Ribosome biogenesis is pivotal in the self-replication of life. In Escherichia coli, three ribosomal RNAs and 54 ribosomal proteins are synthesized and subjected to cooperative hierarchical assembly facilitated by numerous accessory factors. Realizing ribosome biogenesis in vitro is a critical milestone for understanding the self-replication of life and creating artificial cells.
View Article and Find Full Text PDFBackground/aim: This study aimed to predict the optimal timing for adaptive radiation therapy (ART) using two-dimensional X-ray image-based water equivalent thickness (2DWET).
Patients And Methods: Forty patients with oropharyngeal and hypopharyngeal cancer underwent Computed Tomography (CT) rescanning during treatment. An adaptive score (AS) was proposed to guide ART decisions based on changes in four dose indices: target coverage, spinal cord dose, parotid gland dose, and over-dose volume.
Bone-modifying agents (BMAs) have been widely used to reduce skeletal-related events, including pathological fractures. Herein, we aimed to clarify the incidence of pathological fractures caused by high-risk femoral bone metastases after palliative radiotherapy (RT) in the BMA era and evaluate the necessity of prophylactic surgical stabilization. We assessed 90 patients with high-risk femoral bone metastases, indicated by Mirels' scores ≥ 8, without pathological fractures and surgical fixations, who received palliative RT at our institution between January 2009 and December 2018.
View Article and Find Full Text PDFMitochondrial tRNA (mt-tRNA) modifications play pivotal roles in decoding and sustaining tRNA stability, thereby enabling synthesis of essential respiratory complex proteins in mitochondria. Consequently, loss of human mt-tRNA modifications caused by mutations in the mitochondrial or nuclear genome can cause life-threatening mitochondrial diseases such as encephalopathy and cardiomyopathy. In this article, we first provide a comprehensive overview of the functions of mt-tRNA modifications, the responsible modification enzymes, and the diseases caused by loss of mt-tRNA modifications.
View Article and Find Full Text PDFUnlabelled: Over 170 types of chemical modifications have been identified in cellular RNAs across the three domains of life. Modified RNA is eventually degraded to constituent nucleosides, and in mammals, modified nucleosides are released into the extracellular space. By contrast, the fate of modified nucleosides in bacteria remains unknown.
View Article and Find Full Text PDFIn higher eukaryotes, tRNA methyltransferase 10A (TRMT10A) is responsible for N1-methylguanosine modification at position nine of various cytoplasmic tRNAs. Pathogenic mutations in TRMT10A cause intellectual disability, microcephaly, diabetes, and short stature in humans, and generate cytotoxic tRNA fragments in cultured cells; however, it is not clear how TRMT10A supports codon translation or brain functions. Here, we generated Trmt10a null mice and showed that tRNAGln(CUG) and initiator methionine tRNA levels were universally decreased in various tissues; the same was true in a human cell line lacking TRMT10A.
View Article and Find Full Text PDFBackground: This study aimed to evaluate the association between spinopelvic alignment parameters and hip osteoarthritis progression after spinal alignment correction surgery for adult spinal deformity, focusing on the preoperative to postoperative change in spinopelvic alignment.
Methods: This retrospective study enrolled 100 adult spinal deformity patients (196 hip joints) who underwent spinal fusion surgery, after excluding four joints with previous total hip arthroplasty. Acetabular roof obliquity (ARO), center edge angle (CE) and Kellgren and Lawrence (KL) grade were measured in the hip joint.
MTU1 controls intramitochondrial protein synthesis by catalyzing the 2-thiouridine modification of mitochondrial transfer RNAs (mt-tRNAs). Missense mutations in the MTU1 gene are associated with life-threatening reversible infantile hepatic failure. However, the molecular pathogenesis is not well understood.
View Article and Find Full Text PDFBackground/aim: Synchronous colorectal cancer, which occurs in approximately 4.8-8.4% of all colorectal cancers, has a genetic profile with a higher rate of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and microsatellite instability-high than solitary colorectal cancer.
View Article and Find Full Text PDFBackground: Volumetric modulated arc therapy (VMAT) for locally advanced rectal cancer (LARC) has emerged as a promising technique, but the planning process can be time-consuming and dependent on planner expertise. We aimed to develop a fully automated VMAT planning program for LARC and evaluate its feasibility and efficiency.
Methods: A total of 26 LARC patients who received VMAT treatment and the computed tomography (CT) scans were included in this study.
Naked mole-rats (NMRs) have exceptional longevity and are resistant to age-related physiological decline and diseases. Given the role of cellular senescence in aging, we postulated that NMRs possess unidentified species-specific mechanisms to prevent senescent cell accumulation. Here, we show that upon induction of cellular senescence, NMR fibroblasts underwent delayed and progressive cell death that required activation of the INK4a-retinoblastoma protein (RB) pathway (termed "INK4a-RB cell death"), a phenomenon not observed in mouse fibroblasts.
View Article and Find Full Text PDFUnderstanding the physiology of human-induced pluripotent stem cells (iPSCs) is necessary for directed differentiation, mimicking embryonic development, and regenerative medicine applications. Pluripotent stem cells (PSCs) exhibit unique abilities such as self-renewal and pluripotency, but they lack some functions that are associated with normal somatic cells. One such function is the circadian oscillation of clock genes; however, whether or not PSCs demonstrate this capability remains unclear.
View Article and Find Full Text PDFPrevious studies have revealed that age-related hearing loss (AHL) in Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1)-knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis.
View Article and Find Full Text PDFBackground: Carbon-ion radiotherapy (C-ion RT) is effective for head and neck mucosal melanoma (HN-MM), including radioresistant mucosal melanoma. Melanoma also responds effectively to immune checkpoint inhibitors (ICIs). Data on the efficacy and safety of ICIs for HN-MM are insufficient.
View Article and Find Full Text PDFBackground/aim: This study pursued two goals: Firstly, to search for anatomical structures strongly correlating with dose deterioration, and secondly to investigate the effectiveness of image registration focusing on critical anatomy by comparing it with a conventional method. The aim was to achieve robust image registration to correct for anatomical changes during treatment.
Patients And Methods: Twenty patients with head and neck cancer were enrolled, and 68 simulation computed tomography (CT) and rescan CT image sets were retrospectively analyzed.
Int J Radiat Oncol Biol Phys
August 2023
Purpose: This retrospective study aimed to evaluate the safety and efficacy of repeated carbon-ion radiation therapy (CIRT) in patients with intrahepatic recurrent hepatocellular carcinoma (HCC).
Methods And Materials: We reviewed patients who underwent repeated CIRT for intrahepatic recurrent HCC between 2010 and 2020.
Results: Forty-one patients received multiple CIRT courses for HCC.
Cancer stem-like cells (CSCs) have a unique translation mode, but little is understood about the process of elongation, especially the contribution of tRNA modifications to the maintenance of CSCs properties. Here, it is reported that, contrary to the initial aim, a tRNA-modifying methylthiotransferase CDKAL1 promotes CSC-factor SALL2 synthesis by assembling the eIF4F translation initiation complex. CDKAL1 expression is upregulated in patients with worse prognoses and is essential for maintaining CSCs in rhabdomyosarcoma (RMS) and common cancers.
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