Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure

Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies. SEM reveals persistent damage to some surviving outer hair cell stereocilia. However, DPOAE analysis reveals that some function is preserved in low frequency outer hair cells, despite concomitant profound hearing loss. Inner hair cells, auditory synapses and spiral ganglion neurons are all present after noise exposure in the Foxo3KO/KO fourteen days post noise (DPN). We also report anti-Foxo3 immunofluorescence in adult human outer hair cells. Taken together, these data implicate Foxo3 and its transcriptional targets in outer hair cell survival after noise damage. An additional role for Foxo3 in preserving hearing is likely, as low frequency auditory function is absent in noise exposed Foxo3KO/KOs even though all cells and structures are present

Old stellar Galactic disc in near-plane regions according to 2MASS: scales, cut-off, flare and warp

We have pursued two different methods to analyze the old stellar population near the Galactic plane, using data from the 2MASS survey. The first method is based on the isolation of the red clump giant population in the color-magnitude diagrams and the inversion of its star counts to obtain directly the density distribution along the line of sight. The second method fits the parameters of a disc model to the star counts in 820 regions. Results from both independent methods are consistent with each other. The qualitative conclusions are that the disc is well fitted by an exponential distribution in both the galactocentric distance and height. There is not an abrupt cut-off in the stellar disc (at least within R<15 kpc). There is a strong flare (i.e. an increase of scale-height towards the outer Galaxy) which begins well inside the solar circle, and hence there is a decrease of the scale-height towards the inner Galaxy. Another notable feature is the existence of a warp in the old stellar population whose amplitude is coincident with the amplitude of the gas warp. It is shown for low latitude stars (mean height: |z|~300 pc) in the outer disc (galactocentric radius R>6 kpc) that: the scale-height in the solar circle is h_z(R_sun)=3.6e-2 R_sun, the scale-length of the surface density is h_R=0.42 R_sun and the scale-length of the space density in the plane (i.e. including the effect of the flare) is H=0.25 R_sun. The variation of the scale-height due to the flare follows roughly a law h_z(R) =~ h_z(R_sun) exp [(R-R_\odot)/([12-0.6R(kpc)] kpc)] (for R<~15 kpc; R_sun=7.9 kpc). The warp moves the mean position of the disc to a height z_w=1.2e-3 R(kpc)^5.25 sin(phi+(5 deg.)) pc (for R<~13 kpc; R_sun=7.9 kpc).Comment: LaTEX, 20 pages, 23 figures, accepted to be published in A&