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Kozue Nakahara,1 Koji Yamasaki,1 Takahiro Nagai,1 Masato Fujii,1 Takahiro Akioka,1 Hiroki Takamori,1 Naoki Terada,1 Shoichiro Mukai,1 Yuichiro Sato,2 Toshiyuki Kamoto11Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; 2Section of Diagnostic Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, JapanBackground: Matriptase, which is a Type II transmembrane serine protease, has the potential to activate several growth factors, including pro-hepatocyte growth factor (HGF). A G protein-coupled transmembrane cell-surface receptor and a protease-activated receptor 2 (PAR-2) are also required for activation by matriptase. Activation of PAR-2 has been reported to induce the progression of various cancers. In a previous study, we evaluated the correlation between upregulation of MET phosphorylation with high matriptase expression and worse prognosis in patients with muscle invasive bladder cancer; however, expression of PAR-2, matriptase and MET in non-muscle invasive bladder cancer (NMIBC) has not been evaluated.Materials and methods: We retrospectively analyzed the expression of PAR-2, matriptase and MET using 55 paraffin-embedded specimens obtained from patients with NMIBC by immunohistochemistry.Results: MET was significantly expressed in high-grade urothelial carcinoma (UC) and pathological T1 cancers. High expression of PAR-2 was significantly associated with a worse recurrence rate in NMIBC. In subgroup analysis, the expression of PAR-2 was also correlated with high recurrence rate in low-grade UC. In addition, expression of matriptase tended to correlate with worse recurrence rate in high-grade UC.Conclusion: Increased expression of PAR-2 was significantly correlated with worse recurrence rate in patients with NMIBC. In addition, expression of matriptase also indicated a tendency toward recurrence in high-grade UC, suggesting an important role of matriptase-induced PAR-2 activation in NMIBC.Keywords: PAR-2, matriptase, MET, NMIBC

Toyoharu Kamibeppu, Koji Yamasaki, Kozue Nakahara, Takahiro Nagai, Naoki Terada, Hiromasa Tsukino, Shoichiro Mukai, Toshiyuki Kamoto Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake, Japan Background: Caveolin (Cav)-1 and Cav-2 are cell membrane proteins, which are structural proteins of caveolae and are reported to be positive regulators of cell survival and metastasis in prostate cancer (PC). In a previous study, we reported that elevated levels of Cav-1 and Cav-2 were significantly associated with PC progression. However, their functions in PC have not yet been clarified. In this study, we examined the function of Cav-1 and Cav-2 in PC cell invasiveness and motility.Materials and methods: We introduced Cav-1- and Cav-2-specific small interfering into PC3 cells to knock-down (KD) both molecules. We also performed cell proliferation assay, wound healing assay, migration assay, and invasion assay using PC3 cells and compared the results between Cav-1-KD, Cav-2-KD, and negative control PC3 cells. In addition, we performed real-time quantitative PCR (RT-qPCR) and RT2 Profiler PCR Array analysis to identify factors influencing migration.Results: We observed no significant difference in the proliferative and invasive activities of Cav-1-KD and Cav-2-KD PC3 cells; however, the cell motility was significantly decreased compared with negative control PC3 cells. RT-qPCR revealed that the expression of vimentin and N-cadherin was downregulated in Cav-1-KD PC3 cells. In addition, PCR array revealed a decreased expression of MGAT5, MMP13, and MYCL in Cav-1-KD PC3 and ETV4, FGFR4, and SRC in Cav-2-KD PC3.Conclusion: Cav-1 and Cav-2 may positively contribute to the upregulation of castration-resistant PC cell migration. Cav-induced regulation of several molecules including vimentin, N-cadherin, MGAT5, MMP13, MYCL, ETV4, FGFR4, and SRC may have an important role in PC3 cell motility. However, further examination will be required. Keywords: caveolin-1, caveolin-2, CRPC, cell motility

The photoproduction of K0 and Λ on the deuteron was measured in order to investigate the γn → K0Λ reaction process near the threshold (Eγ = 0.8-1.1 GeV). K0 and Λ events were clearly seen in the π+π− and the pπ− invariant mass spectra, respectively. The momentum spectra of the γd → K0X and the γd → ΛX reactions were derived. Additionally, the energy dependence of the integral cross section for the Λ production was also obtained. The K0 momentum spectra were in agreement with the previous results within statistical errors. The angular distribution of the γn → K0Λ reaction in the center of mass system was extracted and it had the backward distribution. The total cross section of the γn → K0Λ reaction, which was estimated by subtracting the contribution of K+Λ process from the Λ production on the deuteron, was almost the same as that of the γp → K+Λ.

The goal of pharmacogenomics research is to discover genetic polymorphisms that underlie variation in drug response. Increasingly, pharmacogenomics research involves large numbers of patients and the application of new technologies and methodologies to enable discovery. The Pharmacogenomics Research Network (PGRN) has become a community-driven network of investigators spanning scientific and clinical disciplines. Here, we highlight the activities and types of resources that enable PGRN members to enhance and drive basic and translational research in pharmacogenomics.

A report from the International Union of Crystallography Commission on Magnetic Structures outlining the recommendations for communicating commensurate magnetic structures. [ABSTRACT FROM AUTHOR]

Boundaries between space plasmas occur in numerous contexts and scales, from astrophysical jets to planetary magnetospheres. Mass and momentum transport across boundaries poses a fundamental problem in magnetospheric physics. Kelvin-Helmholtz instability (KHI) is a promising mechanism to facilitate transport. Although previous studies have suggested KHI occurrence in various space plasmas, theory predicts that compressibility prevents KHI excitation at boundaries with large density gradients because of previously considered boundary structures where density varies with velocity. Based on the observations of a large density gradient boundary by MAVEN at Mars, where we can observe an extreme case, in this study, we show that it is the entropy, instead of the previously considered density, that varies with the velocity in the real velocity-sheared boundary. The entropy-based boundary structure places the velocity shear in a lower-density region than the traditional density-based structure and weakens the compressibility effect. This new boundary structure thus enables KHI excitation even at large density gradient boundaries, such as at the ionopause of unmagnetized planets and the plasmapause of magnetized planets. The result suggests the ubiquitous occurrence of KHI in the plasma universe and emphasizes its important role in planetary cold plasma escape from unmagnetized planets. [ABSTRACT FROM AUTHOR]

Isotopic ratios in water vapour carry important information about the water reservoir on Mars. Localized variations in these ratios can inform us about the water cycle and surface–atmosphere exchanges. On the other hand, the global isotopic composition of the atmosphere carries the imprints of the long-term fractionation, providing crucial information about the early water reservoir and its evolution throughout history. Here, we report the analysis of measurements of the D/H and 18O/16O isotopic ratios in water vapour in different seasons (L S = 15○, 127○, 272○, and 305○) made with the Echelon-Cross-Echelle Spectrograph (EXES) aboard the Stratospheric Observatory for Infrared Astronomy (SOFIA). These measurements, free of telluric absorption, provide a unique tool for constraining the global isotopic composition of Martian water vapour. We find the maximum planetary D/H ratio in our observations during the northern summer (D/H = 5.2 ± 0.2 with respect to the Vienna Standard Mean Ocean Water, VSMOW) and to exhibit relatively small variations throughout the year (D/H = 5.0 ± 0.2 and 4.3 ± 0.4 VSMOW during the northern winter and spring, respectively), which are to first order consistent though noticeably larger than the expectations from condensation-induced fractionation. Our measurements reveal the annually averaged isotopic composition of water vapour to be consistent with D/H = 5.0 ± 0.2 and 18O/16O = 1.09 ± 0.08 VSMOW. In addition, based on a comparison between the SOFIA/EXES measurements and the predictions from a Global Climate Model, we estimate the D/H in the northern polar ice cap to be |$\sim\!{5}~{{\ \rm per\ cent}}$| larger than that in the atmospheric reservoir (D/Hice = 5.3 ± 0.3 VSMOW). [ABSTRACT FROM AUTHOR]

Ion escape has played a key role in atmospheric loss on ancient Mars due to intense solar activity. Under the existence of a strong global intrinsic magnetic field, as expected on ancient Mars, differential flows between different ion species can be important for ion escape. To assess effects of differential flows, we here developed a new global multifluid magnetohydrodynamics model with a cubed sphere grid named Multifluid Atmospheric Escape Simulations Toward Real elucidatiOn (MAESTRO). A test simulation under present‐day Mars conditions showed solar wind‐Mars interactions, for example, plasma boundaries, ionospheric profiles, and tailward outflows, consistent with observations and simulation studies. We then conducted multifluid and multispecies simulations with six different dipole field strengths under ancient Mars conditions. The multifluid cases show asymmetric outflow distributions with respect to the solar wind convection electric field, as pointed out by previous studies on present‐day Mars. Compared with multispecies cases, the multifluid representation increases the escape rates of O2+ and CO2+ by more than two orders of magnitude in the strong dipole field cases where the cusp outflow is dominant. The O+ escape rate is slightly lower in the multifluid cases with no or weak dipole field due to suppression of ion pickup in the −E hemisphere, while it is reduced by one order of magnitude in the strongest dipole field case. The existence of a dipole field can reduce the total escape rate by a factor of six. The impact on atmospheric evolution is diminished but still significant. Plain Language Summary: Mars lost a significant part of the atmosphere during its early period and experienced a drastic climate change. The escape of charged atmospheric particles to space, called ion escape, is a significant removal process of the atmosphere because the activity of the young Sun was much stronger and stripped out the upper atmosphere of early Mars more powerfully. However, it is thought that Mars once had an intrinsic magnetic field like Earth, which can affect the escape of charged particles via electromagnetic forces. To reproduce the realistic processes and morphology of ion escape under the presence of a planetary intrinsic magnetic field, we developed a new simulation model that treats each ion species as a separate fluid. The simulation results of the new model show much stronger molecular ion outflow from the ionosphere at relatively low altitudes compared to our previous studies. The outflow enhancement is more remarkable when a stronger intrinsic magnetic field is assumed. On the other hand, atomic ion escape from high altitudes is not affected largely. The new model indicates that the effects of a planetary intrinsic magnetic field on ion escape are reduced, though still of significance. Key Points: A new global multifluid magnetohydrodynamics (MHD) model of solar wind‐Mars interactions with a cubed sphere grid system named Multifluid Atmospheric Escape Simulations Toward Real elucidatiOn is developedThe multispecies MHD cases underestimate outflows of ionospheric ions in strong dipole field cases where cusp outflow is importantThe effects of the multifluid representation on the O+ escape rate are small in no and weak dipole field cases where ion pickup is dominant [ABSTRACT FROM AUTHOR]