Neural regulation in tooth regeneration of Ambystoma mexicanum

The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration

Fgf- and Bmp-signaling regulate gill regeneration in Ambystoma mexicanum

Gill regeneration has not been well studied compared to regeneration of other appendages, such as limb and tail regeneration. Here, we focused on axolotl gill regeneration and found that Fgf- and Bmp-signaling are involved in their gill regeneration mechanism. Axolotls have three pairs of gill rami, and each gill ramus has multiple gill filaments. The gills consist of mesenchyme rich in extracellular matrix and epidermis. The gill nerves are supplied from the trigeminal ganglia located in the head. Denervation resulted in no gill regeneration responses. Nerves and gills express Bmp and Fgf genes, and treating animals with Fgf- and Bmp-signaling inhibitors results in phenotypes similar to those seen in denervated gills. Inducing an accessory appendage is a standard assay in amphibian regeneration research. In our study, an accessory gill could be induced by lateral wounding, suggesting that thin axon fibers and mesenchymal Fgfs and Bmps contributed to the induction of the accessory structure. Such accessory gill induction was inhibited by the denervation. Exogenous Fgf2+Fgf8+Bmp7, which have been determined to function as a regeneration inducer in urodele amphibians, could compensate for the effects denervation has on accessory blastema formation. Our findings suggest that regeneration of appendages in axolotls is regulated by common Fgf- and Bmp-signaling cascades

2021 Annual Report on Faculty Development Programs at Tokushima University

徳島大学では，2002 年度から全学FD 推進プログラムを通じて，FD の体系化，組織化，日常化を推進してきた。2021 年度も2020 年度に引き続き，新型コロナウイルス感染症の影響を受け，ほとんどのプログラムをオンラインで実施した。2021 年度はコロナ禍2 年目であることから，オンライン授業に関する工夫や実践事例が蓄積されており，「授業について考えるランチセミナー」，「授業設計ワークショップ」では，オンライン授業ですぐに活用できる教育方法やツールを紹介した。「大学教育カンファレンスin 徳島」，「授業について考えるランチセミナー」はオンラインで学外に公開することで，学外からの参加が多数あった。本年度実施した各プログラムの概要を記載し，アンケート結果等からうかがえる成果と今後の課題について考察する。Tokushima University has been promoting the systematization, organization, and routinization of faculty development (FD) through the university-wide FD promotion program since FY2002. In FY2021, most of the programs were conducted online due to the novel coronavirus (COVID-19) pandemic as in FY2020. However, there were many innovative and practical examples regarding online teaching methods based on the experiences of online teachings in the pandemic of COVID-19 during the last year. We have conducted a series of seminars entitled “Lunch Seminar on Thinking about Classes” and the program for new faculty called “Class Design Workshop” to introduce educational methods and tools that can be used immediately in online classes. The "University Education Conference in Tokushima" and the " Lunch Seminar on Thinking about Classes " were open to the public online and attracted many participants from outside the university. An overview of each program conducted in this year, and discussions about challenges for the future based on the results of the questionnaire are described

2023 Annual Report on Faculty Development Programs at Tokushima University

徳島大学では，2002年度から全学FD推進プログラムを通じて，FDの体系化，組織化，日常化を推進してきた。2023年度は，4年ぶりにワークショップ型のプログラムを対面で実施し，参加者同士の情報交換の機会を提供することができた。オンラインツールを活用した双方向FD「授業について考えるランチセミナー」では，2022年度に引き続き高知大学と共同でFDプログラムの開発・運営を行った。「大学教育カンファレンスin徳島」は対面会場での実施をメインとし，一部のプログラムをオンラインで配信するハイブリッド型で開催したことで，参加者同士の情報交換の機会を作ることができた上に，学外からの参加も多数あり，多様な参加ニーズに応えることができた。本年度実施した各プログラムの概要を記載し，アンケート結果等から窺える成果と今後の課題について考察する。Tokushima University has been promoting the systematization, organization, and routinization of faculty development (FD) through the university-wide FD promotion program since FY2002. In FY2023, workshop-style programs were held face-to-face for the first time in four years. Thereby, we were able to provide an opportunity for participants to exchange information with each other. Moreover, following the example from the preceding year, in 2023, the online interactive FD seminar “Lunch Seminar on Thinking about Classes” was developed and managed jointly with Kochi University. Moreover “University Education Conference” was held face-to-face, and some programs were delivered online, so we could create opportunities for participants to exchange information with each other. It is noteworthy that there were many participants from outside the university, and we were able to meet their diverse needs. An overview of each program conducted this year and discussions about future challenges based on the results of the questionnaire are described

2020 Annual Report on Faculty Development Programs at Tokushima University

徳島大学では，2002 年度から全学FD 推進プログラムを通じて，FD の体系化，組織化，日常化を推進してきた。2020 年度は，新型コロナウイルス感染症の拡大に伴い，ほとんどのプログラムをオンラインで実施した。教員個人の教育力向上を目的とした「すぐ使える90 分セミナー」，「授業設計ワークショップ」では，オンライン授業ですぐに活用できる教育方法やツールを紹介した。「大学教育カンファレンスin 徳島」，「すぐ使える90 分セミナー」はオンラインで学外に公開することで，学外からの参加が多数あった。また，新たに博士後期課程の大学院生を対象としたプレFD プログラムも実施した。本年度実施した各プログラムの概要を記載し，アンケート結果等からうかがえる成果と今後の課題について考察する。Tokushima University has been promoting the systematization, organization, and reutilization of faculty development (FD) through the university-wide FD promotion program since FY2002, and in FY2020, most of the programs were conducted online due to the spread of the novel coronavirus infection. “90-minute Seminar for Immediate Use” and “Class Design Workshop” were held to improve the teaching skills of individual faculty members. The "University Education Conference in Tokushima" and the "90-minute Seminar for Immediate Use" were open to the public online and attracted many participants from outside the university. In addition, a new pre-FD program (“Preparing Future Faculty Development”) for doctoral course graduate students was conducted. The following is an overview of each program conducted this year, and a discussion of the results and future issues based on the questionnaire results

Development and Validation of Cutoff Value for Reduced Muscle Mass for GLIM Criteria in Patients with Gastrointestinal and Hepatobiliary–Pancreatic Cancers

The Global Leadership Initiative on Malnutrition (GLIM) criteria recommends using race- and sex-adjusted cutoff values for reduced muscle mass (RMM), but the only cutoff values available for Asians are the skeletal muscle mass index (SMI) established by the Asian Working Group for Sarcopenia (AWGS). This retrospective study aimed to develop and validate cutoff values for the fat-free mass index (FFMI) and arm circumference (AC) of Asians, and to investigate the association between GLIM malnutrition and prognosis. A total of 660 patients with primary gastrointestinal (GI) and hepatobiliary–pancreatic (HBP) cancers who underwent their first resection surgery were recruited and randomly divided into development and validation groups. The FFMI and AC cutoff values were calculated by receiver operating characteristic curve analysis for the AWGS SMI as the gold standard. The cutoff values for each RMM were used to diagnose malnutrition on the basis of GLIM criteria, and the survival rates were compared. The optimal FFMI cutoff values for RMM were 17 kg/m2 for men and 15 kg/m2 for women, and for AC were 27 cm for men and 25 cm for women. In the validation group, the accuracy of the FFMI and AC cutoff values to discriminate RMM were 85.2% and 68.8%, respectively. Using any of the three measures of RMM, overall survival rates were significantly lower in the GLIM malnutrition group. In conclusion, the cutoff values for the FFMI and AC in this study could discriminate RMM, and GLIM malnutrition using these cutoff values was associated with decreased survival

The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance

SARS-CoV-2ラムダ株のウイルス学的・免疫学的性状の解明. 京都大学プレスリリース. 2021-12-23.SARS-CoV-2 Lambda, a variant of interest, has spread in some South American countries; however, its virological features and evolutionary traits remain unknown. In this study, we use pseudoviruses and reveal that the spike protein of the Lambda variant is more infectious than that of other variants due to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies and further augments antibody-mediated enhancement of infection. Although this mutation generates a nascent N-linked glycosylation site, the additional N-linked glycan is dispensable for the virological property conferred by this mutation. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the RSYLTPGD246-253N mutation is closely associated with the substantial spread of the Lambda variant in South America

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Requirement for expression of WW domain containing transcription regulator 1 in bovine trophectoderm development

WW domain-containing transcription regulator 1 (WWTR1) is one of the primary effectors in the Hippo pathway, which plays essential roles in cell differentiation into trophectoderm (TE) and inner cell mass cell lineages at the blastocyst stage. However, little is known about the roles of WWTR1 in preimplantation development. The present study aimed to explore the significance of WWTR1 expression in preimplantation development using an mRNA knockdown (KD) system in bovine embryos. We first quantitated WWTR1 expression at protein and mRNA levels from fertilization to blastocyst stage. WWTR1 proteins gradually shifted from extranuclear localization during the 16-cell stage to nuclear localization by morula stage. WWTR1 mRNA expression was also transiently upregulated at the 16-cell stage. WWTR1 KD efficiently repressed WWTR1 expression at protein and mRNA levels. The WWTR1 KD embryos developed to the blastocyst stage at rates equivalent to those of controls, but TE cell numbers were significantly decreased. Representative TE-expressed genes, including CDX2 and IFNT were also significantly decreased in WWTR1 KD blastocysts. These results provide the first demonstration that WWTR1 expression is responsible for normal TE cell development in preimplantation embryos. (c) 2021 Elsevier Inc. All rights reserved