Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons

Many connections in the basal ganglia are made around birth when animals are exposed to a host of new affective, cognitive, and sensori-motor stimuli. It is thought that dopamine modulates cortico-striatal synapses that result in the strengthening of those connections that lead to desired outcomes. We propose that there must be a time before which stimuli cannot be processed into functional connections, otherwise it would imply an effective link between stimulus, response, and reward in uterus. Consistent with these ideas, we present evidence that early in development dopamine neurons are electrically immature and do not produce high-frequency firing in response to salient stimuli. We ask first, what makes dopamine neurons immature? and second, what are the implications of this immaturity for the basal ganglia? As an answer to the first question, we find that at birth the outward current is small (3nS-V), insensitive to Ca2+, TEA, BK, and SK blockers. Rapidly after birth, the outward current increases to 15nS-V and becomes sensitive to Ca2+, TEA, BK, and SK blockers. We make a detailed analysis of the kinetics of the components of the outward currents and produce a model for BK and SK channels that we use to reproduce the outward current, and to infer the geometrical arrangement of BK and Ca2+ channels in clusters. In the first cluster, T-type Ca2+ and BK channels are coupled within distances of similar to 20 nm (200 parallel to). The second cluster consists of L-type Ca2+ and BK channels that are spread over distances of at least 60 nm. As for the second question, we propose that early in development, the mechanism of action selection is in a "locked-in" state that would prevent dopamine neurons from reinforcing cortico-striatal synapses that do not have a functional experiential-based value.

Using crises, feedback, and fading for online task design

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Formulació matricial de la teoria de pertorbacions de Rayleigh-Schrödringer: monodimensional

Es repassa la formulació de la Teoria de Pertorbacions en notació matricial i s'exposa una aplicació senzilla com és la solució del problema de la partícula sotmesa a un potencial d'atracció dins la caixa quàntica monodimensional

When the rising dragon sees fading stars: China's view of the European Union. CEPS Special Report No. 73, 29 November 2012

This CEPS Special Report gives an overview of China’s perceptions of the EU and the protection of Chinese investments in Europe since the outbreak of the European sovereign debt crisis, especially since the more concrete talks in late 2011 on possible financial support from China. Although the top leadership of the communist party of China (CPC) changed in its recent handover, the perceptions described in this paper are likely to remain the same, just as the main tenets of China’s foreign policy are unlikely to change in the near future. The report argues that while the EU’s image has suffered greatly from the sovereign debt crisis and the way it has been handled, there is room to improve China’s view of Europe and for the EU to maintain a relatively strong negotiation position towards China.

Changes in heron and egret populations on the Laurentian Great Lakes and connecting channels, 1977-2009

Canadian and U.S. federal wildlife agencies completed four decadal surveys, spanning the years 1977 to 2009, to census colonial waterbirds breeding on the Great Lakes and adjoining bodies of water. In this paper, we reports abundance, distribution, and general population trends of three species: Black-crowned Night-Heron (Nycticorax nycticorax), Great Egret (Ardea alba), and Great Blue Heron (Ardea herodias). Estimates of nest numbers ranged from approximately 4000-6100 for the Black-crowned Night-Heron, 250-1900 for the Great Egret, and 3800-6400 for the Great Blue Heron. Average annual rates of change in nest numbers between the first (1977) and fourth (2008) census were −1% for the Black-crowned Night-Heron, +23% for the Great Egret, and −0.27% for the Great Blue Heron. Across the 30-year census, Black-crowned Night-Heron estimates decreased in U.S. (−57%) but increased (+18%) in Canadian waters, Great Egret nests increased 1381% in Canadian waters with a smaller, but still substantial increase in the number of nests at U.S. colonies (+613%), and Great Blue Heron numbers increased 148% in Canadian waters and 713% in U.S. waters. Although a single factor cannot be clearly linked to changes observed in each species’ distribution, hydrological variation, habitat succession, nest competition with Double-crested Cormorants (Phalacrocorax auritus), and land use changes likely all contributed. Management activities should support both breeding and foraging conditions including restoration of early successional habitats and anticipate continued northward expansions in the distributions of these waterbirds.

The counterpropagating Rossby wave perspective on Kelvin Helmholtz instability as a limiting case of a Rayleigh shear layer with zero width

The Kelvin Helmholtz (KH) problem, with zero stratification, is examined as a limiting case of the Rayleigh model of a single shear layer whose width tends to zero. The transition of the Rayleigh modal dispersion relation to the KH one, as well as the disappearance of the supermodal transient growth in the KH limit, are both rationalized from the counterpropagating Rossby wave perspective.

Inhibition of human mesangial cell proliferation by targeting T-Type calcium channels

Background: Aberrant glomerular mesangial cell (MC) proliferation is a common finding in renal diseases. T-type calcium channels (T-CaCN) play an important role in the proliferation of a number of cell types, including vascular smooth muscle cells. The hypothesis that T-CaCN may play a role in the proliferation of human MC was investigated. Methods: The presence of T-CaCN in primary cultures of human MC was examined using voltage clamping and by RT-PCR. The effect of calcium channel inhibitors, and of siRNA directed against the Cav3.2 T-CaCN isoform, on MC proliferation was assessed using the microculture tetrazolium assay and nuclear BrdU incorporation. Results: Human MC express only the Cav3.2 T-CaCN isoform. Co-incubation of MC with a T-CaCN inhibitor (mibefradil, TH1177 or Ni2+) results in a concentration-dependent attenuation of proliferation. This effect cannot be attributed to direct drug-induced cytotoxicity or apoptosis and is not seen with verapamil, an L-type channel blocker. Transfection of MC with siRNA results in knockdown of T-CaCN Cav3.2 mRNA and a clear attenuation of MC proliferation. Conclusions: These results demonstrate for the first time an important role for T-CaCN in human MC proliferation. This could potentially lead to a novel therapy in the treatment of proliferative renal diseases.

Unexpectedly superior enantioselectivity for trans-stilbene cis-dihydroxylation over anchored triosmium carbonyl species in confined Al-MCM-41 channels

Superior enantioselectivity in the dihydroxylation of trans-stilbene catalysed by anchored triosmium carbonyl species without using a chiral modifier is observed inside sterically congested MCM-41 channels; this effect is more pronounced through the introduction of surface Al sites into the silicate.

Design of a new foldamer turn-linker-turn in acyclic hexapeptides and formation of channels through self-assembly

Single crystal X-ray diffraction studies and solvent dependent NMR titration reveal that the designed pepticles I and 11, Boc-Xx(1)-Aib(2)-Yy(3)-NH(CH2)(2)NH-Yy(3)-Aib(2)-Xx(1)-Boc, where Xx and Yy are lie and Leu in peptide I and Leu and Val in peptide 11, respectively, fold into a turn-linker-turn (T-L-T) conformation both in the solid state and in solution. In the crystalline state the T-L-T foldamers; of peptide I and II self-assemble to form a three-dimensional framework of channels. The insides of the channels are hydrophilic and found to contain solvent CHCl3 hydrogen bonded to exposed C=O of Aib located at the turn regions. (c) 2008 Elsevier B.V. All rights reserved.