trauma- and stressor-related disorders. In this regard, it has been shown that stress affects aversive learning and memory processes. In rodents, stress exposure 10 days prior to fear acquisition impairs fear extinction. However, in humans the effect of distal stress on fear conditioning is sparse. Therefore, we examined the influence of distal stress on fear memory in humans in two studies. In Study 1, participants underwent either socially evaluated cold-pressor test (SECPT) or sham procedure 10 days or 40 min before a fear conditioning paradigm (four groups, N = 78). In Study 2, context effects were examined by conducting SECPT and sham procedures 10 days prior conditioning either in the later fear conditioning context or in another context (three groups, N = 69). During acquisition phase, one geometrical shape (conditioned stimulus, CS+) was paired with painful electric shocks (unconditioned stimulus, US), but never a second shape (CS−). Extinction phase was identical to acquisition, but without US delivery. Importantly, for Study 1 these phases were conducted on one day, while for Study 2 on two separated days. Successful fear acquisition was indicated by aversive ratings and startle potentiation to CS+ versus CS− in both studies. Interestingly, participants stressed 10 days earlier showed impaired extinction on the implicit level (startle potentiation to CS+ vs. CS−) in Study 1 and only in the acquisition context on the explicit level (aversive ratings for CS+ vs. CS−) in Study 2. In sum, distal stress may strengthen later acquired fear memories and thereby impair fear extinction. This finding could have clinical implications, showing that prior stress exposure sensitizes later aversive processing and impairs therapy
New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages
Dietary supplementation with L-arginine was shown to improve immune responses in various inflammatory models. However, the molecular mechanisms underlying L-arginine effects on immune cells remain unrecognized. Herein, we tested the hypothesis that a limitation of L-arginine could lead to the uncoupled state of murine macrophage inducible nitric oxide synthase and, therefore, increase inducible nitric-oxide-synthase-derived superoxide anion formation. Importantly, we demonstrated that L-arginine dose- and time dependently potentiated superoxide anion production in bacterial endotoxin-stimulated macrophages, although it did not influence NADPH oxidase expression and activity. Detailed analysis of macrophage activation showed the time dependence between LPS-induced iNOS expression and increased O2∙− formation. Moreover, downregulation of macrophage iNOS expression, as well as the inhibition of iNOS activity by NOS inhibitors, unveiled an important role of this enzyme in controlling O2∙− and peroxynitrite formation during macrophage stimulation. In conclusion, our data demonstrated that simultaneous induction of NADPH oxidase, together with the iNOS enzyme, can result in the uncoupled state of iNOS resulting in the production of functionally important levels of O2∙− soon after macrophage activation with LPS. Moreover, we demonstrated, for the first time that increased concentrations of L-arginine further potentiate iNOS-dependent O2∙− formation in inflammatory macrophages
Field-effect transistors assembled from functionalized carbon nanotubes
We have fabricated field effect transistors from carbon nanotubes using a
novel selective placement scheme. We use carbon nanotubes that are covalently
bound to molecules containing hydroxamic acid functionality. The functionalized
nanotubes bind strongly to basic metal oxide surfaces, but not to silicon
dioxide. Upon annealing, the functionalization is removed, restoring the
electronic properties of the nanotubes. The devices we have fabricated show
excellent electrical characteristics.Comment: 5 pages, 6 figure
An empirical Bayesian approach for model-based inference of cellular signaling networks
Background
A common challenge in systems biology is to infer mechanistic descriptions of biological process given limited observations of a biological system. Mathematical models are frequently used to represent a belief about the causal relationships among proteins within a signaling network. Bayesian methods provide an attractive framework for inferring the validity of those beliefs in the context of the available data. However, efficient sampling of high-dimensional parameter space and appropriate convergence criteria provide barriers for implementing an empirical Bayesian approach. The objective of this study was to apply an Adaptive Markov chain Monte Carlo technique to a typical study of cellular signaling pathways. Results
As an illustrative example, a kinetic model for the early signaling events associated with the epidermal growth factor (EGF) signaling network was calibrated against dynamic measurements observed in primary rat hepatocytes. A convergence criterion, based upon the Gelman-Rubin potential scale reduction factor, was applied to the model predictions. The posterior distributions of the parameters exhibited complicated structure, including significant covariance between specific parameters and a broad range of variance among the parameters. The model predictions, in contrast, were narrowly distributed and were used to identify areas of agreement among a collection of experimental studies. Conclusion
In summary, an empirical Bayesian approach was developed for inferring the confidence that one can place in a particular model that describes signal transduction mechanisms and for inferring inconsistencies in experimental measurements
Mapping of functionalized regions on carbon nanotubes by scanning tunneling microscopy
Scanning tunneling microscopy (STM) gives us the opportunity to map the
surface of functionalized carbon nanotubes in an energy resolved manner and
with atomic precision. But this potential is largely untapped, mainly due to
sample stability issues which inhibit reliable measurements. Here we present a
simple and straightforward solution that makes away with this difficulty, by
incorporating the functionalized multiwalled carbon nanotubes (MWCNT) into a
few layer graphene - nanotube composite. This enabled us to measure energy
resolved tunneling conductance maps on the nanotubes, which shed light on the
level of doping, charge transfer between tube and functional groups and the
dependence of defect creation or functionalization on crystallographic
orientation.Comment: Keywords: functionalization, carbon nanotubes, few layer graphene,
STM, CITS, ST
3D characterization of CdSe nanoparticles attached to carbon nanotubes
The crystallographic structure of CdSe nanoparticles attached to carbon
nanotubes has been elucidated by means of high resolution transmission electron
microscopy and high angle annular dark field scanning transmission electron
microscopy tomography. CdSe rod-like nanoparticles, grown in solution together
with carbon nanotubes, undergo a morphological transformation and become
attached to the carbon surface. Electron tomography reveals that the
nanoparticles are hexagonal-based with the (001) planes epitaxially matched to
the outer graphene layer.Comment: 7 pages, 8 figure
Thermoelectric properties of lead chalcogenide core-shell nanostructures
We present the full thermoelectric characterization of nanostructured bulk
PbTe and PbTe-PbSe samples fabricated from colloidal core-shell nanoparticles
followed by spark plasma sintering. An unusually large thermopower is found in
both materials, and the possibility of energy filtering as opposed to grain
boundary scattering as an explanation is discussed. A decreased Debye
temperature and an increased molar specific heat are in accordance with recent
predictions for nanostructured materials. On the basis of these results we
propose suitable core-shell material combinations for future thermoelectric
materials of large electric conductivities in combination with an increased
thermopower by energy filtering.Comment: 12 pages, 8 figure
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