Optineurin provides a mitophagy contact site for TBK1 activation.

Tank-binding kinase 1 (TBK1) is a Ser/Thr kinase that is involved in many intracellular processes, such as innate immunity, cell cycle, and apoptosis. TBK1 is also important for phosphorylating the autophagy adaptors that mediate the selective autophagic removal of damaged mitochondria. However, the mechanism by which PINK1-Parkin-mediated mitophagy activates TBK1 remains largely unknown. Here, we show that the autophagy adaptor optineurin (OPTN) provides a unique platform for TBK1 activation. Both the OPTN-ubiquitin and the OPTN-pre-autophagosomal structure (PAS) interaction axes facilitate assembly of the OPTN-TBK1 complex at a contact sites between damaged mitochondria and the autophagosome formation sites. At this assembly point, a positive feedback loop for TBK1 activation is initiated that accelerates hetero-autophosphorylation of the protein. Expression of monobodies engineered here to bind OPTN impaired OPTN accumulation at contact sites, as well as the subsequent activation of TBK1, thereby inhibiting mitochondrial degradation. Taken together, these data show that a positive and reciprocal relationship between OPTN and TBK1 initiates autophagosome biogenesis on damaged mitochondria.

Epidemiological patterns of traumatic musculoskeletal injuries and non-traumatic disorders in Japan Self-Defense Forces.

BACKGROUND: The epidemiological patterns of musculoskeletal injuries or disorders in military personnel have not been well documented and a better understanding is required for proper preventative measures and treatment. Here, we investigated musculoskeletal injuries or disorders among members of the Japan Self-Defense Forces. METHODS: All orthopedic patients (n = 22,340) who consulted to Japan Self-Defense Forces Hospitals were investigated for their type of injury or disorder, the injured body part, the mechanism, and the cause of injuries. RESULTS: Thirty-nine percent of the cases were classified as traumatic injuries, and 61% were classified as non-traumatic disorders. Of the traumatic injury patients, the injured body part was the upper extremity in 32%, the trunk in 23%, and the lower extremities in 45% of the cases. The most common injured body location was the knee followed by the hand/finger and ankle. Exercise was the most common cause of injury, followed by traffic accident and military training. Contusions were the most common traumatic injuries, followed by sprains and fractures. Of non-traumatic disorders, the lower extremities were reported as the injured part in 43% of the disorders. Lumbar spine disorders were the most common non-traumatic disorders, followed by tendon and joint disorders. CONCLUSIONS: Over one-third of orthopedic cases among members of the Japan Self-Defense Forces are traumatic injuries, with the knee being the body part most commonly injured and exercise being the leading cause of injury.

Magnetoresistance effect in rubrene-based spin valves at room temperature.

We fabricate spin-valve devices with an Fe3O4/AlO/rubrene/Co stacking structure. Their magnetoresistance (MR) effects at room temperature and low temperatures are systemically investigated based on the measurement of MR curves, current-voltage response, etc. A large MR ratio of approximately 6% is achieved at room temperature, which is one of the highest MR ratios reported to date in organic spin valves. With decreasing measurement temperatures, we observe that the MR ratios increase because of decrease in spin scattering, and the width of the MR curves becomes larger owing to increase in the coercivity of the electrodes at low temperature. A nonlinear current-voltage dependence is clearly observed in these organic spin valves. From the measurement of MR curve for the spin valves with different rubrene layer thickness, we observe that the MR ratios monotonously decrease with increasing rubrene-layer thickness. We discuss the spin-dependent transport mechanisms in these devices based on our experimental results and the present theoretical analysis. Moreover, we note that the devices exhibit smaller MR ratios after annealing compared to their counterparts without annealing. On the basis of atomic force microscopy analysis of the organic films and device resistances, we deduce that the increase of interface spin scattering induced by large surface roughness after annealing most probably leads to reduction in the MR ratios.

Engineered Heusler Ferrimagnets with a Large Perpendicular Magnetic Anisotropy.

Synthetic perpendicular magnetic anisotropy (PMA) ferrimagnets consisting of 30-nm-thick D022-MnGa and Co2MnSi (CMS) cubic Heusler alloys with different thicknesses of 1, 3, 5, 10 and 20 nm, buffered and capped with a Cr film, are successfully grown epitaxially on MgO substrate. Two series samples with and without post annealing at 400 °C are fabricated. The (002) peak of the cubic L21 structure of CMS films on the MnGa layer is observed, even for the 3-nm-thick CMS film for both un-annealed and annealed samples. The smaller remnant magnetization and larger switching field values of CMS (1-20 nm)/MnGa (30 nm) bilayers compared with 30-nm-thick MnGa indicates antiferromagnetic (AFM) interfacial exchange coupling (Jex) between MnGa and CMS films for both un-annealed and annealed samples. The critical thickness of the CMS film for observing PMA with AFM coupling in the CMS/MnGa bilayer is less than 10 nm, which is relatively large compared to previous studies.

Effects of reloading after simulated microgravity on proteoglycan metabolism in the nucleus pulposus and anulus fibrosus of the lumbar intervertebral disc: an experimental study using a rat tail suspension model.

STUDY DESIGN: An experiment to measure proteoglycan (PG) content and PG-related gene mRNA expressions in the lumbar intervertebral disc (IVD) of rats tail-suspended (TS) for up to 6 weeks with subsequent reloading. OBJECTIVE: To assess the effects of reloading after simulated microgravity on PG metabolism in nucleus pulposus (NP) and anulus fibrosus (AF). SUMMARY OF BACKGROUND DATA: Although the PG content of rat lumbar IVD is reportedly decreased by low compressive force (due to so-called microgravity) during spaceflight, it is unknown whether it recovers completely on reloading and whether these effects differ between NP and AF. METHODS: Eighty-five F344/N rats were divided as follows: caged control (C) or TS for either 3 or 6 weeks, with some TS rats reloaded for 1 or 2 days or 3 weeks after 3 weeks' suspension (TS+RL-1d, -2d, or -3w). The glycosaminoglycan content and mRNA levels for aggrecan, TIMP1, MMP3, and ADAMTS4 were measured in NP and AF. RESULTS: The glycosaminoglycan contents of NP and AF were significantly decreased (by 27%-42%) in the TS groups, whereas in the TS+RL-3w group recovery was complete in NP, but incomplete in AF, without histologic degenerative changes at any time point. In NP, the aggrecan mRNA level was significantly downregulated in TS-3w, but recovered to control level on reloading (TS+RL-3w). In AF, the MMP3 mRNA level was significantly elevated in TS-6w. In the early (1-2 days) response of PG-related gene expressions to reloading, mRNA levels were significantly increased for aggrecan, TIMP1, and ADAMTS4 in NP and for MMP3 in AF, but significantly decreased for ADAMTS4 in AF (vs. the TS-3w group). CONCLUSION: Our results suggest that in IVD maintenance against the present type of mechanical stress, modulation of PG plays an important role and may be associated with molecular changes in PG-related genes.

Anterior cruciate reconstruction with bioactive Leeds-Keio ligament (LKII): preliminary report.

The scaffold type Leeds-Keio artificial ligament (LK) for ligament reconstruction of the knee provides sufficient strength to require minimal sacrifice of autogenous tissue. This implant works not only as prosthesis but also as scaffold onto which natural tissue grows from the synovium. LK has been in clinical use for anterior cruciate ligament (ACL) reconstruction since 1982, although the operative procedure has been modified and has undergone significant development since that time. Recently, we developed radio frequency-generated glow discharge (RFGGD)-treated LK ligament (LKII, previously indicated as Bio-LK) to improve tissue induction and reported that cell proliferation and cell attachment to artificial fibers increased considerably with this hydrophilic treatment. In this study, we report the findings of reconstructed ACL using LKII, which has been in clinical use since 2003. At reconstruction, LKII was covered with the remnant of the original ACL as much as possible in order to preserve the nerve ending system. Thirteen cases with over 12 months' postoperative history were reviewed. Knee stability was regained after reconstruction without any complications such as joint effusion and chronic synovitis. In one case, postoperative arthroscopy showed that the reconstructed ACL was completely covered with newly formed tissue at 8 weeks postoperatively. Biopsy revealed abundant fibroblasts, collagenous fibers, and vessels around the artificial fibers without marked inflammatory findings. Transmission electron microscope study showed abundant thin collagen fibers, which demonstrated regular orientation to some extent. Fibroblasts were observed with extensive amount of rough endoplasmic reticulum. According to these results, we consider LKII to be superior to LK in tissue induction and maturation.

The effect of hyperbaric oxygen therapy on the bout of treatment for soft tissue infections.

OBJECTIVES: Hyperbaric oxygen (HBO) therapy is often combined with antibiotic therapy for infections such as gas gangrene and osteomyelitis. Although numerous investigations have been undertaken to assess the effect of adjunctive HBO therapy on the treatment of infections, the bout of treatment has not been referred in the previous investigations. The purpose of this retrospective study was to evaluate the efficacy of HBO therapy on the bout of treatment for soft tissue infections. PATIENTS AND METHODS: In the period between 1994 and 2001, we treated 23 patients with soft tissue infections. Nine patients were treated with antibiotic chemotherapy alone, and 14 patients were treated with a combination of antibiotic chemotherapy and HBO therapy. The mean bout of treatment was compared between these two groups. RESULTS: The mean bout treated with a combination of antibiotic and HBO was significantly shorter than that with antibiotic alone. CONCLUSION: Our result indicates that HBO therapy combined with antibiotic therapy is able to shorten the bout of treatment for soft tissue infections. Therefore, we recommend HBO therapy combined with antibiotic therapy for soft tissue infections.