2,209 research outputs found
Error-Related Activity and Correlates of Grammatical Plasticity
Cognitive control involves not only the ability to manage competing task demands,
but also the ability to adapt task performance during learning. This study
investigated how violation-, response-, and feedback-related
electrophysiological (EEG) activity changes over time during language learning.
Twenty-two Dutch learners of German classified short prepositional phrases
presented serially as text. The phrases were initially presented without
feedback during a pre-test phase, and then with feedback in a training phase on
two separate days spaced 1 week apart. The stimuli included
grammatically correct phrases, as well as grammatical violations of gender and
declension. Without feedback, participants’ classification was near
chance and did not improve over trials. During training with feedback,
behavioral classification improved and violation responses appeared to both
types of violation in the form of a P600. Feedback-related negative and positive
components were also present from the first day of training. The results show
changes in the electrophysiological responses in concert with improving
behavioral discrimination, suggesting that the activity is related to grammar
learning
Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones
This work was funded by The BBSRC (BB/D004659/1) the Wellcome Trust (080980/Z/06/Z) and the Medical Research Council (G0701003). Colin Hay was funded by the Chief Scientist Office, Scotland. Scott Davidson was funded by a BBSRC strategic studentship (BBS/S/2005/12001). Philip Cowie was funded by the Scottish Universities Life Sciences Alliance (SULCA).Peer reviewedPublisher PD
EPEC Recruits a Cdc42-Specific GEF, Frabin, To Facilitate PAK Activation and Host Cell Colonization.
Enteropathogenic Escherichia coli (EPEC) is an extracellular pathogen that tightly adheres to host cells by forming "actin pedestals" beneath the bacteria, a critical step in pathogenesis. EPEC injects effector proteins that manipulate host cell signaling cascades to trigger pedestal assembly. We have recently shown that one such effector, EspG, hijacks p21-activated kinase (PAK) and sustains its activated state to drive the cytoskeletal changes necessary for attachment of the pathogen to target cells. This EspG subversion of PAK required active Rho family small GTPases in the host cell. Here we show that EPEC itself promotes the activation of Rho GTPases by recruiting Frabin, a host guanine nucleotide exchange factor (GEF) for the Rho GTPase Cdc42. Cells devoid of Frabin showed significantly lower EPEC-induced PAK activation, pedestal formation, and bacterial attachment. Frabin recruitment to sites of EPEC attachment was driven by EspG and required localized enrichment of phosphatidylinositol 4,5-bisphosphate (PIP2) and host Arf6. Our findings identify Frabin as a key target for EPEC to ensure the activation status of cellular GTPases required for actin pedestal formation.IMPORTANCE Enteropathogenic Escherichia coli (EPEC) is a leading cause of diarrhea in children, especially in the developing world. EPEC initiates infection by attaching to cells in the host intestine, triggering the formation of actin-rich "pedestal" structures directly beneath the adherent pathogen. These bacteria inject their own receptor into host cells, which upon binding to a protein on the pathogen surface triggers pedestal formation. Multiple other proteins are also delivered into the cells of the host intestine, which work together to hijack host signaling pathways to drive pedestal production. Here we show how EPEC hijacks a host protein, Frabin, which creates the conditions in the cell necessary for the pathogen to manipulate a specific pathway that promotes pedestal formation. This provides new insights into this essential early stage in disease caused by EPEC.Wellcome Trust
Medical Research Council (MRC
Virulence attenuation of Dengue virus due to augmented glycosaminoglycan-binding affinity and restriction in extraneural dissemination
To gain insight into the role of cell surface glycosaminoglycans (GAG) in dengue virus (DEN) cell tropism and virulence, DEN-2 mouse brain-adapted vaccine candidate, neurovirulent prototype strain (NGC) and low-passage strain, PUO-218, were passaged in BHK-21 and SW13 cells to isolate variants with high affinity for GAG. Sequence comparisons of parent and passage variants revealed five GAG-binding determinants, which all cluster in a surface-exposed region in domain II of the three-dimensional structure of the DEN envelope protein. Using an infectious cDNA clone of NGC and an NGC/PUO-218 prM-E chimeric clone, it was demonstrated that the GAG-binding determinants augment the specific infectivity for BHK-21 and/or SW13 cells by 10- to 170-fold and in some cases marginally reduce that for Vero cells. This altered cell tropism was due to a greater dependence of the variants on cell surface GAG for attachment/entry, given their increased susceptibility to heparin inhibition. The effect of the GAG-binding determinants on virulence was examined in mice deficient in alpha/beta/gamma interferon responses. High GAG affinity strongly correlated with low neuroinvasiveness due to rapid virus clearance from the blood. It was speculated that this mechanism accounts for the attenuation in primates of some DEN vaccine candidates. Interestingly, the GAG-binding variants did not display marked attenuation of neurovirulence and the opposing effect of enhanced neurovirulence was associated with one determinant (Lys126) already present in mouse brain-adapted NGC. This discrepancy of attenuated neuroinvasiveness and augmented neurovirulence may be reconciled by the existence of different mechanisms of virus dissemination in the brain and in extraneural tissues
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Arf6 Can Trigger Wave Regulatory Complex-Dependent Actin Assembly Independent of Arno.
The small GTPase ADP-ribosylation factor 6 (Arf6) anchors at the plasma membrane to orchestrate key functions, such as membrane trafficking and regulating cortical actin cytoskeleton rearrangement. A number of studies have identified key players that interact with Arf6 to regulate actin dynamics in diverse cell processes, yet it is still unknown whether Arf6 can directly signal to the wave regulatory complex to mediate actin assembly. By reconstituting actin dynamics on supported lipid bilayers, we found that Arf6 in co-ordination with Rac1(Ras-related C3 botulinum toxin substrate 1) can directly trigger actin polymerization by recruiting wave regulatory complex components. Interestingly, we demonstrated that Arf6 triggers actin assembly at the membrane directly without recruiting the Arf guanine nucleotide exchange factor (GEF) ARNO (ARF nucleotide-binding site opener), which is able to activate Arf1 to enable WRC-dependent actin assembly. Furthermore, using labelled E. coli, we demonstrated that actin assembly by Arf6 also contributes towards efficient phagocytosis in THP-1 macrophages. Taken together, this study reveals a mechanism for Arf6-driven actin polymerization
Deposition And Drying Dynamics Of Liquid Crystal Droplets
Drop drying and deposition phenomena reveal a rich interplay of fundamental science and engineering, give rise to fascinating everyday effects (coffee rings), and influence technologies ranging from printing to genotyping. Here we investigate evaporation dynamics, morphology, and deposition patterns of drying lyotropic chromonic liquid crystal droplets. These drops differ from typical evaporating colloidal drops primarily due to their concentration-dependent isotropic, nematic, and columnar phases. Phase separation occurs during evaporation, and in the process creates surface tension gradients and significant density and viscosity variation within the droplet. As a result, the drying multiphase drops exhibit different convective currents, drop morphologies, and deposition patterns (coffee-rings)
Effects of intervention upon precompetition state anxiety in elite junior tennis players: The relevance of the matching hypothesis
Reproduced with permission of publisher from:
Terry, P., Coakley, L., & Karageorghis, C. Effects of intervention upon precompetition state anxiety in elite junior tennis players: the relevance of the matching hypothesis. Perceptual and Motor Skills, 1995, 81, 287-296. © Perceptual and Motor Skills 1995The matching hypothesis proposes that interventions for anxiety should be matched to the modality in which anxiety is experienced. This study investigated the relevance of the matching hypothesis for anxiety interventions in tennis. Elite junior tennis players (N = 100; Age: M = 13.9 yr., SD = 1.8 yr.) completed the Competitive State Anxiety Inventory-2 before and after one of four randomly assigned intervention strategies approximately one hour prior to competition at a National Junior Championship. A two-factor multivariate analysis of variance (group x time) with repeated measures on the time factor gave no significant main effect by group but indicated significant reductions in somatic anxiety and cognitive anxiety and a significant increase in self-confidence following intervention. A significant group by time interaction emerged for self-confidence. The results question the need to match intervention strategy to the mode of anxiety experienced
Double Time Window Targeting Technique: Real time DMRG dynamics in the PPP model
We present a generalized adaptive time-dependent density matrix
renormalization group (DMRG) scheme, called the {\it double time window
targeting} (DTWT) technique, which gives accurate results with nominal
computational resources, within reasonable computational time. This procedure
originates from the amalgamation of the features of pace keeping DMRG
algorithm, first proposed by Luo {\it et. al}, [Phys.Rev. Lett. {\bf 91},
049701 (2003)], and the time-step targeting (TST) algorithm by Feiguin and
White [Phys. Rev. B {\bf 72}, 020404 (2005)]. Using the DTWT technique, we
study the phenomena of spin-charge separation in conjugated polymers (materials
for molecular electronics and spintronics), which have long-range
electron-electron interactions and belong to the class of strongly correlated
low-dimensional many-body systems. The issue of real time dynamics within the
Pariser-Parr-Pople (PPP) model which includes long-range electron correlations
has not been addressed in the literature so far. The present study on PPP
chains has revealed that, (i) long-range electron correlations enable both the
charge and spin degree of freedom of the electron, to propagate faster in the
PPP model compared to Hubbard model, (ii) for standard parameters of the PPP
model as applied to conjugated polymers, the charge velocity is almost twice
that of the spin velocity and, (iii) the simplistic interpretation of
long-range correlations by merely renormalizing the {\it U} value of the
Hubbard model fails to explain the dynamics of doped holes/electrons in the PPP
model.Comment: Final (published) version; 39 pages, 13 figures, 1 table; 2 new
references adde
SPIFI: a Direct-Detection Imaging Spectrometer for Submillimeter Wavelengths
The South Pole Imaging Fabry-Perot Interferometer (SPIFI) is the first instrument of its kind -a direct-detection imaging spectrometer for astronomy in the submillimeter band. SPIFI ’s focal plane is a square array of 25 silicon bolometers cooled to 60 mK; the spectrometer consists of two cryogenic scanning Fabry-Perot interferometers in series with a 60-mK bandpass filter. The instrument operates in the short submillimeter windows (350 and 450 μm) available from the ground, with spectral resolving power selectable between 500 and 10,000. At present, SPIFI’s sensitivity is within a factor of 1.5-3 of the photon background limit, comparable with the best heterodyne spectrometers. The instrument ’s large bandwidth and mapping capability provide substantial advantages for specific astrophysical projects, including deep extragalactic observations. We present the motivation for and design of SPIFI and its operational characteristics on the telescope
Short-Pulse, Compressed Ion Beams at the Neutralized Drift Compression Experiment
We have commenced experiments with intense short pulses of ion beams on the
Neutralized Drift Compression Experiment (NDCX-II) at Lawrence Berkeley
National Laboratory, with 1-mm beam spot size within 2.5 ns full-width at half
maximum. The ion kinetic energy is 1.2 MeV. To enable the short pulse duration
and mm-scale focal spot radius, the beam is neutralized in a 1.5-meter-long
drift compression section following the last accelerator cell. A
short-focal-length solenoid focuses the beam in the presence of the volumetric
plasma that is near the target. In the accelerator, the line-charge density
increases due to the velocity ramp imparted on the beam bunch. The scientific
topics to be explored are warm dense matter, the dynamics of radiation damage
in materials, and intense beam and beam-plasma physics including select topics
of relevance to the development of heavy-ion drivers for inertial fusion
energy. Below the transition to melting, the short beam pulses offer an
opportunity to study the multi-scale dynamics of radiation-induced damage in
materials with pump-probe experiments, and to stabilize novel metastable phases
of materials when short-pulse heating is followed by rapid quenching. First
experiments used a lithium ion source; a new plasma-based helium ion source
shows much greater charge delivered to the target.Comment: 4 pages, 2 figures, 1 table. Submitted to the proceedings for the
Ninth International Conference on Inertial Fusion Sciences and Applications,
IFSA 201
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