Beta1 Activity Research Articles

Effect Of Caffeine On Ratings Of Perceived Exertion (rpe) And Electroencephalography (eeg) Activity During Exercise

One of the explanations for the ergogenic effect caffeine has on endurance performance is the reduction in RPE during exercise. The physiological mechanisms accounting for the decrease in RPE remain unclear. PURPOSE: To examine the influence of caffeine on RPE and EEG during 30 min of continuous cycling. EEG was measured to determine the degree of central nervous system functioning during exercise and possibly provide an explanation for any EEG differences due to caffeine ingestion. METHODS: 9 subjects unaccustomed to cycling performed a VO2peak test using a cycle ergometer (mean VO2peak = 35.8 ± 8.7 ml·kg-1·min-1). Subjects then returned for 2, 30-min cycling tests performed on successive days at a workload equal to approximately 60% VO2peak. Prior to the 30-min tests subjects either ingested caffeine (3 mg·kg-1) or a placebo, with the order randomized and the experimenters blinded to order. Fifteen channels of EEG were recorded according to the International 10-20 system of electrode placement. Recordings occurred prior to cycling during a warm-up, at minutes 4-5, 9-10, 14-15, 19-20, 24-25, 29-30, and during cool down. Heart rate (HR) and RPE were also collected during these periods. RESULTS: Peak RPE during the placebo trial was 16.8 ± 2.9 and during the caffeine trial RPE reached 15.8 ± 1.9. While RPE significantly increased in both trials (p = 0.002) the differences between the trials only approached significance (p = 0.074). No significant differences were observed for heart rate between the placebo and caffeine trials at any point before (102.4 ± 9.3 and 100.9 ± 13, respectively), during (peak HR 172.2 ± 18.1 and 173 ± 18.7, respectively), or after (158 ± 9.9 and 159 ± 8.5, respectively) the cycle ergometry test (p = 0.271). The expected EEG response to exercise was observed with an increase in delta wave activity and a decrease in higher frequencies such as beta1 activity (F(10,1131) = 8.326; p=0.00). No significant differences were observed for any EEG variables between the placebo and caffeine trials (p = 0.794). CONCLUSION: The absence of any differences in EEG following caffeine ingestion do not support a central nervous system basis for RPE decreases associated with caffeine ingestion during exercise. However, the findings from this study are limited by the small sample size.

How to Keep the Brain Awake? The Complex Molecular Pharmacogenetics of Wake Promotion

Wake-promoting drugs are widely used to treat excessive daytime sleepiness. The neuronal pathways involved in wake promotion are multiple and often not well characterized. We tested d-amphetamine, modafinil, and YKP10A, a novel wake-promoting compound, in three inbred strains of mice. The wake duration induced by YKP10A and d-amphetamine depended similarly on genotype, whereas opposite strain differences were observed after modafinil. Electroencephalogram (EEG) analysis during drug-induced wakefulness revealed a transient approximately 2 Hz slowing of theta oscillations and an increase in beta-2 (20-35 Hz) activity only after YKP10A. Gamma activity (35-60 Hz) was induced by all drugs in a drug- and genotype-dependent manner. Brain transcriptome and clustering analyses indicated that the three drugs have both common and specific molecular signatures. The correlation between specific EEG and gene-expression signatures suggests that the neuronal pathways activated to stay awake vary among drugs and genetic background.

Murine Pancreatic Beta TC3 Cells Show Greater2′,5′-Oligoadenylate Synthetase (2′5′AS) Antiviral Enzyme Activity and Apoptosis Following IFN-αor Poly(I:C) Treatment than Pancreatic Alpha TC3 Cells

Type 1 diabetes is caused by autoimmune destruction of pancreatic beta cells, possibly virus initiated. Virus infection induces alpha-interferon (IFN-α), leading to upregulation of genes encoding double-stranded (ds) RNA-dependent antiviral enzymes 2′, 5′-oligoadenylate synthetase (2′5′AS) and PKR (p68). To investigate whether beta cell specificity could be due to antiviral differences between beta and alpha cells, we treated beta and alpha TC3 cell lines with IFN-α and/or poly(I:C) (a synthetic dsRNA). Results showed that, following IFN-α stimulation, increases in 2′5′AS levels and activities were significantly higher in beta than alpha cells (P < .001), whereas increases in PKR level and activity were comparable in the two cell types. Poly(I:C) stimulated 2′5′AS activity in beta but not alpha cells, and co-transfection IFN-α plus poly(I:C) induced apoptosis in beta but not alpha cells. These findings suggest that the elevated 2′5′AS response of pancreatic beta cells could render them particularly vulnerable to damage and/or apoptosis during virus infection.

Monitoring effects of acute hypoxia on brain cortical activity by using electromagnetic tomography

The influences of inadequate brain oxygen supply on cognitive and sensorimotor performance are well documented. However, hemodynamic neuroimaging of brain processes under hypoxic conditions has been limited by the organisational constraints of the methodological framework. This study proposes that standardised low-resolution brain electromagnetic tomography (sLORETA) is a suitable and feasible tool for localising brain cortical processes under hypoxic conditions. Electroencephalograms (EEG) from 21 subjects were recorded prior to, and following 40 min of, exposure to normoxic (21 kPa PIO 2) or hypoxic (12.7 kPa PIO 2) conditions, Changes in brain cortical activity were localised using sLORETA. Subjects showed an increase in beta-1 activity following hypoxic exposure. This increase in activity was localised in the right superior frontal gyrus (Brodmann area 10). The results are discussed in terms of the relationship between the activation of prefrontal areas under hypoxic conditions and performance deficits. Furthermore, the study demonstrates that sLORETA can be a valuable and reliable alternative for brain imaging when hemodynamic approaches, such as PET or fMRI, are not feasible.

Rhythm Generation through Period Concatenation in Rat Somatosensory Cortex

Rhythmic voltage oscillations resulting from the summed activity of neuronal populations occur in many nervous systems. Contemporary observations suggest that coexistent oscillations interact and, in time, may switch in dominance. We recently reported an example of these interactions recorded from in vitro preparations of rat somatosensory cortex. We found that following an initial interval of coexistent gamma (∼25 ms period) and beta2 (∼40 ms period) rhythms in the superficial and deep cortical layers, respectively, a transition to a synchronous beta1 (∼65 ms period) rhythm in all cortical layers occurred. We proposed that the switch to beta1 activity resulted from the novel mechanism of period concatenation of the faster rhythms: gamma period (25 ms)+beta2 period (40 ms) = beta1 period (65 ms). In this article, we investigate in greater detail the fundamental mechanisms of the beta1 rhythm. To do so we describe additional in vitro experiments that constrain a biologically realistic, yet simplified, computational model of the activity. We use the model to suggest that the dynamic building blocks (or motifs) of the gamma and beta2 rhythms combine to produce a beta1 oscillation that exhibits cross-frequency interactions. Through the combined approach of in vitro experiments and mathematical modeling we isolate the specific components that promote or destroy each rhythm. We propose that mechanisms vital to establishing the beta1 oscillation include strengthened connections between a population of deep layer intrinsically bursting cells and a transition from antidromic to orthodromic spike generation in these cells. We conclude that neural activity in the superficial and deep cortical layers may temporally combine to generate a slower oscillation.

Intermittent patterns of synchronous activity in human basal ganglia

Introduction Basal ganglia (BG) are involved in control of movement and are impacted in Parkinson's disease (PD). This impact is believed to be responsible for the symptoms. Recent studies provided evidence for the significance of oscillatory activity in beta and gamma bands for BG physiology in both health and disease, such as PD and dystonia [1,2]. The dynamics of the oscillations and their mechanisms are the subjects of this study. Methods We record intraoperatively from subthalamic nucleus (STN) of patients undergoing stereotactic surgery in PD. We use the network of conductance based models of excitatory subthalamic and inhibitory pallidal cells (following [3]) to study intermittent activity in the model of BG circuits. We rely on the approach of detection of statistically significant episodes of phase-locking activity developed by us and colleagues [4] to characterize intermittent from Seventeenth Annual Computational Neuroscience Meeting: CNS*2008 Portland, OR, USA. 19–24 July 2008

Slow Brain Potential and Oscillatory EEG Manifestations of Impaired Temporal Preparation in Parkinson's Disease

Performance in behavioral tasks is influenced by temporal expectations shaped by the temporal structure of the task. Such implicit temporal preparation is reflected in slow brain potentials and electroencephalographic oscillations and is attributed to interval timing mechanisms that probably depend on intact basal ganglia function. We investigated implicit timing in Parkinson's disease using a choice reaction task with two temporally regular stimulus presentation regimes, both including occasional deviant interstimulus intervals. Control subjects, but not patients, demonstrated temporal preparation in the form of an adjustment in time course of slow brain potentials to the duration of the interstimulus interval. However, in both groups, timing perturbations were accompanied by a slow brain potential amplitude drop at the time of expected stimulus occurrence, demonstrating intact representation of time in patients. In patients, oscillatory activity in beta and alpha bands showed attenuated preparatory desynchronization and reduced postmovement event-related synchronization, reflecting abnormal engagement and disengagement of sensorimotor and parietal areas. The results demonstrate profoundly deficient temporal preparation with preserved encoding of temporal information, a dissociation that may be explained by impaired dopamine-dependent motor learning. The results are discussed in the context of recent work on oscillatory activity in the basal ganglia.

Transforming Growth Factor-β1 Effects on Endothelial Monolayer Permeability Involve Focal Adhesion Kinase/Src

Transforming growth factor (TGF)-beta1 activity has been shown to increase vascular endothelial barrier permeability, which is believed to precede several pathologic conditions, including pulmonary edema and vessel inflammation. In endothelial monolayers, TGF-beta1 increases permeability, and a number of studies have demonstrated the alteration of cell-cell contacts by TGF-beta1. We hypothesized that focal adhesion complexes also likely contribute to alterations in endothelial permeability. We examined early signal transduction events associated with rapid changes in monolayer permeability and the focal adhesion complex of bovine pulmonary artery endothelial cells. Western blotting revealed rapid tyrosine phosphorylation of focal adhesion kinase (FAK) and Src kinase in response to TGF-beta1; inhibition of both of these kinases using pp2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), ameliorates TGF-beta1-induced monolayer permeability. Activation of FAK/Src requires activation of the epidermal growth factor receptor downstream of the TGF-beta receptors, and is blocked by the epidermal growth factor receptor inhibitor AG1478. Immunohistochemistry showed that actin and the focal adhesion proteins paxillin, vinculin, and hydrogen peroxide-inducible clone-5 (Hic-5) are rearranged in response to TGF-beta1; these proteins are released from focal adhesion complexes. Rearrangement of paxillin and vinculin by TGF-beta1 is not blocked by the FAK/Src inhibitor, pp2, or by SB431542 inhibition of the TGF-beta type I receptor, anaplastic lymphoma kinase 5; however, pp1 (4-Amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), which inhibits both type I and type II TGF-beta receptors, does block paxillin and vinculin rearrangement. Hic-5 protein rearrangement requires FAK/Src activity. Together, these results suggest that TGF-beta1-induced monolayer permeability involves focal adhesion and cytoskeletal rearrangement through both FAK/Src-dependent and -independent pathways.

Increased Ca2+ sensitivity and protein expression of SERCA 2a in situations of chronic β3-adrenoceptor deficiency

This study investigated the influence of chronic beta(3)-adrenoceptor deficiency on myocardial function. Therefore, we investigated Ca(2+)-regulatory proteins, SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild-type (WT, n=7) and beta(3)-adrenoceptor knockout mice (beta(3)-KNO, n=7). Morphometric heart analysis showed no difference between WT and beta(3)-KNO. No alterations were observed for the protein expression of the ryanodine receptor or phospholamban. However, in beta(3)-KNO mice, protein expression of SERCA 2a and phospholamban phosphorylation were significantly increased. These changes were accompanied by an increased SERCA 2a activity in beta(3)-KNO. Alterations in phospholamban phosphorylation were independent of alterations in beta(1)/beta(2)-adrenoceptor distribution and protein expression of G proteins in beta(3)-KNO. Measurement of myofibrillar Ca(2+) sensitivity showed no difference in the Ca(2+)/force relation for WT and beta(3)-KNO. The same seems to hold true for mitochondrial function since the protein expressions of cytochrome c, uncoupling protein 3 and cytochrome c oxidase subunit IV were similar in WT and beta(3)-KNO. The conclusion is that depression of beta(3)-adrenergic stimulation may modulate the protein expression of SERCA 2a and phospholamban phosphorylation, thereby improving sarcoplasmic reticulum Ca(2+) uptake. Thus, beta(3)-adrenergic depression may be a therapeutic aim in situations of impaired SERCA 2a activity, e.g. for the treatment of heart failure.

Psychophysiological correlates of lucid dreaming.

The main goal of the present study was to explore electrophysiologicaldifferences between lucid and nonlucid dreams in REM sleep. Seven men andfour women experienced in lucid dreaming underwent polysomnographicrecordings in the sleep laboratory on two consecutive nights. EEG signalswere subjected to spectral analysis to obtain Þve different frequency bandsbetween 1 and 20 Hz. Lucidity was determined by both subjective dreamreports and eye-movement signals made by the subjects in response to lightstimuli indicating a REM period. The main discrimination factor betweenlucid and nonlucid dreaming was found in the beta-1 frequency band (13Ð19Hz), which in lucid dreaming was increased in both parietal regions. Theratio of frontal to parietal beta-1 activity was 1 to 1.16 in nonlucid and 1to 1.77 in lucid dreaming. A tendency towards the greatest increase wasobserved in the left parietal lobe (P3), an area of the brain considered to berelated to semantic understanding and self-awareness.

Role of the Mitogen-Activated Protein Kinases in Cytokine-Mediated Inhibition of Insulin Gene Expression

BackgroundFollowing islet transplant, inflammatory cells in the vicinity of the transplant graft elaborate cytokines that contribute to islet graft dysfunction. To better understand the mechanism for this effect of cytokines...

An intrinsic 5′-deoxyribose-5-phosphate lyase activity in DNA polymerase beta from Leishmania infantum supports a role in DNA repair

Leishmania infantum is a parasitic protozoan which infects humans. This paper reports the expression in Escherichia coli and purification of the L. infantum gene product ( AF182167), as well as its characterization as a DNA polymerase beta (Polβ)-like, template-dependent DNA repair enzyme, with a metal preference for Mn 2+ over Mg 2+. As is the case with mammalian Polβ and DNA polymerase lambda (Polλ), L. infantum DNA polymerase beta (Li Polβ) prefers gapped-DNA substrates having a 5′-phosphate end, in agreement with its role in DNA repair reactions. Purified Li Polβ also displayed a 5′-deoxyribose-5-phosphate (dRP) lyase activity, consistent with a β-elimination mechanism. The concerted action of dRP lyase and DNA polymerization activities of Li Polβ on a uracil-containing DNA suggests its participation in “single-nucleotide” base excision repair (BER). Analysis of Li Polβ DNA polymerization activity at different stages of the L. infantum infective cycle supports a role for Li Polβ in nuclear DNA repair after the oxidative damage occurring inside the macrophage.

Hepatitis C Virus-Replicating Hepatocytes Induce Fibrogenic Activation of Hepatic Stellate Cells

The mechanism by which hepatitis C virus induces liver fibrosis remains largely obscure. To characterize the profibrogenic potential of hepatitis C virus, we used the hepatitis C virus replicon cell line Huh-7 5-15, which stably expresses the nonstructural hepatitis C virus genes NS3 through NS5B, and hepatic stellate cells as fibrogenic effector cells. Rat and human hepatic stellate cells were incubated with conditioned media from replicon cells, and expression of fibrosis-related genes was quantified by using real-time polymerase chain reaction, protein, and functional assays. Transforming growth factor beta1 activity was determined by bioassay. Hepatitis C virus replicon cells release factors that differentially modulate hepatic stellate cell expression of key genes involved in liver fibrosis in a clearly profibrogenic way, up-regulating procollagen alpha1(I) and procollagen alpha1(III) and down-regulating fibrolytic matrix metalloproteinases. Transforming growth factor beta1 expression and bioactivity were increased severalfold in hepatitis C virus-replicating vs mock-transfected hepatoma cells. However, transforming growth factor beta1 activity was responsible for only 50% of the profibrogenic activity. Hepatitis C virus nonstructural genes induce an increased expression of transforming growth factor beta1 and other profibrogenic factors in infected hepatocytes. The direct induction of profibrogenic mediators by hepatitis C virus in infected hepatocytes explains the frequent observation of progressive liver fibrosis despite a low level of inflammation and suggests novel targets for antifibrotic therapies in chronic hepatitis C.

Characteristics of Brain Bioelectrical Activity in Post-Traumatic Korsakov's Syndrome

A total of 32 patients (21 with reversible and 11 with chronic Korsakov's syndrome of traumatic origin) and 20 healthy controls were studied. Visual and spectral coherence analysis was applied to EEG recordings and the three-dimensional localization of equivalent dipole sources of beta1 activity in the frequency range 13-20 Hz. Stable increases in the coherence of EEG beta1 activity generated by a limited number of sources (mostly frontobasal and brainstem locations) had negative prognostic significance in Korsakov's syndrome. Comparison with clinical data allow this EEG phenomenon to be linked to the inhibitory state of the corresponding cortical zones.

Trait anxiety impact on posterior activation asymmetries at rest and during evoked negative emotions: EEG investigation

The main objective of the present investigation was to examine how high trait anxiety would influence cortical EEG asymmetries under non-emotional conditions and while experiencing negative emotions. The 62-channel EEG was recorded in control ( n=21) and high anxiety (HA, n=18) non-patient individuals. Results showed that in HA subjects, the lowest level of arousal (eyes closed) was associated with stronger right-sided parieto-temporal theta-1 (4–6 Hz) and beta-1 (12–18 Hz) activity, whereas increased non-emotional arousal (eyes open, viewing neutral movie clip) was marked by persisting favored right hemisphere beta-1 activity. In turn, viewing aversive movie clip by the HA group led to significant lateralized decrease of the right parieto-temporal beta-1 power, which was initially higher in the emotionally neutral conditions. The EEG data suggests that asymmetrical parieto-temporal theta-1 and beta-1 EEG activity might be better interpreted in terms of Gray's BAS and BIS theory.

Growth-associated protein of 43 kDa (GAP-43) is cleaved nonprocessively by the 20S proteasome.

Purified, nonubiquitinated growth-associated protein of 43 kDa (GAP-43) was attacked by purified reticulocyte 20S proteasome but not by the 26S proteasome. Cleavage yielded 12 N-terminally labelled GAP-43 fragments that could be resolved by SDS/PAGE. Inhibitor experiments suggested that proteasome beta1 activity yielded the resolved bands and that proteasomebeta5 activity generated nonresolvable fragments. Processive degradation, yielding only nonresolvable fragments, therefore did not occur. Most of the resolved fragments co-migrated with fragments formed in the reticulocyte lysate translation mixture used for GAP-43 synthesis, which suggested that the fragments were also produced in the translation mixture by the endogenous reticulocyte lysate proteasome. Consistent with this idea, the addition of proteasome inhibitors to translation mixtures blocked fragment production. Ubiquitinated GAP-43 appeared to be the source of the fragments in the presence of ATP, and nonubiquitinated GAP-43 the source in the absence of ATP. The results therefore suggest that the lack of processing seen with the 20S proteasome is not an artefact arising from the way in which the 20S proteasome was purified. In one purification protocol, the GAP-43 fragments formed in translation mixtures co-purified with full-length GAP-43. These fragments were digested to nonresolvable products upon addition of purified 20S proteasome. Addition of calmodulin or G-actin blocked the consumption of both full-length GAP-43 and the co-purified GAP-43 fragments. This showed that the resolved fragments can re-enter the proteasome and be cleaved to nonresolvable products, indicating that the lack of processivity is not a result of their resistance to further proteasome attack. The difficult step therefore appears to be the transfer of the large fragments within the proteasome from the beta1 to the beta5 activity for further attack.

Electro-encephalogram disturbances in different sleep-wake states following exposure to high environmental heat.

In this study, cerebral electrical activity or electro-encephalogram (EEG) was studied following exposure to high environmental heat, in three different age groups of freely moving rats. Each age group was subdivided into three groups: the acute heat stress group, subjected to a single exposure of 4 h at 38 degrees C in the biological oxygen demand incubator; the chronic heat stress group, exposed for 21 days, for 1 h each day, at 38 degrees C in the incubator; and the handling control group. The polygraphic sleep-wake recordings involved simultaneous recordings of cortical EEG, electro-oculogram (EOG), and electromyogram (EMG), on paper and in digital form on computer hard disk, just after the heat exposure for the acute stressed rats and on the 22nd day for the chronic stressed rats. The power spectrum was calculated for 2s epochs of the EEG signals. Quantitative analyses of EEG (qEEG) showed that, in all three age groups, changes in higher-frequency components (beta2) were significant in all sleep-wake states following both acute and chronic heat stress conditions. The power of beta2 activity in all three age groups after acute heat exposure was significantly decreased during slow wave sleep (SWS) (p < 0.05) and rapid eye movement sleep (p < 0.05), whereas the reverse was observed in the awake state (p < 0.05). Following chronic heat exposure, beta2 activity was found to increase in all three sleep-wake stages in all groups of rats (p < 0.01 for SWS in the weaning group and p < 0.05 for other data). Thus the study demonstrated that the cortical EEG is sensitive to environmental heat, and alterations in EEG frequencies in different states of mental consciousness due to high heat can be differentiated efficiently by EEG power spectrum analysis.

Angiogenic modulators in valve development and disease: does valvular disease recapitulate developmental signaling pathways?

Neovascularization is a recognized feature of many valvular diseases and is established by numerous angiogenic modulators. Less known is that angiogenic modulators are multifunctional and have additional roles in valve development and disease. Recent advancements in this area are described. Initiation of epithelial to mesenchymal transformation, a developmental induction that specifies primordial interstitial cells (mesenchymal cells), requires vascular endothelial growth factor A, which stimulates matrix metalloproteinase 2 production and the invasive migration of mesenchymal cells. Epithelial to mesenchymal transformation also requires the matrix component hyaluronan to facilitate signaling through ErbB2/ErbB3 receptors and then is terminated by an increase in vascular endothelial growth factor A expression. Fibroblast growth factor 4 has been implicated in stimulating the following stage of proliferative expansion. Subsequently, in the remodeling phase, heparin-binding epidermal growth factor-like growth factor limits mesenchymal cell proliferation by signaling through the EGFR/ErbB1 receptor. Many adult valvular lesions appear similar to the embryonic proliferative expansion phase as they exhibit accumulations of extracellular matrix and myofibroblasts (a mesenchyme-like interstitial cell). The origins of such lesions may involve transforming growth factor beta 1. Similar to epithelial to mesenchymal transformation, tumor growth factor beta1 can induce cultured valvular endothelial cells to transdifferentiate to a myofibroblast-like phenotype. This scenario may occur in carcinoid valve disease because serotonin can induce interstitial cell expression of tumor growth factor beta1. Additionally, prolonged tumor growth factor beta1 activity may predispose to calcific degeneration. Calcific leaflets also exhibit tenascin-C, which may facilitate inflammatory cell migration through upregulation of pro-matrix metalloproteinase 2. Numerous angiogenic modulators control multiple stages of valvulogenesis and in the context of adult valvular disease may recapitulate their embryonic roles. Thus, lessons learned from valvulogenesis may provide insights into the molecular basis of adult valvular disease.

Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD.

Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA binding domain (DBD) and represses the transcriptional activity of various nuclear receptors. In this study, we examined the novel cross talk between SHP and BETA2/NeuroD, a basic helix-loop-helix transcription factor. In vitro and in vivo protein interaction studies showed that SHP physically interacts with BETA2/NeuroD, but not its heterodimer partner E47. Moreover, confocal microscopic study and immunostaining results demonstrated that SHP colocalized with BETA2 in islets of mouse pancreas. SHP inhibited BETA2/NeuroD-dependent transactivation of an E-box reporter, whereas SHP was unable to repress the E47-mediated transactivation and the E-box mutant reporter activity. In addition, SHP repressed the BETA2-dependent activity of glucokinase and cyclin-dependent kinase inhibitor p21 gene promoters. Gel shift and in vitro protein competition assays indicated that SHP inhibits neither dimerization nor DNA binding of BETA2 and E47. Rather, SHP directly repressed BETA2 transcriptional activity and p300-enhanced BETA2/NeuroD transcriptional activity by inhibiting interaction between BETA2 and coactivator p300. We also showed that C-terminal repression domain within SHP is also required for BETA2 repression. However, inhibition of BETA2 activity was not observed by naturally occurring human SHP mutants that cannot interact with BETA2/NeuroD. Taken together, these results suggest that SHP acts as a novel corepressor for basic helix-loop-helix transcription factor BETA2/NeuroD by competing with coactivator p300 for binding to BETA2/NeuroD and by its direct transcriptional repression function.

Comparative EEG activation to skin pain and muscle pain induced by capsaicin injection

Skin pain differs from muscle pain in quality and affective dimension, but it is unknown how the brain processes the nociceptive inputs from skin and muscle differently. To delineate the differential effects of nociceptive inputs from skin and muscle, the EEG topography and power spectra were analysed on the basis of two databases acquired from two separate studies regarding skin (Neurosci. Lett. 305 (2001b) 49) and muscle pain (Exp. Brain Res. 141 (2001c) 195). The same experimental protocol was applied to the same subject-group in the two separate experiments. In the two independent experiments, skin pain and muscle pain were, respectively, induced by intracutaneous and intramuscular injection of capsaicin in the left forearm. Visual analogue scale (VAS) and EEG data acquired before, during the vehicle and capsaicin injections were quantitatively compared. The results showed that the VAS profiles for skin and muscle pain are highly similar in spite of distinct qualities perceived. Skin pain produced a similar but not identical EEG topographic pattern as muscle evoked. Muscle pain induced a significant increase of beta-2 activity in the extensive frontal, parietal and occipital areas compared to skin pain. No difference was found between the vehicle-induced non-painful sensations in skin and muscle. These results implicate that the nociceptive inputs from muscle and skin are processed differently in the similar neural matrix of the brain.