A5079780173- DNA Repair Mechanisms
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Carcinogens and Genotoxicity Assessment
- Neuroscience and Neuropharmacology Research
- Plant Genetic and Mutation Studies
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Heat shock proteins research
- RNA modifications and cancer
- Radiation Therapy and Dosimetry
- Single-cell and spatial transcriptomics
- Amyotrophic Lateral Sclerosis Research
- Pluripotent Stem Cells Research
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Gout, Hyperuricemia, Uric Acid
- Molecular Biology Techniques and Applications
- RNA Interference and Gene Delivery
- Molecular Spectroscopy and Structure
- Chemical Reactions and Isotopes
- Cell death mechanisms and regulation
- Cellular Mechanics and Interactions
- Congenital heart defects research
- Cancer therapeutics and mechanisms
Nara Medical University
2016-2025
Nara Medical University Hospital
2008-2024
The University of Texas Southwestern Medical Center
2013-2019
Saga University
2014-2016
Southwestern Medical Center
2016
Texas Oncology
2015
Kyowa Kirin (Japan)
2010
Kyorin University
2010
Carestream (United States)
1996
Kodak (United States)
1996
Significance A hexanucleotide repeat expansion in the first intron of C9orf72 gene represents most prominent form heritable amyotrophic lateral sclerosis. Bidirectional transcription and ATG-independent translation expanded (GGGGCC) n specifies production toxic glycine:arginine (GR ) proline:arginine (PR poly-dipeptides. The present study provides evidence that PR poly-dipeptide binds directly to central channel nuclear pores, causing inhibition both import export macromolecules from...
Abstract To identify critical events associated with heat-induced cell killing, we examined foci formation of γH2AX (histone H2AX phosphorylated at serine 139) in heat-treated cells. This assay is known to be quite sensitive and a specific indicator for the presence double-strand breaks. We found that number increased rapidly reached maximum 30 minutes after heat treatment, as well X-ray irradiation. When cells were heated 41.5°C 45.5°C, observed linear increase time foci. An inflection...
WRN, the protein defective in Werner syndrome (WS), is a multifunctional nuclease involved DNA damage repair, replication, and genome stability maintenance. It was assumed that activities of WRN were critical for these functions. Here, we report nonenzymatic role preserving nascent strands following replication stress. We found lack led to shortening after Furthermore, discovered exonuclease activity MRE11 responsible newly replicated absence WRN. Mechanistically, N-terminal FHA domain NBS1...
The brainstem is a posterior region of the brain, composed three parts, midbrain, pons, and medulla oblongata. It critical in controlling heartbeat, blood pressure, respiration, all which are life-sustaining functions, therefore, damages to or disorders can be lethal. Brain organoids derived from human pluripotent stem cells (hPSCs) recapitulate course brain development expected useful for medical research on central nervous system disorders. However, existing organoid models limited extent...
Recently, researchers have developed protocols for human cerebral organoids using pluripotent stem cells, which mimic the structure of developing brain. Existing research demonstrated that undergo short cultivation periods, contain astrocytes, neurons, and neural but lacked mature oligodendrocytes, mature, fully functional neurons. In this study, we analyzed induced from H9 embryonic (ES) cells were cultivated as long six months. We observed positive MBP (myelin-basic protein), GAD67...
Low complexity (LC) head domains 92 and 108 residues in length are, respectively, required for assembly of neurofilament light (NFL) desmin intermediate filaments (IFs). As studied isolation, these IF interconvert between states conformational disorder labile, β-strand-enriched polymers. Solid-state NMR (ss-NMR) spectroscopic studies NFL domain polymers reveal spectral patterns consistent with structural order. A combination intein chemistry segmental isotope labeling allowed preparation...
Abstract Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic deficit. However, the molecular basis for toxicity toward function as modifiers remains unidentified. Here we show that impede ability to RBPs. Isothermal titration calorimetry size-exclusion chromatography revealed...
The ATR (ATM [ ataxia telangiectasia -mutated]- and Rad3-related) checkpoint is a crucial DNA damage signaling pathway. While the pathway known to transmit signals through ATR–Chk1 kinase cascade, whether post-translational modifications other than phosphorylation are important for this remains largely unknown. Here, we show that protein SUMOylation plays key role in ATRIP, regulatory partner of ATR, modified by SUMO2/3 at K234 K289. An ATRIP mutant lacking sites fails localize support...
Human stem cell-derived organoids have great potential for modelling physiological and pathological processes. They recapitulate in vitro the organization function of a respective organ or part an organ. midbrain (hMOs) been described to contain midbrain-specific dopaminergic neurons that release neurotransmitter dopamine. However, human contains also additional neuronal cell types, which are functionally interacting with each other. Here, we analysed hMOs at high-resolution by means...
Non-homologous end-joining (NHEJ) and homologous recombination (HR) are the two prominent pathways responsible for repair of DNA double-strand breaks (DSBs). NHEJ is not restricted to a cell-cycle stage, whereas HR active primarily in S/G2 phases suggesting there cell cycle-specific mechanisms that play role choice between HR. Here we show attenuated S phase via modulation autophosphorylation status factor DNA-PKcs at serine 2056 by pro-HR BRCA1. BRCA1 interacts with cycle-regulated manner...
Abstract In humans, uric acid is an end-product of purine metabolism. Urate excretion from the human kidney tightly regulated by reabsorption and secretion. At least eleven genes have been identified as renal urate transporters. However, it remains unclear whether all tubular cells express same set Here, we show are divided into three distinct cell populations for handling. Analysis healthy kidneys at single-cell resolution revealed that not expressed Only 32% were related to both secretion,...
Following stroke, B cells enter brain regions outside of the ischemic injury to mediate functional recovery. Although produce neurotrophins that support remote plasticity, including brain-derived neurotrophic factor (BDNF), it remains unclear which signal(s) activate in absence infarct-localized pro-inflammatory cues. Activation N-methyl-d-aspartate (NMDA)-type receptor (NMDAR) subunits on neurons can upregulate mature BDNF (mBDNF) production from a pro-BDNF precursor, but whether this...
Although mutations in the p53 gene can lead to resistance radiotherapy, chemotherapy and thermotherapy, high linear energy transfer (LET) radiation induces apoptosis regardless of status cancer cells. The aim this study was clarify mechanisms involved LET radiation‐induced apoptosis. Human gingival cells (Ca9‐22 cells) containing a mutated (m ) were irradiated with X‐rays, C‐ion (13–100 KeV/µm), or Fe‐ion beams (200 KeV/µm). Cellular sensitivities determined using colony forming assays....
Nimustine (ACNU) and temozolomide (TMZ) are DNA alkylating agents which commonly used in chemotherapy for glioblastomas. ACNU is a cross-linking agent TMZ methylating agent. The therapeutic efficacy of these limited by the development resistance. In this work, role Fanconi anemia (FA) repair pathway damage induced or was examined. Cultured mouse embryonic fibroblasts were used: FANCA−/−, FANCC−/−, FANCA−/−C−/−, FANCD2−/− cells their parental cells, Chinese hamster ovary lung fibroblast...
Increasing evidence suggests that disease-associated microglia play a protective role in neurodegenerative diseases. Microglia are known to polarize into two reciprocate forms response external cues - inflammatory M1 state and anti-inflammatory M2 state. These cells perform key functions the development of brain, such as circuit refinement, neurogenesis, neuronal growth. In this study, we analyzed secretion effect on neural stem/progenitor cell (NSPC) proliferation differentiation. We...
Abstract Reverse transcription quantitative PCR (RT-qPCR) is used to quantify gene expression and require standardization with reference genes. We sought identify the genes best suited for experiments that induce osteogenic differentiation from human induced pluripotent stem cells. They were cultured in an undifferentiated maintenance medium after confluence, further 28 days. RT-qPCR was performed on undifferentiation markers, osteoblast osteocyte candidates. The stability of each candidate...