Plasticity of GABA(B) receptor-mediated heterosynaptic interactions at mossy fibers after status epilepticus

Several neurotransmitters, including GABA acting at presynaptic GABAB receptors, modulate glutamate release at synapses between hippocampal mossy fibers and CA3 pyramidal neurons. This phenomenon gates excitation of the hippocampus and may therefore prevent limbic seizure propagation. Here we report that status epilepticus, triggered by either perforant path stimulation or pilocarpine administration, was followed 24 hr later by a loss of GABAB receptor-mediated heterosynaptic depression among populations of mossy fibers. This was accompanied by a decrease in the sensitivity of mossy fiber transmission to the exogenous GABAB receptor agonist baclofen. Autoradiography revealed a reduction in GABAB receptor binding in the stratum lucidum after status epilepticus. Failure of GABAB receptor-mediated modulation of mossy fiber transmission at mossy fibers may contribute to the development of spontaneous seizures after status epilepticus

Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus

Persistent activation of GABAA receptors by extracellular GABA (tonic inhibition) plays a critical role in signal processing and network excitability in the brain. In hippocampal principal cells, tonic inhibition has been reported to be mediated by {alpha}5-subunit-containing GABAA receptors ({alpha}5GABAARs). Pharmacological or genetic disruption of these receptors improves cognitive performance, suggesting that tonic inhibition has an adverse effect on information processing. Here, we show that {alpha}5GABAARs contribute to tonic currents in pyramidal cells only when ambient GABA concentrations increase (as may occur during increased brain activity). At low ambient GABA concentrations, activation of {delta}-subunit-containing GABAA receptors predominates. In epileptic tissue, {alpha}5GABAARs are downregulated and no longer contribute to tonic currents under conditions of raised extracellular GABA concentrations. Under these conditions, however, the tonic current is greater in pyramidal cells from epileptic tissue than in pyramidal cells from nonepileptic tissue, implying substitution of {alpha}5GABAARs by other GABAA receptor subtypes. These results reveal multiple components of tonic GABAA receptor-mediated conductance that are activated by low GABA concentrations. The relative contribution of these components changes after the induction of epilepsy, implying an adaptive plasticity of the tonic current in the presence of spontaneous seizures

Structure of protease-cleaved escherichia coliα-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

Bacterial -2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli -2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli -2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli -2-macroglobulin and human -2-macro­globulin, this protease-activation mechanism is likely to operate across the diverse members of this group

In-medium broadening of nucleon resonances

We analyze the effects of an in-medium broadening of nucleon resonances on the exclusive photoproduction of mesons on nuclei as well as on the total photoabsorption cross sections in a transport calculation. We show that the resonance widths observed in semi-inclusive photoproduction on nuclei are insensitive to an in-medium broadening of nucleon resonances. This is due to a simple effect: the sizeable width of the nuclear surface and Fermi motion.Comment: 4 pages, 3 figures, minor changes in the tex

Confined granular packings: structure, stress, and forces

The structure and stresses of static granular packs in cylindrical containers are studied using large-scale discrete element molecular dynamics simulations in three dimensions. We generate packings by both pouring and sedimentation and examine how the final state depends on the method of construction. The vertical stress becomes depth-independent for deep piles and we compare these stress depth-profiles to the classical Janssen theory. The majority of the tangential forces for particle-wall contacts are found to be close to the Coulomb failure criterion, in agreement with the theory of Janssen, while particle-particle contacts in the bulk are far from the Coulomb criterion. In addition, we show that a linear hydrostatic-like region at the top of the packings unexplained by the Janssen theory arises because most of the particle-wall tangential forces in this region are far from the Coulomb yield criterion. The distributions of particle-particle and particle-wall contact forces $P(f)$ exhibit exponential-like decay at large forces in agreement with previous studies.Comment: 11 pages, 11 figures, submitted to PRE (v2) added new references, fixed typo

Incoherent Photoproduction of η\eta-mesons from the Deuteron near Threshold

Incoherent photoproduction of the $\eta$-meson on the deuteron is studied for photon energies from threshold to 800 MeV. The dominant contribution, the $\gamma$N-$\eta$N amplitude, is described within an isobar model. The final state interaction derived from the CD-Bonn potential is included and found to be important for the description of the production cross section close to threshold. Possible effects from the $\eta N$ final state interaction are discussed.Comment: 11 pages, revtex, including 6 figure

Law, politics and the governance of English and Scottish joint-stock companies 1600-1850

This article examines the impact of law on corporate governance by means of a case study of joint-stock enterprise in England and Scotland before 1850. Based on a dataset of over 450 company constitutions together with qualitative information on governance practice, it finds little evidence to support the hypothesis that common-law regimes such as England were more supportive of economic growth than civil-law jurisdictions such as Scotland: indeed, levels of shareholder protection were slightly stronger in the civil-law zone. Other factors, such as local political institutions, played a bigger role in shaping organisational forms and business practice

Multi-Periodic Oscillations in Cepheids and RR Lyrae-Type Stars

Classical Cepheids and RR Lyrae-type stars are usually considered to be textbook examples of purely radial, strictly periodic pulsators. Not all the variables, however, conform to this simple picture. In this review I discuss different forms of multi-periodicity observed in Cepheids and RR Lyrae stars, including Blazhko effect and various types of radial and nonradial multi-mode oscillations.Comment: Proceedings of the 20th Stellar Pulsation Conference Series: "Impact of new instrumentation & new insights in stellar pulsations", 5-9 September 2011, Granada, Spai

Utilization of the Building-Block Approach in Structural Mechanics Research

In the last 20 years NASA has worked in collaboration with industry to develop enabling technologies needed to make aircraft safer and more affordable, extend their lifetime, improve their reliability, better understand their behavior, and reduce their weight. To support these efforts, research programs starting with ideas and culminating in full-scale structural testing were conducted at the NASA Langley Research Center. Each program contained development efforts that (a) started with selecting the material system and manufacturing approach; (b) moved on to experimentation and analysis of small samples to characterize the system and quantify behavior in the presence of defects like damage and imperfections; (c) progressed on to examining larger structures to examine buckling behavior, combined loadings, and built-up structures; and (d) finally moved to complicated subcomponents and full-scale components. Each step along the way was supported by detailed analysis, including tool development, to prove that the behavior of these structures was well-understood and predictable. This approach for developing technology became known as the "building-block" approach. In the Advanced Composites Technology Program and the High Speed Research Program the building-block approach was used to develop a true understanding of the response of the structures involved through experimentation and analysis. The philosophy that if the structural response couldn't be accurately predicted, it wasn't really understood, was critical to the progression of these programs. To this end, analytical techniques including closed-form and finite elements were employed and experimentation used to verify assumptions at each step along the way. This paper presents a discussion of the utilization of the building-block approach described previously in structural mechanics research and development programs at NASA Langley Research Center. Specific examples that illustrate the use of this approach are included from recent research and development programs for both subsonic and supersonic transports

Polariton Pattern Formation and Photon Statistics of the Associated Emission

We report on the formation of a diverse family of transverse spatial polygon patterns in a microcavity polariton fluid under coherent driving by a blue-detuned pump. Patterns emerge spontaneously as a result of energy-degenerate polariton-polariton scattering from the pump state to interfering high order vortex and antivortex modes, breaking azimuthal symmetry. The interplay between a multimode parametric instability and intrinsic optical bistability leads to a sharp spike in the value of second order coherence g (2)(0) of the emitted light, which we attribute to the strongly superlinear kinetics of the underlying scattering processes driving the formation of patterns. We show numerically by means of a linear stability analysis how the growth of parametric instabilities in our system can lead to spontaneous symmetry breaking, predicting the formation and competition of different pattern states in good agreement with experimental observations