Wnt proteins are emerging key regulators of the plasticity and functions of adult brains. However, the mechanisms by which the expression of Wnt proteins is regulated in neurons are unclear. Using cortical primary cultures, we show here that activation of NMDA receptors (NMDARs) induces rapid Wnt5a protein synthesis and secretion. This NMDAR-regulated Wnt5a synthesis does not require transcription and is a result of activity-dependent translation. We also show that NMDAR-regulated Wnt5a translation depends on MAPK signaling but not mTOR signaling. Our findings suggest that the synaptic activity of CNS neurons activates NMDARs, which in turn stimulate translation from stored Wnt5a mRNA via the MAPK signaling pathway.

BackgroundMonogenic diabetes is a genetic disease often caused by mutations in genes involved in beta-cell function. Correct sub-categorization of the disease is a prerequisite for appropriate treatment and genetic counseling. Target-region capture sequencing is a combination of genomic region enrichment and next generation sequencing which might be used as an efficient way to diagnose various genetic disorders. We aimed to develop a target-region capture sequencing platform to screen 117 selected candidate genes involved in metabolism for mutations and to evaluate its performance using monogenic diabetes as a study-model.ResultsThe performance of the assay was evaluated in 70 patients carrying known disease causing mutations previously identified in HNF4A, GCK, HNF1A, HNF1B, INS, or KCNJ11. Target regions with a less than 20-fold sequencing depth were either introns or UTRs. When only considering translated regions, the coverage was 100% with a 50-fold minimum depth. Among the 70 analyzed samples, 63 small size single nucleotide polymorphisms and indels as well as 7 large deletions and duplications were identified as being the pathogenic variants. The mutations identified by the present technique were identical with those previously identified through Sanger sequencing and Multiplex Ligation-dependent Probe Amplification.ConclusionsWe hereby demonstrated that the established platform as an accurate and high-throughput gene testing method which might be useful in the clinical diagnosis of monogenic diabetes.

through a skyrmion, its twisted spins endow these electrons with an emergent electromagnetic field, yielding a variety of unconventional magnetoelectronic phenomena, such as topological Hall effect [12] and ultralow current density for skyrmion motion. [23][24][25][26] These properties together with the nanoscale size and topological stability, make magnetic skyrmion promising potential for future highdensity, low-power-consuming magnetic memory devices. [1][2][3] Like many quasiparticles in condensed matter physics, magnetic skyrmion also has a particle-like characteristic. [1][2][3] Owing to this feature, multiple skyrmions can aggregate and dissipate in a defined geometry, which holds promise for applications beyond conventional binary memories, such as multi-level memories, [1,28,29] neuromorphic computing, [28][29][30] probabilistic computing, [31] and nano-oscillators. [32,33] In previous work, the experiment demonstrated an accumulation and dissipation of isolated skyrmions in micrometer-sized geometries using the spin-polarized pulse current. [30] However, since the skyrmion-skyrmion interaction between different Magnetic skyrmions are topological swirling spin configurations that hold promise for building future magnetic memories and logic circuits. Skyrmionic devices typically rely on the electrical manipulation of a single skyrmion, but controllably manipulating a group of skyrmions can lead to more compact and memory-efficient devices. Here, an electric-field-driven cascading transition of skyrmion clusters in a nanostructured ferromagnetic/ferroelectric multiferroic heterostructure is reported, which allows a continuous multilevel transition of the number of skyrmions in a one-by-one manner. Most notably, the transition is non-volatile and reversible, which is crucial for multi-bit memory applications. Combined experiments and theoretical simulations reveal that the switching of skyrmion clusters is induced by the strain-mediated modification of both the interfacial Dzyaloshinskii-Moriya interaction and effective uniaxial anisotropy. The results not only open up a new direction for constructing low-power-consuming, non-volatile, and multi-bit skyrmionic devices, but also offer valuable insights into the fundamental physics underlying the voltage manipulation of skyrmion clusters.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.202107908.

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Skyrmion Clusters An electric‐field‐driven cascading transition of skyrmion clusters in a nanostructured ferromagnetic/ferroelectric multiferroic heterostructure is realized by Zhipeng Hou, Yangfan Hu, and co‐workers, as described in article number 2107908, allowing a continuous multilevel transition of the number of skyrmions in a one‐by‐one manner. Most notably, the transition is nonvolatile and reversible. These results open up a new direction for constructing low‐power‐consuming, nonvolatile, and multibit skyrmionic devices.