Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade

The inhibitory receptor programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV) infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions of bovine PD-L1 are still unknown. To investigate the role of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD-L1 expression in BLV-infected cattle in comparison with uninfected cattle. The deduced amino acid sequence of bovine PD-L1 shows high homology to the human and mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells, was upregulated in cattle with the late stage of the disease compared to cattle at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1 positive cells correlated positively with prediction markers for the progression of the disease such as leukocyte number, virus load and virus titer whilst on the contrary, it inversely correlated with the degree of interferon-gamma expression. Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody upregulated the production of interleukin-2 and interferon-gamma, and correspondingly, downregulated the BLV provirus load and the proportion of BLV-gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be a potential target for developing immunotherapies against BLV infection

Deterioration of CLT under Humid and Dry Cyclic Climate

Cross laminated timber (CLT) are composed of longitudinal layers and cross layers. And as the laminations of the adjoin layers are glued orthogonally deterioration of the laminations such as check and shake and delamination can be rather frequently come out when CLT is exposed to humid and dry cyclic climate. In Japan more than 100 CLT buildings have been constructed and the number of CLT building is increasing. In some buildings the CLT is designed as to be the exterior members and exposed to the outdoor climate. Several CLT buildings that have CLT as exterior members was investigated to make clear what was ongoing on the CLT panels exposed to outdoor climate. Remarkable check and shake, warp and delamination was observed for the CLT in some of the investigated buildings. To bring out the mechanism of the distortion of CLT under humid and dry cyclic climate and to give a solution to prevent deterioration of CLT a series of laboratory tests were conducted. The CLT panels were set in a climate chamber and exposed to a humid and dry cyclic climate. And the moisture content and the movement of the laminations of CLT were measured. The movement was affected by the species of the laminations and also by the direction of the surface, sap-side or heart-side. And the film forming type painting worked well as to prevent the deterioration and the penetrating type painting could slightly reduce the deterioration

Changes in Anterior Segment Morphology of Iris Bombe before and after Laser Peripheral Iridotomy in Patients with Uveitic Secondary Glaucoma

Purpose. To quantify changes in anterior segment (AS) parameters after laser peripheral iridotomy (LPI) using AS-optical coherence tomography (OCT) of iris bombe. Method. AS images of eight eyes were captured before and after iris bombe and more than 2 weeks after LPI (post-LPI) using AS-OCT. We compared the following AS parameters: anterior chamber depth (ACD), anterior chamber volume (ACV), iris curvature (IC), iris thickness at 500 μm from the scleral spur (IT-1) in the middle between the iris root and pupillary margin (IT-2) and 500 μm from the pupillary margin (IT-3) to the anterior chamber angle (ACA) (angle opening distance [AOD750]), and trabecular iris space area. Results. Mean IT-1 and IT-3, but not IT-2, were lower after iris bombe (IT-1, P=0.001; IT-2, P=0.081; and IT-3, P=0.001). There were no significant differences between ACD at pre-LPI and before iris bombe (P=0.096). The mean ACV and AOD750 of iris bombe increased at post-LPI (ACV, P<0.01, and AOD750, P<0.05). The mean IT-1, IT-2, and IT-3 increased at post-LPI (all, P≤0.01). IC decreased at post-LPI (P<0.001), and ACD at post-LPI did not change. Conclusions. The iris extends and becomes thinner during iris bombe. LPI during bombe decreases the IC and increases the ACV and ACA

Predictive Factors of Rectal Toxicity After Permanent iodine-125 Seed Implantation: Prospective Cohort Study in 2339 Patients

Purpose: To evaluate the incidence and the associated factors of rectal toxicity in patients with prostate cancer undergoing permanent seed implantation (PI) with or without external beam radiation therapy (EBRT) in a nationwide prospective cohort study in Japan (J-POPS) during the first 2 years. Methods and materials: A total of 2,339 subjects were available for the analyses. Rectal toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: The 3-year cumulative incidence for grade ≥2 rectal toxicity was 2.88%, 1.76%, and 6.53% in all subjects, PI group and EBRT combination therapy group, respectively. On multivariate analysis, among all subjects, grade ≥2 rectal toxicity was associated with rectal volumes receiving 100% of the prescribed dose (R100; p Conclusions: Rectal toxicity was relatively rare in this study compared with previous reports. For Japanese prostate cancer patients, R100 < 1 mL in both PI and EBRT combination therapy groups and interactive planning in EBRT combination therapy group may be effective in decreasing the incidence of rectal toxicity

Potential of ferritin 2 as an antigen for the development of a universal vaccine for avian mites, poultry red mites, tropical fowl mites, and northern fowl mites

IntroductionPoultry red mites (PRMs, Dermanyssus gallinae), blood-sucking ectoparasites, are a threat to the poultry industry because of reduced production caused by infestation. In addition, tropical fowl mites (TFMs, Ornithonyssus bursa) and northern fowl mites (NFMs, Ornithonyssus sylviarum) are hematophagous, distributed in various regions, genetically and morphologically close to PRMs, and cause similar problems to the poultry industry. Vaccine approaches have been studied for PRM control, and several molecules have been identified in PRMs as candidates for effective vaccine antigens. The development of an anti-PRM vaccine as a universal vaccine with broad efficacy against avian mites could improve the productivity of poultry farms worldwide. Molecules that are highly conserved among avian mites and have critical functions in the physiology and growth of mites could be ideal antigen candidates for the development of universal vaccines. Ferritin 2 (FER2), an iron-binding protein, is critical for the reproduction and survival of PRMs and has been reported as a useful vaccine antigen for the control of PRMs and a candidate for the universal vaccine antigen in some tick species.Method and resultsHerein, we identified and characterized FER2 in TFMs and NFM. Compared with the sequence of PRM, the ferroxidase centers of the heavy chain subunits were conserved in FER2 of TFMs and NFMs. Phylogenetic analysis revealed that FER2 belongs to clusters of secretory ferritins of mites and other arthropods. Recombinant FER2 (rFER2) proteins from PRMs, TFMs, and NFMs exhibited iron-binding abilities. Immunization with each rFER2 induced strong antibody responses in chickens, and each immune plasma cross-reacted with rFER2 from different mites. Moreover, mortality rates of PRMs fed with immune plasma against rFER2 from TFMs or NFMs, in addition to PRMs, were higher than those of control plasma.DiscussionrFER2 from each avian mite exhibited anti-PRM effects. This data suggests that it has the potential to be used as an antigen candidate for a universal vaccine against avian mites. Further studies are needed to access the usefulness of FER2 as a universal vaccine for the control of avian mites