A5083113822- Alzheimer's disease research and treatments
- Immune Cell Function and Interaction
- Protein Structure and Dynamics
- DNA Repair Mechanisms
- Medical Imaging and Pathology Studies
- Immunotherapy and Immune Responses
- Signaling Pathways in Disease
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cytokine Signaling Pathways and Interactions
- Cardiac Fibrosis and Remodeling
- Cancer Immunotherapy and Biomarkers
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Prion Diseases and Protein Misfolding
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Congenital gastrointestinal and neural anomalies
- Protein Tyrosine Phosphatases
- Cell death mechanisms and regulation
- Protein Interaction Studies and Fluorescence Analysis
- Endoplasmic Reticulum Stress and Disease
- Occupational and environmental lung diseases
- NF-κB Signaling Pathways
- MXene and MAX Phase Materials
- Galectins and Cancer Biology
- interferon and immune responses
RIKEN Center for Biosystems Dynamics Research
2018-2025
Culture Resource
2020
Genetic Resources Center
2019
Eisai (Japan)
2015-2017
Osaka University
2003-2006
Japan Science and Technology Agency
2005-2006
Protein Research Foundation
2005-2006
Centre for Cellular and Molecular Biology
2005
University of Fukui
2005
The PD-1 receptor triggers a negative immunoregulatory mechanism that prevents overactivation of immune cells and subsequent inflammatory diseases. Because its biological significance, has been drug target for modulating responses. Immunoenhancing anti–PD-1 blocking antibodies have become widely used cancer treatment; however, little is known about the required characteristics to be capable stimulating immunosuppressive activity. Here, we show agonists exist in group recognizing...
The molecular etiology of idiopathic pulmonary fibrosis (IPF) has been extensively investigated to identify new therapeutic targets. Although anti-inflammatory treatments are not effective for patients with IPF, damaged alveolar epithelial cells play a critical role in lung fibrogenesis. Here, we establish an organoid-based model using mouse and human tissues assess the direct communication between type II (AT2)-lineage fibroblasts by excluding immune cells. Using this vitro genetics,...
Investigation of factors that modulate amyloid formation proteins is important to understand and mitigate amyloid-related diseases. To the role electrostatic interactions effect ionic cosolutes, especially anions, on formation, we have investigated salts such as NaCl, NaI, NaClO(4), Na(2)SO(4) fibril growth beta(2)-microglobulin, protein involved in dialysis-related amyloidosis. Under acidic conditions, these exhibit characteristic optimal concentrations where favored. The presence leads an...
To obtain insight into the mechanism of fibril formation, we examined effects ultrasonication, a strong agitator, on beta2-microglobulin (beta2-m), protein responsible for dialysis-related amyloidosis. Upon sonication an acid-unfolded beta2-m solution at pH 2.5, thioflavin T fluorescence increased markedly after lag time 1-2 h with simultaneous increase light scattering. Atomic force microscopy images showed formation large number short fibrils 3 nm in diameter. When sonication-induced were...
ABSTRACT Retrotransposon Gag-like 5 [RTL5, also known as sushi-ichi-related retrotransposon homolog 8 (SIRH8)] and RTL6 (also SIRH3) are eutherian-specific genes presumably derived from a retrovirus phylogenetically related to each other. They, respectively, encode strongly acidic extremely basic protein, well conserved among the eutherians. Here, we report that RTL5 microglial with roles in front line of innate brain immune response. Venus mCherry knock-in mice exhibited expression...
Beta2-microglobulin (beta2-m) is a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. Recent studies have focused on the mechanism by which are formed under physiological conditions, had been difficult to reproduce quantitatively. Yamamoto et al. (Yamamoto, S., Hasegawa, K., Yamaguchi, I., Tsutsumi, Kardos, J., Goto, Y., Gejyo, F. & Naiki, H. (2004) Biochemistry 43, 11075-11082) showed that combination seed prepared acidic conditions and low...
Humoral immunity is vital for host protection, yet aberrant antibody responses can trigger harmful inflammation and immune-related disorders. T follicular helper (Tfh) cells, central to humoral immunity, have garnered significant attention unraveling immune mechanisms. This study shows the role of B-cell Oct-binding protein 1 (Bob1), a transcriptional coactivator, in Tfh cell regulation. Our investigation, utilizing conditional Bob1-deficient mice, suggests that Bob1 plays critical...
Beta2-microglobulin (beta2-m), a protein responsible for dialysis-related amyloidosis, adopts an immunoglobulin domain fold in its native state. Although beta2-m has Trp residues at positions 60 and 95, both are located near the surface of domain. Hence, does not have conserved common to other domains, which is buried close proximity disulfide bond. To study structure amyloid fibrils relation their fold, we prepared series mutants. Trp60 Trp95 were replaced with Phe, single was introduced...
Abstract Hirschsprung disease (HSCR) is characterized by congenital absence of enteric neurons in distal portions the gut. Although recent studies identified Schwann cell precursors (SCPs) as a novel cellular source neurons, it unknown how SCPs contribute to phenotype HSCR. Using cell‐specific genetic labeling, we investigated SCP‐derived neurogenesis two mouse models HSCR; Sox10 haploinsufficient mice exhibiting colonic aganglionosis and Ednrb knockout showing small intestinal...
Neural circuits are composed of numerous neurons that perform diverse functions. Understanding the mechanisms neural processing requires elucidating connections among individual neurons. Rabies virus (RV)-mediated trans-synaptic tracing enables visualization direct presynaptic a defined population, facilitating precise mapping across various brain regions. This method relies on RV mutants require expression TVA receptor and rabies glycoprotein to infect spread Traditionally, adeno-associated...
Abstract Mammalian oocytes undergo a long‐term meiotic arrest that can last for almost the entire reproductive lifespan. This occurs after DNA replication and is prolonged with age, which poses challenge to in maintaining replication‐dependent chromosomal proteins required completion of meiosis. In this study, we show histones are reduced age mouse oocytes. Both types histone H3 variants, H3.1/H3.2 replication‐independent H3.3, decrease age. Aging‐associated reduction associated...
Endochondral ossification is regulated by transcription factors that include SRY-box factor 9, runt-related protein 2 (Runx2), and Osterix. However, the sequential harmonious regulation of multiple steps endochondral unclear. This study identified zinc finger homeodomain 4 (Zfhx4) as a crucial transcriptional partner We found Zfhx4 was highly expressed in cartilage deficient mice had reduced expression matrix metallopeptidase 13 inhibited calcification matrices. These phenotypes were very...
A common variant in the RAB27A gene adults was recently found to be associated with fractional exhaled nitric oxide level, a marker of eosinophilic airway inflammation. The small GTPase Rab27 is known regulate intracellular vesicle traffic, although its role allergic responses unclear. We demonstrated that exophilin-5, Rab27-binding protein, predominantly expressed both major IL-33 producers, lung epithelial cells, and specialized IL-5 IL-13 producers CD44hiCD62LloCXCR3lo pathogenic Th2 cell...
AimsAccumulating evidence demonstrates that cardiomyocyte death contributes to the onset and progression of heart failure (HF) after myocardial injury. Recent studies revealed immune/inflammatory reactions play important roles in cardiovascular diseases. However, it remains unclear whether immunosurveillance system, which eliminates cytopathic cells, including infected or malignant cancer is involved death, though cardiomyocytes are exposed pathological stresses during post-infarct...
The interactions between tumor necrosis factor (TNF) receptor-associated 6 (TRAF6) and TNF superfamily receptors (TNFRSFs) are promising targets for rheumatoid arthritis (RA) treatment. However, due to the challenging nature of protein-protein (PPIs), a potent inhibitor that surpasses affinity TRAF6-TNFRSF has not been developed. We developed small-molecule PPI using NMR in silico techniques. most compound, TRI4, exhibited an higher than those TNFRSFs competitively inhibited interaction....
Protein tyrosine phosphatase receptor type Z (PTPRZ) is preferentially expressed in the central nervous system as two transmembrane isoforms PTPRZ-A/B and one secretory isoform PTPRZ-S. Ptprz-knockout mice lacking expression of all three show behavioral, learning, neurological abnormalities, including increased exploratory activities to novelty, deficits spatial contextual reduced responses methamphetamine, relative wild-type mice. To investigate whether PTPRZ play distinct physiological...
Nucleoside diphosphate (NDP) kinase contributes to the maintenance of cellular pools all nucleoside triphosphates (NTPs) by catalyzing transfer gamma-phosphoryl group from an NTP donor NDP acceptor. extreme thermophilic bacterium Thermus thermophilus HB8 was overexpressed in Escherichia coli and crystallized at 297 K using polyethylene glycol 8000 as precipitant means hanging-drop vapour-diffusion procedure. The crystals belong hexagonal system, space P6(3)22, with unit-cell parameters a = b...
Abstract The success of immunoenhancing anti-PD-1 blocking antibodies in cancer treatment indicates the biological significance PD-1-dependent immunoregulation human immune system. Active stimulation PD-1 is potentially an effective approach treating various inflammatory disorders; however, agonistic stimulating immunosuppressive activity are not clearly defined. Here, by assessing activities anti-human mAbs, we have identified functional agonists antibody group recognizing membrane-proximal...
<h3>Background and aims</h3> The toll-like receptors (TLRs) are critical participants in vertebrate innate immune recognition of pathogen-associated molecular patterns (PAMPs). Diverse ligands act as "danger signals" detected by this component the system. TLR7 8 located endosomes specific subpopulations, activated single-stranded RNA from viruses or autologous fragments bound to complexes, inducing generation cytokines such interferons (specifically IFN-alpha) IL-6. Strong genetic evidence...