Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells

AbstractConnexin (Cx) makes up a type of intercellular channel called gap junction (GJ). GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43) (the most ubiquitous Cx subtype) expression on sunitinib (SU)-induced cytotoxicity in malignant mesothelioma (MM) cells. Increased Cx43 expression in an MM cell line (H28) improved the ability of SU to inhibit receptor tyrosine kinase (RTK) signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active) form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells

Functional disability trajectories at the end of life among Japanese older adults: findings from the Japan Gerontological Evaluation Study (JAGES)

BACKGROUND: this study aimed to identify distinct subgroups of trajectories of disability over time before 3 years of death and examine the factors associated with trajectory group membership probabilities among community-dwelling Japanese older adults aged 65 years and above. METHODS: participants included 4, 875 decedents from among community-dwelling Japanese older adults, aged ≥ 65 years at baseline (men: 3, 020; women: 1, 855). The certified long-term care levels of the national long-term care insurance (LTCI) system were used as an index of functional disability. We combined data from the 2010 Japan Gerontological Evaluation Study and data from the 2010 to 2016 LTCI system. Group-based mixture models and multinominal logistic regression models were used for data analysis. RESULTS: five distinct trajectories of functional disability in the last 3 years of life were identified: 'persistently severe disability' (10.3%), 'persistently mild disability' (13.0%), 'accelerated disability' (12.6%), 'catastrophic disability' (18.8%) and 'minimum disability' (45.2%). Multinominal logistic regression analysis found several factors associated with trajectory membership; self-rated health was a common predictor regardless of age and gender. The analysis also showed a paradoxical association; higher education was associated with trajectory group membership probabilities of more severe functional decline in men over 85 years at death. CONCLUSIONS: individual perception of health was a strong predictor of trajectories, independent of demographic factors and socio-economic status. Our findings contribute to the development of policies for the long-term care system, particularly for end-of-life care, in Asian countries

外来シダ植物と在来オシダ属（オシダ科）との推定新雑種カツモウシラネワラビ

A putative natural hybrid between Dryopteris intermedia and D. uniformis found in Agematsu-ma-chi, Nagano Prefecture, Central Japan, is reported. It exhibits intermediate features between the two putative parent species in lamina morphology, while it is similar to D.uniformis in color and density of scales. On the other hand, it is distinguished from D. intermedia by shallowly-tripinnatifid laminae with ovate-elliptic shape and dark brown scales densely born on the petiole and rachis. It differs from D. uniformis characterized by oblong-elliptic bipinnate laminae with thick-herbaceous nature. Spores are aberrantly formed. This finding represents an example that an alien fern hybridized with an indig-enous fern in a natural habitat

Fundamental Parameters of the Milky Way Galaxy Based on VLBI astrometry

We present analyses to determine the fundamental parameters of the Galaxy based on VLBI astrometry of 52 Galactic maser sources obtained with VERA, VLBA and EVN. We model the Galaxy's structure with a set of parameters including the Galaxy center distance R_0, the angular rotation velocity at the LSR Omega_0, mean peculiar motion of the sources with respect to Galactic rotation (U_src, V_src, W_src), rotation-curve shape index, and the V component of the Solar peculiar motions V_sun. Based on a Markov chain Monte Carlo method, we find that the Galaxy center distance is constrained at a 5% level to be R_0 = 8.05 +/- 0.45 kpc, where the error bar includes both statistical and systematic errors. We also find that the two components of the source peculiar motion U_src and W_src are fairly small compared to the Galactic rotation velocity, being U_src = 1.0 +/- 1.5 km/s and W_src = -1.4 +/- 1.2 km/s. Also, the rotation curve shape is found to be basically flat between Galacto-centric radii of 4 and 13 kpc. On the other hand, we find a linear relation between V_src and V_sun as V_src = V_sun -19 (+/- 2) km/s, suggesting that the value of V_src is fully dependent on the adopted value of V_sun. Regarding the rotation speed in the vicinity of the Sun, we also find a strong correlation between Omega_0 and V_sun. We find that the angular velocity of the Sun, Omega_sun, which is defined as Omega_sun = Omega_0 + V_sun/R_0, can be well constrained with the best estimate of Omega_sun = 31.09 +/- 0.78 km/s/kpc. This corresponds to Theta_0 = 238 +/- 14 km/s if one adopts the above value of R_0 and recent determination of V_sun ~ 12 km/s.Comment: 14 pages, 6 figures, PASJ in pres

Astrometric VLBI observations of H2_2O masers in an extreme OH/IR star candidate NSV17351

Results of astrometric very long baseline interferometry (VLBI) observations towards an extreme OH/IR star candidate NSV17351 are presented. We used the VERA (VLBI Exploration of Radio Astrometry) VLBI array to observe 22\,GHz H$_2$O masers of NSV17351. We derived an annual parallax of 0.247$\pm$0.035 mas which corresponds to a distance of 4.05$\pm$0.59 kpc. By averaging the proper motions of 15 maser spots, we obtained the systemic proper motion of NSV17351 to be ($\mu_{\alpha}\cos{\delta}, \mu_{\delta}$)$^{\mathrm{avg}}$ $=$ ($-$1.19 $\pm$ 0.11, 1.30 $\pm$ 0.19) mas\,yr$^{-1}$. The maser spots spread out over a region of 20 mas $\times$ 30 mas, which can be converted to a spatial distribution of $\sim$80 au $\times$ $\sim$120 au at the source distance. Internal motions of the maser spots suggest an outward moving maser region with respect to the estimated position of the central star. From single dish monitoring of the H$_2$O maser emission, we estimate the pulsation period of NSV17351 to be 1122$\pm$24 days. This is the first report of the periodic activity of NSV17351, indicating that NSV17351 could have a mass of $\sim$4\,M$_{\odot}$. We confirmed that the time variation of H$_2$O masers can be used as a period estimator of variable OH/IR stars. Furthermore, by inspecting dozens of double-peaked H$_2$O maser spectra from the last 40 years, we detected a long-term acceleration in the radial velocity of the circumstellar matter to be $0.17\pm0.03$ km\,s$^{-1}$\,yr$^{-1}$ Finally, we determined the position and kinematics of NSV17351 in the Milky Way Galaxy and found that NSV17351 is located in an interarm region between the Outer and Perseus arms. We note that astrometric VLBI observations towards extreme OH/IR stars are useful samples for studies of the Galactic dynamics.Comment: Published in the Publications of the Astronomical Society of Japa