Deep sequencing of pre-translational mRNPs reveals hidden flux through evolutionarily conserved alternative splicing nonsense-mediated decay pathways.

Background: Alternative splicing, which generates multiple mRNA isoforms from single genes, is crucial for the regulation of eukaryotic gene expression. The flux through competing splicing pathways cannot be determined by traditional RNA-Seq, however, because different mRNA isoforms can have widely differing decay rates. Indeed, some mRNA isoforms with extremely short half-lives, such as those subject to translation-dependent nonsense-mediated decay (AS-NMD), may be completely overlooked in even the most extensive RNA-Seq analyses.

A method for quantification of exportin-1 (XPO1) occupancy by Selective Inhibitor of Nuclear Export (SINE) compounds.

Selective Inhibitor of Nuclear Export (SINE) compounds are a family of small-molecules that inhibit nuclear export through covalent binding to cysteine 528 (Cys528) in the cargo-binding pocket of Exportin 1 (XPO1/CRM1) and promote cancer cell death. Selinexor is the lead SINE compound currently in phase I and II clinical trials for advanced solid and hematological malignancies. In an effort to understand selinexor-XPO1 interaction and to establish whether cancer cell response is a function of drug-target engagement, we developed a quantitative XPO1 occupancy assay.

Long-term persistence and development of induced pancreatic beta cells generated by lineage conversion of acinar cells.

Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, the survival and function of lineage-reprogrammed cells in vivo over the long term has not been examined. Here, using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, we show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet-like structures and support normoglycemia in diabetic mice.

The ventral uvula of the mouse cerebellum: a neural target of ethanol and vestibular stimuli.

The present study demonstrates that mice exposed to vertical translation stimulation exhibit a distinct parasagittal pattern of Fos-immunoreactive (Fos-IR) granule cells in the ventral uvula of the cerebellum. This pattern is identical to one produced by acute ethanol treatment. In contrast, yaw stimulation produces an entirely different pattern in this same region of the cerebellum.

Acute ethanol administration produces specific patterns of localization of Fos-immunoreactivity in the cerebellum and inferior olive of two inbred strains of mice.

Genes play an important role in behavioral responses to ethanol. We examined the response of neurons within the inferior olivary complex (IO) and cerebellum of C57Bl6/J and C3H/HeJ mice to acute ethanol, using immunodetection of Fos (Fos-IR) protein as a marker of neuronal activation. The results demonstrate specific but different patterns of Fos-IR within the IO and cerebellum, especially lobule IX, in each strain.

Alcohol differentially affects c-Fos expression in the supraoptic nucleus of long-sleep and short-sleep mice.

Ethanol administration in long-sleep (LS) and short-sleep (SS) mice results in a large number of Fos-IR neurons in the supraoptic nucleus (SON) in LS, and almost no Fos-IR neurons in the same nucleus in SS mice. In contrast, isotonic saline, hypertonic saline, with or without ethanol, resulted in a similar pattern of Fos-IR in both strains. These data indicate a differential effect of ethanol on c-Fos signaling specifically in the SON.