Regeneration of Bone- and Tendon/Ligament-Like Tissues Induced by Gene Transfer of Bone Morphogenetic Protein-12 in a Rat Bone Defect

Members of the bone morphogenetic protein (BMP) family have diverse physiological roles. For instance, BMP-2 stimulates osteogenesis, while BMP-12 induces the formation of tendon/ligament-like tissues. Here, we designed a study to determine whether BMP-12 has bone and/or cartilage regeneration abilities similar to those of BMP-2. We implanted plasmid vectors encoding either BMP-2 or BMP-12 in rats with femur defects, and monitored the bone healing process for 8-weeks. The BMP-12 transgene induced prominent fibrogenesis by 2 weeks, with bone substitution occurring by 8 weeks. BMP-2, however, was associated predominantly with osteogenesis throughout the 8 week period. Thus, we conclude that BMP-12 does not function similarly to BMP-2 during bone healing. Further work is needed to better understand the mechanisms by which it stimulates bony growths to replace the connective tissues formed during the first stages of bone healing

Kaplan–Meier survival analysis and Cox regression analyses regarding right ventricular septal pacing: Data from Japanese pacemaker cohort

AbstractThe presented data were obtained from 982 consecutive patients receiving their first pacemaker implantation with right ventricular (RV) lead placement between January 2008 and December 2013 at two centers in Japan. Patients were divided into RV apical and septal pacing groups. Data of Kaplan–Meier survival analysis and Cox regression analysis are presented. Refer to the research article “Implications of right ventricular septal pacing for medium-term prognosis: propensity-matched analysis” (Mizukami et al., in press) [1] for further interpretation and discussion

Effect of Reduction in Thickness and Rolling Conditions on Mechanical Properties and Microstructure of Rolled Mg-8Al-1Zn-1Ca Alloy

A cast Mg-8Al-1Zn-1Ca magnesium alloy was multipass hot rolled at different sample and roll temperatures. The effect of the rolling conditions and reduction in thickness on the microstructure and mechanical properties was investigated. The optimal combination of the ultimate tensile strength, 351 MPa, yield strength, 304 MPa, and ductility, 12.2%, was obtained with the 3 mm thick Mg-8Al-1Zn-1Ca rolled sheet, which was produced with a roll temperature of 80°C and sample temperature of 430°C. This rolling process resulted in the formation of a bimodal structure in the α-Mg matrix, which consequently led to good ductility and high strength, exclusively by the hot rolling process. The 3 mm thick rolled sheet exhibited fine (mean grain size of 2.7 μm) and coarse grain regions (mean grain size of 13.6 μm) with area fractions of 29% and 71%, respectively. In summary, the balance between the strength and ductility was enhanced by the grain refinement of the α-Mg matrix and by controlling the frequency and orientation of the grains

Short communication: epidemiological evidence that simian T-lymphotropic virus type 1 in Macaca fuscata has an alternative transmission route to maternal infection.

Serological inspection of Simian T-lymphotropic Virus Type 1 was conducted for a wild colony of Macaca fuscata, which was captured in the middle Honshu, Japan. The increase of positive rate after the juvenile stage with the positive rate reaching 100% (or 35/35) in youngster and adult stages, was observed. This finding suggests that, in contrast with human T-lymphotropic Virus Type 1, horizontal transmission play an important role in increasing prevalence of STLV-1 with age among M. fuscata

Spectral Properties of Prompt Emission of Four Short Gamma-Ray Bursts Observed by the Suzaku-WAM and the Konus-Wind

We have performed a joint analysis of prompt emission from four bright short gamma-ray bursts (GRBs) with the Suzaku-WAM and the Konus-Wind experiments. This joint analysis allows us to investigate the spectral properties of short-duration bursts over a wider energy band with a higher accuracy. We find that these bursts have a high E$_{\rm peak}$, around 1 MeV and have a harder power-law component than that of long GRBs. However, we can not determine whether these spectra follow the cut-off power-law model or the Band model. We also investigated the spectral lag, hardness ratio, inferred isotropic radiation energy and existence of a soft emission hump, in order to classify them into short or long GRBs using several criteria, in addition to the burst duration. We find that all criteria, except for the existence of the soft hump, support the fact that our four GRB samples are correctly classified as belonging to the short class. In addition, our broad-band analysis revealed that there is no evidence of GRBs with a very large hardness ratio, as seen in the BATSE short GRB sample, and that the spectral lag of our four short GRBs is consistent with zero, even in the MeV energy band, unlike long GRBs. Although our short GRB samples are still limited, these results suggest that the spectral hardness of short GRBs might not differ significantly from that of long GRBs, and also that the spectral lag at high energies could be a strong criterion for burst classification.Comment: 23 pages, 6 figures, accepted for Publications of the Astronomical Society of Japa

A Proteomic Approach for Comprehensively Screening Substrates of Protein Kinases Such as Rho-Kinase

BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity

Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement in antigen-specific cancer immunotherapy

Antigen-specific cancer immunotherapy is a promising strategy for improving cancer treatment. Recently, many tumor-associated antigens and their epitopes recognized by cytotoxic T lymphocytes (CTLs) have been identified. However, the density of endogenously presented antigen-derived peptides on tumor cells is generally sparse, resulting in the inability of antigen-specific CTLs to work effectively. We hypothesize that increasing the density of an antigen-derived peptide would enhance antigen-specific cancer immunotherapy. Here, we demonstrated that intratumoral peptide injection leads to additional peptide loading onto major histocompatibility complex class I molecules of tumor cells, enhancing tumor cell recognition by antigen-specific CTLs. In in vitro studies, human leukocyte antigen (HLA)-A*02:01-restricted glypican-3(144-152) (FVGEFFTDV) and cytomegalovirus(495-503) (NLVPMVATV) peptide-specific CTLs showed strong activity against all peptide-pulsed cell lines, regardless of whether the tumor cells expressed the antigen. In in vivo studies using immunodeficient mice, glypican-3(144-152) and cytomegalovirus(495-503) peptides injected into a solid mass were loaded onto HLA class I molecules of tumor cells. In a peptide vaccine model and an adoptive cell transfer model using C57BL/6 mice, intratumoral injection of ovalbumin(257-264) peptide (SIINFEKL) was effective for tumor growth inhibition and survival against ovalbumin-negative tumors without adverse reactions. Moreover, we demonstrated an antigen-spreading effect that occurred after intratumoral peptide injection. Intratumoral peptide injection enhances tumor cell antigenicity and may be a useful option for improvement in antigen-specific cancer immunotherapy against solid tumors