Early pathological signs in young dysf(-/-) mice are improved by halofuginone
. NEUROMUSCULAR DISORDERS 2020
Dysferlinopathies are a non-lethal group of late-onset muscular dystrophies. Here, we evaluated the fusion ability of primary myoblasts from young dysf(-/-) mice and the muscle histopathology prior to, and during early stages of disease onset. The ability of primary myoblasts of 5-week-old dysf(-/-) mice to form large myotubes was delayed compared to their wild-type counterparts, as evaluated by scanning electron microscopy. However, their fusion activity, as reflected by the presence of actin filaments connecting several cells, was enhanced by the antifibrotic drug halofuginone. Early dystrophic signs were already apparent in 4-week-old dysf(-/-) mice; their collagen level was double that in wild-type mice and continued to rise until 5 months of age. Continuous treatment with halofuginone from 4 weeks to 5 months of age reduced muscle fibrosis in a phosphorylated-Smad3 inhibition-related manner. Halofuginone also enhanced myofiber hypertrophy, reduced the percentage of centrally nucleated myofibers, and increased muscle performance. Together, the data suggest an inhibitory effect of halofuginone on the muscle histopathology at very early stages of dysferlinopathy, and enhancement of muscle performance. These results offer new opportunities for early pharmaceutical treatment in dysferlinopathies with favorable outcomes at later stages of life. (C) 2020 Elsevier B.V. All rights reserved.
Farewell to Professor David Yaffe - A pillar of the myogenesis field
. EUROPEAN JOURNAL OF TRANSLATIONAL MYOLOGY 2020
It is with great sadness that we have learned about the passing of Professor David Yaffe (1929-2020, Israel). Yehi Zichro Baruch - May his memory be a blessing. David was a man of family, science and nature. A native of Israel, David grew up in the historic years that preceded the birth of the State of Israel. He was a member of the group that established Kibbutz Revivim in the Negev desert, and in 1948 participated in Israel's War of Independence. David and Ruth eventually joined Kibbutz Givat Brenner by Rehovot, permitting David to be both a kibbutz member and a life-long researcher at the Weizmann Institute of Science, where David received his PhD in 1959. David returned to the Institute after his postdoc at Stanford. Here, after several years of researching a number of tissues as models for studying the process of differentiation, David entered the myogenesis field and stayed with it to his last day. With his dedication to the field of myogenesis and his commitment to furthering the understanding of the People and the Land of Israel throughout the international scientific community, David organized the first ever myogenesis meeting that took place in Shoresh, Israel in 1975. This was followed by the 1980 myogenesis meeting at the same place and many more outstanding meetings, all of which brought together myogenesis, nature and scenery. Herein, through the preparation and publication of this current manuscript, we are meeting once again at a ``David Yaffe myogenesis meeting''. Some of us have been members of the Yaffe lab, some of us have known David as his national and international colleagues in the myology field. One of our contributors has also known (and communicates here) about David Yaffe's earlier years as a kibbutznick in the Negev. Our collective reflections are a tribute to Professor David Yaffe. We are fortunate that the European Journal of Translational Myology has provided us with tremendous input and a platform for holding this 2020 distance meeting ``Farwell to Professor David Yaffe - A Pillar of the Myogenesis Field''.
Timing Is Everything-The High Sensitivity of Avian Satellite Cells to Thermal Conditions During Embryonic and Posthatch Periods
. FRONTIERS IN PHYSIOLOGY 2020
Myofiber formation is essentially complete at hatch, but myofiber hypertrophy increases posthatch through the assimilation of satellite cell nuclei into myofibers. Satellite cell proliferation and differentiation occur during the early growth phase, which in meat-type poultry terminates at around 8 days posthatch. Thus, any factor that affects the accumulation of satellite cells during late-term embryogenesis or early posthatch will dictate long-term muscle growth. This review will focus on the intimate relationship between thermal conditions during chick embryogenesis and the early posthatch period, and satellite cell myogenesis and pectoralis growth and development. Satellite cells are highly sensitive to temperature changes, particularly when those changes occur during crucial periods of their myogenic activity. Therefore, timing, temperature, and duration of thermal treatments have a great impact on satellite cell activity and fate, affecting muscle development and growth in the long run. Short and mild thermal manipulations during embryogenesis or thermal conditioning in the early posthatch period promote myogenic cell proliferation and differentiation, and have long-term promotive effects on muscle growth. However, chronic heat stress during the first 2 weeks of life has adverse effects on these parameters and may lead to muscle myopathies.