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Recurring mutations in genes encoding 3' splice-site recognition proteins, U2AF1 and ZRSR2 are associated with human cancers. Here, we determined binding sites of the proteins to reveal that U2-type and U12-type splice sites are recognized by U2AF1 and ZRSR2, respectively. However, some sites are spliced by both the U2-type and U12-type spliceosomes, indicating that well-conserved consensus motifs in some U12-type introns could be recognized by the U2-type spliceosome. Nucleotides flanking splice sites of U12-type introns are different from those flanking U2-type introns. Remarkably, the AG dinucleotide at the positions -1 and -2 of 5' splice sites of U12-type introns with GT-AG termini is not present. AG next to 5' splice site introduced by a single nucleotide substitution at the -2 position could convert a U12-type splice site to a U2-type site. The class switch of introns by a single mutation and the bias against G at the -1 position of U12-type 5' splice site support the notion that the identities of nucleotides in exonic regions adjacent to splice sites are fine-tuned to avoid recognition by the U2-type spliceosome. These findings may shed light on the mechanism of selectivity in U12-type intron splicing and the mutations that affect splicing.
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Sitios de Empalme de ARN , Ribonucleoproteínas , Empalmosomas , Factor de Empalme U2AF , Humanos , Sitios de Unión , Intrones , Nucleótidos/metabolismo , Ribonucleoproteínas/metabolismo , Empalme del ARN , ARN Nuclear Pequeño/genética , ARN Nuclear Pequeño/metabolismo , Proteínas de Unión al ARN/metabolismo , Empalmosomas/genética , Empalmosomas/metabolismo , Factor de Empalme U2AF/genética , Factor de Empalme U2AF/metabolismoRESUMEN
L1TD1 is a cytoplasmic RNA-binding protein specifically expressed in pluripotent stem cells and, unlike its mouse ortholog, is essential for the maintenance of stemness in human cells. Although L1TD1 is the only known protein-coding gene domesticated from a LINE-1 (L1) retroelement, the functional legacy of its ancestral protein, ORF1p of L1, and how it is manifested in L1TD1 are still unknown. Here, we determined RNAs associated with L1TD1 and found that, like ORF1p, L1TD1 binds L1 RNAs and localizes to high-density ribonucleoprotein (RNP) condensates. Unexpectedly, L1TD1 enhanced the translation of a subset of mRNAs enriched in the condensates. L1TD1 depletion promoted the formation of stress granules in embryonic stem cells. In HeLa cells, ectopically expressed L1TD1 facilitated the dissolution of stress granules and granules formed by pathological mutations of TDP-43 and FUS. The glutamate-rich domain and the ORF1-homology domain of L1TD1 facilitated dispersal of the RNPs and induced autophagy, respectively. These results provide insights into how L1TD1 regulates gene expression in pluripotent stem cells. We propose that the ability of L1TD1 to dissolve stress granules may provide novel opportunities for treatment of neurodegenerative diseases caused by disturbed stress granule dynamics.
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Células Madre Embrionarias , Proteínas de Unión al ARN , Ribonucleoproteínas , Animales , Humanos , Ratones , Gránulos Citoplasmáticos/metabolismo , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Células HeLa , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
A flexible liquid metal loudspeaker (LML) is demonstrated consisting of a gallium-based eutectic liquid metal (Galinstan) and basic aqueous electrolyte (NaOH(aq) ). The LML is driven by liquid metal motion induced by the electrochemically controlled interfacial tension of the Galinstan in NaOH(aq) electrolyte under an applied alternating current (AC) voltage. The fabricated LML produces sound waves in the human audible frequency band with a sound pressure level of ≈40-50 dB at 1 cm from the device and exhibits mechanical stability under bending deformation with a bending radius of 3 mm. Various sounds can be generated with the LML from a single tone to piano notes and human voices. To understand the underlying mechanism of sound generation by the LML, motion analyses, sound measurements, and electrical characterization are conducted at various frequencies. For the first time, this work suggests a new type of liquid metal-based electrochemically driven sound generator in the field of flexible acoustic devices that can be applied to future wearable electronics.
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Electroquímica/métodos , Metales/química , Aleaciones/química , Electrólitos/química , Galio/química , Humanos , Metales Pesados/química , Hidróxido de Sodio/química , Tensión SuperficialRESUMEN
MicroRNAs (miRNAs) are a class of non-coding RNAs that act as regulators of disease. An evolutionary approach to the disease could reveal factors such as diagnosis, treatment, and prognosis prediction. The expression patterns of transposable element (TEs)-derived miRNAs could help elucidate diseases, and their evolutionary patterns are also valuable. The 34 miRNAs were compared in terms of stage survival and tumor status in 33 carcinomas from TCGA. Expression levels were compared using a t-test and presented as differentially expressed miRNAs (DEMs). For DEMs showing statistically specific expression patterns for 3 conditions (normal and cancer, early and advanced stage, and survival), interactions with related genes in 10 species, including humans, were compared. The enrichment term was discovered for the gene-miRNA interactions. In 18 out of the 33 carcinomas, at least one miRNA was retrieved with P < .05 and |fold change| >.05. A total of 128 DEMs for the 9 miRNAs were identified. Based on the TargetScan database, interactions between miRNAs and genes in 10 species, including humans, were confirmed. The evolutionarily conserved miR-130a was observed in all 10 species, whereas miR-151a was only observed in humans. GO terms of related genes were selected for the miRNAs commonly found in each species. Evolutionary analysis of TE-derived disease-associated miRNAs was performed, and the evolutionarily conserved miR-130a-related carcinomas included renal and thyroid cancers. Human and rhesus monkey-specific miR-625 is associated with various carcinomas.
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One of the core technologies for wearable electronics is the use of an interactive display device that is attached to the body or clothes to transmit various bio-signals and environmental stimuli to the user. In this study, we report a flexible audiovisual display device consisting of a polyvinylidene difluoride (PVDF) thin-film speaker stacked on an 8 × 8 array of quantum-dot light-emitting diodes (QD-LEDs) and a multi-functional sensor consisting of temperature and ultraviolet (UV) sensors connected to a pressure sensor, allowing the body temperature and UV exposure to be displayed both visually and acoustically. Polydimethylsiloxane is employed as an insulator between the carbon nanotube (CNT)/polyaniline temperature sensor and the ZnO/CNT UV sensor to form a capacitor-type pressure sensor. With the use of a stretchable polymer substrate, liquid metal Galinstan interconnections, and the flexible Au-grid electrodes, both the PVDF speaker and the QD-LED array are stable under repeated cycles of bending deformation with a bending radius of 7.5 mm. By connecting the audiovisual display device to the skin-attached multi-functional sensor, changes in the body temperature and UV exposure are displayed as LED patterns with accompanying acoustic alarms. This study demonstrates the significant potential of our proposed audiovisual monitoring device and multi-functional sensor for use in health-monitoring applications, especially for the elderly and infants requiring prompt care.
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Textile-based electronics have attracted much attention as they can perfectly combine the functionality of wearable devices with the soft and comfortable properties of flexible textile fibers. In this work, we report a dynamically stretchable high-performance supercapacitor for powering an integrated sensor in an all-in-one textile system to detect various biosignals. The supercapacitor fabricated with MWCNT/MoO3 nanocomposite electrodes and nonaqueous gel electrolyte, along the course direction of the fabric, exhibits stable and high electrochemical performance under dynamic and static deformation, including stretching in real time, regardless of the strain rate. The strain sensor created along the wale direction of the fabric shows a high sensitivity of 46.3 under an applied strain up to 60%, a fast response time of 50 ms, and high stability over 10â¯000 cycles of stretching/releasing. Finally, the supercapacitor and strain sensor are integrated into an all-in-one textile system via liquid-metal interconnections, and the sensor is powered by the stored energy in the supercapacitor. This system sewed into cloth successfully detects strain due to joint movement and the wrist pulse. This work demonstrates the high feasibility of utilizing the fabricated stretchable all-in-one textile system for real-time health monitoring in everyday wearable devices.
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Técnicas Biosensibles , Capacidad Eléctrica , Textiles , Electroquímica , Molibdeno/química , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestructura , Nanocables/química , Nanocables/ultraestructura , Imagen Óptica , Óxidos/químicaRESUMEN
For practical applications of high-performance supercapacitors as wearable energy storage devices attached to skin or clothes, the supercapacitors are recommended to have stable mechanical and electrochemical performances during dynamic deformations, including stretching, due to real-time movements of the human body. In this work, we demonstrate a skin-like, dynamically stretchable, planar supercapacitor (SPS). The SPS consists of buckled manganese/molybdenum (Mn/Mo) mixed oxide@multiwalled carbon nanotube (MWCNT) electrodes; organic gel polymer electrolyte of adiponitrile, succinonitrile, lithium bis(trifluoromethanesulfonyl)imide, and poly(methyl methacrylate); and a porous, elastomeric substrate. The addition of an Mn/Mo mixed oxide to the MWCNT film produces an 8-fold increase in the areal capacitance. The use of an organic solvent-based electrolyte enhances the operation cell voltage to 2 V and air stability to one month under ambient air conditions. The fabricated planar supercapacitors are biaxially stretchable up to 50% strain and maintain â¼90% of their initial capacitance after 1000 repetitive stretching/releasing cycles. Furthermore, the SPS exhibits stable electrochemical performance under dynamic stretching in real time regardless of the strain rate and performs reliably during repetitive bending/spreading motions of an index finger while attached to skin.
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In this study, we demonstrate the fabrication of a highly sensitive flexible temperature sensor with a bioinspired octopus-mimicking adhesive. A resistor-type temperature sensor consisting of a composite of poly(N-isopropylacrylamide) (pNIPAM)-temperature sensitive hydrogel, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, and carbon nanotubes exhibits a very high thermal sensitivity of 2.6%·°C-1 between 25 and 40 °C so that the change in skin temperature of 0.5 °C can be accurately detected. At the same time, the polydimethylsiloxane adhesive layer of octopus-mimicking rim structure coated with pNIPAM is fabricated through the formation of a single mold by utilizing undercut phenomenon in photolithography. The fabricated sensor shows stable and reproducible detection of skin temperature under repeated attachment/detachment cycles onto skin without any skin irritation for a long time. This work suggests a high potential application of our skin-attachable temperature sensor to wearable devices for medical and health-care monitoring.
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Calor , Adhesivos , Nanotubos de Carbono , PielRESUMEN
As part of increased efforts to develop wearable healthcare devices for monitoring and managing physiological and metabolic information, stretchable electrochemical sweat sensors have been investigated. In this study, we report on the fabrication of a stretchable and skin-attachable electrochemical sensor for detecting glucose and pH in sweat. A patterned stretchable electrode was fabricated via layer-by-layer deposition of carbon nanotubes (CNTs) on top of patterned Au nanosheets (AuNS) prepared by filtration onto stretchable substrate. For the detection of glucose and pH, CoWO4/CNT and polyaniline/CNT nanocomposites were coated onto the CNT-AuNS electrodes, respectively. A reference electrode was prepared via chlorination of silver nanowires. Encapsulation of the stretchable sensor with sticky silbione led to a skin-attachable sweat sensor. Our sensor showed high performance with sensitivities of 10.89 µA mM-1 cm-2 and 71.44 mV pH-1 for glucose and pH, respectively, with mechanical stability up to 30% stretching and air stability for 10 days. The sensor also showed good adhesion even to wet skin, allowing the detection of glucose and pH in sweat from running while being attached onto the skin. This work suggests the application of our stretchable and skin-attachable electrochemical sensor to health management as a high-performance healthcare wearable device.
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Sudor , Electrodos , Glucosa , Concentración de Iones de Hidrógeno , Nanotubos de CarbonoRESUMEN
Here, we report on a highly conductive, stretchable, and transparent electrode of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) fabricated via modification with triblock copolymer, poly(ethylene glycol)- block-poly(propylene glycol)- block-poly(ethylene glycol) (PEO20-PPO70-PEO20, Pluronic P123), and post-treatment with sulfuric acid. The fabricated electrode exhibits high transparency (89%), high electrical conductivity (â¼1700 S/cm), and minimal change in resistance (â¼4%) under repetitive stretch-release cycles at 40% tensile strain after stabilization. P123 acts as a secondary dopant and plasticizer, resulting in enhanced electrical conductivity and stretchability of PEDOT:PSS. Furthermore, after sulfuric acid post-treatment, P123 helps the electrode to maintain its stretchability. A successful demonstration of the stretchable interconnection was shown by stretching the P123-modified PEDOT:PSS electrodes, which were connected with light-emitting diodes (LEDs) in series. Finally, a stretchable and transparent touch sensor consisting of our fabricated electrodes and an LED array and stretchable semitransparent supercapacitor were presented, suggesting a great potential of our electrodes in the application to various deformable devices.
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A highly-durable, highly-flexible transparent electrode (FTE) is developed by applying a composite made of a thin metal grid and a doped conducting polymer onto a colorless polyimide-coated NOA63 substrate. The proposed FTE exhibits a transparency of 90.7% at 550 nm including the substrate and a sheet resistance of 30.3 Ω/sq and can withstand both moderately high-temperature annealing (â¼180 °C) and acidic solution (70 °C, pH 0.3) processes without performance degradation. The fabricated FTE yielded good mechanical stability under 10 000 cycles of bending deformations at a bending radius less than 1 mm without degradation of electrical conductivity. The high durability of the proposed FTE allows for the fabrication of flexible energy harvesting devices requiring harsh conditions, such as highly flexible perovskite solar cells (FPSCs) with a steady-state power conversion efficiency (PCE) of 12.7%. Notably, 93% of the original PCE is maintained after 2000 bending cycles at an extremely small bending radius of 1.5 mm. The FPSCs installed on curved surfaces of commercial devices drive them under various environments. The applicability of the proposed FTE is further confirmed via the fabrication of a flexible perovskite light-emitting diode. The proposed FTE demonstrates great potential for applications in the field of flexible optoelectronic devices.
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In this study, we report on the development of a stretchable, transparent, and skin-attachable strain sensor integrated with a flexible electrochromic device as a human skin-inspired interactive color-changing system. The strain sensor consists of a spin-coated conductive nanocomposite film of poly(vinyl alcohol)/multi-walled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) on a polydimethylsiloxane substrate. The sensor exhibits excellent performance of high sensitivity, high durability, fast response, and high transparency. An electrochromic device (ECD) made of electrochemically synthesized polyaniline nanofibers and V2O5 on an indium-tin-oxide-coated polyethylene terephthalate film experiences a change in color from yellow to dark blue on application of voltage. The strain sensor and ECD are integrated on skin via an Arduino circuit for an interactive color change with the variation of the applied strain, which enables a real-time visual display of body motion. This integrated system demonstrates high potential for use in interactive wearable devices, military applications, and smart robots.
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A stretchable polyaniline nanofiber temperature sensor array with an active matrix consisting of single-walled carbon nanotube thin-film transistors is demonstrated. The integrated temperature sensor array gives mechanical stability under biaxial stretching of 30%, and the resultant spatial temperature mapping does not show any mechanical or electrical degradation.
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Considering the various applications of wearable and bio-implantable devices, it is desirable to realize stretchable acoustic devices for body-attached applications such as sensing biological signals, hearing aids, and notification of information via sound. In this study, we demonstrate the facile fabrication of a Stretchable Acoustic Device (SAD) using liquid metal coil of Galinstan where the SAD is operated by the electromagnetic interaction between the liquid metal coil and a Neodymium (Nd) magnet. To fabricate a liquid metal coil, Galinstan was injected into a micro-patterned elastomer channel. This fabricated SAD was operated simultaneously as a loudspeaker and a microphone. Measurements of the frequency response confirmed that the SAD was mechanically stable under both 50% uniaxial and 30% biaxial strains. Furthermore, 2000 repetitive applications of a 50% uniaxial strain did not induce any noticeable degradation of the sound pressure. Both voice and the beeping sound of an alarm clock were successfully recorded and played back through our SAD while it was attached to the wrist under repeated deformation. These results demonstrate the high potential of the fabricated SAD using Galinstan voice coil in various research fields including stretchable, wearable, and bio-implantable acoustic devices.
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Acústica/instrumentación , Electrónica/instrumentación , Metales , Diseño de EquipoRESUMEN
We report on the successful fabrication of stretchable microsupercapacitor (MSC) arrays on a deformable polymer substrate that exhibits high electrochemical performance even under mechanical deformation such as bending, twisting, and uniaxial strain of up to 40%. We designed the deformable substrate to minimize the strain on MSCs by adopting a heterogeneous structure consisting of stiff PDMS islands (on which MSCs are attached) and a soft thin film (mixture of Ecoflex and PDMS) between neighboring PDMS islands. Finite element method analysis of strain distribution showed that an almost negligible strain of 0.47% existed on the PDMS islands but a concentrated strain of 107% was present on the soft thin film area under a uniaxial strain of 40%. The use of an embedded interconnection of the liquid metal Galinstan helped simplify the fabrication and provided mechanical stability under deformation. Furthermore, double-sided integration of MSCs increased the capacitance to twice that of MSCs on a conventional planar deformable substrate. In this study, planar-type MSCs with layer-by-layer assembled hybrid thin film electrodes of MWNT/Mn3O4 and PVA-H3PO4 electrolyte were fabricated; when they are integrated into a circuit, these MSCs increase the output voltage beyond the potential of the electrolyte used. Therefore, various LEDs that require high voltages can be operated under a high uniaxial strain of 40% without any decrease in their brightness. The results obtained in this study demonstrate the high potential of our stretchable MSC arrays for their application as embedded stretchable energy storage devices in bioimplantable and future wearable nanoelectronics.