Environmentally Robust Triboelectric Tire Monitoring System for Self-Powered Driving Information Recognition via Hybrid Deep Learning in Time-Frequency Representation.

Developing a robust artificial intelligence of things (AIoT) system with a self-powered triboelectric sensor for harsh environment is challenging because environmental fluctuations are reflected in triboelectric signals. This study presents an environmentally robust triboelectric tire monitoring system with deep learning to capture driving information in the triboelectric signals generated from tire-road friction. The optimization of the process and structure of a laser-induced graphene (LIG) electrode layer in the triboelectric tire is conducted, enabling the tire to detect universal driving information for vehicles/robotic mobility, including rotation speeds of 200-2000 rpm and contact fractions of line. Employing a hybrid model combining short-term Fourier transform with a convolution neural network-long short-term memory, the LIG-based triboelectric tire monitoring (LTTM) system decouples the driving information, such as traffic lines and road states, from varied environmental conditions of humidity (10%-90%) and temperatures (50-70 °C). The real-time line and road state recognition of the LTTM system is confirmed on a mobile platform across diverse environmental conditions, including fog, dampness, intense sunlight, and heat shimmer. This work provides an environmentally robust monitoring AIoT system by introducing a self-powered triboelectric sensor and hybrid deep learning for smart mobility.

Role of the proline-rich disordered domain of DROSHA in intronic microRNA processing.

DROSHA serves as a gatekeeper of the microRNA (miRNA) pathway by processing primary transcripts (pri-miRNAs). While the functions of structured domains of DROSHA have been well documented, the contribution of N-terminal proline-rich disordered domain (PRD) remains elusive. Here we show that the PRD promotes the processing of miRNA hairpins located within introns. We identified a DROSHA isoform (p140) lacking the PRD, which is produced by proteolytic cleavage. Small RNA sequencing revealed that p140 is significantly impaired in the maturation of intronic miRNAs. Consistently, our minigene constructs demonstrated that PRD enhances the processing of intronic hairpins, but not those in exons. Splice site mutations did not affect the PRD's enhancing effect on intronic constructs, suggesting that the PRD acts independently of splicing reaction by interacting with sequences residing within introns. The N-terminal regions from zebrafish and Xenopus DROSHA can replace the human counterpart, indicating functional conservation despite poor sequence alignment. Moreover, we found that rapidly evolving intronic miRNAs are generally more dependent on PRD than conserved ones, suggesting a role of PRD in miRNA evolution. Our study reveals a new layer of miRNA regulation mediated by a low-complexity disordered domain that senses the genomic contexts of miRNA loci.

L1 retrotransposons exploit RNA m6A modification as an evolutionary driving force.

L1 retrotransposons can pose a threat to genome integrity. The host has evolved to restrict L1 replication. However, mechanisms underlying L1 propagation out of the host surveillance remains unclear. Here, we propose an evolutionary survival strategy of L1, which exploits RNA m6A modification. We discover that m6A 'writer' METTL3 facilitates L1 retrotransposition, whereas m6A 'eraser' ALKBH5 suppresses it. The essential m6A cluster that is located on L1 5' UTR serves as a docking site for eukaryotic initiation factor 3 (eIF3), enhances translational efficiency and promotes the formation of L1 ribonucleoprotein. Furthermore, through the comparative analysis of human- and primate-specific L1 lineages, we find that the most functional m6A motif-containing L1s have been positively selected and became a distinctive feature of evolutionarily young L1s. Thus, our findings demonstrate that L1 retrotransposons hijack the RNA m6A modification system for their successful replication.

Impact of Sleep Disorder as a Risk Factor for Dementia in Men and Women.

Sleep is an essential physiological process, especially for proper brain function through the formation of new pathways and processing information and cognition. Therefore, when sleep is insufficient, this can result in pathophysiologic conditions. Sleep deficiency is a risk factor for various conditions, including dementia, diabetes, and obesity. Recent studies have shown that there are differences in the prevalence of sleep disorders between genders. Insomnia, the most common type of sleep disorder, has been reported to have a higher incidence in females than in males. However, sex/gender differences in other sleep disorder subtypes are not thoroughly understood. Currently, increasing evidence suggests that gender issues should be considered important when prescribing medicine. Therefore, an investigation of the gender-dependent differences in sleep disorders is required. In this review, we first describe sex/gender differences not only in the prevalence of sleep disorders by category but in the efficacy of sleep medications. In addition, we summarize sex/gender differences in the impact of sleep disorders on incident dementia. This may help understand gender-dependent pathogenesis of sleep disorders and develop therapeutic strategies in men and women.

fCLIP-seq for transcriptomic footprinting of dsRNA-binding proteins: Lessons from DROSHA.

CLIP-seq (crosslinking immunoprecipitation and sequencing) is widely used to map the binding sites of a protein of interest on the transcriptome, and generally employs UV to induce the covalent bonds between protein and RNA, which allows stringent washing. However, dsRNA is inefficiently crosslinked by UV, making it difficult to study the interactions between dsRNA binding proteins and their substrates. A dsRNA endoribonuclease DROSHA initiates the maturation of microRNA (miRNA) by cleaving primary miRNA (pri-miRNA). Despite the importance of DROSHA in miRNA maturation and sequence determination, accurate mapping of DROSHA cleavage sites has not been feasible due to rapid processing, modification, and degradation of the cleaved products in cells. Here, we present a high-throughput sequencing method that allows the mapping of in vivo DROSHA cleavage sites at single nucleotide resolution, termed formaldehyde crosslinking, immunoprecipitation, and sequencing (fCLIP-seq). The fCLIP-seq protocol has been improved significantly over the standard CLIP-seq methods by (1) using formaldehyde for efficient and reversible crosslinking, (2) employing polyethylene glycol and adaptors with randomized sequences to enhance ligation efficiency and minimize bias, and (3) performing ligation after elution, which exposes the RNA termini for efficient ligation. fCLIP-seq successfully captures the nascent products of DROSHA, which allows precise mapping of the DROSHA processing sites. Moreover, from the analysis of the distinctive cleavage pattern, we discover previously unknown substrates of DROSHA. fCLIP-seq is a useful tool to obtain transcriptome-wide information on DROSHA activity and can be applied further to investigate other dsRNA-protein interactions.

PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs.

Protein kinase RNA-activated (PKR) induces immune response by sensing viral double-stranded RNAs (dsRNAs). However, growing evidence suggests that PKR can also be activated by endogenously expressed dsRNAs. Here, we capture these dsRNAs by formaldehyde-mediated crosslinking and immunoprecipitation sequencing and find that various noncoding RNAs interact with PKR. Surprisingly, the majority of the PKR-interacting RNA repertoire is occupied by mitochondrial RNAs (mtRNAs). MtRNAs can form intermolecular dsRNAs owing to bidirectional transcription of the mitochondrial genome and regulate PKR and eIF2α phosphorylation to control cell signaling and translation. Moreover, PKR activation by mtRNAs is counteracted by PKR phosphatases, disruption of which causes apoptosis from PKR overactivation even in uninfected cells. Our work unveils dynamic regulation of PKR even without infection and establishes PKR as a sensor for nuclear and mitochondrial signaling cues in regulating cellular metabolism.

Genome-wide Mapping of DROSHA Cleavage Sites on Primary MicroRNAs and Noncanonical Substrates.

MicroRNA (miRNA) maturation is initiated by DROSHA, a double-stranded RNA (dsRNA)-specific RNase III enzyme. By cleaving primary miRNAs (pri-miRNAs) at specific positions, DROSHA serves as a main determinant of miRNA sequences and a highly selective gatekeeper for the canonical miRNA pathway. However, the sites of DROSHA-mediated processing have not been annotated, and it remains unclear to what extent DROSHA functions outside the miRNA pathway. Here, we establish a protocol termed "formaldehyde crosslinking, immunoprecipitation, and sequencing (fCLIP-seq)," which allows identification of DROSHA cleavage sites at single-nucleotide resolution. fCLIP identifies numerous processing sites, suggesting widespread end modifications during miRNA maturation. fCLIP also finds many pri-miRNAs that undergo alternative processing, yielding multiple miRNA isoforms. Moreover, we discovered dozens of DROSHA substrates on non-miRNA loci, which may serve as cis-elements for DROSHA-mediated gene regulation. We anticipate that fCLIP-seq could be a general tool for investigating interactions between dsRNA-binding proteins and structured RNAs.

LIN28A is a suppressor of ER-associated translation in embryonic stem cells.

LIN28 plays a critical role in developmental transition, glucose metabolism, and tumorigenesis. At the molecular level, LIN28 is known to repress maturation of let-7 microRNAs and enhance translation of certain mRNAs. In this study, we obtain a genome-wide view of the molecular function of LIN28A in mouse embryonic stem cells by carrying out RNA crosslinking-immunoprecipitation-sequencing (CLIP-seq) and ribosome footprinting. We find that, in addition to let-7 precursors, LIN28A binds to a large number of spliced mRNAs. LIN28A recognizes AAGNNG, AAGNG, and less frequently UGUG, which are located in the terminal loop of a small hairpin. LIN28A is localized to the periendoplasmic reticulum (ER) area and inhibits translation of mRNAs that are destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins. Our study suggests a selective regulatory mechanism for ER-associated translation and reveals an unexpected role of LIN28A as a global suppressor of genes in the secretory pathway.