Identification of a Novel ACVRL1 Gene Mutation (c.100T>A, p.Cys34Ser) in a Japanese Patient with Possible Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease)

Hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu disease) is an autosomal dominant genetic disorder that causes frequent epistaxis, mucocutaneous telangiectasia, and visceral arteriovenous malformations. Four genes (ENG, ACVRL1, SMAD4, and GDF2) have been identified as pathogenic in HHT. We describe the case of a 50-year-old Japanese man highly suspected of having HHT due to recurrent epistaxis, mucocutaneous telangiectasia, and a family history. Genomic analysis revealed a novel missense mutation of c.100T>A, p.Cys34Ser in the patient’s ACVRL1 gene. We used 6 freeware programs to perform an in silico analysis of this mutation. The results demonstrated the mutation’s high pathogenicity

Utilization of Chinese fast-growing trees and the effect of alternating lamination using mixed-species eucalyptus and poplar veneers

Over the past few decades, the sustainable forest area in China has increased remarkably, with 2400 million cubic meters of eucalyptus produced in 2018 in Guangxi which is the largest plantation area in China. In this study, the effect of alternating lamination using soft poplar veneers and hard eucalyptus veneers, on the mechanical properties of laminated veneer lumber (LVL), was examined. Eucalyptus and poplar veneers were imported from China to Japan to manufacture the LVL. For both eucalyptus and poplar veneers, the pith side (innerwood) sheets were lighter in density than the bark side (outerwood) sheets. The specific Young’s modulus of alternating LVL with hard eucalyptus veneers and soft poplar veneers was smaller than that of the mono-species LVL of eucalyptus and poplar. Strain distributions were obtained with the compression test by using the digital image correlation method. Normal strains showed that the hard eucalyptus layer behaved as a thin plate, whereas the soft poplar layer mitigated the movement of the hard eucalyptus layer. Alternating lamination decreased the variation in the elastic modulus of LVL made from fast-growing species. Therefore, the soft layers mitigated the movement of the hard layers, which had large variations in mechanical properties

Sonodynamic Therapy With Anticancer Micelles and High-Intensity Focused Ultrasound in Treatment of Canine Cancer

Sonodynamic therapy (SDT) is a minimally invasive anticancer therapy involving a chemical sonosensitizer and high-intensity focused ultrasound (HIFU). SDT enables the reduction of drug dose and HIFU irradiation power compared to those of conventional monotherapies. In our previous study, mouse models of colon and pancreatic cancer were used to confirm the effectiveness of SDT vs. drug-only or HIFU-only therapy. To validate its usefulness, we performed a clinical trial of SDT using an anticancer micelle (NC-6300) and our HIFU system in four pet dogs with spontaneous tumors, including chondrosarcoma, osteosarcoma, hepatocellular cancer, and prostate cancer. The fact that no adverse events were observed, suggests the usefulness of SDT

Physiological functions of calcium signaling via Orai1 in cancer

Abstract Intracellular calcium (Ca2+) signaling regulates many cellular functions, including cell proliferation and migration, in both normal cells and cancer cells. Store-operated Ca2+ entry (SOCE) is a major mechanism by which Ca2+ is imported from the extracellular space to the intracellular space, especially in nonexcitable cells. Store-operated Ca2+ entry (SOCE) is also a receptor-regulated Ca2+ entry pathway that maintains Ca2+ homeostasis by sensing reduced Ca2+ levels in the endoplasmic reticulum (ER). In general, the activation of G protein-coupled receptors (GPCRs) or immunoreceptors, such as T-cell, B-cell and Fc receptors, results in the production of inositol 1,4,5-trisphosphate (IP3). IP3 binds to IP3 receptors located in the ER membrane. The, IP3 receptors in the ER membrane trigger a rapid and transient release of Ca2+ from the ER store. The resulting depletion of ER Ca2+ concentrations is sensed by the EF-hand motif of stromal interaction molecule (STIM), i.e., calcium sensor, which then translocates to the plasma membrane (PM). STIM interacts with Orai Ca2+ channel subunits (also known as CRACM1) on the PM, leading to Ca2+ influx from the extracellular space to increase intracellular Ca2+ concentrations. The physiological functions of Orai and STIM have been studied mainly with respect to their roles in the immune system. Based on numerous previous studies, Orai channels (Orai1, Orai2 and Orai3 channels) control Ca2+ release-activated Ca2+ (CRAC) currents and contribute to SOCE currents in other types of cells, including various cancer cells. There are many reports that Orai1 is involved in cell proliferation, migration, metastasis, apoptosis and epithelial–mesenchymal transition (EMT) in various cancers. We previously found that Orai1 plays important roles in cell apoptosis and migration in melanoma. Recently, we reported novel evidence of Orai1 in human oral squamous cell carcinoma (OSCC) cells and human cardiac fibroblasts (HCFs). In this review, we present multiple physiological functions of Orai1 in various cancer cells and cardiac fibroblasts, including our findings

In vitro demonstration of neural transmission of avian influenza A virus

Neural involvement following infections of influenza viruses can be serious. The neural transport of influenza viruses from the periphery to the central nervous system has been indicated by using mouse models. However, no direct evidence for neuronal infection has been obtained in vitro and the mechanisms of neural transmission of influenza viruses have not been reported. In this study, the transneural transmission of a neurotropic influenza A virus was examined using compartmentalized cultures of neurons from mouse dorsal root ganglia, and the results were compared with those obtained using the pseudorabies virus, a virus with well-established neurotransmission. Both viruses reached the cell bodies of the neurons via the axons. This is the first report on axonal transport of influenza A virus in vitro. In addition, the role of the cytoskeleton (microtubules, microfilaments and intermediate filaments) in the neural transmission of influenza virus was investigated by conducting cytoskeletal perturbation experiments. The results indicated that the transport of avian influenza A virus in the neurons was independent of microtubule integrity but was dependent on the integrity of intermediate filaments, whereas pseudorabies virus needed both for neural spread

Methotrexate-Transferrin-Functionalized Fe(Salen)-Polypyrrole Nanocomposites for Targeted Photo-/Magneto-Thermal Cancer Treatments

Designing multi-modal topical drug delivery nanocarriers using nano-hybrid particles has received significant interest in targeted cancer therapy. In this study, magnetic Fe(salen)-conducting copolymer nanocomposites based on our previous iron salt-free synthesis method are surface-functionalized with methotrexate and transferrin proteins. The nano-hybrids show near-infrared-/magnetic field-responsive hyperthermal activity in vitro, which can be extraordinarily useful in magnetically guidable local cancer targeting as a versatile multi-modal therapeutic drug delivery system

Methotrexate-Transferrin-Functionalized Fe(Salen)-Polypyrrole Nanocomposites for Targeted Photo-/Magneto-Thermal Cancer Treatments

Designing multi-modal topical drug delivery nanocarriers using nano-hybrid particles has received significant interest in targeted cancer therapy. In this study, magnetic Fe(salen)-conducting copolymer nanocomposites based on our previous iron salt-free synthesis method are surface-functionalized with methotrexate and transferrin proteins. The nano-hybrids show near-infrared-/magnetic field-responsive hyperthermal activity in vitro, which can be extraordinarily useful in magnetically guidable local cancer targeting as a versatile multi-modal therapeutic drug delivery system

Evaluation of bovine viral diarrhoea virus control strategies in dairy herds in Hokkaido, Japan, using stochastic modelling

Bovine viral diarrhoea virus (BVDV) infection in cattle can result in growth retardation, reduced milk production, reproductive disorders and death. Persistently infected animals are the primary source of infection. In Hokkaido, Japan, all cattle entering shared pastures in summer are vaccinated before movement for disease control. Additionally, these cattle may be tested for BVDV and culled if positive. However, the effectiveness of this control strategy aiming to reduce the number of BVDV-infected animals has not been assessed. The aim of this study was to evaluate the effectiveness of various test-and-cull and/or vaccination strategies on BVDV control in dairy farms in two districts of Hokkaido, Nemuro and Hiyama. A stochastic model was developed to compare the different control strategies over a 10-year period. The model was individual-based and simulated disease dynamics both within and between herds. Parameters included in the model were obtained from the literature, the Hokkaido government and the Japanese Ministry of Agriculture, Forestry and Fisheries. Nine different scenarios were compared as follows: no control, test-and-cull strategies based on antigen testing of either calves or only cattle entering common pastures, vaccination of all adult cattle or only cattle entering shared pastures and combinations thereof. The results indicate that current strategies for BVDV control in Hokkaido slightly reduced the number of BVDV-infected animals; however, alternative strategies such as testing all calves and culling any positives or vaccinating all susceptible adult animals dramatically reduced those. To our knowledge, this is the first report regarding the comparison of the effectiveness between the current strategies in Hokkaido and the alternative strategies for BVDV control measures