cells. Finally, we found that the core fucosylation of N-glycans is required for the binding of the EGF to its receptor, whereas no effect was observed for the expression levels of EGFR on the cell surface. Collectively, these results strongly suggest that core fucosylation is essential for EGF receptor-mediated biological functions.
Mammalian alpha1,6-fucosyltransferase (FUT8) catalyses the transfer of a fucose residue from a donor substrate, guanosine 5'-diphosphate-beta-L-fucose to the reducing terminal N-acetylglucosamine (GlcNAc) of the core structure of an asparagine-linked oligosaccharide. Alpha1,6-fucosylation, also referred to as core fucosylation, plays an essential role in various pathophysiological events. Our group reported that FUT8 null mice showed severe growth retardation and emphysema-like lung-destruction as a result of the dysfunction of epidermal growth factor and transforming growth factor-beta receptors. To elucidate the molecular basis of FUT8 with respect to pathophysiology, the crystal structure of human FUT8 was determined at 2.6 A resolution. The overall structure of FUT8 was found to consist of three domains: an N-terminal coiled-coil domain, a catalytic domain, and a C-terminal SH3 domain. The catalytic region appears to be similar to GT-B glycosyltransferases rather than GT-A. The C-terminal part of the catalytic domain of FUT8 includes a Rossmann fold with three regions that are conserved in alpha1,6-, alpha1,2-, and protein O-fucosyltransferases. The SH3 domain of FUT8 is similar to other SH3 domain-containing proteins, although the significance of this domain remains to be elucidated. The present findings of FUT8 suggest that the conserved residues in the three conserved regions participate in the Rossmann fold and act as the donor binding site, or in catalysis, thus playing key roles in the fucose-transferring reaction.
Background and aims Needle tract seeding after preoperative endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) for pancreatic body and tail cancer has been reported. This study aimed to investigate the long‐term outcomes, including the needle tract seeding ratio, of patients undergoing distal pancreatectomy for pancreatic body and tail cancer diagnosed preoperatively by EUS‐FNA. Methods This retrospective, observational cohort study assessed patients from three university hospitals and 11 tertiary referral centers. All patients who underwent distal pancreatectomy for invasive cancer of the pancreatic body and tail between January 2006 and December 2015 were identified and reviewed. Needle tract seeding rate, recurrence‐free survival (RFS), and overall survival (OS) were evaluated. Results Of the 301 total patients analyzed, 176 underwent preoperative EUS‐FNA (EUS‐FNA group) and 125 did not (non‐EUS‐FNA group). The median follow‐up periods of the EUS‐FNA group and non‐EUS‐FNA group were 32.8 and 30.1 months. Six patients (3.4%) in the EUS‐FNA group were diagnosed as having needle tract seeding. The 5‐year cumulative needle tract seeding rate estimated using Fine and Gray's method was 3.8% (95% CI 1.6–7.8%). The median RFS or OS was not significantly different between the EUS‐FNA group and the non‐EUS‐FNA group (23.7 vs 16.9 months: P = 0.205; 48.0 vs 43.9 months: P = 0.392). Conclusion Although preoperative EUS‐FNA for pancreatic body and tail cancer has no negative effect on RFS or OS, needle tract seeding after EUS‐FNA was observed to have a non‐negligible rate. (UMIN000030719)
FUT8, mammalian alpha1,6-fucosyltransferase, catalyzes the transfer of a fucose residue from the donor substrate, guanosine 5'-diphosphate (GDP)-beta-L-fucose, to the reducing terminal GlcNAc of the core structure of asparagine-linked oligosaccharide via an alpha1,6-linkage. FUT8 is a typical type II membrane protein, which is localized in the Golgi apparatus. We have previously shown that two neighboring arginine residues that are conserved among alpha1,2-, alpha1,6-, and protein O-fucosyltransferases play an important role in donor substrate binding. However, details of the catalytic and reaction mechanisms and the ternary structure of FUT8 are not understood except for the substrate specificity of the acceptor. To develop a better understanding of FUT8, we established a large-scale production system for recombinant human FUT8, in which the enzyme is produced in soluble form by baculovirus-infected insect cells. Kinetic analyses and inhibition studies using derivatives of GDP-beta-L-fucose revealed that FUT8 catalyzes the reaction which depends on a rapid equilibrium random mechanism and strongly recognizes the base portion and diphosphoryl group of GDP-beta-L-fucose. These results may also be applicable to other fucosyltransferases and glycosyltransferases.
The purpose of this study was to introduce dynamic joint control training and to assess its effects in improving neuromuscular coordination of injured knees using the Kin-Com Isokinetic Dynamometer. Although four patients had a sensation of "giving way" on one knee, all eight knees were trained for 3 months using unstable boards with added sudden force given by a therapist. The training group (four patients) was examined during four sessions and the control group (five subjects) was examined during three sessions within a 3 month period. All subjects were instructed to react to the sudden forward movement of the input arm of the Kin-Com Isokinetic Dynamometer with contraction of the hamstring. Results of the first and final trials of peak torque time (PTT) and rising torque value (RTV) of the hamstring between the training and control groups showed significant improvement. There was no correlation between isometric muscle strength (IMS) and PTT in the total 76 sessions. There is a strong implication that simple muscle training does not increase the speed of muscular reaction but dynamic joint control training has the potential to shorten the time lag of muscular reaction.
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