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For more information or to register concerns or complain about video content, please visit the yahoo Network for Features for more information. You can specify Windows to install only important and recommended updates or important updates. For more information about using cookies and managing your preferences, see Cookie Information. We can offer many of these services by just giving your personal information to provide custom content and ads. You warrant that you: (1) No Prohibited Parties are on an Exclusion Export List of Government (see, for example) (2) does not render the Services again or use to transfer software, technology or other technical data to forbidden parties or countries and (3) use the Services of Military, Nuclear, Rocket, Chemical or Biological Weapons of Different Purposes, or perform other activities related to services that violate the US export and import laws. The Epson EPL-6200 monochrome laser printer is valuable, and in this group of tests is just below the middle of the model. For products or services offered in an account without logging in, these Privacy Policy will apply from for these products and services. 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Rapid vesicle turnover requires sufficient amounts of the hair cell C 2‐domain protein otoferlin (Roux et al, 2006 Pangršič et al, 2010) that when defective causes human hearing impairment (Yasunaga et al, 1999 Varga et al, 2006). Indeed, sustained exocytosis of up to 70 Hz from each of the ~10–15 release sites of the AZ composing the readily releasable pool (RRP) was reported (Pangršič et al, 2010) requiring rapid reloading. Such vivid firing requires the AZ to indefatigably release vesicles at even higher rates, because some release events fail to trigger a spike due to neural refractoriness. ![]() Even during continued stimulation, each SGN can fire at hundreds of Hz in response to release from a single IHC AZ (Matthews & Fuchs, 2010 Pangršič et al, 2012 Safieddine et al, 2012). ![]() Hearing relies on sound encoding at ribbon synapses between IHCs and spiral ganglion neurons (SGNs). We propose that binding of AP‐2 to otoferlin facilitates replenishment of release sites, for example, via speeding AZ clearance of exocytosed material, in addition to a role of AP‐2 in synaptic vesicle reformation. Finally, we show that AP‐2 sorts its IHC‐cargo otoferlin. Sustained strong stimulation led to accumulation of endosome‐like vacuoles, fewer clathrin‐coated endocytic intermediates, and vesicle depletion of the membrane‐distal synaptic ribbon in AP‐2μ‐deficient IHCs, indicating a further role of AP‐2μ in clathrin‐dependent vesicle reformation on a timescale of many seconds. Sound‐driven postsynaptic spiking was reduced in a use‐dependent manner, and the altered interspike interval statistics suggested a slowed reloading of release sites. We show that hair cell‐specific disruption of AP‐2μ slows IHC exocytosis immediately after fusion of the readily releasable pool of vesicles, despite normal abundance of membrane‐proximal vesicles and intact endocytic membrane retrieval. ![]() ![]() Here, we report that the endocytic adaptor protein 2μ ( AP‐2μ) is required for release site replenishment and hearing. Active zones ( AZs) of inner hair cells ( IHCs) indefatigably release hundreds of vesicles per second, requiring each release site to reload vesicles at tens per second. ![]() ![]() ![]() The activity culminates in the eldest daughter being attacked by a spirit that looks like an elderly woman. At night, their young daughter Cindy sleepwalks into the eldest daughter’s bedroom, where she bangs her head repeatedly against an old wardrobe. Over the next couple of days, various paranormal activities occur doors open and close seemingly by themselves and Carolyn hears clapping when nobody is there. 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