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Overeating and inactivity are associated with type 2 diabetes. This study aimed to investigate its pathological basis using integrated omics and db/db/mice, a model representing this condition. The study involved housing 8‐week‐old db/mand db/dbmice for 8 weeks. Various analyses were conducted, including gene expression in skeletal muscle and small intestine using next‐generation sequencing; cytokine arrays of serum; assessment of metabolites in skeletal muscle, stool, and serum; and analysis of the gut microbiota. Histone modifications in small intestinal epithelial cells were profiled using CUT&Tag. Compared with db/mmice, db/dbmice had 22.4% lower grip strength and approximately five times the visceral fat weight (P< 0.0001). Serum cytokine arrays showed a 2.8‐fold relative concentration of VEGF‐A in db/dbmice (P< 0.0001) and lower concentrations of several other cytokines. mRNA sequencing revealed downregulation of Myhexpression in skeletal muscle, upregulation of lipid and glucose transporters, and downregulation of amino acid transporters in the small intestine of db/db/mice. The concentrations of saturated fatty acids in skeletal muscle were significantly higher, and the levels of essential amino acids were lower in db/dbmice. Analysis of the gut microbiota, 16S rRNA sequencing, revealed lower levels of the phylum Bacteroidetes (59.7% vs. 44.9%) and higher levels of the phylum Firmicutes (20.9% vs. 31.4%) in db/dbmice (P= 0.003). The integrated signal of histone modifications of lipid and glucose transporters was higher, while the integrated signal of histone modifications of amino acid transporters was lower in the db/dbmice. The multi‐omics approach provided insights into the epigenomic alterations in the small intestine, suggesting their involvement in the pathogenesis of inactivity‐induced muscle atrophy in obese mice.

In this study, we aimed to identify the cerebellum-related electromyographic (EMG) response that appeared in the upper limbs musculature. Thirty times averaged transcranial magnetic stimulation (TMS) with a double-cone coil placed over the cerebellar hemisphere elicited long latency EMG responses at the bilateral extensor carpi radialis (ECR) muscles. The peak latency of this EMG response was 70.7±12.7 ms in the ipsilateral ECR and 62.9±10.2 ms in the contralateral ECR of the TMS side. These latencies were much longer than the latency of the muscle evoked potential when we stimulated pyramidal tracts at the foramen magnum level. Cerebellar hemisphere loading by the finger target pursuit test made this EMG response faster during TMS on the ipsilateral side of the cerebellum and slower during TMS on the contralateral side of the cerebellum. Furthermore, the deeper the level of drowsiness, the slower the peak latency of this EMG response became. These results suggest that this EMG potential is a specific response of the cerebellum and brainstem reticular formation, and may be conducted from the cerebellar structure to the ECR muscle through the polysynaptic transmission of the reticulospinal tract.

We have studied the “S-acyl isopeptide method” for the synthesis of peptides containing difficult sequences. The S-acyl isopeptide, which contains a ß-thioester instead of the native N-acyl bond at a Cys residue, can be converted into the target peptide via an S-to-Nintramolecular acyl migration reaction. However, the synthesis of the S-acyl isopeptide structure by Fmoc-based SPPS is hampered by repetitive base treatments; decomposition of the thioester and the epimerization of the thioesterified residue are commonly observed. Here, we adopted allyloxycarbonyl (Aloc) protective group to avoid the problem. Catalytic amount of Pd in the presence of scavengers such as PhSiH3and dimedone selectively removed the Aloc group with neither decomposition of the thioester structure nor epimerization at the thioesterified residue. A model pentapeptide and amylin(1-12) with difficult sequences were efficiently synthesized by the improved S-acyl isopeptides method. Finally, the isolated S-acyl isopeptides were quantitatively converted into the desired peptides via the S-to-Nintramolecular acyl migration reaction. The S-acyl isopeptide method will be a useful method to prepare the difficult sequence-containing peptides with Cys residue. © 2010 Wiley Periodicals, Inc.Biopolymers (Pept Sci) 96: 228–239, 2011.

Intramolecular interaction energies are calculated for nylon 66 and nylon 6 with the amide planes fixed, rotating all skeletal bonds of hexamethylene moiety of nylon 66 and those of pentamethylene moiety of nylon 6. Five stable conformations with an inversion center are found to exist for nylon 66, while only the all-trans conformation is shown to be stable for nylon 6. This is consistent with the fact that the phase transition is observed only in nylon 66 crystal.