Fragile X syndrome (FXS) is the foremost monogenic cause of autism spectrum disorder and intellectual disability, caused by FMR1 gene silencing. Here, we report that common marmosets carrying FMR1 mutation, a non-human primate model for FXS, share common features in behavioral and molecular phenotypes with patients with FXS. Founder mutants with markedly reduced fragile X messenger ribonucleoprotein expression display hyperactivity, spontaneous seizures, and transcriptome changes in synapse-related genes that overlap with those reported in patients with FXS.
View Article and Find Full Text PDFMany cnidarian animals possess multiple opsins, including a type known as cnidopsin, which is found throughout the phylum Cnidaria and is divided into several subgroups. Previous studies have suggested that cnidopsins from jellyfish and coral can light-dependently elevate intracellular cAMP levels, likely via activation of Gs-type G protein in cultured cells. However, their spectroscopic properties remain largely unclear, with the exception of jellyfish opsins.
View Article and Find Full Text PDFAnimal opsins are G protein-coupled receptors that have evolved to sense light by covalently binding a retinal chromophore via a protonated (positively charged) Schiff base. A negatively charged amino acid in the opsin, acting as a counterion, stabilizes the proton on the Schiff base, which is essential for sensitivity to visible light. In this study, we investigate the spectroscopic properties of a unique class of opsins from a reef-building coral belonging to the anthozoan-specific opsin II group (ASO-II opsins), which intriguingly lack a counterion residue at any of established sites.
View Article and Find Full Text PDFMosquito saliva facilitates pathogen transmission and enhances the severity of diseases caused by mosquito-borne viruses; however, the underlying mechanisms are unknown. Here, we demonstrate that mosquito salivary gland extracts (SGEs) enhance flaviviral pathogenicity in vivo by activating innate immune responses following the accumulation of immune cells at the infection site. Among the innate immune signaling pathways, the TLR2 pathway enhances flaviviral pathogenicity in a manner similar to that of SGEs.
View Article and Find Full Text PDFNeuropsin (Opn5), a UV-sensitive 'non-visual' opsin, has the potential to be used as optogenetic tools applicable to tissues outside of the eye because of its broad expression. However, its sensitivity to poorly tissue-penetrating UV light poses challenges for its application. In this study, we focused on human OPN5 (hOPN5) to identify amino acid(s) responsible for the UV sensitivity.
View Article and Find Full Text PDFRett syndrome (RTT) is a severe neurodevelopmental disorder mainly caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Previous studies reported sleep problems characterized by changes in architecture and sleep-wake patterns in both RTT patients and animal models of RTT. However, little is known about the neural mechanisms underlying the sleep-wake problems in humans or animals.
View Article and Find Full Text PDFDecellularization and recellularization can help address the gap between organ demand and availability. Although several whole organ engineered liver constructs have been reported, they are unable to maintain long-term function. Additionally, the effect of the early stage on cells after implantation is not described in detail.
View Article and Find Full Text PDFAn 11-year-old, Damaraland mole-rat queen died after several months of abdominal distension with no other clinical signs, and a necropsy was performed. Grossly, numerous red-white, smooth masses, ranging from a few millimeters to 1 cm in diameter, were widely scattered across the surfaces of the diaphragm, mesentery, and peritoneum. The pulmonary hilar, mediastinal, mesenteric, and renal lymph nodes were enlarged.
View Article and Find Full Text PDFProtein methylesterase-1 (PME-1) is an essential enzyme that catalyzes the demethylation of protein phosphatases 2A (PP2A) and PP4 catalytic subunits to alter the composition of holoenzymes. Elevated PME-1 protein levels are observed in neurodegenerative diseases and cancer, suggesting the involvement of dysregulation of PP2A/PP4 methylation. However, PME-1 also forms stable complexes with the catalytic subunit of PP2A to interfere with phosphatase activity, and it remains unclear what roles the functions as a methylesterase and as a PP2A inhibitory protein each play in vivo.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
June 2025
The persistent threat of SARS-CoV-2 and the emergence of new variants has prompted the development of a novel, easily administered modality that can overcome viral mutations. The engineered ACE2 decoy shows neutralizing activity comparable to monoclonal antibodies and is broadly effective against SARS-CoV-2 variants and ACE2-utilizing sarbecoviruses. In addition to intravenous administration, this decoy has shown antiviral efficacy through nebulized aerosol inhalation in murine and primate models, offering a dose-sparing advantage.
View Article and Find Full Text PDFMost animals capture light through opsins, which are light-sensitive G protein-coupled receptors (GPCRs). Recent genome analyses of anthozoans, including corals and sea anemones, have identified novel opsins that are phylogenetically classified into two groups distinct from previously known opsin groups. Despite their significance in clarifying biological functions, the specific molecular properties of these opsins remain largely unknown.
View Article and Find Full Text PDFBackground/aim: This study aimed to clarify the feasibility of creating coplanar single-isocenter volumetric modulated arc therapy (SI-VMAT) with a Halcyon using a knowledge-based planning system based on non-coplanar plans for treating multiple brain metastases.
Patients And Methods: A knowledge-based RapidPlan (RP) planning model was built using 32 TrueBeam SI-VMAT plans including one full arc and three non-coplanar partial arcs. To confirm its applicability across different beam geometries using the Halcyon system, the model was validated on the basis of the root-mean-square error (RSME), deviation rate, and absolute differences between estimated and actual dose-volume histograms (DVHs).
Clin Spine Surg
January 2025
Study Design: Retrospective cohort study using prospective database.
Objective: This study aimed to establish a risk-scoring system for predicting severe complications after pyogenic spondylodiscitis surgery.
Summary Of Background Data: Pyogenic spondylodiscitis surgery can cause severe complications.
Background/aim: Soft tissue sarcoma (STS) is a mesenchymal tumor affecting multiple organs in dogs. Previous studies identified activation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB, AKT) pathway in canine STS cell lines and clinical samples, but the underlying mechanism remains unclear. This study investigated PTEN loss, PIK3CA mutation, and EGFR over-expression as potential drivers of PI3K/AKT pathway activation in STS.
View Article and Find Full Text PDFAsthma, an allergic disease of the airways, is a risk factor for severity of common respiratory viral infections; however, the relationship between asthma and severity in COVID-19 remains unclear. Here, we examined the effects of SARS-CoV-2 (Omicron BA.5 strain) infection in a mouse model of airway allergy.
View Article and Find Full Text PDFThe E2 protein of bovine viral diarrhea virus (BVDV) is a known protective antigen and a major target for DNA vaccines. DNA vaccines have various advantages; however, their immunogenicity needs to be enhanced by using adjuvants or drug delivery systems. In this study, we used mouse lysosome-associated membrane protein 1 (mLAMP1) as a molecular adjuvant and developed a DNA vaccine encoding an mLAMP1-BVDV E2 chimeric protein (pVax-mLAMP1-E2).
View Article and Find Full Text PDFSince Mongolian gerbils are broadly susceptible to hepatitis E virus (HEV), including genotypes 1, 4, 5, and 8 (HEV-1, HEV-5, HEV-5, and HEV-8) and rat HEV, they are a useful small animal model for HEV. However, we have observed that the subtypes HEV-3k and HEV-3ra in genotype 3 HEV (HEV-3) were not infected efficiently in the gerbils. A small-animal model for HEV-3 is also needed since HEV-3 is responsible for major zoonotic HEV infections.
View Article and Find Full Text PDFOne Health
December 2024
Production of hard X-ray via inverse Compton scattering at photon energies below 100 keV range aimed at potential applications in medicine and material research is reported. Experiments have been performed at the Brookhaven National Laboratory, Accelerator Test Facility, employing the counter collision of a 70 MeV, 0.3 nC electron beam with a near infra-red Nd: YAG laser (1064 nm wavelength) pulse containing ~ 100 mJ in a single shot basis.
View Article and Find Full Text PDFAligning spawning timing with seasonal environmental changes is critical for both terrestrial and aquatic organisms. However, mechanisms to regulate reproductive activity in response to environmental factors are not well understood, partly owing to the technical difficulty in maintaining detailed long-term observational data of the reproductive activities in the same population across years. In this study, we present an application of the aquarium system to examine the long-term spawning properties of corals.
View Article and Find Full Text PDFBackground/aim: The activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway has been implicated in canine soft tissue sarcoma (STS) and may serve as a prognostic marker. This study investigated the correlation between PI3K/Akt activation in tumor cells and tumor-infiltrating lymphocytes (TILs).
Materials And Methods: A total of 59 STS samples were labeled via immunohistochemistry to calculate the density of TILs, including CD3+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ regulatory T cells.