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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]

It is well known that unknown modeling errors cannot be avoided in practice. Such unmeasured uncertainties are usually denoted as unknown nonlinear functions that exist in every channel of the system equation. This paper aims to develop an output feedback adaptive control scheme by constructing state estimation filters to address such unknown modeling errors. In the controller design, these uncertainties caused by modeling errors will be accumulated to the last step for compensation. Unknown parameters existing in the upper bound functions of unknown nonlinear functions and system parameters are estimated synchronously based on tuning function approaches. It is shown that the designed output feedback controller can ensure the stability and tracking performance of the closed‐loop system, and the transient performance in terms of a truncated norm is also established. [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]

Abnormal activation of the classical Wnt pathway has been reported in non-small-cell lung cancer (NSCLC) previously. Pygo family genes, the core regulators of Wnt/β-catenin signaling, were also reported to be involved in tumorigenesis. However, the role of the homolog Pygo1 in human lung cancer remains unclear. In the current study, we demonstrated an association of increased Pygo1 expression with consistent high nuclear β-catenin signals across pathological tissue samples of early-stage human NSCLC. Overexpression of Pygo1 in lung cancer cells resulted in enhanced G1/S cell phase transformation, reduced apoptosis, and increased cell proliferation. These changes were accompanied by the downregulation of cell cycle-related proteins, such as RB, p16, p53, and p27Kip1, and increased expression of CyclinE1. Migration, wound healing, and colony formation assays revealed that Pygo1 overexpression enhanced the invasion and migration of lung cancer cells, increased the formation of clones, and suppressed E-cadherin expression. In addition, overexpression of Pygo1 in lung cancer cells led to an increase of β-catenin/TCF4 complex, as well as upregulated expression of target genes of β-catenin. In vivo experiments also revealed that Pygo1 overexpression promoted the tumorigenicity of a xenograft tumor model, while Wnt inhibition partially blocked the effect of Pygo1 overexpression. In conclusion, Pygo1 affects human NSCLC via the canonical Wnt/β-catenin pathway, which provides new clues for lung cancer pathology. [ABSTRACT FROM AUTHOR]

The detection of methane has always been an important part of coal mine safety. In order to improve the methane measurement accuracy in coal mines and to determine the influence of environmental interference factors on the measurement results, we designed a spherical, experimental chamber simulating the on-site environment of an underground coal mine containing methane, in which various environmental interference factors can be superimposed. The simulation chamber can generate a uniform and controllable dust environment, a controllable methane environment with concentrations below that which would trigger an alarm, controllable humidity, and environments characterized by other interference factors. Based on computational simulations of the experimental chamber with varying dust-particle-concentration distributions using a single particle size, an optimal design for the chamber has been realized in terms of the rapid mixing of dust and the flow field. Finally, we constructed an underground methane concentration measurement system for coal mines and assessed the influences of different dust concentrations and relative humidity values on the performance of methane measurements, providing a means for improving the measurement accuracy of underground coal mine, spectral, absorption-type methane sensors. [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 [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.10.026 Byline: Jiandong Liu, Li Qian, Zhe Han, Xiushan Wu, Rolf Bodmer Keywords: Drosophila; Heart; Cardiogenesis; Cell specification; Transcriptional regulation; Epicardium Abstract: Individual cardiac progenitors emerge at defined positions within each segment in the trunk mesoderm. Their specification depends on segmental information from the pre-patterned ectoderm, which provides positional information to the underlying cardiac mesoderm via inductive signals. This pattern is further reinforced by repressive interactions between transcription factors that are expressed in neighboring sets of cardiac progenitors. For example, even-skipped (eve) and ladybird early (lbe) gene products mark adjacent cardiac cell clusters within a segment, and their antagonistic interaction results in mutually exclusive expression domains. Lbe acts directly on the eve mesodermal enhancer (eme) to participate in restricting its expression anteriorly. We hypothesized that additional repressive activities must regulate the precise pattern of eve expression in the cardiac mesoderm via this enhancer. In this study, we identified two additional repressor motifs: 4 copies of an 'AT'-rich motif (M1a-d) and 2 copies of an 'GC'-rich motif (M2a,b), which when mutated cause expansion of eme-dependent reporter gene expression. We have also examined potential negative regulators of eve and found that their overexpression is sufficient to repress eve as well as the eme enhancer via these sites. Our data suggest that a combination of factors is likely to interact with multiple essential repressor sites to confer precise spatial specificity of eve expression in the cardiac mesoderm. Author Affiliation: Development and Aging Program, Center for Neuroscienes, Aging and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA Article History: Received 10 June 2007; Revised 11 October 2007; Accepted 18 October 2007

Stem cells possess regenerative powers and multidirectional differentiation potential and play an important role in disease treatment and basic medical research. Urine-derived stem cells (USCs) represent a newly discovered type of stem cell with biological characteristics similar to those of mesenchymal stromal cells (MSCs), including their doubling time and immunophenotype. USCs are noninvasive and can be readily obtained from voided urine and steadily cultured. Based on advances in this field, USCs and their secretions have increasingly emerged as ideal sources. USCs may play regulatory roles in the cellular immune system, oxidative stress, revascularization, apoptosis and autophagy. This review summarizes the applications of USCs in tissue regeneration and various disease treatments. Furthermore, by analysing their limitations, we anticipate the development of more feasible therapeutic strategies to promote USC-based individualized treatment. [ABSTRACT FROM AUTHOR]

A plasmonic refractive index nanosensor structure consisting of a metal-insulator-metal (MIM) waveguide with two symmetrical rectangle baffles coupled with a connected-concentric-double rings resonator (CCDRR) is presented. In this study, its transmission characteristics were investigated using the finite element method (FEM). The consequences, studied via simulation, revealed that the transmission spectrum of the system presents a sharp asymmetric Fano profile due to the destructive interference between the wide-band mode of two rectangle baffles on the bus waveguide and the narrow-band mode of the CCDRR. The effects of the geometric parameters of the structure on the transmission characteristics were investigated comprehensively. A sensitivity of 2260 nm/RIU and figure of merit (FOM) of 56.5 were the best levels of performance that the designed structure could achieve. In addition, the system could act as a sensor for use for temperature sensing, with a sensitivity that could reach 1.48 nm/°C. The designed structure advances with technology with new detection positions and has good application prospects in other high-sensitivity nanosensor fields, for example, acting as a biosensor to detect the hemoglobin level in the blood. [ABSTRACT FROM AUTHOR]

Herein, a novel nanosensor consisting of a ring resonator with two rectangular stubs and a metalâ€"insulatorâ€"metal waveguide with two triangular stubs is proposed. By adopting the finite element method, a Fano resonance is found in the transmission spectrum, which results from the coupling between the discrete narrowband mode and the continuous wideband mode. The physical mechanism is analyzed by the normalized magnetic field distribution, and the effects of structural geometric parameters on the transmission characteristics are studied carefully. The results demonstrate that the maximum sensitivity could reach 2660 nm RIUâˆ'1 with the corresponding figure of merit of 66.5. The applications of the structure for hemoglobin concentration detection and temperature measurement are discussed, and the sensitivity of the two applications can reach up to 2.524 nm·l gâˆ'1 and 0.831 nm °Câˆ'1, respectively. The proposed structure with extremely high sensitivity and compactness can provide an excellent case for designing high-performance integrated plasmonic devices. [ABSTRACT FROM AUTHOR]

Herein, a high-sensitivity multifunctional nanosensor comprising a metal-insulator-metal (MIM) waveguide and an inverted M-type cavity (IMTC) is presented. Fano resonances are generated owing to the interactions between different light pathways. Two contrastive structures are proposed to illustrate that a proper interference area leads to better propagation characteristics. The influence of geometric parameters on sensing properties is studied. Four derived structures are investigated to discuss the main factor for improving sensitivity. The designed structure can detect temperature and NaCl solution concentration with sensitivities reaching 1.444 nm/°C and 6.6 nm/%, respectively. The designed structures can also potentially be applied to other nanoscale devices. [ABSTRACT FROM AUTHOR]

The design of micro-nano optical structure is the key problem in the improvement of integrated optical device. In this work, a compact nanosensor structure comprising metal-insulator-metal (MIM) waveguide and a ring with a matchstick-shape cavity (RMSC), is proposed and numerically simulated by using the finite element method. The transmission characteristics of this nanosensor structure are systematically analyzed. Moreover, the influences of the position of matchstick-shape structure inside the ring and the various structural parameters of RMSC on Fano resonance are discussed. The sensitivity and figure of merit (FOM) are used to describe the sensing performance. The maximum sensitivity can achieve 2162 nm/RIU with a FOM of 52.73. Furthermore, the applications of designed structure are investigated, which include biological detection and temperature sensing. The temperature sensitivity reaches as high as 1.525 nm/°C, and the best sensitivity of biosensor for detecting glucose concentration is 0.45 (nm $\cdot $ L)/g. The results pave a promising route toward ultra-compact plasmonic sensors for achieving high sensitivity and smaller scales, and applying in optical on-chip nanodevice in the future. [ABSTRACT FROM AUTHOR]

Exercise-induced cardiac remodeling has aroused public concern for some time, as sudden cardiac death is known to occur in athletes; however, little is known about the underlying mechanism of exercise-induced cardiac injury. In the present study, we established an excessive exercise-induced pathologic cardiac hypertrophy model in zebrafish with increased myocardial fibrosis, myofibril disassembly, mitochondrial degradation, upregulated expression of the pathological hypertrophy marker genes in the heart, contractile impairment, and cardiopulmonary function impairment. High-throughput RNA-seq analysis revealed that the differentially expressed genes were enriched in the regulation of autophagy, protein folding, and degradation, myofibril development, angiogenesis, metabolic reprogramming, and insulin and FoxO signaling pathways. FOXO proteins may be the core mediator of the regulatory network needed to promote the pathological response. Further, PPI network analysis showed that pik3c3 , gapdh , fbox32 , fzr1 , ubox5 , lmo7a , kctd7 , fbxo9 , lonrf1l , fbxl4 , nhpb2l1b , nhp2 , fbl , hsp90aa1.1 , snrpd3l , dhx15 , mrto4 , ruvbl1 , hspa8b , and faub are the hub genes that correlate with the pathogenesis of pathological cardiac hypertrophy. The underlying regulatory pathways and cardiac pressure-responsive molecules identified in the present study will provide valuable insights for the supervision and clinical treatment of pathological cardiac hypertrophy induced by excessive exercise. [ABSTRACT FROM AUTHOR]

Background: Atrioventricular nodal reentry tachycardia (AVNRT) is the most common manifestation of paroxysmal supraventricular tachycardia (PSVT). Increasing data have indicated familial clustering and participation of genetic factors in AVNRT, and no pathogenic genes related to AVNRT have been reported. Methods: Whole‐exome sequencing (WES) was performed in 82 patients with AVNRT and 100 controls. Reference genes, genome‐wide association analysis, gene‐based collapsing, and pathway enrichment analysis were performed. A protein‐protein interaction (PPI) network was then established; WES database in the UK Biobank and one only genetic study of AVNRT in Denmark were used for external data validation. Results: Among 95 reference genes, 126 rare variants in 48 genes were identified in the cases (minor allele frequency < 0.001). Gene‐based collapsing analysis and pathway enrichment analysis revealed six functional pathways related to AVNRT as with neuronal system/neurotransmitter release cycles and ion channel/cardiac conduction among the top 30 enriched pathways, and then 36 candidate pathogenic genes were selected. By combining with PPI analysis, 10 candidate genes were identified, including RYR2, NOS1, SCN1A, CFTR, EPHB4, ROBO1, PRKAG2, MMP2, ASPH, and ABCC8. From the UK Biobank database, 18 genes from candidate genes including SCN1A, PRKAG2, NOS1, and CFTR had rare variants in arrhythmias, and the rare variants in PIK3CB, GAD2, and HIP1R were in patients with PSVT. Moreover, one rare variant of RYR2 (c.4652A > G, p.Asn1551Ser) in our study was also detected in the Danish study. Considering the gene functional roles and external data validation, the most likely candidate genes were SCN1A, PRKAG2, RYR2, CFTR, NOS1, PIK3CB, GAD2, and HIP1R. Conclusion: The preliminary results first revealed potential candidate genes such as SCN1A, PRKAG2, RYR2, CFTR, NOS1, PIK3CB, GAD2, and HIP1R, and the pathways mediated by these genes, including neuronal system/neurotransmitter release cycles or ion channels/cardiac conduction, might be involved in AVNRT. [ABSTRACT FROM AUTHOR]