Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues

[structure: see text] Apoptolidin (1) exhibits potent and highly selective apoptosis inducing activity against sensitive cancer cell lines and is hypothesized to act by inhibition of mitochondrial F(0)F(1)-ATP synthase. A series of apoptolidin derivatives, including a new intermolecular Diels-Alder adduct, were analyzed for antiproliferative activity in E1A-transformed rat fibroblasts. Potent F(0)F(1)-ATPase inhibition was not a sufficient determinant of antiproliferative activity for several analogues, suggesting the existence of a secondary biological target or more complex mode of action for apoptolidin.     

Bending modulus of lipid bilayers in a liquid-crystalline phase including an anomalous swelling regime estimated by neutron spin echo experiments

Membrane fluctuations of dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) were investigated by neutron spin echo spectroscopy. The intermediate structure factor was analyzed in terms of the model proposed by Zilman and Granek (Phys. Rev. Lett. 77, 4788 (1996)), and the bending modulus of lipid bilayers was derived. The hardening of a lipid bilayer upon approaching the main transition point in the anomalous swelling regime was observed, which naturally connects the bending modulus in the gel phase below the main transition temperature.     

Measurement of 24-hr whole-body retention of 99mTc-MDP with a thyroid uptake probe (author's transl)

A new method for measurement of 24-hr whole-body retention (WBR) of 99mTc-MDP, using a thyroid uptake probe was established and its clinical significance was evaluated in various bone diseases. (1) Reproducibility of 24-hr WBR in 9 patients was very good. Correlation coefficient was 0.997 and coefficient of variability was only 1.83%. (2) Radiochemical purity of 99mTc-MDP was 97.8 +/- 0.7% (n = 5), indicating no significant inter-lot variations. (3) 24-hr WBR of normal adult males (n = 5) was 30.0 +/- 4.9%, which was significantly elevated compared to the reported 99mTc-HEDP WBR of 19.2 +/- 1.7%. Whole-body retentions of chronic renal failure, metastatic bone disease and hyperthyroidism groups were significantly elevated compared to that of the normal group. However, WBR of steroid-induced osteoporotic group was significantly decreased. Based on these results, this thyroid uptake probe method was simple, reproducible and accurate to measure 24-hr WBR of 99mTc-MDP. Quantification of WBR of 99mTc-MDP was of great clinical value to diagnose metabolic bone disease and to follow-up metabolic and metastatic bone diseases.     

Classification of polarized manifolds admitting homogeneous varieties as ample divisors

We give a complete classification of smooth polarized varieties (X, L) such that the linear system |L| has a homogeneous member A.     

Simultaneous analysis of benzophenone sunscreen compounds in water sample by stir bar sorptive extraction with in situ derivatization and thermal desorption-gas chromatography-mass spectrometry

A method for the simultaneous measurement of benzophenone (BP) sunscreen compounds, its derivatives 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3), 2-hydroxy-4-methoxy-4'-methylbenzophenone (BP-10), 2-hydroxybenzophenone (2OH-BP), 3-hydroxybenzophenone (3OH-BP) and 4-hydroxybenzophenone (4OH-BP), in water samples was developed using stir bar sorptive extraction (SBSE) with in situ derivatization followed by thermal desorption (TD)-gas chromatography-mass spectrometry (GC-MS). The detection limit is 0.5-2 ng L(-1) (ppt) for the seven BPs. The method shows good linearity and the correlation coefficients are equal to or higher than 0.990 for all the analyte. The average recoveries of BPs range from 102.0 to 128.1% (RSD<15.4%, n=6). Trace amounts of BPs in river water samples were determined by the present method.     

How does the mobility of phospholipid molecules at a water/oil interface reflect the viscosity of the surrounding oil?

The mobility of phospholipid molecules at a water/oil interface on cell-sized phospholipid-coated microdroplets was investigated through the measurement of diffusion constants by fluorescence recovery after photobleaching. It is found that the diffusion constant of phospholipids showed the relation D approximately (eta water + eta oil) -0.85, where D is the diffusion constant, eta water is the viscosity of water, and eta oil is the viscosity of oil. This observation indicates that the viscosity of the surrounding oil is the primary factor that determines the diffusibility of phospholipids at a water/oil interface.     

Detector area expansion at iNSE neutron spin echo spectrometer

Expansion of a detection area is an effective method to increase the measurement efficiency of a neutron spin echo (NSE) spectrometer as well as other spectrometers. For this purpose, we installed a new π/2 spin flipper and Fresnel coil of iNSE spectrometer at JRR-3, Tokai, Japan, for wide-area data acquisition. In this study, we propose a data reduction method to correct the phase inhomogeneity due to the path difference of neutrons on the large detection area. This method can convert many NSE signals at small areas to one NSE signal at a large area with taking the phase offset due to the phase inhomogeneity into account. The measurement efficiency increased by approximately one order of magnitude as a result of the detection area expansion.     

Increased expression and phosphorylation of liver glutamine synthetase in well-differentiated hepatocellular carcinoma tissues from patients infected with hepatitis C virus

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers, and chronic infection with hepatitis C virus (HCV) is thought to be one of the main causes in Japan. To identify diagnostic or therapeutic biomarkers for HCC associated with HCV (HCV-HCC), we tried to elucidate the factors related to the products from cancerous tissues of HCV-infected patients. From proteomic differential display analysis of liver tissue samples from HCV-HCC cancerous tissues and corresponding non-cancerous tissues from patients, three protein spots of the same molecular mass (42 kDa), whose expression increased in well-differentiated cancerous tissues, were detected. Although their pI were different, they were identified as glutamine synthetase (GS) by PMF with MALDI-TOF MS and by Western blotting using anti-GS specific mAb. Immunohistochemical analysis showed that tumor tissue consists of two parts, GS-positive cell and GS-negative cell regions, suggesting that GS-producing cells grew in the tumor tissue as a nodule in nodules. The tryptic peptides of the most acidic GS isoform lost the signal of 899.5 Da, corresponding a peptide of SASIRIPR, and gained a signal of 1059.5 Da, which was submitted to PSD analysis. PSD analysis showed the neutral loss by elimination of two phosphate groups, supposed to be on serine residues of the 899.5-Da peptide, from serine 320 to arginine 327 in GS. PMF followed by PSD analysis is thought to be useful for the determination of phosphorylation sites of proteins showing molecular heterogeneity.     

Two distinct pathways for essential metabolic precursors for isoprenoid biosynthesis

Isoprenoids are a diverse group of molecules found in all organisms, where they perform such important biological functions as hormone signaling (e.g., steroids) in mammals, antioxidation (e.g., carotenoids) in plants, electron transport (e.g., ubiquinone), and cell wall biosynthesis intermediates in bacteria. All isoprenoids are synthesized by the consecutive condensation of the five-carbon monomer isopentenyl diphosphate (IPP) to its isomer, dimethylallyl diphosphate (DMAPP). The biosynthetic pathway for the formation of IPP from acetyl-CoA (i.e., the mevalonate pathway) had been established mainly in mice and the budding yeast Saccharomyces cerevisiae. Curiously, most prokaryotic microorganisms lack homologs of the genes in the mevalonate pathway, even though IPP and DMAPP are essential for isoprenoid biosynthesis in bacteria. This observation provided an impetus to search for an alternative pathway to synthesize IPP and DMAPP, ultimately leading to the discovery of the mevalonate-independent 2-C-methyl-D-erythritol 4-phosphate pathway. This review article focuses on our significant contributions to a comprehensive understanding of the biosynthesis of IPP and DMAPP.     

Upgrade of the nuclear resonant scattering beamline, BL09XU in SPring-8

An Upgrade of the nuclear resonant scattering beamline, BL09XU in SPring-8 has been conducted. A liquid nitrogen cooled high-heat load monochromator was installed and a 2nd experimental hutch was constructed. The instruments installed in the hutch allow for a variety of sample conditions. Newly developed high-resolution monochromators with better stability including the back scattering geometry monochromator have opened up the easy access to more isotopes and more precise measurements.