Tetrodotoxin-sensitive, voltage-dependent sodium currents in hair cells from the alligator cochlea

We have used whole-cell patch clamp techniques to record from tall hair cells isolated from the apical half of the alligator cochlea. Some of these cells gave action potentials in response to depolarizing current injections. When the same cells were voltage clamped, large transient inward currents followed by smaller outward currents were seen in response to depolarizing steps. We studied the transient inward current after the outward current had been blocked by external tetraethylammonium (20 mM) or by replacing internal potassium with cesium. It was found to be a sodium current because it was abolished by either replacing external sodium with choline or by external application of tetrodotoxin (100 nM). The sodium current showed voltage-dependent activation and inactivation. Most of the spiking hair cells came from the apex of the cochlea, where they would be subject to low-frequency mechanical stimulation in vivo

Developmental regulation of nicotinic synapses on cochlear inner hair cells

In the mature cochlea, inner hair cells (IHCs) transduce acoustic signals into receptor potentials, communicating to the brain by synaptic contacts with afferent fibers. Before the onset of hearing, a transient efferent innervation is found on IHCs, mediated by a nicotinic cholinergic receptor that may contain both α9 and α10 subunits. Calcium influx through that receptor activates calcium-dependent (SK2-containing) potassium channels. This inhibitory synapse is thought to disappear after the onset of hearing [after postnatal day 12 (P12)]. We documented this developmental transition using whole-cell recordings from IHCs in apical turns of the rat organ of Corti. Acetylcholine elicited ionic currents in 88-100% of IHCs between P3 and P14, but in only 1 of 11 IHCs at P16-P22. Potassium depolarization of efferent terminals caused IPSCs in 67% of IHCs at P3, in 100% at P7-P9, in 93% at P10-P12, but in only 40% at P13-P14 and in none of the IHCs tested between P16 and P22. Earlier work had shown by in situ hybridization that α9 mRNA is expressed in adult IHCs but that α10 mRNA disappears after the onset of hearing. In the present study, antibodies to α10 and to the associated calcium-dependent (SK2) potassium channel showed a similar developmental loss. The correlated expression of these gene products with functional innervation suggests that Alpha10 and SK2, but not Alpha9, are regulated by synaptic activity. Furthermore, this developmental knock-out of α10, but not α9, supports the hypothesis that functional nicotinic acetylcholine receptors in hair cells are heteromers containing both these subunits.Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Gómez-Casati, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Super D-branes from BRST Symmetry

Recently a new formalism has been developed for the covariant quantization of superstrings. We study properties of Dp-branes and p-branes in this new framework, focusing on two different topics: effective actions and boundary states for Dp-branes. We present a derivation of the Wess-Zumino terms for super (D)p-branes using BRST symmetry. To achieve this we derive the BRST symmetry for superbranes, starting from the approach with/without pure spinors, and completely characterize the WZ terms as elements of the BRST cohomology. We also develope the boundary state description of Dp-branes by analyzing the boundary conditions for open strings in the completely covariant (i.e., without pure spinors) BRST formulation.Comment: 31 pp; journal version, expended discussion of D-brane pure spinor constraints in Section 2.

Superstar in Noncommutative Superspace via Covariant Quantization of the Superparticle

A covariant quantization method is developed for the off-shell superparticle in 10 dimensions. On-shell it is consistent with lightcone quantization, while off-shell it gives a noncommutative superspace that realizes non-linearly a hidden 11-dimensional super Poincare symmetry. The non-linear commutation rules are then used to construct the supersymmetric generalization of the covariant Moyal star product in noncommutative superspace. As one of the possible applications, we propose this new product as the star product in supersymmetric string field theory. Furthermore, the formalism introduces new techniques and concepts in noncommutative (super)geometry.Comment: 17 pages, LaTe

Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing

Efferent inhibition of cochlear hair cells is mediated by α9α10 nicotinic cholinergic receptors (nAChRs) functionally coupled to calcium-activated, small conductance (SK2) potassium channels. Before the onset of hearing, efferent fibers transiently make functional cholinergic synapses with inner hair cells (IHCs). The retraction of these fibers after the onset of hearing correlates with the cessation of transcription of the Chrna10 (but not the Chrna9) gene in IHCs. To further analyze this developmental change, we generated a transgenic mice whose IHCs constitutively express α10 into adulthood by expressing the α10 cDNA under the control of the Pou4f3 gene promoter. In situ hybridization showed that the α10 mRNA is expressed in IHCs of 8-week-old transgenic mice, but not in wild-type mice. Moreover, this mRNA is translated into a functional protein, since IHCs from P8-P10 α10 transgenic mice backcrossed to a Chrna10 -/- background (whose IHCs have no cholinergic function) displayed normal synaptic and acetylcholine (ACh)-evoked currents in patch-clamp recordings. Thus, the α10 transgene restored nAChR function. However, in the α10 transgenic mice, no synaptic or ACh-evoked currents were observed in P16-18 IHCs, indicating developmental down-regulation of functional nAChRs after the onset of hearing, as normally observed in wild-type mice. The lack of functional ACh currents correlated with the lack of SK2 currents. These results indicate that multiple features of the efferent postsynaptic complex to IHCs, in addition to the nAChR subunits, are down-regulated in synchrony after the onset of hearing, leading to lack of responses to ACh. © 2009 Association for Research in Otolaryngology.Fil:Taranda, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Ballestero, J.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Wedemeyer, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Gómez-Casati, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Lipovsek, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Light scattering from disordered overlayers of metallic nanoparticles

We develop a theory for light scattering from a disordered layer of metal nanoparticles resting on a sample. Averaging over different disorder realizations is done by a coherent potential approximation. The calculational scheme takes into account effects of retardation, multipole excitations, and interactions with the sample. We apply the theory to a system similar to the one studied experimentally by Stuart and Hall [Phys. Rev. Lett. {\bf 80}, 5663 (1998)] who used a layered Si/SiO$_2$/Si sample. The calculated results agree rather well with the experimental ones. In particular we find conspicuous maxima in the scattering intensity at long wavelengths (much longer than those corresponding to plasmon resonances in the particles). We show that these maxima have their origin in interference phenomena in the layered sample.Comment: 19 pages, 12 figure

Generalized twisted modules associated to general automorphisms of a vertex operator algebra

We introduce a notion of strongly C^{\times}-graded, or equivalently, C/Z-graded generalized g-twisted V-module associated to an automorphism g, not necessarily of finite order, of a vertex operator algebra. We also introduce a notion of strongly C-graded generalized g-twisted V-module if V admits an additional C-grading compatible with g. Let V=\coprod_{n\in \Z}V_{(n)} be a vertex operator algebra such that V_{(0)}=\C\one and V_{(n)}=0 for n<0 and let u be an element of V of weight 1 such that L(1)u=0. Then the exponential of 2\pi \sqrt{-1} Res_{x} Y(u, x) is an automorphism g_{u} of V. In this case, a strongly C-graded generalized g_{u}-twisted V-module is constructed from a strongly C-graded generalized V-module with a compatible action of g_{u} by modifying the vertex operator map for the generalized V-module using the exponential of the negative-power part of the vertex operator Y(u, x). In particular, we give examples of such generalized twisted modules associated to the exponentials of some screening operators on certain vertex operator algebras related to the triplet W-algebras. An important feature is that we have to work with generalized (twisted) V-modules which are doubly graded by the group C/Z or C and by generalized eigenspaces (not just eigenspaces) for L(0), and the twisted vertex operators in general involve the logarithm of the formal variable.Comment: Final version to appear in Comm. Math. Phys. 38 pages. References on triplet W-algebras added, misprints corrected, and expositions revise

Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

BACKGROUND: Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. METHODS: HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. RESULTS: All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. CONCLUSIONS: Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted

Higher string functions, higher-level Appell functions, and the logarithmic ^sl(2)_k/u(1) CFT model

We generalize the string functions C_{n,r}(tau) associated with the coset ^sl(2)_k/u(1) to higher string functions A_{n,r}(tau) and B_{n,r}(tau) associated with the coset W(k)/u(1) of the W-algebra of the logarithmically extended ^sl(2)_k conformal field model with positive integer k. The higher string functions occur in decomposing W(k) characters with respect to level-k theta and Appell functions and their derivatives (the characters are neither quasiperiodic nor holomorphic, and therefore cannot decompose with respect to only theta-functions). The decomposition coefficients, to be considered ``logarithmic parafermionic characters,'' are given by A_{n,r}(tau), B_{n,r}(tau), C_{n,r}(tau), and by the triplet \mathscr{W}(p)-algebra characters of the (p=k+2,1) logarithmic model. We study the properties of A_{n,r} and B_{n,r}, which nontrivially generalize those of the classic string functions C_{n,r}, and evaluate the modular group representation generated from A_{n,r}(tau) and B_{n,r}(tau); its structure inherits some features of modular transformations of the higher-level Appell functions and the associated transcendental function Phi.Comment: 34 pages, amsart++, times. V2: references added; minor changes; some nonsense in B.3.3. correcte

Conformal Field Theory Approach to the 2-Impurity Kondo Problem: Comparison with Numerical Renormalization Group Results

Numerical renormalization group and conformal field theory work indicate that the two impurity Kondo Hamiltonian has a non-Fermi liquid critical point separating the Kondo-screening phase from the inter-impurity singlet phase when particle-hole (P-H) symmetry is maintained. We clarify the circumstances under which this critical point occurs, pointing out that there are two types of P-H symmetry. Only one of them guarantees the occurance of the critical point. Much of the previous numerical work was done on models with the other type of P-H symmetry. We analyse this critical point using the boundary conformal field theory technique. The finite-size spectrum is presented in detail and compared with about 50 energy levels obtained using the numerical renormalization group. Various Green's functions, general renormalization group behaviour, and a hidden $SO(7)$ are analysed.Comment: 38 pages, RevTex. 2 new sections clarify the circumstances under which a model will exhibit the non-trivial critical point (hence potentially resolving disagreements with other Authors) and explain the hidden SO(7) symmetry of the model, relating it to an alternative approach of Sire et al. and Ga