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CaMKII has long been known to be a key effector for synaptic plasticity. Recent studies have shown that a variety of modulators interact with the subunits of CaMKII to regulate the long-term potentiation (LTP) of hippocampal neurons. However, whether long non-coding RNAs modulate the activity of CaMKII and affect synaptic plasticity is still elusive. Here, we identify a previously uncharacterized long non-coding RNA Carip that functions as a scaffold, specifically interacts with CaMKIIβ, and regulates the phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor subunits in the hippocampus. The absence of Carip causes dysfunction of synaptic transmission and attenuates LTP in hippocampal CA3-CA1 synapses, which further leads to impairment of spatial learning and memory. In summary, our findings demonstrate that Carip modulates long-term synaptic plasticity by changing AMPA receptor and NMDA receptor activities, thereby affecting spatial learning and memory in mice.

The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system is a widely used genome-editing tool with great clinical potential. However, its application is limited because of low editing efficiency of some target sequences and off-target effects. As this system contains only the Cas9 protein and a single-guide RNA (sgRNA; engineered from crRNA and tracrRNA), the structure and function of these components should be studied in detail to address the current clinical needs. Consequently, we investigated the structural and sequence features of the core hairpin (the first stem loop of sgRNA) of SpCas9 sgRNA. We showed that the core hairpin structure of sgRNA is essential for SpCas9/sgRNA-mediated DNA cleavage and that the internal loop structure in the core hairpin plays a vital role in target DNA cleavage. We observed that the root stem structure within the core hairpin preferentially forms Watson-Crick base pairs and should be of a specific length to maintain an appropriate spatial conformation for Cas9 binding. However, the length of the leaf stem structure of the core hairpin is flexible, having a variable nucleotide composition. Furthermore, extension of the leaf stem structure enhances the DNA cleavage activity of the Cas9/sgRNA complex, and this could be used to enhance the efficiency of gene editing. These observations provide insight into the sgRNA/Cas9 interaction, indicating that sgRNA modification could be a strategy for improved DNA editing efficiency, and optimized sgRNA can be further used for genome-wide functional screening and clinical application.

Supplemental material, Supplementary_Data for Core Hairpin Structure of SpCas9 sgRNA Functions in a Sequence- and Spatial Conformation–Dependent Manner by Mingjun Jiang, Yanzhen Ye and Juan Li in SLAS Technology

Recently, crowdsourcing has been promoted as a promising solution for fingerprint-based indoor localization systems. However, when using crowdsourced fingerprints to construct an indoor radio map, the following challenges should be first addressed: inaccurate location information, nonuniform spatial density, fingerprint dimension diversity and collection device diversity. In this paper, we propose a radio map construction scheme based on crowdsourced fingerprint splitting and fitting to deal with the first three challenges. Our objective is to construct a grid radio map from crowdsourced fingerprints. We propose to split a crowdsourced fingerprint into several neighboring grid cells with some probability. For each grid cell, we propose to first filter out some unimportant features when composing a grid cell fingerprint. Furthermore, for a grid cell with very few or non supporting crowdsourced fingerprints, we propose to construct its fingerprint by using the surface fitting technique. We conduct field measurements and experiments to examine the localization performance. Results show that the proposed scheme can achieve 1.48m mean localization error and is more robustness to location annotation errors.