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Long-lasting forms of synaptic plasticity that underlie learning and memory require new transcription and translation for their persistence. The remarkable polarity and compartmentalization of neurons raises questions about the spatial and temporal regulation of gene expression within neurons. Alternative cleavage and polyadenylation (APA) generates mRNA isoforms with different 3' untranslated regions (3'UTRs) and/or coding sequences. Changes in the 3'UTR composition of mRNAs can alter gene expression by regulating transcript localization, stability and/or translation, while changes in the coding sequences lead to mRNAs encoding distinct proteins. Using specialized 3' end deep sequencing methods, we undertook a comprehensive analysis of APA following induction of long-term potentiation (LTP) of mouse hippocampal CA3-CA1 synapses. We identified extensive LTP-induced APA changes, including a general trend of 3'UTR shortening and activation of intronic APA isoforms. Comparison with transcriptome profiling indicated that most APA regulatory events were uncoupled from changes in transcript abundance. We further show that specific APA regulatory events can impact expression of two molecules with known functions during LTP, including 3'UTR APA of Notch1 and intronic APA of Creb1. Together, our results reveal that activity-dependent APA provides an important layer of gene regulation during learning and memory.

AMPA-type glutamate receptors mediate fast, excitatory neurotransmission in the brain, and their concentrations at synapses are important determinants of synaptic strength. We investigated the post-transcriptional regulation of GluA2, the calcium-impermeable AMPA receptor subunit, by examining the subcellular distribution of its mRNA and evaluating its translational regulation by microRNA in cultured mouse hippocampal neurons. Using computational approaches, we identified a conserved microRNA-124 (miR-124) binding site in the 3'UTR of GluA2 and demonstrated that miR-124 regulated the translation of GluA2 mRNA reporters in a sequence-specific manner in luciferase assays. While we hypothesized that this regulation might occur in dendrites, our biochemical and fluorescent in situ hybridization (FISH) data indicate that GluA2 mRNA does not localize to dendrites or synapses of mouse hippocampal neurons. In contrast, we detected significant concentrations of miR-124 in dendrites. Overexpression of miR-124 in dissociated neurons results in a 30% knockdown of GluA2 protein, as measured by immunoblot and quantitative immunocytochemistry, without producing any changes in GluA2 mRNA concentrations. While total GluA2 concentrations are reduced, we did not detect any changes in the concentration of synaptic GluA2. We conclude from these results that miR-124 interacts with GluA2 mRNA in the cell body to downregulate translation. Our data support a model in which GluA2 is translated in the cell body and subsequently transported to neuronal dendrites and synapses, and suggest that synaptic GluA2 concentrations are modified primarily by regulated protein trafficking rather than by regulated local translation.

Presents a lawyers' perspective on the use of parent coordinators in resolving parental conflict over children's issues during the divorce process. Duties of parent coordinators; Types of assistance provided to parents; Relationship of parent coordinators with lawyers.

The effluent of textile industries containing synthetic dyes contributed to substantial pollution to water bodies. The biosorption process of Congo Red dye was successfully performed by integrating ultrasonication in the adsorption step with spent brewery yeast as a novel and renewable biosorbent. The adsorption process was hindered when ultrasonication was employed together with the biosorbent, indicating that desorption process had occurred. The adsorption process showed that 4 g/L of biosorbent was the optimum dosage for adsorption of 50 mg/L of Congo Red dye, and that the adsorption equilibrium fitted to the Langmuir model, with kinetics best fitted with pseudo-second order model. The maximum capacity of the adsorption was 52.6 mg/g, showing the potential of spent brewery yeast to aid in removing wastewater pollutants. Maximal Congo Red dye recovery (100%) was achieved in the sonication-assisted desorption studies using 0.01M NaOH as the eluting agent. The ultrasonication effects contributed to the efficient recovery of dye and good conversion of spent brewery yeast to biosorbent can be beneficial for treating pollution from textile wastewater., (Copyright © 2021. Published by Elsevier Inc.)