Stepwise fate conversion of supporting cells to sensory hair cells in the chick auditory epithelium

In contrast to mammals, the avian cochlea, specifically the basilar papilla, can regenerate sensory hair cells, which involves fate conversion of supporting cells to hair cells. To determine the mechanisms for converting supporting cells to hair cells, we used single-cell RNA sequencing during hair cell regeneration in explant cultures of chick basilar papillae. We identified dynamic changes in the gene expression of supporting cells, and the pseudotime trajectory analysis demonstrated the stepwise fate conversion from supporting cells to hair cells. Initially, supporting cell identity was erased and transition to the precursor state occurred. A subsequent gain in hair cell identity progressed together with downregulation of precursor-state genes. Transforming growth factor β receptor 1-mediated signaling was involved in induction of the initial step, and its inhibition resulted in suppression of hair cell regeneration. Our data provide new insights for understanding fate conversion from supporting cells to hair cells in avian basilar papillae

Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial, or peritoneal lining. Although surgery, chemotherapy, radiotherapy, and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there are no published reports regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti-GM2 antibody BIW-8962 as an anti-MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. BIW-8962 showed a significant antibody-dependent cellular cytotoxicity activity against the GM2-expressing MPM cell line MSTO-211H, the effect of which depended on the antibody concentration and effector/target ratio. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. In this study, the anti-GM2 antibody BIW-8962 first showed a significant ADCC activity against malignant pleural mesothelioma (MPM) cell line and therapeutic activity in an in vivo orthotropic mouse model using the cell line. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

SARS-CoV-2オミクロンBA.2.75株（通称ケンタウロス）のウイルス学的性状の解明. 京都大学プレスリリース. 2022-10-12.The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5

Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions

Practical Effects of Using a Dental Magnifier in a Dental Hygienist Training School

Abstract：In recent years, the use of dental magnifying glass has been spreading for the accurate diagnosis and treatments. In this research, we decided to introduce a dental magnifying glass during a practical training course at a training school and to verify its usefulness. The subjects were 52 2nd year students enrolled in a prefectural school in 2015 and 51 2nd year students enrolled in fiscal year 2016, totaling 103 people. In both 2015 and 2016-from April to November, we introduced a magnifying glass for jaw model practice and mutual practice of the dental preventive treatment subjects. The subjects were asked to detect and remove the artificial dental calculus (protrusions) in phantom head, jaw and teeth models with and without the dental magnifying glass as a practical test. The use effect of dental magnifying glass was evaluated by the total numbers of detected and removed protrusions. After the test, a questionnaire was also conducted to the subjects to subjectively evaluate the use effect of dental magnifying glass. Both detection and removal numbers with the dental magnifying glass were significantly higher than those without the dental magnifying glass. The result of questionnaire showed a positive attitude toward the use of dental magnifying glass. By using a magnifying glass in a practical training in a training school, it improved the ability to detect protrusions corresponding to dental calculus, you can gain many benefits such as improving motivation for future hygienist work, it was suggested that its introduction is useful for practical training

Proteomic Analysis of Phagocytosis in the Enteric Protozoan Parasite Entamoeba histolytica

Proteomic analysis of phagosomes isolated from Entamoeba histolytica by liquid chromatography and mass spectrometry identified 85 proteins involved in surface recognition, actin cytoskeleton rearrangement, vesicular trafficking, and degradation. Phagosome localization of representative proteins was verified by immunofluorescence assay. This study should provide a basis for molecular identification and characterization of phagosome biogenesis

Diffusion-Weighted Whole Body Imaging With Background Body Signal Suppression (DWIBS)

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) is a technique designed for whole-body screening of cancer. In the breast, it can provide stable fat suppression and excellent contrast between the tumor and the background mammary glandular tissue. Thanks to its effective attenuation of surface body fat, DWIBS is useful to depict lesions on maximum intensity projection images, and this feature translates into an efficient reading speed. Therefore DWIBS is a promising magnetic resonance imaging (MRI) method for noncontrast-enhanced breast cancer screening. However, it is important to use DWIBS in combination with other sequences because only relying on the detection of high-signal-intensity areas on DWIBS could result in a high number of false positives. In addition, because the image quality of DWIBS may vary across scanner vendors, but also between the same types of scanners of the same vendor, some standardization is necessary to continuously check and monitor image quality to ensure that the signal intensity of the mammary gland is sufficiently higher than that of the surrounding fat