Impaired flagellar development and impaired motility of sperm is a cause of infertility in males. Several genes, including those of the AKAP, CCDC, CFAP, and DNAH families, among others, are involved in the‘‘multipl...Impaired flagellar development and impaired motility of sperm is a cause of infertility in males. Several genes, including those of the AKAP, CCDC, CFAP, and DNAH families, among others, are involved in the‘‘multiple morphological abnormalities of the flagella"(MMAF) phenotype;these are the most common causes of male infertility. The Cilia-and flagella-associated protein(CFAP) family includes six members reported to cause MMAF phenotypes: CFAP43, CFAP44, CFAP69, CFAP65, CFAP70, and CFAP251. Here, we found that cilia-and flagella-associated protein 61(Cfap61) is highly expressed specifically in murine testes and show that the Cfap61-knockout male mice demonstrate MMAF phenotype, including sperm with short, coiled, and irregular flagella. Deletion of Cfap61 resulted in severe morphological and behavior abnormalities in sperm, reduced total sperm counts, impaired sperm motility, and led to male infertility.Notably, absence of Cfap61 impaired sperm flagella ultrastructural abnormalities on account of numerous distortions in multiple flagellum components. Immunostaining experiments in wild-type mice and healthy adult humans indicated that Cfap61 is initially localized at the neck of sperm, where it potentially functions in flagellum formation, and is later localized to the midpiece of the sperm. Thus, our study provides compelling evidence that dysregulation of Cfap61 affects sperm flagellum development and induces male infertility in mice. Further investigations of the CFAP61 gene in humans alongside clinical evidence showing MMAF phenotype in humans should contribute to our understanding of developmental processes underlying sperm flagellum formation and the pathogenic mechanisms that cause male infertility.展开更多
Volume contract as a new regime was introduced into the Rotterdam Rules by the proposal of the U.S. Delegation, which has pros and cons in terms of its inclusion. We shall, admit that, since the early form of service ...Volume contract as a new regime was introduced into the Rotterdam Rules by the proposal of the U.S. Delegation, which has pros and cons in terms of its inclusion. We shall, admit that, since the early form of service contract has been successfully applied in the transportation trade in the U.S., this regime indeed has its vitality. The author hereunder focuses on the inclusion of volume contract in the Rotterdam Rules, and introduces the history of the advent of service contract in the U.S. and then the advantages of the service contract of its application. Furthermore, the author analyzes the relevant provisions regarding volume contract in the Rotterdam Rules, as well as some critiques with respect to the concept of volume contract and provisions accordingly in the rules.展开更多
基金We thank Zhang Jie for her assistance in confocal analysis(Advanced Medical Research Institute,Shandong University).This work was supported by the National Key Research and Development Programs of China(2018YFC1003400)the Young Scholars Program of Shandong University(2016WLJH50)the Natural Science Foundation of Shandong Province(ZR2017MH049).
文摘Impaired flagellar development and impaired motility of sperm is a cause of infertility in males. Several genes, including those of the AKAP, CCDC, CFAP, and DNAH families, among others, are involved in the‘‘multiple morphological abnormalities of the flagella"(MMAF) phenotype;these are the most common causes of male infertility. The Cilia-and flagella-associated protein(CFAP) family includes six members reported to cause MMAF phenotypes: CFAP43, CFAP44, CFAP69, CFAP65, CFAP70, and CFAP251. Here, we found that cilia-and flagella-associated protein 61(Cfap61) is highly expressed specifically in murine testes and show that the Cfap61-knockout male mice demonstrate MMAF phenotype, including sperm with short, coiled, and irregular flagella. Deletion of Cfap61 resulted in severe morphological and behavior abnormalities in sperm, reduced total sperm counts, impaired sperm motility, and led to male infertility.Notably, absence of Cfap61 impaired sperm flagella ultrastructural abnormalities on account of numerous distortions in multiple flagellum components. Immunostaining experiments in wild-type mice and healthy adult humans indicated that Cfap61 is initially localized at the neck of sperm, where it potentially functions in flagellum formation, and is later localized to the midpiece of the sperm. Thus, our study provides compelling evidence that dysregulation of Cfap61 affects sperm flagellum development and induces male infertility in mice. Further investigations of the CFAP61 gene in humans alongside clinical evidence showing MMAF phenotype in humans should contribute to our understanding of developmental processes underlying sperm flagellum formation and the pathogenic mechanisms that cause male infertility.
文摘Volume contract as a new regime was introduced into the Rotterdam Rules by the proposal of the U.S. Delegation, which has pros and cons in terms of its inclusion. We shall, admit that, since the early form of service contract has been successfully applied in the transportation trade in the U.S., this regime indeed has its vitality. The author hereunder focuses on the inclusion of volume contract in the Rotterdam Rules, and introduces the history of the advent of service contract in the U.S. and then the advantages of the service contract of its application. Furthermore, the author analyzes the relevant provisions regarding volume contract in the Rotterdam Rules, as well as some critiques with respect to the concept of volume contract and provisions accordingly in the rules.
