M. Kattenhorn, G. A. Korbel, B. M. Kessler, E. Spooner, and H. L. Ploegh,

LY2835219 manufacturer Mol. Cell 19: 547-557, 2005), efficiently released ubiquitin but not ubiquitin-like modifications from a hemagglutinin peptide substrate. Mutating the active-site residues Cys24 or His162 (C24S and H162A, respectively) abolished this activity. The HCMV UL48 and HSV UL36(USP) DUBs cleaved both Lys48- and Lys63-linked ubiquitin dimers and oligomers, showing more activity toward Lys63 linkages. The DUB activity of the full-length UL48 protein immunoprecipitated from virus-infected cells also showed a better cleavage of Lys63-linked ubiquitinated substrates. An HCMV (Towne) mutant virus in which the UL48 DUB activity was destroyed [UL48(C24S)] produced 10-fold less progeny virus and reduced amounts of viral proteins compared to wild-type virus at a low multiplicity of infection. The mutant virus also produced perceptibly less overall deubiquitination than the wild-type virus. Our findings demonstrate that the

HCMV UL48 DUB contains both a ubiquitin-specific carboxy-terminal hydrolase activity and an isopeptidase activity that favors ubiquitin Lys63 linkages and that these activities can influence virus replication in cultured cells.”
“Action potentials from the brain control the activity of spinal neural networks to produce, by as yet unknown mechanisms, Selleck SRT1720 a variety of motor behaviors. Particularly lacking are details on how identified descending neurons integrate diverse sensory inputs to generate specific locomotor patterns. We have examined AZD5582 mouse the operations of the principal neurons in an intriguing midbrain nucleus, the nucleus of the medial longitudinal fasciculus (nMLF), in the larval zebrafish. The nMLF is the most rostral grouping of neurons that projects from the brain well into the spinal cord of teleost fishes, yet there

is little direct physiological data available regarding its function. We report here that a distinct set of large, individually-identifiable neurons in nMLF (the MeL and MeM neurons) are activated by diverse sensory stimuli and contribute to distinct locomotor behaviors. Using in vivo confocal calcium imaging we observed that both photic and mechanical stimuli elicit calcium responses indicative of the firing of action potentials. Calcium responses were observed simultaneously with distinct swimming, turning and struggling movements of the larval trunk. While selectively contralateral responses were at times observed in response to a head-tap stimulus, these nMLF cells showed roughly similar numbers of bilateral responses. Calcium responses were observed at a range of latencies, suggesting involvement with both slow swimming patterns and the burst swimming component of the escape behavior. The MeL cells in particular were strongly activated during light-evoked slow swimming.