Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis

Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA [17-phenyl-(3α,5α)-androst-16-en-3-ol], a blocker of neurosteroid effects on GABA(A) receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN (2-[2-(4-fluorophenyl)-1H-indol-3-yl]-N,N-dihexylacetamide), a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated 1 d before midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity

Infrared generation in low-dimensional semiconductor heterostructures via quantum coherence

A new scheme for infrared generation without population inversion between subbands in quantum-well and quantum-dot lasers is presented and documented by detailed calculations. The scheme is based on the simultaneous generation at three frequencies: optical lasing at the two interband transitions which take place simultaneously, in the same active region, and serve as the coherent drive for the IR field. This mechanism for frequency down-conversion does not rely upon any ad hoc assumptions of long-lived coherences in the semiconductor active medium. And it should work efficiently at room temperature with injection current pumping. For optimized waveguide and cavity parameters, the intrinsic efficiency of the down-conversion process can reach the limiting quantum value corresponding to one infrared photon per one optical photon. Due to the parametric nature of IR generation, the proposed inversionless scheme is especially promising for long-wavelength (far- infrared) operation.Comment: 4 pages, 1 Postscript figure, Revtex style. Replacement corrects a printing error in the authors fiel

Relations Between Molecular Cloud Structure Sizes and Line Widths in the Large Magellanic Cloud

We present a comparative study of the size-line width relation for substructures within six molecular clouds in the Large Magellanic Cloud (LMC) mapped with the Atacama Large Millimeter/submillimeter Array (ALMA). Our sample extends our previous study, which compared a Planck detected cold cloud in the outskirts of the LMC with the 30 Doradus molecular cloud and found the typical line width for 1 pc radius structures to be 5 times larger in 30 Doradus. By observing clouds with intermediate levels of star formation activity, we find evidence that line width at a given size increases with increasing local and cloud-scale 8${\mu}$m intensity. At the same time, line width at a given size appears to independently correlate with measures of mass surface density. Our results suggest that both virial-like motions due to gravity and local energy injection by star formation feedback play important roles in determining intracloud dynamics.Comment: 20 pages, to appear in ApJ. Data presented in this paper can be found at https://mmwave.astro.illinois.edu/almalmc

Identifying chemokines as therapeutic targets in renal disease: Lessons from antagonist studies and knockout mice

Chemokines, in concert with cytokines and adhesion molecules, play multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage and accumulation of chemokine receptor-bearing leukocytes. Chemokines play important roles in leukocyte trafficking and blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicates additional roles of chemokines in the regulation of innate and adaptive immune responses, which may adversively affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential of anti-chemokine strategies, including potential side effects, in renal disease. Copyright (C) 2004 S. Karger AG, Basel

Neutral and Cationic Rare Earth Metal Alkyl and Benzyl Compounds with the 1,4,6-Trimethyl-6-pyrrolidin-1-yl-1,4-diazepane Ligand and Their Performance in the Catalytic Hydroamination/Cyclization of Aminoalkenes

A new neutral tridentate 1,4,6-trimethyl-6-pyrrolidin-1-yl-1,4-diazepane (L) was prepared. Reacting L with trialkyls M(CH2SiMe3)3(THF)2 (M = Sc, Y) and tribenzyls M(CH2Ph)3(THF)3 (M = Sc, La) yielded trialkyl complexes (L)M(CH2SiMe3)3 (M = Sc, 1; M = Y, 2) and tribenzyl complexes (L)M(CH2Ph)3 (M = Sc, 3; M = La, 4). Complexes 1 and 2 can be converted to their corresponding ionic compounds [(L)M(CH2SiMe3)2(THF)][B(C6H5)4] (M = Sc, Y) by reaction with [PhNMe2H][B(C6H5)4] in THF. Complexes 3 and 4 can be converted to cationic species [(L)M(CH2Ph)2]+ by reaction with [PhNMe2H][B(C6F5)4] in C6D5Br in the absence of THF. The neutral complexes 1-4 and their cationic derivatives were studied as catalysts for the hydroamination/cyclization of 2,2-diphenylpent-4-en-1-amine and N-methylpent-4-en-1-amine reference substrates and compared with ligand-free Sc, Y, and La neutral and cationic catalysts. The most effective catalysts in the series were the cationic L-yttrium catalyst (for 2,2-diphenylpent-4-en-1-amine) and the cationic lanthanum systems (for N-methylpent-4-en-1-amine). For the La catalysts, evidence was obtained for release of L from the metal during catalysis.

Avaliação sócio-ambiental da integração tecnológica Embrapa Pecuária Sudeste para produção leiteira na agricultura familiar.

Duas características da pecuária leiteira podem ser destacadas na atualidade: a) o baixo valor do leite, que dificulta a adoção de tecnologias que favoreçam a produtividade e b) a concentração da produção leiteira em estabelecimentos pequenos, nos quais predomina a atividade em nível de subsistência, com mão-de-obra familiar e renda mensal que não ultrapassa um salário mínimo. Um projeto de pesquisa e transferência de tecnologia da Embrapa Pecuária Sudeste (São Carlos, Estado de São Paulo) vem sendo desenvolvido desde 1998 para melhoria desse cenário. Uma vez implantado o projeto em uma série de estabelecimentos na região de Votuporanga, Estado de São Paulo, desenvolveu-se este estudo, para avaliar os impactos sócio-ambientais da adoção da tecnologia. Os resultados indicam que o desempenho dos estabelecimentos melhora em função do tempo desde a adoção e que a tecnologia contribui positivamente para o desenvolvimento sustentável, sendo recomendada para transferência

Compensation of the Crossing Angle with Crab Cavities at KEKB

Crab cavities have been installed in the KEKB B--Factory rings to compensate the crossing angle at the collision point and thus increase luminosity. The beam operation with crab crossing has been done since February 2007. This is the first experience with such cavities in colliders or storage rings. The crab cavities have been working without serious issues. While higher specific luminosity than the geometrical gain has been achieved, further study is necessary and under way to reach the prediction of simulation.Comment: Submitted to Particle Accelerator Conference 2007, MOZAKI01, Albuquerqu

Observation of the decay B^0->D+D*-

We report the first observation of the decay B^0->D+-D*-+ with the Belle detector at the KEKB e^+e^- collider operated at the Upsilon(4S) resonance. The sum of branching fractions B(B^0->D+D*-)+B(B^0->D-D*+) is measured to be (1.17+-0.26+0.22-0.25)x10^-3 using the full reconstruction method where both charmed mesons from B^0 decays are reconstructed. A consistent value ((1.48+-0.38+0.28-0.31)x10^-3) is obtained using a partial reconstruction technique that only uses the slow pion from the D*- ->bar D^0pi- decay and a fully reconstructed D+ to reconstruct the B^0.Comment: 10 pages, 3 figure