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Pygopus (Pygo) has been identified as a specific nuclear co-activator of the canonical Wingless (Wg)/Wnt signaling pathway in Drosophila melanogaster. Pygo proteins consist of two conserved domains: an N-terminal homologous domain (NHD) and a C-terminal plant homologous domain (PHD). The PHD's ability to bind to di- and trimethylated lysine 4 of histone H3 (H3K4me2/3) appears to be independent of Wnt signaling. There is ongoing debate regarding the significance of Pygo's histone-binding capacity. Drosophila Pygo orthologs have a tryptophan (W) > phenylalanine (F) substitution in their histone pocket-divider compared to vertebrates, leading to reduced histone affinity. In this research, we utilized CRISPR/Cas9 technology to introduce the Pygo-F773W point mutation in Drosophila, successfully establishing a viable homozygous Pygo mutant line for the first time. Adult mutant flies displayed noticeable abnormalities in reproduction, locomotion, heart function, and lifespan. RNA-seq and cluster analysis indicated that the mutation primarily affected pathways related to immunity, metabolism, and posttranslational modification in adult flies rather than the Wnt signaling pathway. Additionally, a reduction in H3K9 acetylation levels during the embryonic stage was observed in the mutant strains. These findings support the notion that Pygo plays a wider role in chromatin remodeling, with its involvement in Wnt signaling representing only a specific aspect of its chromatin-related functions. [ABSTRACT FROM AUTHOR]

Ankyrin repeat and suppression-of-cytokine-signaling box (Asb) proteins, a subset of ubiquitin ligase E3, include Asb5 with six ankyrin-repeat domains. Zebrafish harbor two asb5 gene isoforms, asb5a and asb5b. Currently, the effects of asb5 gene inactivation on zebrafish embryonic development and heart function are unknown. Using CRISPR/Cas9, we generated asb5a-knockout zebrafish, revealing no abnormal phenotypes at 48 h post-fertilization (hpf). In situ hybridization showed similar asb5a and asb5b expression patterns, indicating the functional redundancy of these isoforms. Morpholino interference was used to target asb5b in wild-type and asb5a-knockout zebrafish. Knocking down asb5b in the wild-type had no phenotypic impact, but simultaneous asb5b knockdown in asb5a-knockout homozygotes led to severe pericardial cavity enlargement and atrial dilation. RNA-seq and cluster analyses identified significantly enriched cardiac muscle contraction genes in the double-knockout at 48 hpf. Moreover, semi-automatic heartbeat analysis demonstrated significant changes in various heart function indicators. STRING database/Cytoscape analyses confirmed that 11 cardiac-contraction-related hub genes exhibited disrupted expression, with three modules containing these genes potentially regulating cardiac contractile function through calcium ion channels. This study reveals functional redundancy in asb5a and asb5b, with simultaneous knockout significantly impacting zebrafish early heart development and contraction, providing key insights into asb5's mechanism. [ABSTRACT FROM AUTHOR]

High‐power piezoelectric ceramics are typically driven to output vibration velocity (v0) under high AC electric fields. Herein, the Fe2O3 doped 0.125 Pb(Zn1/3Nb2/3) O3–0.075 Pb(Mn1/3Nb2/3)O3–0.8 Pb(Zr0.48Ti0.52)O3(PZMNZT–xFe; x = 0.05–0.35) piezoelectric ceramics were prepared to enhance v0, and the favorable comprehensive electrical properties, such as d33 = 315 pC/N, Qm = 1738, kp = 0.58, kt = 0.48, εr = 1156, tan δ = 0.4%, and Tc = 320°C, were achieved in the PZMNZT–0.15Fe ceramic. Most importantly, the PZMNZT–0.15Fe ceramic presented a reliable v0 of 0.90 m/s, which was 2.25 times of the commercial PZT4 ceramic (∼0.40 m/s). The excellent high‐power performance should be attributed to ordering functional elements such as crystal grains and ferroelectric domains. Overall, this work reveals that the PZMNZT–0.15Fe ceramic is competitive for high‐power applications. [ABSTRACT FROM AUTHOR]

High-power ultrasonic transducers need piezoelectric ceramics with a high piezoelectric coefficient, d33, high quality factor, Qm, large coercivity field, EC, high Curie temperature TC , etc, so that they can work in a high electric field for a long time. Here, 0.04Pb (Mn1/3Nb2/3) O3–0.96Pb (Zr0.515Ti0.485) O3-xmol%Nb2O5 (PMN–PZT-x%Nb2O5, x = 0.0–1.0) ceramics with high piezoelectric performance and cost-effective merits were prepared using low-cost industry-grade raw materials. The PMN–PZT-0.6%Nb2O5 ceramic shows the optimal comprehensive electrical properties, such as a high d33 of 411 pC/N, a Qm of 653, a dielectric loss tanδ of 0.30%, a relative permittivity εr of 1457, an electromechanical coupling factor kp of 0.58, a high TC of 355°C, and a large EC of 1.3 kV/mm. Under the electric field of 100 V/mm, the PMN–PZT-0.4%Nb2O5 ceramic shows a large vibration velocity of 0.9 m/s. Since PMN–PZT-x%Nb2O5 ceramics have the merits of high quality, high-cost performance ratio, and easy mass production, they are promising for applications of high-power devices. [ABSTRACT FROM AUTHOR]

Human YPEL4 is a member of YPEL family. II contains a Yippee domain, which is a putative zinc-finger-like, metal-binding domain. The human YPEL4 gene maps to chromosome 11q12.1, is ubiquitously expressed in adult tissues, and encodes a nuclear protein of 127 amino acids, the function of which remains unknown. To gain insights into the cellular function of this protein, we searched for YPEL4-interacting proteins using a yeast two-hybrid screen. The major vault protein (MVP), a lung resistance associated protein, was identified as a binding partner of YPEL4. The interaction between YPEL4 and MVP in mammalian cells was further demonstrated by a series of biochemical assays including the mammalian two-hybrid assay. GST pull-down assay, co-immunoprecipilation assay, and immunocyiochemistry. Using a reporter system, we found that MVP can inhibit YPEL4's ability to activate Elk-1 in the MAPK signaling pathway. This study provides new clues for understanding the molecular mechanism of YPEL4 in cell division and signal transduction pathways and should be helpful for understanding molecular functions of the YPEL family. Key words: YPEL4, MVP, interaction, MAPK signaling pathway. La proteine humaine YPEL4 appartient a la famille YPEL. Elle contient un domaine Yippee, un domaine presume de liaison des metaux de type << doigt de zinc >>. Le gene codant YPEL4 se situe sur le chromosome 11q12,l, est exprime de facon ubiquiste dans les tissus adultes et code une proteine nucleaire de 127 acides amines; sa fonetion demeure cependant inconnue. Attn d'en apprendre davantage sur la fonetion cellulaire de cette proteine, nous avons recherche les proteines qui interagissent avec YPEL4 par un criblage en double hybride. La proteine majeure vault (MVP), une proteine associee a la resistance du poumon, etait un partenaire de liaison de YPEL4. L'interaction entre YPEL4 et MVP dans les cellules mammileres a ete plus amplemeni demontree par une serie d'essais biochimiques, noiamment par un systeme en double hybride mammilere, par un essai de co-precipitation par GST, par co-immunoprecipiialion, et par immunocylochimie. A l'aide d'un systeme rapporteur, nous avons trouve que MVP peut inhiber la capacite de YPEL4 a activer Elk-1 dans la voie de signalisation de MAPK. Cette etude fournit de nouvelle pistes dans la comprehension du mecanisme moleculaire d'action de YPEL4 dans la division cellulaire et la transduction de signaux, et devrait pouvoir etre utile pour comprendre les fonctions moleculaires de la famille YPEL. Mots-cles : YPEL4, MVP, interaction, voie de signalisation de MAPK. [Traduit par la Redaction], Introduction The YPEL gene family was characterized as the first highly conserved family of genes coding for proteins containing putative zinc-finger-like metal-binding domains, and is found in a wide spectrum [...]

High-performance piezoelectric materials for actuators, sensors, and transducers are urgently required. It would be ideal to always have high piezoelectric performance and high ferroelectric-ferroelectric phase transition temperature, but we have only one in most cases. Pb(In0.5Nb0.5)O3–PbTiO3 (PIN-PT) crystals have a high rhombohedral-tetragonal phase transition temperature (TRT), but the piezoelectric performance is not very satisfactory. Here, Nd-doped PIN-0.33PT single crystals were grown, where the enhanced piezoelectric d33 and electromechanical coupling coefficient k33 are 2100 pC/N and 91%, which are 80% and 5.8% higher than those for virgin PIN-0.33PT single crystals (1160 pC/N and 86%) and are superior to that of other compositions of PIN-PT crystals. Piezo-response force microscopy was adopted to study the domain structure, and the domain size was found to decrease after Nd doping, which contributes to the enhanced piezoelectric performance. This study offers a good paradigm for enhancing the piezoelectric performance of high Curie temperature ferroelectric single crystals. [ABSTRACT FROM AUTHOR]