Using the described methodology, we show that a ninth segment can also be incorporated by manipulation of the PB2 or PA segment-specific packaging signals. This approach offers a means of generating a bivalent influenza virus vaccine.”
“Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by epilepsy, progressive motor and cognitive decline, blindness, and by the accumulation of autofluorescent lipopigment. Late-infantile onset forms (LINCL) include those linked to mutations in CLN8 gene, encoding a transmembrane protein at the endoplasmic reticulum (ER). In the motor neuron degeneration (mnd) mouse model check details of the CLN8-LINCL (CLN8(mnd)),

we carried out an analysis of ER stress-related molecules in CN5 structures that exhibit a variable rate of disease progression (early retinal

degeneration and delayed brain and motoneuron dysfunction). At the presymptomatic state of 1-month-old CLN8(mnd) mice, we found an upregulation of GRP78 and activation of the transcription factor-6 (ATF6) in Nec-1s all structures examined, an activation of a CHOP-dependent pathway in the cerebellum, hippocampus and retina, a caspase-12-dependent pathway in the retina and no activation of these two pathways in the cerebral cortex and spinal cord. An increased CHOP expression was detected in the cortex and spinal cord at the early symptomatic state (4 months). Caspase-3 cleavage occurred presymptomatically in the cerebellum, hippocampus and retina, and symptomatically in the cerebral cortex and spinal cord. We also monitored activation of NF-kappa B, which is engaged in the alarming phase of ER stress, together with increased levels of TRAF2, TNF-alpha and TNFR1, and no activation of ASK-1/JNK signalling pathway, all over mnd structures. The results suggest that early ER-stress responses distinctly combined

and ER-stress pathways integrated with inflammatory responses may contribute to the progression of the CLN8(mnd) disease in CNS structures. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“The PF299804 mouse structures of polio-, coxsackie-, and rhinovirus polymerases have revealed a conserved yet unusual protein conformation surrounding their buried N termini where a beta-strand distortion results in a solvent-exposed hydrophobic amino acid at residue 5. In a previous study, we found that coxsackievirus polymerase activity increased or decreased depending on the size of the amino acid at residue 5 and proposed that this residue becomes buried during the catalytic cycle. In this work, we extend our studies to show that poliovirus polymerase activity is also dependent on the nature of residue 5 and further elucidate which aspects of polymerase function are affected. Poliovirus polymerases with mutations of tryptophan 5 retain wild-type elongation rates, RNA binding affinities, and elongation complex formation rates but form unstable elongation complexes.