1: A synthetic synaptic organizer protein restores glutamatergic neuronal circuits
Science of the Month - October 2020
Science.
2020 Aug 28;369(6507):eabb4853. doi: 10.1126/science.abb4853.
Kunimichi Suzuki†, Jonathan Elegheert, Inseon Song, Hiroyuki Sasakura, Oleg Senkov, Keiko Matsuda, Wataru Kakegawa, Amber J Clayton, Veronica T Chang, Maura Ferrer-Ferrer, Eriko Miura, Rahul Kaushik, Masashi Ikeno, Yuki Morioka, Yuka Takeuchi, Tatsuya Shimada, Shintaro Otsuka, Stoyan Stoyanov, Masahiko Watanabe, Kosei Takeuchi, Alexander Dityatev, A Radu Aricescu, Michisuke Yuzaki* (†First author, *Corresponding author)
The brain and spinal cord consist of a vast number of interconnected nerve cells that form complex neural circuits to precisely control functions such as memory and movement. The junctions between these nerve cells are called "synapses," where proper information transmission is mediated by synaptic connector molecules. The breakdown of these synapses can lead to various psychiatric and neurological disorders. We discovered Cbln1, which functions as a synaptic connector in the cerebellum, and have been conducting research on it. In this study, we combined Cbln1 with another synaptic molecule called NP1 to significantly expand its function, developing a completely new artificial synaptic connector, "CPTX," capable of forming synapses in any region of the nervous system. A single local injection of the CPTX protein into disease model mice for cerebellar ataxia, Alzheimer's disease, and spinal cord injury resulted in the recovery of depleted synapses within a few days, successfully ameliorating their respective conditions, such as gait disturbance, memory and learning deficits, and motor dysfunction. Further improvements in the design and administration methods of this artificial synaptic connector are expected to enable the connection of diverse neural circuits, contributing to basic neuroscience research and the treatment of psychiatric and neurological disorders.
(Kunimichi Suzuki and Michisuke Yuzaki, Department of Physiology, equivalent to the class of 1964)
2: Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes
N Engl J Med
2020; 383:721-732.DOI: 10.1056/NEJMoa2003697
Mihoko Yoshino, Brandon D. Kayser, Jun Yoshino, Richard I. Stein, Dominic Reeds, J. Christopher Eagon, Shaina R. Eckhouse, Jeramie D. Watrous, Mohit Jain, Rob Knight, Kenneth Schechtman, Bruce W. Patterson, and Samuel Klein
At the Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, where I am currently based, we are conducting pioneering clinical metabolic research centered around Professor Samuel Klein, who also serves as a Guest Professor at the Juku School of Medicine. This study was conducted to address a critical question in the field of diabetes research: "Does gastric bypass surgery have therapeutic effects on diabetes that exceed the effects of weight loss alone?" Specifically, patients with type 2 diabetes and obesity underwent either gastric bypass surgery or dietary therapy. Before and after an approximate 18% weight loss in both groups, we performed measurements of diabetes control factors in an inpatient setting. These included analysis of 24-hour postprandial glucose metabolism and homeostasis using non-radioactive isotopes, organ-specific insulin sensitivity using a three-step euglycemic clamp with controlled portal-systemic insulin concentrations, and pancreatic β-cell function. The results showed that weight loss led to a significant reduction in diabetes medication in both groups and increased insulin secretion and sensitivity. In terms of 24-hour postprandial glucose metabolism, despite differences in temporal changes between the groups due to rapid fluctuations in blood glucose and insulin levels associated with gastric bypass, both the gastric bypass and diet groups showed a marked and equivalent improvement in glucose homeostasis. From these findings, it can be said that a definitive answer has been provided to the aforementioned question. Finally, I would like to take this opportunity to express my sincere gratitude to Professor Hiroshi Ito (Department of Internal Medicine) for his guidance and support from my student days to the present.
(Mihoko Yoshino, Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, equivalent to the class of 1979)
Other Published Papers
1: Correlations between tear fluid and aqueous humor cytokine levels in bullous keratopathy.
Ocul Surf.
2020 Jul 28;S1542-0124(20)30107-5. doi: 10.1016/j.jtos.2020.06.010
Daisuke Tomida, Yukari Yagi-Yaguchi, Kazunari Higa, Yoshiyuki Satake, Jun Shimazaki, Takefumi Yamaguchi