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Pre-Mrna Secondary Structures Influence Exon Recognition, Michael Hiller, Zhaiyi Zhang, Rolf Backofen, Stefan Stamm
Pre-Mrna Secondary Structures Influence Exon Recognition, Michael Hiller, Zhaiyi Zhang, Rolf Backofen, Stefan Stamm
Molecular and Cellular Biochemistry Faculty Publications
The secondary structure of a pre-mRNA influences a number of processing steps including alternative splicing. Since most splicing regulatory proteins bind to single-stranded RNA, the sequestration of RNA into double strands could prevent their binding. Here, we analyzed the secondary structure context of experimentally determined splicing enhancer and silencer motifs in their natural pre-mRNA context. We found that these splicing motifs are significantly more single-stranded than controls. These findings were validated by transfection experiments, where the effect of enhancer or silencer motifs on exon skipping was much more pronounced in single-stranded conformation. We also found that the structural context of …
Induction Of Insulin Secretion In Engineered Liver Cells By Nitric Oxide, Latha Muniappan, Sabire Özcan
Induction Of Insulin Secretion In Engineered Liver Cells By Nitric Oxide, Latha Muniappan, Sabire Özcan
Molecular and Cellular Biochemistry Faculty Publications
BACKGROUND: Type 1 Diabetes Mellitus results from an autoimmune destruction of the pancreatic beta cells, which produce insulin. The lack of insulin leads to chronic hyperglycemia and secondary complications, such as cardiovascular disease. The currently approved clinical treatments for diabetes mellitus often fail to achieve sustained and optimal glycemic control. Therefore, there is a great interest in the development of surrogate beta cells as a treatment for type 1 diabetes. Normally, pancreatic beta cells produce and secrete insulin only in response to increased blood glucose levels. However in many cases, insulin secretion from non-beta cells engineered to produce insulin occurs …
Expansion Of The Calcium Hypothesis Of Brain Aging And Alzheimer's Disease: Minding The Store, Olivier Thibault, John C. Gant, Philip W. Landfield
Expansion Of The Calcium Hypothesis Of Brain Aging And Alzheimer's Disease: Minding The Store, Olivier Thibault, John C. Gant, Philip W. Landfield
Pharmacology and Nutritional Sciences Faculty Publications
Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. …
Functional Dissociation In Frontal And Striatal Areas For Processing Of Positive And Negative Reward Information, Xun Liu, David K. Powell, Hongbin Wang, Brian T. Gold, Christine R. Corbly, Jane E. Joseph
Functional Dissociation In Frontal And Striatal Areas For Processing Of Positive And Negative Reward Information, Xun Liu, David K. Powell, Hongbin Wang, Brian T. Gold, Christine R. Corbly, Jane E. Joseph
Neuroscience Faculty Publications
Reward-seeking behavior depends critically on processing of positive and negative information at various stages such as reward anticipation, outcome monitoring, and choice evaluation. Behavioral and neuropsychological evidence suggests that processing of positive (e.g., gain) and negative (e.g., loss) reward information may be dissociable and individually disrupted. However, it remains uncertain whether different stages of reward processing share certain neural circuitry in frontal and striatal areas, and whether distinct but interactive systems in these areas are recruited for positive and negative reward processing. To explore these issues, we used a monetary decision-making task to investigate the roles of frontal and striatal …