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

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

Structure near K−K^-+pp+pp threshold in the in-flight 3^3He(K−,Λp)n(K^-,\Lambda p)n reaction

To search for an S= -1 di-baryonic state which decays to $\Lambda p$, the ${\rm{}^3He}(K^-,\Lambda p)n_{missing}$ reaction was studied at 1.0 GeV/$c$. Unobserved neutrons were kinematically identified from the missing mass $M_X$ of the ${\rm{}^3He}(K^-,\Lambda p)X$ reaction in order to have a large acceptance for the $\Lambda pn$ final state. The observed $\Lambda p n$ events, distributed widely over the kinematically allowed region of the Dalitz plot, establish that the major component comes from a three nucleon absorption process. A concentration of events at a specific neutron kinetic energy was observed in a region of low momentum transfer to the $\Lambda p$. To account for the observed peak structure, the simplest S-wave pole was assumed to exist in the reaction channel, having Breit-Wigner form in energy and with a Gaussian form-factor. A minimum $\chi^2$ method was applied to deduce its mass $M_X\ =$ 2355 $^{+ 6}_{ - 8}$ (stat.) $\pm 12$ (syst.) MeV/c$^2$, and decay-width $\Gamma_X\ =$ 110 $^{+ 19}_{ - 17}$ (stat.) $\pm 27$ (syst.) MeV/c$^2$, respectively. The form factor parameter $Q_X \sim$ 400 MeV/$c$ implies that the range of interaction is about 0.5Comment: 12pages, 8 figure

Measurement of the strong interaction induced shift and width of the 1s state of kaonic deuterium at J-PARC

The antikaon-nucleon interaction close to threshold provides crucial information on the interplay between spontaneous and explicit chiral symmetry breaking in low-energy QCD. In this context the importance of kaonic deuterium X-ray spectroscopy has been well recognized, but no experimental results have yet been obtained due to the difficulty of the measurement. We propose to measure the shift and width of the kaonic deuterium 1s state with an accuracy of 60 eV and 140 eV respectively at J-PARC. These results together with the kaonic hydrogen data (KpX at KEK, DEAR and SIDDHARTA at DAFNE) will then permit the determination of values of both the isospin I=0 and I=1 antikaon-nucleon scattering lengths and will provide the most stringent constraints on the antikaon-nucleon interaction, promising a breakthrough. Refined Monte Carlo studies were performed, including the investigation of background suppression factors for the described setup. These studies have demonstrated the feasibility of determining the shift and width of the kaonic deuterium atom 1s state with the desired accuracy of 60 eV and 140 eV.Comment: 12 pages, 9 figure