Crystal structure of 1-aminocyclopropane-1-carboxylate deaminase from Hansenula saturnus

This research was originally published in Journal of Biological Chemistry. Min Yao, T. Ose, Hiroshi Sugimoto, Atsushi Horiuchi, Atsushi Nakagawa, Soichi Wakatsuki, Daisuke Yokoii, Toyotaka Murakamii, Mamoru Honmai, and Isao Tanaka. Crystal structure of 1-aminocyclopropane-1-carboxylate deaminase from Hansenula saturnus. J. Biol. Chem. 2000; 275, 34557-34565. © the American Society for Biochemistry and Molecular Biology

Risk factors related to the reduction of subjective taste ability in middle-to old-aged nursing home residents in Sri Lanka : a cross-sectional study

The purpose of this study is to verify the factors significantly related to the reduction of subjective taste ability of 1,015 middle-aged and elderly (50 - 96 years old) at 25 randomized selected nursing homes in Sri Lanka. Binary logistic regression analyses by gender were performed using IBM SPSS on following variables. A dependent variable is taste ability, and 27 independent variables are age, daily lifestyle, nutritional problems, general status, dental status and physiological thresholds of taste abilities (sweet, salt, sour, bitter, and umami). Smell ability (p < 0.001 - 0.05) and the Self-Report Questionnaire, 20-item version :SRQ 20 (p < 0.01 - 0.05) were significant risk factors of reducing taste ability in both genders. Especially, smell ability was closely linked to taste ability. Existence of comprehensive perception of “flavor” composed of taste and smell ability was illustrated. Significant gender differences factors were observed in long term care needs (p < 0.05), sleeping (p < 0.01 - 0.001), bowel condition (p < 0.05) in males; and height (p < 0.05), weight (p < 0.05), BMI 3 categories (p < 0.05), and brushing (p < 0.05) in females. Other variables such as age and five types of physiological taste ability were not significant in both genders. The results of this investigation also strongly indicated that the perception of subjective sense of taste was different from the objective sense of taste. Epidemiological studies such as cohort or intervention studies focusing on a relationship between subjective taste ability and sense of smell are necessary to identify more accurate and changeable risk factors for dysgeusia in order to improve elderly’s nutritional intake in Sri Lanka

Recruitment of distinct immune cell populations to the lung after intratracheal TLR4 signaling activation by two different stimulations

The toll-like receptor 4 (TLR4)-mediated immune response is considered as one of the triggers of acute respiratory distresssyndrome. The agonistic monoclonal antibody UT12 specific for the TLR4/MD2 complex induces immune activation in a mannerdistinct from lipopolysaccharide (LPS). In order to compare the effects of this differential TLR4 signaling activation, we examinedimmune cell recruitment to the lung following intratracheal inoculation with UT12 and LPS in mice. The increase in pulmonaryneutrophils was much higher after LPS treatment compared with UT12 treatment, while CD11bhiCD11＋cells increased to similarlevels following both treatments. These changes were MyD88-dependent and TRIF-independent. These differential effects onimmune cell recruitment to the lung suggest distinct underlying mechanisms in response to TLR4 stimulation. These findingsfurther indicate that TLR signaling can lead to different outcomes depending on the ligand and activation pathway, which mayrelate to the complex pathogenesis of inflammatory lung diseases

Prostate cancer stromal cells and LNCaP cells coordinately activate the androgen receptor through synthesis of testosterone and dihydrotestosterone from dehydroepiandrosterone

金沢大学附属病院泌尿器科金沢大学附属病院泌尿器科One of the mechanisms through which advanced prostate cancer (PCa) usually relapses after androgen deprivation therapy (ADT) is the adaptation to residual androgens in PCa tissue. It has been observed that androgen biosynthesis in PCa tissue plays an important role in this adaptation. In the present study, we investigated how stromal cells affect adrenal androgen dehydroepiandrosterone (DHEA) metabolism in androgen-sensitive PCa LNCaP cells. DHEA alone had little effect on prostate-specific antigen (PSA) promoter activity and the proliferation of LNCaP cells. However, the addition of prostate stromal cells or PCa-derived stromal cells (PCaSC) increased DHEA-induced PSA promoter activity via androgen receptor activation in the LNCaP cells. Moreover, PCaSC stimulated the proliferation of LNCaP cells under physiological concentrations of DHEA. Biosynthesis of testosterone or dihydrotestosterone from DHEA in stromal cells and LNCaP cells was involved in this stimulation of LNCaP cell proliferation. Androgen biosynthesis from DHEA depended upon the activity of various steroidogenic enzymes present in stromal cells. Finally, the dual 5a-reductase inhibitor dutasteride appears to function not only as a 5a-reductase inhibitor but also as a 3b-hydroxysteroid dehydrogenase inhibitor in LNCaP cells. Taken together, this coculture assay system provides new insights of coordinate androgen biosynthesis under the microenvironment of PCa cells before and after ADT, and offers a model system for the identification of important steroidogenic enzymes involved in PCa progression and for the development of the corresponding inhibitors of androgen biosynthesis. © 2009 Society for Endocrinology

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

Prognostic value of plasminogen activator inhibitor-1 in biomarker exploration using multiplex immunoassay in patients with metastatic renal cell carcinoma treated with axitinib

Background and AimsVascular endothelial growth factor-directed therapies play a significant role in patients with metastatic renal cell carcinoma (mRCC). Biomarkers for predicting treatment efficacy and resistance are required to develop personalized medicine. We evaluated multiple serum cytokine levels in patients with mRCC treated with axitinib to explore predictive biomarkers. MethodsFrom September 2012 to October 2015, serum samples were collected from 44 patients with mRCC before treatment and 4weeks after axitinib initiation. Bio-Plex Pro Human Cancer Biomarker Panels 1 and 2 were used to measure levels of 34 serum biomarkers related to angiogenesis and cell proliferation. ResultsPatients with partial response or stable disease had significantly decreased serum plasminogen activator inhibitor-1 (PAI-1) level from pre-treatment to 4weeks after axitinib initiation compared with those with progressive disease (P = .022). The median progression-free survival (PFS) and median overall survival (OS) in patients with increased serum PAI-1 level from pre-treatment to 4weeks after axitinib initiation were significantly shorter than those with decreased serum PAI-1 level (P = .027 and P = .026, respectively). Increased serum PAI-1 level from pre-treatment to 4weeks after axitinib initiation was an independent prognostic marker for shorter PFS and OS in multivariate analyses (P = .015 and P = .032, respectively). The immunohistochemical staining intensity of PAI-1 in tumor specimens was significantly associated with Fuhrman grade and presence of distant metastasis (P = .026 and P = .010, respectively). ConclusionsThe initial change in serum PAI-1 level in the early stage of axitinib treatment could be a useful prognostic biomarker in patients with mRCC