Critical role of canonical transient receptor potential channel 7 in initiation of seizures

Status epilepticus (SE) is a life-threatening disease that has been recognized since antiquity but still causes over 50,000 deaths annually in the United States. The prevailing view on the pathophysiology of SE is that it is sustained by a loss of normal inhibitory mechanisms of neuronal activity. However, the early process leading to the initiation of SE is not well understood. Here, we show that, as seen in electroencephalograms, SE induced by the muscarinic agonist pilocarpine in mice is preceded by a specific increase in the gamma wave, and genetic ablation of canonical transient receptor potential channel (TRPC) 7 significantly reduces this pilocarpine-induced increase of gamma wave activity, preventing the occurrence of SE. At the cellular level, TRPC7 plays a critical role in the generation of spontaneous epileptiform burst firing in cornu ammonis (CA) 3 pyramidal neurons in brain slices. At the synaptic level, TRPC7 plays a significant role in the long-term potentiation at the CA3 recurrent collateral synapses and Schaffer collateral-CA1 synapses, but not at the mossy fiber-CA3 synapses. Taken together, our data suggest that epileptiform burst firing generated in the CA3 region by activity-dependent enhancement of recurrent collateral synapses may be an early event in the initiation process of SE and that TRPC7 plays a critical role in this cellular event. Our findings reveal that TRPC7 is intimately involved in the initiation of seizures both in vitro and in vivo. To our knowledge, this contribution to initiation of seizures is the first identified functional role for the TRPC7 ion channel.Fil: Phelan, K. D.. University of Arkansas for Medical Sciences; Estados UnidosFil: Shwe, U. T.. University of Arkansas for Medical Sciences; Estados UnidosFil: Abramowitz, J.. National Institute of Environmental Health Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences; Estados UnidosFil: Zheng, F.. University of Arkansas for Medical Sciences; Estados Unido

Dusty Sources at the Galactic Center: The N- and Q-band view with VISIR

We present mid-infrared N- and Q-band photometry of the Galactic Center from images obtained with the mid-infrared camera VISIR at the ESO VLT in May 2004. The high resolution and sensitivity possible with VISIR enables us to investigate a total of over 60 point-like sources, an unprecedented number for the Galactic Center at these wavelengths. Combining these data with previous results at shorter wavelengths (Viehmann et al. 2005) enables us to construct SEDs covering the H- to Q-band regions of the spectrum, i.e. 1.6 to 19.5 $\mu$m. We find that the SEDs of certain types of Galactic Center sources show characteristic features. We can clearly distinguish between luminous Northern Arm bow-shock sources, lower luminosity bow-shock sources, hot stars, and cool stars. This characterization may help clarify the status of presently unclassified sources.Comment: 18 pages, 4 figures, 1 table, accepted for publication in the Astrophysical Journa

Extensive training of elementary finger tapping movements changes the pattern of motor cortex excitability

There is evidence of a strong capacity for functional and structural reorganization in the human motor system. However, past research has focused mainly on complex movement sequences over rather short training durations. In this study we investigated changes in corticospinal excitability associated with longer training of elementary, maximum-speed tapping movements. All participating subjects were consistent right-handers and were trained using either the right (experiment 1) or the left thumb (experiment 2). Transcranial magnetic stimulation was applied to obtain motor evoked potentials (MEPs) from the abductor pollicis brevis (APB) muscle of the right and the left hand before and after training. As a result of training, a significant increase was observed in tapping speed accompanied by increased MEPs, recorded from the trained APB muscle, following contralateral M1 stimulation. In the case of subdominant-hand training we additionally demonstrate increased MEP amplitudes evoked at the right APB (untrained hand) in the first training week. Enhanced corticospinal excitability associated with practice of elementary movements may constitute a necessary precursor for inducing plastic changes within the motor system. The involvement of the ipsilateral left M1 likely reflects the predominant role of the left M1 in the general control (modification) of simple motor parameters in right-handed subject

The Einstein relation generalized to non-equilibrium

The Einstein relation connecting the diffusion constant and the mobility is violated beyond the linear response regime. For a colloidal particle driven along a periodic potential imposed by laser traps, we test the recent theoretical generalization of the Einstein relation to the non-equilibrium regime which involves an integral over measurable velocity correlation functions

Validity of Landauer's principle in the quantum regime

We demonstrate the validity of Landauer's erasure principle in the strong coupling quantum regime by treating the system-reservoir interaction in a consistent way. We show that the initial coupling to the reservoir modifies both energy and entropy of the system and provide explicit expressions for the latter in the case of a damped quantum harmonic oscillator. These contributions are related to the Hamiltonian of mean force and dominate in the strong damping limit. They need therefore to be fully taken into account in any low-temperature thermodynamic analysis of quantum systems.Comment: 4 pages, 2 figure

32P-Postlabeling of a DNA adduct derived from 4,4′-methylenedianiline, in the olfactory epithelium of rats exposed by inhalation to 4,4′-methylenediphenyl diisocyanate

Tissues obtained from female Wistar rats exposed to a 0.9 μm aerosol of 4,4′-methylenediphenyl diisocyanate (MDI) for 17 h per day, 5 days per week, for one year, at levels of 0, 0.3, 0.7 and 2.0 mg/m3, were analyzed for DNA adducts. A 32P-postlabeling method was used to detect (i). adducts formed by the reaction of the isocyanate group(s) of MDI with DNA; and a 32P-postlabeling method was adapted to detect (ii), a DNA adduct formed by 4,4′-methylenedianiline (MDA), a hydrolysis/decarboxylation product of MDI. In the lung, neither isocyanate adducts nor the arylamine adduct were detectable. The same negative result was seen in the liver, the bladder, the kidney, the respiratory epithelium and in peripheral lymphocytes. In the olfactory epithelium, on the other hand, the aryl-amine-derived DNA adduct was detected, at the very low levels of 5, 9 and 10 adduct-nucleotides per 1010 nucleotides, for the three dose groups, respectively. The adduct co-chromatographed with the one formed in the liver of rats after oral gavage of MDA. The results are discussed in terms of the importance of genotoxic versus nongenotoxic aspects of carcinogenesi

Multi-wavelength photometric variation of PG1605+072

In a large coordinated attempt to further our understanding of the $p$-mode pulsating sdB star PG1605+072, the Multi-Site Spectroscopic Telescope (MSST) collaboration has obtained simultaneous time-resolved spectroscopic and photometric observations. The photometry was extended by additional WET data which increased the time base. This contribution outlines the analysis of the MSST photometric light curve, including the four-colour BUSCA data from which chromatic amplitudes have been derived, as well as supplementary FUV spectra and light curves from two different epochs. These results have the potential to complement the interpretation of the published spectroscopic information.Comment: 6 pages, to be published in "Interpretation of asteroseismic data", proceedings of the HELAS NA5 Workshop, eds. W. Dziembowski, M. Breger and M. Thompson, Communications in Asteroseismology, 15

Electron microscopy of melanophagocytosis the human skin window

A modification of a tissue culture technique successfully applied to obtain preparations of the inflammatory response studied by the human skin window technique, is described. Previously described melanin granules in macrophages in Cape Coloured responses could be shown to consist of nests of melanosomes. Afr. Med. J., 48, 265 (1974)