Chimeric Antigen Receptor T Cell Bearing Herpes Virus Entry Mediator Co-Stimulatory Signal Domain Exhibits Exhaustion-Resistant Properties.

Improving chimeric antigen receptor (CAR)-T cell therapeutic outcomes and expanding its applicability to solid tumors requires further refinement of CAR-T cells. We previously reported that CAR-T cells bearing a herpes virus entry mediator (HVEM)-derived co-stimulatory signal domain (CSSD) (HVEM-CAR-T cells) exhibit superior functions and characteristics. Here, we conducted comparative analyses to evaluate the impact of different CSSDs on CAR-T cell exhaustion.

Dissemination of the Flavivirus Subgenomic Replicon Genome and Viral Proteins by Extracellular Vesicles.

Extracellular vesicles (EVs) such as exosomes have been shown to play physiological roles in cell-to-cell communication by delivering various proteins and nucleic acids. In addition, several studies revealed that the EVs derived from the cells that are infected with certain viruses could transfer the full-length viral genomes, resulting in EVs-mediated virus propagation. However, the possibility cannot be excluded that the prepared EVs were contaminated with infectious viral particles.

Application of the Luminescence Syncytium Induction Assay to Identify Chemical Compounds That Inhibit Bovine Leukemia Virus Replication.

Bovine leukemia virus (BLV) infection causes endemic bovine leukemia and lymphoma, resulting in lower carcass weight and reduced milk production by the infected cattle, leading to economic losses. Without effective measures for treatment and prevention, high rates of BLV infection can cause problems worldwide. BLV research is limited by the lack of a model system to assay infection.

Atypical integrative element with strand-biased circularization activity assists interspecies antimicrobial resistance gene transfer from Vibrio alfacsensis.

The exchange of antimicrobial resistance (AMR) genes between aquaculture and terrestrial microbial populations has emerged as a serious public health concern. However, the nature of the mobile genetic elements in marine bacteria is poorly documented. To gain insight into the genetic mechanisms underlying AMR gene transfer from marine bacteria, we mated a multidrug-resistant Vibrio alfacsensis strain with an Escherichia coli strain, and then determined the complete genome sequences of the donor and the transconjugant strains.

Phenotypic Characteristics of Prototheca Species Occurring in Humans and Animals.

The genus Prototheca consists of achlorophyllic algae that are ubiquitous in the environment and also occur in animal intestines; occasionally, infections in humans and animals are observed. In this study, we conducted tests of assimilative abilities and thermotolerance in comparison with morphological characteristics of six opportunistic species (Prototheca blaschkeae, Prototheca bovis, Prototheca ciferrii, Prototheca cutis, Prototheca miyajii, and Prototheca wickerhamii) along with Prototheca paracutis. Five of the seven species could be differentiated by physiological characteristics, but P.

Characterization of Prototheca CYP51/ERG11 as a possible target for therapeutic drugs.

Unlabelled: Prototheca spp. are achlorophyllous algae, ubiquitous in nature. An increasing number of human and animal cases of Prototheca infection (protothecosis) are reported, and antifungal azoles, which inhibit sterol 14α-demethylase (CYP51/ERG11) involved in ergosterol biosynthesis, have empirically been used for the treatment of protothecosis.

Development of biliary stent applying the antibacterial activity of silver: A literature review.

Background: Endoscopic transpapillary stenting is commonly performed in patients with obstructive jaundice caused by a biliary stricture. Although the plastic stent (PS) is widely used for biliary drainage because of the low-cost and easy procedure, patency is short after placement in the bile duct because of the small diameter. Dysfunction of PS is primarily caused by biliary sludge that forms as a result of bacterial adhesion and subsequent biofilm formation on the inner surface of the stent.

Protothecosis in Dogs and Cats-New Research Directions.

Protothecosis refers to disease of humans and animals caused by infection with fungus-like, colourless microalgae of the genus Prototheca. Although protothecosis remains an uncommon infection, increasing numbers of human and animal cases are being diagnosed worldwide. This review summarises major new findings in basic science (sequencing analyses of sterol 14α-demethylase (CYP51/ERG11) genes and organelle genomes of Prototheca wickerhamii) to elucidate taxonomic features of this pathogen.

Effects of the Japanese Encephalitis Virus Genotype V-Derived Sub-Viral Particles on the Immunogenicity of the Vaccine Characterized by a Novel Virus-Like Particle-Based Assay.

Japanese encephalitis virus (JEV) is classified into five genotypes labelled I through V. Although the genotype V (GV) JEV was originally found and had apparently been limited in Malaysia for more than 50 years, its emergence in Korea and China has recently been reported. Therefore, the GV JEV might be spreading over new geographical regions as a cause of potential public health problems.

A Short Peptide Derived from the ZorO Toxin Functions as an Effective Antimicrobial.

Antimicrobial peptides are potential molecules for the development of novel antibiotic agents. The ZorO toxin of a type I toxin-antitoxin system in O157:H7 is composed of 29 amino acids and its endogenous expression inhibits growth. However, little is known about its inhibitory mechanism.

Chimeric Antigen Receptor T Cell Bearing Herpes Virus Entry Mediator Co-stimulatory Signal Domain Exhibits High Functional Potency.

Chimeric antigen receptor (CAR) is a hybrid molecule consisting of an antigen-binding domain and a signal transduction domain. The artificial T cells expressing CAR (CAR-T cells) are expected to be a useful tool for treatment of various diseases, such as cancer. The addition of a co-stimulatory signal domain (CSSD) to CAR is shown to be critical for modulating CAR-T cell activities.

Multiple antiviral activities of the antimalarial and anti-hepatitis C drug candidates N-89 and N-251.

The chemically synthesized endoperoxide compound N-89 and its derivative N-251 were shown to have potent antimalarial activity. We previously demonstrated that N-89 and N-251 potently inhibited the RNA replication of hepatitis C virus (HCV), which belongs to the family. Since antimalarial and anti-HCV mechanisms have not been clarified, we were interested whether N-89 and N-251 possessed the activity against viruses other than HCV.

Case report of cutaneous protothecosis caused by Prototheca wickerhamii designated as genotype 2 and current status of human protothecosis in Japan.

An 85-year-old Japanese woman presented with infiltrative erythema and ulceration on the extensor surface of her right forearm. Direct microscopic examination demonstrated spherical and morula-like sporangia, while histopathology revealed numerous microorganisms with a mulberry-like appearance in the dermis. Staining of the microorganisms also showed mulberry-like sporangia that resembled the spokes of a wheel.

Molecular Characterization of Prototheca strains isolated in China revealed the first cases of protothecosis associated with Prototheca zopfii genotype 1.

In this study, six strains of Prototheca isolated in China from human patients diagnosed as protothecosis and cows with mastitis were characterized by polymerase chain reaction (PCR) and nucleotide sequencing of the ribosomal RNA gene (rDNA) and by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). The results indicated that three strains isolated from the human patients were P. zopfii genotype 1, revealing the first cases of human protothecosis associated with P.

Structural insights into the inhibition mechanism of bacterial toxin LsoA by bacteriophage antitoxin Dmd.

Bacteria have obtained a variety of resistance mechanisms including toxin-antitoxin (TA) systems against bacteriophages (phages), whereas phages have also evolved to overcome bacterial anti-phage mechanisms. Dmd from T4 phage can suppress the toxicities of homologous toxins LsoA and RnlA from Escherichia coli, representing the first example of a phage antitoxin against multiple bacterial toxins in known TA systems. Here, the crystal structure of LsoA-Dmd complex showed Dmd is inserted into the deep groove between the N-terminal repeated domain (NRD) and the Dmd-binding domain (DBD) of LsoA.

Prototheca miyajii sp. nov., isolated from a patient with systemic protothecosis.

Species of the genus Prototheca are achlorophyllous algae and ubiquitous in nature, and so far, six species have been listed in this genus: Prototheca wickerhamii, Prototheca zopfii, Prototheca blaschkeae, Prototheca cutis, Prototheca stagnora and Prototheca ulmea. A strain of the genus Prototheca, IFM 53848T, was isolated in Japan from a patient with systemic protothecosis and had been designated P. wickerhamii.

Construction of an infectious molecular clone of Japanese encephalitis virus genotype V and its derivative subgenomic replicon capable of expressing a foreign gene.

Japanese encephalitis virus (JEV) genotype V was originally isolated in Malaysia in 1952 and has long been restricted to the area. In 2009, sudden emergence of the genotype V in China and Korea was reported, suggesting expansion of its geographical distribution. Although studies on the genotype V are becoming more important, they have been limited partly due to lack of its infectious molecular clone.

Various pAQU plasmids possibly contribute to disseminate tetracycline resistance gene tet(M) among marine bacterial community.

Emergence of antibiotic-resistant bacteria in the aquaculture environment is a significant problem for disease control of cultured fish as well as in human public health. Conjugative mobile genetic elements (MGEs) are involved in dissemination of antibiotic resistance genes (ARGs) among marine bacteria. In the present study, we first designed a PCR targeting traI gene encoding essential relaxase for conjugation.

Ribosomal internal transcribed spacer of Prototheca wickerhamii has characteristic structure useful for identification and genotyping.

Prototheca species are achlorophyllous algae ubiquitous in nature and known to cause localized and systemic infection both in humans and animals. Although identification of the Prototheca species in clinical specimens is a challenge, there are an increasing number of cases in which molecular techniques have successfully been used for diagnosis of protothecosis. In this study, we characterized nuclear ribosomal DNA (rDNA) of a strain of Prototheca (FL11-0001) isolated from a dermatitis patient in Japan for its species identification.

Novel conjugative transferable multiple drug resistance plasmid pAQU1 from Photobacterium damselae subsp. damselae isolated from marine aquaculture environment.

The emergence of drug-resistant bacteria is a severe problem in aquaculture. The ability of drug resistance genes to transfer from a bacterial cell to another is thought to be responsible for the wide dissemination of these genes in the aquaculture environment; however, little is known about the gene transfer mechanisms in marine bacteria. In this study, we show that a tetracycline-resistant strain of Photobacterium damselae subsp.

O-sulfate groups of heparin are critical for inhibition of ecotropic murine leukemia virus infection by heparin.

There is increasing evidence that soluble glycosaminoglycans such as heparin can interfere with the infectivity of various viruses, including ecotropic murine leukemia viruses (MLVs). The ecotropic MLV, Friend MLV (F-MLV) and the neuropathogenic variants A8 MLV and PVC-211 MLV, were susceptible to heparin-mediated inhibition of infection of NIH 3T3 cells. To investigate the interaction between the envelope glycoprotein (Env) of MLV and heparin, we prepared vesicular stomatitis virus-based pseudotyped viruses carrying the Env of F-, A8, or PVC-211 MLVs.

A chemical compound for controlled expression of nmt1-driven gene in the fission yeast Schizosaccharomyces pombe.

The fission yeast Schizosaccharomyces pombe is a useful model organism for studying a variety of eukaryotic cellular events such as the cell cycle control mechanisms. For inducible expression of exogenous genes in S. pombe, vectors carrying the nmt1 (no message in thiamine 1) promoter are most commonly used.