Background: Osteosarcoma is a highly malignant bone tumor with poor prognosis and limited treatment options due to resistance and side effects.
Objectives: This study investigates the effects of N6-(2-hydroxyethyl)-adenosine (HEA) on osteosarcoma cells and its impact on the IGF1 signaling pathway.
Methods: Saos2 and MG63 cell lines were treated with HEA.
Heterozygous de novo loss-of-function mutations in the gene expression regulator HNRNPU cause an early-onset developmental and epileptic encephalopathy. To gain insight into pathological mechanisms and lay the potential groundwork for developing targeted therapies, we characterized the neurophysiologic and cell-type-specific transcriptomic consequences of a mouse model of HNRNPU haploinsufficiency. Heterozygous mutants demonstrated global developmental delay, impaired ultrasonic vocalizations, cognitive dysfunction and increased seizure susceptibility, thus modeling aspects of the human disease.
View Article and Find Full Text PDFFront Cell Infect Microbiol
October 2022
The microsporidian (EHP) has become a critical threat to the global shrimp aquaculture industry, thus necessitating early detection by screening. Development of a rapid and accurate assay is crucial both for the active surveillance and for the assessment of shrimp with EHP infection. In the present study, a distinct strain of .
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 2021
TANK-binding kinase 1 (TBK1) is a multifunctional kinase with an essential role in mitophagy, the selective clearance of damaged mitochondria. More than 90 distinct mutations in TBK1 are linked to amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia, including missense mutations that disrupt the abilities of TBK1 to dimerize, associate with the mitophagy receptor optineurin (OPTN), autoactivate, or catalyze phosphorylation. We investigated how ALS-associated mutations in TBK1 affect Parkin-dependent mitophagy using imaging to dissect the molecular mechanisms involved in clearing damaged mitochondria.
View Article and Find Full Text PDFPhase measuring deflectometry is a powerful measuring method of complex optical surfaces that captures the reflected fringe images associated with a displaying screen and calculates the normal vectors of the surface under test (SUT) accordingly. The captured images are usually set conjugate to the SUT, which in turn makes the screen defocused. As a result, the blurring effect caused by the defocus and aberrations of the off-axis catadioptric imaging system can severely degrade the phases solved from the blurred images.
View Article and Find Full Text PDFOff-axis deflectometry is widely applied in the measurement of specular surfaces. However, the measuring accuracy depends on the reliability of geometrical calibration. Existing methods are inconvenient to be utilized due to their disadvantages of low efficiency and operational complexity.
View Article and Find Full Text PDFDNA sequence variants in the TBK1 gene associate with or cause sporadic or familial amyotrophic lateral sclerosis (ALS). Here we show that mice bearing human ALS-associated TBK1 missense loss-of-function mutations, or mice in which the Tbk1 gene is selectively deleted in motor neurons, do not display a neurodegenerative disease phenotype. However, loss of TBK1 function in motor neurons of the SOD1 mouse model of ALS impairs autophagy, increases SOD1 aggregation, and accelerates early disease onset without affecting lifespan.
View Article and Find Full Text PDFExonic DNA sequence variants in the gene associate with both sporadic and familial amyotrophic lateral sclerosis (ALS). Here, we examine functional defects in 25 missense TBK1 mutations, focusing on kinase activity and protein-protein interactions. We identified kinase domain (KD) mutations that abolish kinase activity or display substrate-specific defects in specific pathways, such as innate immunity and autophagy.
View Article and Find Full Text PDFIn the phase measuring deflectometry, two groups of fringe patterns in orthogonal directions are usually applied to establish the correspondences between the pixel pairs on the screen and camera. Usually, 16 phase-shifting fringe patterns with different spatial frequencies are required in order to calculate the absolute phases in the conventional temporal phase unwrapping algorithms. This requirement makes the measurement inefficient and not robust against environmental noise.
View Article and Find Full Text PDFDuring pregnancy, fetal extravillous trophoblasts (EVT) play a key role in the regulation of maternal T cell and NK cell responses. EVT display a unique combination of human leukocyte antigens (HLA); EVT do not express HLA-A and HLA-B, but do express HLA-C, HLA-E, and HLA-G. The mechanisms establishing this unique HLA expression pattern have not been fully elucidated.
View Article and Find Full Text PDFZhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
May 2014
Objective: To study the effect of titanium particles on the proliferation, differentiation, and cytomorphology of osteoblasts, and to explore the possible internal relations and mechanism.
Methods: Calvarial osteoblasts were separated from 10 newborn Sprague Dawley rats by repeated enzyme digestion, and were cultured in vitro. The cells were identified by alkaline phosphatase (ALP) staining and alizarin red staining.
The MAVS protein plays a critical role in the assembly of an antiviral signaling complex on mitochondrial membranes. Hou et al. (2011) now report that virus infection induces a conformational change in MAVS, leading to the prion-like formation of functional self-aggregates that provide a sensitive trigger for antiviral signaling.
View Article and Find Full Text PDFThe production of type I interferons (IFNs) in response to viral infections is critical for antiviral immunity. However, IFN production is transient, and continued expression can lead to inflammatory or autoimmune diseases. Thus, understanding the mechanisms underlying the negative regulation of IFN expression could lead to the development of novel therapeutic approaches to the treatment of these diseases.
View Article and Find Full Text PDFNat Chem Biol
January 2011
Here we report that bufalin and other cardiac glycoside inhibitors of the sodium-potassium ATPase (sodium pump) potently inhibit the induction of the interferon-β (IFNβ) gene by virus, double-stranded RNA or double-stranded DNA. Cardiac glycosides increase the intracellular sodium concentration, which appears to inhibit the ATPase activity of the RNA sensor RIG-I, an essential and early component in the IFNβ activation pathway. This, in turn, prevents the activation of the critical transcription factors IRF3 and NFκB.
View Article and Find Full Text PDFR2 retrotransposable elements exclusively insert into a conserved region of the tandemly organized 28S rRNA genes. Despite inactivating a subset of these genes, R2 elements have persisted in the ribosomal DNA (rDNA) loci of insects for hundreds of millions of years. Controlling R2 proliferation was addressed in this study using lines of Drosophila simulans previously shown to have either active or inactive R2 retrotransposition.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2006
Non-LTR retrotransposons insert into eukaryotic genomes by target-primed reverse transcription (TPRT), a process in which cleaved DNA targets are used to prime reverse transcription of the element's RNA transcript. Many of the steps in the integration pathway of these elements can be characterized in vitro for the R2 element because of the rigid sequence specificity of R2 for both its DNA target and its RNA template. R2 retrotransposition involves identical subunits of the R2 protein bound to different DNA sequences upstream and downstream of the insertion site.
View Article and Find Full Text PDFAbout half of the rRNA gene units (rDNA units) of Drosophila melanogaster are inserted by the retrotransposable elements R1 and R2. Because transcripts to R1 and R2 were difficult to detect on blots and electron microscopic observations of rRNA synthesis suggested that only uninserted rDNA units were transcribed, it has long been postulated that inserted rDNA units are in a repressed (inactive) chromatin structure. Studies described here suggest that inserted and uninserted units are equally accessible to DNase I and micrococcal nuclease and contain similar levels of histone H3 and H4 acetylation and H3K9 methylation.
View Article and Find Full Text PDFZhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
May 2004
Objective: To compare advantage and disadvantage of internal fixation method for tibia intercondylar eminence fracture between absorbable screw and metallic screw.
Methods: From 1996 to 2002, 200 patients with fracture of tibia intercondylar eminence were divided into group A (with absorbable screw, n = 120) and group B (with metallic screw, n = 80). And the biological compatibility, biomechanics, bone union and complications were compared between two groups.
R2 retrotransposons insert into the 28S rRNA genes of insects. Integration occurs by specific cleavage of the target site and utilization of the released DNA end to prime reverse transcription of the RNA transcript. Specificity of the protein to the target site is dependent upon nucleotide sequence recognition extending from 35 bp upstream to 15 bp downstream of the cleavage site.
View Article and Find Full Text PDFZhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
July 2002
Objective: To study the difference between two internal fixation methods Kaneda and Z-plate in the operation of anterior surgical approach and decompression after thoracolumbar fractures.
Methods: The bio-mechanical structure of the internal fixture, install when operating, complications and time of the operation were compared in the cases by Kaneda and Z-plate.
Results: Z-plate method had the following characteristics: reasonable of the bio-mechanical structure; stability after internal fixture being installed; capability of completely propping up the injured centrum and keeping the height of middle-column; simple operation when installing internal fixture and shorter time of operation (1.