细胞外信号调节蛋白激酶-cAMP反应元件结合蛋白信号通路在应激所致抑郁行为障碍中的作用

Stress is the most important factor in the vulnerability to depression and other behavioral disorders, but the mechanisms that stress signals are transferred into depression are far from understanding. To date, the neurotransmitters, neurotrophins and signal pathway have been concerned in the topic focusing on the pathophysiology of depression, but there are still many puzzles. Increasing evidence has indicated that the alteration in neuronal plasticity is the “trace” of stress-induced damages. The extracellular signal-regulated protein kinase(ERK)-cyclic-AMP-responsive element（CRE）-binding protein(CREB)signal pathway is a powerful intracellular signal transduction pathway participating in neuronal plasticity which is involved in higher brain cognitive functions such as learning and memory. However, so far, little is known about the role of the ERK-CREB signal pathway in response to stress and emotional modulations. Thus the aim of the study was to systematically investigate the role of the ERK-CEB signal pathway in depressive-like behaviors induced by stress. Depression animal models, antidepressant agent treatment and disruption of signal pathway in specific brain regions were applied. In the present study, three experiment sessions were designed to make sure whether the ERK-CREB signal pathway was indeed one of pathophysiological mechanisms of depressive-like behaviors induced by stress. In experiment one, two different stress animal models were applied, chronic forced swim stress and chronic empty water bottle stress. After stress, all animals were tested behaviorally using open-field, elevated-plus maze and saccharine preference test, and brain samples were processed for determination of ERK, P-ERK, CREB and P-CREB using western blot. The relationships between the proteins of ERK, P-ERK, CREB and P-CREB in the brain and the behavioral variables were also analyzed. In experiment two, rats were treated with antidepressant agent fluoxetine once a day for 21 consecutive days, then the brain levels of ERK, P-ERK, CREB and P-CREB was determined, the depressive-like behaviors were also examined. In experiment three, mitogen activated extracellular-signal-regulated kinase kinase (MEK) inhibitor U0126 was administrated to inhabit the activation of ERK in the hippocampus and prefrontal cortex respectively, then behavioral measurements and protein detection were conducted. The main results of the study were as the following: (1) Chronic forced swim stress induced animals to suffer depression and disrupted the ERK-CREB signal pathway in hippocampus and prefrontal cortex. There were significant correlations between P-ERK2, P-CREB and multiple variables of depressive-like behaviors. (2) Chronic empty water bottle stress did not induce depressive-like behaviors. Such stress decreased the brain level of P-ERK2 in hippocampus and prefrontal cortex, but the level of P-CREB in the hippocampus was increased. (3) The antidepressant agent fluoxetine relieved depressive-like behaviors and increased the activities of the ERK-CREB signal pathway in stressed animals. (4) Animals treated with U0126 injection into hippocampus showed decreased activities of the ERK-CREB signal pathway in the hippocampus, and suffered depression comorbid with anxiety. (5) Animals treated with U0126 injection into prefrontal cortex showed decreased activities of the ERK-CREB signal pathway in the prefrontal cortex, and exhibited depressive-like behaviors. In conclusion, The ERK-CREB signal pathway in the hippocampus and prefrontal cortex was involved in stress responses and significantly correlated with depressive-like behaviors; The ERK-CREB signal pathway in the hippocampus and prefrontal cortex participated in the mechanism that fluoxetine reversed stress-induced behavioral disorders, and might be the target pathway of the therapeutic action of antidepressants; The disruption of the ERK-CREB signal pathway in the hippocampus or prefrontal cortex led to depressive-like behaviors in animals, suggesting that disruption of ERK-CREB pathway in the hippocampus or prefrontal cortex was involved in the pathophysiology of depression, and might be at least one of the mechanisms of depression induced by stress.

Miniature Eye Movements Enhance Fine Spatial Details

Our eyes are constantly in motion. Even during visual fixation, small eye movements continually jitter the location of gaze. It is known that visual percepts tend to fade when retinal image motion is eliminated in the laboratory. However, it has long been debated whether, during natural viewing, fixational eye movements have functions in addition to preventing the visual scene from fading. In this study, we analysed the influence in humans of fixational eye movements on the discrimination of gratings masked by noise that has a power spectrum similar to that of natural images. Using a new method of retinal image stabilization18, we selectively eliminated the motion of the retinal image that normally occurs during the intersaccadic intervals of visual fixation. Here we show that fixational eye movements improve discrimination of high spatial frequency stimuli, but not of low spatial frequency stimuli. This improvement originates from the temporal modulations introduced by fixational eye movements in the visual input to the retina, which emphasize the high spatial frequency harmonics of the stimulus. In a natural visual world dominated by low spatial frequencies, fixational eye movements appear to constitute an effective sampling strategy by which the visual system enhances the processing of spatial detail.

Edmund Burke and the heritage of oral culture

The dissertation proposes that one of the more fruitful ways of interpreting Burke's work is to evaluate him as an oral performer rather than a literary practitioner and it argues that in his voice can be heard the modulations of the genres and conventions of oral composition of eighteenth-century Gaelic Ireland. The first chapter situates Burke in the milieu of the Gaelic landed class of eighteenth-century Ireland. The next chapter examines how the rich oral culture of the Munster Gaelic gentry, where Burke spent his childhood days, was to provide a lasting influence on the form and content of Burke's work. His speeches on the British constitution are read in the context of the historical and literary culture of the Jacobites, specifically the speculum principis, Párliament na mBán. The third chapter surveys the tradition of Anglo-Irish theoretical writings on oratory and discusses how Burke is aligned with this school. The focus is on how Burke's thought and practice, his 'idioms', might be understood as being mediated through the criterion of orality rather than literature. The remaining chapters discuss Burke's politics and performance in the light of Gaelic cultural practices such as the rituals of the courts of poetry, the Warrant Poems or Barántas; the performance of funeral laments and elegies, Caoineadh, the laments for the fallen nobility, Marbhna na daoine uaisle, the satires and the political vision allegories of Munster, Aislingí na Mumhan; to show how they provide us with a remarkable context for discussing Burke's poetical-political performance. In hearing Burke's voice through the body of Gaelic culture our understanding of Burke's position in the wider world of the eighteenth century (and hence his meaning) is profoundly affected.

Correction for Eddy Current-Induced Echo-Shifting Effect in Partial-Fourier Diffusion Tensor Imaging.

In most diffusion tensor imaging (DTI) studies, images are acquired with either a partial-Fourier or a parallel partial-Fourier echo-planar imaging (EPI) sequence, in order to shorten the echo time and increase the signal-to-noise ratio (SNR). However, eddy currents induced by the diffusion-sensitizing gradients can often lead to a shift of the echo in k-space, resulting in three distinct types of artifacts in partial-Fourier DTI. Here, we present an improved DTI acquisition and reconstruction scheme, capable of generating high-quality and high-SNR DTI data without eddy current-induced artifacts. This new scheme consists of three components, respectively, addressing the three distinct types of artifacts. First, a k-space energy-anchored DTI sequence is designed to recover eddy current-induced signal loss (i.e., Type 1 artifact). Second, a multischeme partial-Fourier reconstruction is used to eliminate artificial signal elevation (i.e., Type 2 artifact) associated with the conventional partial-Fourier reconstruction. Third, a signal intensity correction is applied to remove artificial signal modulations due to eddy current-induced erroneous T2(∗) -weighting (i.e., Type 3 artifact). These systematic improvements will greatly increase the consistency and accuracy of DTI measurements, expanding the utility of DTI in translational applications where quantitative robustness is much needed.

Temporal phenomena in inductively coupled chlorine and argon-chlorine discharges

Reproducible modulations in low-pressure, inductively coupled discharges operating in chlorine and argon-chlorine mixtures have been observed and studied. Changes in the light output, floating potential, negative ion fraction, and charged particle densities were observed. Here we report two types of unstable operational modes in an inductively coupled discharge. On the one hand, when the discharge was matched, to minimize reflected power, instabilities were observed in argon-chlorine plasmas over limited operating conditions of input power and gas pressure. The instability window decreased with increasing chlorine content and was observed for chlorine concentrations between 30% and 60% only. However, when operating at pressures below 5 mTorr and the discharge circuit detuned to increase the reflected power, modulations were observed in a pure chlorine discharge. These modulations varied in nature from a series of sharp bursts to a very periodic behavior and can be controlled, by variation of the matching conditions, to produce an apparent pulsed plasma environment. (C) 2005 American Institute of Physics.

Clinical implementation of dynamic multileaf collimation for compensated bladder treatments.

BACKGROUND AND PURPOSE: To describe the clinical implementation of dynamic multileaf collimation (DMLC). Custom compensated four-field treatments of carcinoma of the bladder have been used as a simple test site for the introduction of intensity modulated radiotherapy.MATERIALS AND METHODS: Compensating intensity modulations are calculated from computed tomography (CT) data, accounting for scattered, as well as primary radiation. Modulations are converted to multileaf collimator (MLC) leaf and jaw settings for dynamic delivery on a linear accelerator. A full dose calculation is carried out, accounting for dynamic leaf and jaw motion and transmission through these components. Before treatment, a test run of the delivery is performed and an absolute dose measurement made in a water or solid water phantom. Treatments are verified by in vivo diode measurements and real-time electronic portal imaging. RESULTS: Seven patients have been treated using DMLC. The technique improves dose homogeneity within the target volume, reducing high dose areas and compensating for loss of scatter at the beam edge. A typical total treatment time is 20 min. CONCLUSIONS: Compensated bladder treatments have proven an effective test site for DMLC in an extremely busy clinic.

Plasma ion evolution in the wake of a high-intensity ultrashort laser pulse

Experimental investigations of the late-time ion structures formed in the wake of an ultrashort, intense laser pulse propagating in a tenuous plasma have been performed using the proton imaging technique. The pattern found in the wake of the laser pulse shows unexpectedly regular modulations inside a long, finite width channel. On the basis of extensive particle in cell simulations of the plasma evolution in the wake of the pulse, we interpret this pattern as due to ion modulations developed during a two-stream instability excited by the return electric current generated by the wakefield.

Phasic modulation of corticomotor excitability during passive movement of the upper limb: effects of movement frequency and muscle specificity

Modulations in the excitability of spinal reflex pathways during passive rhythmic movements of the lower limb have been demonstrated by a number of previous studies [4]. Less emphasis has been placed on the role of supraspinal pathways during passive movement, and on tasks involving the upper limb. In the present study, transcranial magnetic stimulation (TMS) was delivered to subjects while undergoing passive flexion-extension movements of the contralateral wrist. Motor evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the movement cycle during three different frequencies of movement. Evidence of marked modulations in pathway excitability was found in the MEP amplitudes of the FCR muscle, with responses inhibited and facilitated from static values in the extension and flexion phases, respectively. The results indicated that at higher frequencies of movement there was greater modulation in pathway excitability. Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals revealed modulations in the extent of inhibition in MEP amplitude at high movement frequencies. In the APE muscle, there was some evidence of phasic modulations of response amplitude, although the effects were less marked than those observed in FCR. It is speculated that these modulatory effects are mediated via Ia afferent pathways and arise as a consequence of the induced forearm muscle shortening and lengthening. Although the level at which this input influences the corticomotoneuronal pathway is difficult to discern, a contribution from cortical regions is suggested. (C) 2001 Published by Elsevier Science B.V.

Time-resolved optical photometry of the ultracompact binary 4U 0614+091

We present a detailed optical study of the ultracompact X-ray binary 4U 0614+091. We have used 63 hr of time-resolved optical photometry taken with three different telescopes (IAC80, NOT, and SPM) to search for optical modulations. The power spectra of each data set reveals sinusoidal modulations with different periods, which are not always present. The strongest modulation has a period of 51.3 minutes, a semiamplitude of 4.6 mmag, and is present in the IAC80 data. The SPM and NOT data show periods of 42 minutes and 64 minutes, respectively, but with much weaker amplitudes, 2.6 mmag and 1.3 mmag, respectively. These modulations arise from either X-ray irradiation of the inner face of the secondary star and/or a superhump modulation from the accretion disk, or quasiperiodic modulations in the accretion disk. It is unclear whether these periods/quasi-periodic modulations are related to the orbital period; however, the strongest period of 51.3 minutes is close to earlier tentative orbital periods. Further observations taken over a long baseline are encouraged.

Phonological oddballs in the focus of attention elicit a normal P3b in dyslexic adults

Difficulties in phonological processing have been proposed to be the core symptom of developmental dyslexia. Phoneme awareness tasks have been shown to both index and predict individual reading ability. In a previous experiment, we observed that dyslexic adults fail to display a P3a modulation for phonological deviants within an alliterated word stream when concentrating primarily on a lexical decision task [Fosker and Thierry, 2004, Neurosci. Lett. 357, 171-174]. Here we recorded the P3b oddball response elicited by initial phonemes within streams of alliterated words and pseudo-words when participants focussed directly on detecting the oddball phonemes. Despite significant verbal screening test differences between dyslexic adults and controls, the error rates, reactions times, and main components (P2, N2, P3a, and P3b) were indistinguishable across groups. The only difference between groups was found in the NI range, where dyslexic participants failed to show the modulations induced by phonological pairings (/b/-/p/ versus /r/ /g/) in controls. In light of previous P3a differences, these results suggest an important role for attention allocation in the manifestation of phonological deficits in developmental dyslexia. (c) 2005 Elsevier B.V. All rights reserved.

Creation of persistent, straight, 2 mm long laser driven channels in underdense plasmas

The experimental study of the behavior of deuterium plasma with densities between 2 X 1018 and 2 x 10(20) cm(-3), subjected to a 6 TW, 30 ps, 3 X 10(18) W cm(-2) laser pulse, is presented Conclusive experimental proof that a single straight channel is generated when the laser pulse interacts with the lowest densities is provided This channel shows no small-scale longitudinal density modulations, extends up to 2 mm in length and persists for up to 150 ps after the peak of the interaction Bifurcation of the channel after 1 mm propagation distance is observed for the first time For higher density interactions, above the relativistic self-focusing threshold, bubblelike structures are observed to form at late times These observations have implications for both laser wakefield accelerators and fast ignition inertial fusion studies (C) 2010 American Institute of Physics [doi 10 1063/1 3505305]

Music, rhythm, rise time perception and developmental dyslexia: Perception of musical meter predicts reading and phonology

Introduction: Rhythm organises musical events into patterns and forms, and rhythm perception in music is usually studied by using metrical tasks. Metrical structure also plays an organisational function in the phonology of language, via speech prosody, and there is evidence for rhythmic perceptual difficulties in developmental dyslexia. Here we investigate the hypothesis that the accurate perception of musical metrical structure is related to basic auditory perception of rise time, and also to phonological and literacy development in children. Methods: A battery of behavioural tasks was devised to explore relations between musical metrical perception, auditory perception of amplitude envelope structure, phonological awareness (PA) and reading in a sample of 64 typically-developing children and children with developmental dyslexia. Results: We show that individual differences in the perception of amplitude envelope rise time are linked to musical metrical sensitivity, and that musical metrical sensitivity predicts PA and reading development, accounting for over 60% of variance in reading along with age and I.Q. Even the simplest metrical task, based on a duple metrical structure, was performed significantly more poorly by the children with dyslexia. Conclusions: The accurate perception of metrical structure may be critical for phonological development and consequently for the development of literacy. Difficulties in metrical processing are associated with basic auditory rise time processing difficulties, suggesting a primary sensory impairment in developmental dyslexia in tracking the lower-frequency modulations in the speech envelope. © 2010 Elsevier.

Novae in the SuperWASP data base

We present the results of trawling through the SuperWASP data base for classical and recurrent novae. We report light curves for a nova in eruption, and for classical novae and a recurrent nova in quiescence. For five objects in quiescence, we report periodicity, arising in most cases from orbital modulation of the light from the cool secondary star. The stability of the SuperWASP system means that these data have huge potential for the study not only of novae in eruption, but also of the long-term modulations of light during quiescence.

Bright quasi-phase-matched soft-x-ray harmonic radiation from argon ions

Selective enhancement (> 10(3)) of harmonics extending to the water window (similar to 4 nm) generated in an argon gas filled straight bore capillary waveguide is demonstrated. This enhancement is in good agreement with modeling which indicates that multimode quasi-phase-matching is achieved by rapid axial intensity modulations caused by beating between the fundamental and higher-order capillary modes. Substantial pulse energies (> 10 nJ per pulse per harmonic order) at wavelengths beyond the carbon K edge (similar to 4.37 nm, similar to 284 eV) up to similar to 360 eV are observed from argon ions for the first time.

SPECTRALLY MODULATED 2ND-HARMONIC EMISSION FROM LASER-PLASMA FILAMENTS

Spectra of forward emitted second harmonic light from laser interaction with filamentary plasmas have been experimentally studied. Rather regular modulations in the frequency domain have been observed into overall red-shifted spectra. The observed spectral features are consistent with self-phase-modulation of the intense laser light in growing filaments. A model accounts for this effect.