Discovery of a lectin domain that regulates enzyme activity in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A)

N-Glycosylation is a common post-translational modification, and the number of GlcNAc branches in N-glycans impacts glycoprotein functions. N-Acetylglucosaminyltransferase-IVa (GnT-IVa, also designated as MGAT4A) forms a β1-4 GlcNAc branch on the α1-3 mannose arm in N-glycans. Downregulation or loss of GnT-IVa causes diabetic phenotypes by dysregulating glucose transporter-2 in pancreatic β-cells. Despite the physiological importance of GnT-IVa, its structure and catalytic mechanism are poorly understood. Here, we identify the lectin domain in mouse GnT-IVa’s C-terminal region. The crystal structure of the lectin domain shows structural similarity to a bacterial GlcNAc-binding lectin. Comprehensive glycan binding assay using 157 glycans and solution NMR reveal that the GnT-IVa lectin domain selectively interacts with the product N-glycans having a β1-4 GlcNAc branch. Point mutation of the residue critical to sugar recognition impairs the enzymatic activity, suggesting that the lectin domain is a regulatory subunit for efficient catalytic reaction. Our findings provide insights into how branching structures of N-glycans are biosynthesized

Ambulatory Surgery for Pilonidal Sinus : Tract Excision and Open Treatment Followed by At-Home Irrigation

Pilonidal sinus is a cystic disease that occurs most often in the sacrococcygeal region. Surgical excision and coverage with a skin flap require postoperative bed rest. Most affected patients are young adults who find it difficult to obtain adequate postoperative bed rest owing to their work. The purpose of this study is to review the effectiveness of our ambulatory surgery procedure for pilonidal sinus, which involves tract excision and open treatment followed by at-home irrigation. We reviewed the 9 cases of chronic pilonidal sinus treated at our out-patient clinic by ambulatory surgery consisting of open excision without skin closure. Patients were sent home after careful observation for hemostasis at the surgical site. Postoperative wound treatment and irrigation were performed at home by the patients themselves. The mean immediate postoperative follow-up period was 22.3 days (13 to 31 days), and the mean number of follow-up visits was 3.3. No serious complication and recurrence was noted during the long-term follow-up period of 26.3 months (1 to 60 months). Although the healing time following our ambulatory procedure was not short, no postoperative rest was required, and the recurrence rate was zero. We believe this procedure is useful for selected patients with pilonidal sinus

Risk factors for sternal wound infection

Background Although the utility of flaps for the treatment of sternal wound infections following median sternotomy has been reported for 30 years, there have been few reports on the risk factors for complications after reconstruction. The objective of this investigation was to identify factors related to complications after the reconstruction of sternal wound infections. Methods A retrospective analysis of 74 patients with reconstructive surgery after sternal wound infection over a 5-year period was performed. Clinical data including age, sex, body mass index (BMI), comorbidities, bacterial culture, previous cardiac surgery, wound depth, mortality rate, type of reconstructive procedure, and complication rate were collected. Results The patients' BMI ranged from 15.2 to 33.6 kg/m2 (mean, 23.1±3.74 kg/m2). Wound closure complications after reconstructive surgery were observed in 36.5% of the cases. The mortality rate was 2.7%. Diabetes mellitus significantly affected the rate of wound closure complications (P=0.041). A significant difference in the number of complications was seen between Staphylococcus aureus (S. aureus) and coagulase-negative Staphylococci (P=0.011). There was a correlation between harvesting of the internal thoracic artery and postoperative complications (P=0.048). The complication rates of the pectoralis major flap, rectus abdominis flap, omentum flap, a combination of pectoralis major flap and rectus abdominis flap, and direct closure were 23.3%, 33.3%, 100%, 37.5%, and 35.7%, respectively. Conclusions Diabetes mellitus, S. aureus, harvesting of the internal thoracic artery, and omentum flap were significant factors for complications after reconstruction. The omentum flap volume may be related to the complications associated with the omentum flap transfer in the present study

Proximal nail fold flap for digital mucous cyst excision

The skin covering a digital mucous cyst is often very thin and is often excised with the cyst. Thus, transfer of a skin flap is needed for the defect. We have developed a proximal nail fold flap technique by which the thin skin covering the cyst can be preserved. We conducted a retrospective study to assess the effectiveness and reliability of this technique for digital mucous cyst excision. The study group comprised 26 patients treated for 28 digital mucous cysts. The flap was elevated on the nail matrix to expose the distal interphalangeal joint capsule. To preserve the skin in cases in which the skin covering the cyst was exceptionally thin, we did not excise the upper part of the cyst wall. Excision of the cyst and stalk was successful in all cases. Additional excision of the joint capsule or osteophyte(s) was achieved in 20 cases and 5 cases, respectively. No flap necrosis, skin defect or nail deformity resulted. Three of the cysts recurred and were treated successfully by reoperation involving the same flap elevation technique. We conclude that the proximal nail fold flap is useful for excision and reliable for wound coverage after digital mucous cyst excision

Fundamental physics activities with pulsed neutron at J-PARC(BL05)

"Neutron Optics and Physics (NOP/ BL05)" at MLF in J-PARC is a beamline for studies of fundamental physics. The beamline is divided into three branches so that different experiments can be performed in parallel. These beam branches are being used to develop a variety of new projects. We are developing an experimental project to measure the neutron lifetime with total uncertainty of 1 s (0.1%). The neutron lifetime is an important parameter in elementary particle and astrophysics. Thus far, the neutron lifetime has been measured by several groups; however, different values are obtained from different measurement methods. This experiment is using a method with different sources of systematic uncertainty than measurements conducted to date. We are also developing a source of pulsed ultra-cold neutrons (UCNs) produced from a Doppler shifter are available at the unpolarized beam branch. We are developing a time focusing device for UCNs, a so called "rebuncher", which can increase UCN density from a pulsed UCN source. At the low divergence beam branch, an experiment to search an unknown intermediate force with nanometer range is performed by measuring the angular dependence of neutron scattering by noble gases. Finally the beamline is also used for the research and development of optical elements and detectors. For example, a position sensitive neutron detector that uses emulsion to achieve sub-micrometer resolution is currently under development. We have succeeded in detecting cold and ultra-cold neutrons using the emulsion detector.Comment: 9 pages, 5 figures, Proceedings of International Conference on Neutron Optics (NOP2017

Beam and SKS spectrometers at the K1.8 beam line

High-resolution spectrometers for both incident beams and scattered particles have been constructed at the K1.8 beam line of the Hadron Experimental Facility at J-PARC. A point-to-point optics is realized between the entrance and exit of QQDQQ magnets for the beam spectrometer. Fine-pitch wire chamber trackers and hodoscope counters are installed in the beam spectrometer to accept a high rate beam up to 107 Hz. The superconducting kaon spectrometer for scattered particles was transferred from KEK with modifications to the cryogenic system and detectors. A missing-mass resolution of 1.9 ± 0.1 MeV/c2 (FWHM) was achieved for the ∑ peaks of (π±, K+) reactions on a proton target in the first physics run of E19 in 2010

Development of Ribityllumazine Analogs as Mucosal-associated Invariant T Cell Activators

Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells abundant in human tissues that play a significant role in defense against bacterial and viral infections and in tissue repair. MAIT cells are activated by recognizing microbial-derived small-molecule ligands presented by the MHC class I related-1 protein. Although several MAIT cell modulators have been identified in the last decade, potent and chemically stable ligands remain limited. Herein, we carried out a structure-activity relationship study of ribityllumazine derivatives and found chemically stable MAIT cell activators with a pteridine core and a 2-oxopropyl group as the Lys-reactive group. The activators showed high potency toward a co-cultivation assay using model cell lines of antigen-presenting cells and MAIT cells (EC50 = 20 nM). The X-ray crystallographic analysis revealed the binding mode of the activator to MR1 and T cell receptor, indicating that it forms a covalent bond with MR1 via Shiff base formation. Furthermore, we found that one activator stimulated proliferation of human MAIT cells in human peripheral blood mononuclear cells and showed an adjuvant effect in mice. Our developed activator is one of the most potent among chemically stable MAIT cell activators, contributing to accelerating therapeutic applications of MAIT cells