Activity of nAChRs containing α9 subunits modulates synapse stabilization via bidirectional signaling programs

Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) α9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR α9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in α9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the α9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult α9 null mice. Finally, by using mice expressing the nondesensitizing α9 L90T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation. © 2009 Wiley Periodicals, Inc.Fil: Murthy, Vidya. Tufts University School of Medicine; EslovaquiaFil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Tufts University School of Medicine; EslovaquiaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaFil: Vetter, Douglas E.. Tufts University School of Medicine; Eslovaqui

Localization of aeroelastic modes in mistuned high-energy turbines

The effects of blade mistuning on the aerodynamic characteristics of a class of bladed-disk assemblies, namely high energy turbines, are discussed. The specific rotor analyzed is the first stage of turbine blades of the oxidizer turbopump in the Space Shuttle Main Engine. The common occurrence of fatigue cracks for these turbine blades indicates the possibility of high dynamic loading. Since mistuning under conditions of weak interblade coupling has been shown to increase blade response amplitudes drastically for simple structural models of blade assemblies, it provides a plausible explanation for the occurrence of cracks. The focus here is on the effects of frequency mistuning on the aeroelastic stability of the assembly and on the aeroelastic mode shapes

Combined first-principles and model Hamiltonian study of the perovskite series RMnO3 (R = La, Pr, Nd, Sm, Eu and Gd)

We merge advanced ab initio schemes (standard density functional theory, hybrid functionals and the GW approximation) with model Hamiltonian approaches (tight-binding and Heisenberg Hamiltonian) to study the evolution of the electronic, magnetic and dielectric properties of the manganite family RMnO3 (R = La, Pr, Nd, Sm, Eu and Gd). The link between first principles and tight-binding is established by downfolding the physically relevant subset of 3d bands with e_g character by means of maximally localized Wannier functions (MLWFs) using the VASP2WANNIER90 interface. The MLWFs are then used to construct a tight-binding Hamiltonian. The dispersion of the TB e_g bands at all levels are found to match closely the MLWFs. We provide a complete set of TB parameters which can serve as guidance for the interpretation of future studies based on many-body Hamiltonian approaches. In particular, we find that the Hund's rule coupling strength, the Jahn-Teller coupling strength, and the Hubbard interaction parameter U remain nearly constant for all the members of the RMnO3 series, whereas the nearest neighbor hopping amplitudes show a monotonic attenuation as expected from the trend of the tolerance factor. Magnetic exchange interactions, computed by mapping a large set of hybrid functional total energies onto an Heisenberg Hamiltonian, clarify the origin of the A-type magnetic ordering observed in the early rare-earth manganite series as arising from a net negative out-of-plane interaction energy. The obtained exchange parameters are used to estimate the Neel temperature by means of Monte Carlo simulations. The resulting data capture well the monotonic decrease of the ordering temperature down the R series, in agreement with experiments.Comment: 13 pages, 9 figures, 3 table

Fuel quality-processing study. Volume 2: Literature survey

The validity of initial assumptions about raw materials choices and relevant upgrading processing options was confirmed. The literature survey also served to define the on-site (at the turbine location) options for fuel treatment and exhaust gas treatment. The literature survey also contains a substantial compilation of specification and physical property information about liquid fuel products relevant to industrial gas turbines

Ethnomedicinal Observations from the Maha-Mutharam and Yamanpally Tribal Villages of Karimangar, East Forest Division of Andhra Pradesh, India

Several field trips were conducted during years 2003-2005 to document the ethnobotanical remedies for various ailments of the ethnic tribes inhabiting the Maha-Muttaram and Yamanpally villages of Karimnagar East forest division of Andhra Pradesh, India. In the present study, we report more than 20 ethno-medicinal plants from the tribal people. Our collections of ethno-medicinal plant specimens from this area were deposited in the Kakatiya University Herbarium (KUH), Warangal, India

Sec6 mutations and the Drosophila exocyst complex

To allow a detailed analysis of exocyst function in multicellular organisms, we have generated sec6 mutants in Drosophila. We have used these mutations to compare the phenotypes of sec6 and sec5 in the ovary and nervous system, and we find them to be similar. We also find that Sec5 is mislocalized in sec6 mutants. Additionally, we have generated an epitope-tagged Sec8 that localized with Sec5 on oocyte membranes and was mislocalized in sec5 and sec6 germ-line clones. This construct further revealed a genetic interaction of sec8 and sec5. These data, taken together, provide new information about the organization of the exocyst complex and suggest that Sec5, Sec6 and Sec8 act as a complex, each member dependent on the others for proper localization and function

Critical Crossover Between Yosida-Kondo Dominant Regime and Magnetic Frustration Dominant Regime in the System of a Magnetic Trimer on a Metal Surface

Quantum Monte Carlo simulations were carried out for the system of a magnetic trimer on a metal surface. The magnetic trimer is arranged in two geometric configurations, viz., isosceles and equilateral triangles. The calculated spectral density and magnetic susceptibility show the existence of two phases: Yosida-Kondo dominant phase and magnetic frustration dominant phase. Furthermore, a critical transition between these two phases can be induced by changing the configuration of the magnetic trimers from isosceles to equilateral triangle.Comment: 8 pages, 4 figures; accepted for publication in J. Phys. Soc. Jp

Room temperature soft ferromagnetism in the nanocrystalline form of YCo2 - a well-known bulk Pauli paramagnet

The Laves phase compound, YCo2, is a well-known exchange-enahnced Pauli paramagnet. We report here that, in the nanocrystalline form, this compound interestingly is an itinerant ferromagnet at room temperature with a low coercive-field. The magnitude of the saturation moment (about 1 Bohr-magneton per formula unit) is large enough to infer that the ferromagnetism is not a surface phenomenon in these nanocrystallites. Since these ferromagnetic nanocrystallines are easy to synthesize with a stable form in air, one can explore applications, particularly where hysteresis is a disadvantage

Dynamic analysis of a pre-and-post ice impacted blade

The dynamic characteristics of an engine blade are evaluated under pre-and-post ice impact conditions using the NASA in-house computer code BLASIM. The ice impacts the leading edge of the blade causing severe local damage. The local structural response of the blade due to the ice impact is predicted via a transient response analysis by modeling only a local patch around the impact region. After ice impact, the global geometry of the blade is updated using deformations of the local patch and a free vibration analysis is performed. The effects of ice impact location, size and ice velocity on the blade mode shapes and natural frequencies are investigated. The results indicate that basic nature of the mode shapes remains unchanged after impact and that the maximum variation in natural frequencies occurs for the twisting mode of the blade

Structural tailoring of aircraft engine blade subject to ice impact constraints

Results are presented for the minimum weight design of SR2 unswept blade made of (titanium/graphite-epoxy/titanium) sub s fiber composite. The blade which is rotating at high RPM is subject to ice impact. The root chord length, blade thicknesses at five stations, and graphite-epoxy ply orientation are chosen as design variables. Design constraints are placed on the behavior variables: local leading edge strain and root damage parameter (combined stress failure criteria) as a function due to ice impact, maximum spanwise centrifugal stress at the root of the deformed blade due to local damage, first three natural frequencies, and resonance margin after impact. The method of feasible directions is employed to solve the inequality constrained minimization problem. The effect of ice speed and the ice impact location on the final design are discussed