Induction by rapamycin and proliferation‑promoting activity of Hspb1 in a ‑deficient cell line.

Tuberous sclerosis complex (TSC) is an intractable inherited disease caused by a germline mutation in either the TSC complex subunit 1 () or tumor suppressor genes. Recent progress in the treatment of TSC with rapamycin has provided benefits to patients with TSC. However, the complete elimination of tumors is difficult to achieve as regrowth often occurs after a drug is suspended; thus, more efficient medication and novel therapeutic targets are required.

Bcat1 is controlled by Tsc2/mTORC1 pathway at expression levels and its deficiency together with Bcat2 inactivation suppresses the growth of a Tsc2 tumor cell line.

The tuberous sclerosis complex (TSC) gene products (TSC1/TSC2) negatively regulate mTORC1. Although mTORC1 inhibitors are used for the treatment of TSC, incomplete tumor elimination and the adverse effects from long-term administration are problems that need to be solved. Branched-chain amino acid (BCAA) metabolism is involved in the growth of many tumor cells via the mTORC1 pathway.

Two different regimes in alcohol-induced coil-helix transition: effects of 2,2,2-trifluoroethanol on proteins being either independent of or enhanced by solvent structural fluctuations.

Inhomogeneous distribution of constituent molecules in a mixed solvent has been known to give remarkable effects on the solute, e.g., conformational changes of biomolecules in an alcohol-water mixture.

Unique phase behavior of a room-temperature ionic liquid, trimethylpropylammonium bis(fluorosulfonyl)amide: surface melting and its crystallization.

The phase behavior of a representative ammonium-based ionic liquid, trimethylpropylammonium bis(fluorosulfonyl)amide ([N1113][FSA]), was investigated using a laboratory-made differential scanning calorimeter (DSC). The apparatus possesses extremely high sensitivities with stability of ±2 nW in thermal flux and ±1 mK in temperature and a very slow scanning rate of 0.001 mK s-1 in the slowest scanning speed.

Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells.

Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin-3a.

Changes of Dyspeptic Symptom after Successful Eradication in Helicobacter pylori-Associated Dyspepsia.

Background: Helicobacter pylori (H. pylori) gastritis could cause dyspepsia, and eradication is recommended as the first-line treatment. Patients who continuously have their symptoms under control > 6 months after eradication are defined as having H.

[Development of an HPLC-UV Method for Free Asparagine in Grains].

A novel analytical method was developed for the determination of free asparagine (Asn), which is a precursor of acrylamide, in grains. Asn was extracted from a sample with 5% (w/v) aqueous trichloroacetic acid solution, and the crude extract was cleaned up using a reversed-phase solid-phase cartridge. The cleaned extract was derivatized with dansyl chloride and analyzed by HPLC-UV.

Effects of H and OH on HO as probed by the 1-propanol probing methodology: differential thermodynamic approach.

We applied what we call the "1-propanol (1P) probing methodology" on the effects of H and OH on liquid HO. We found that H is an amphiphile with a modest hydrophobic and an equally modest hydrophilic contribution. Its hydration number is 2 ± 1, suggesting that the equilibrium hydration structure is like the Zundel type (HO).

Mixing scheme of an aqueous solution of tetrabutylphosphonium trifluoroacetate in the water-rich region.

We have studied the mixing scheme of an aqueous solution of ionic liquid tetrabutylphosphonium trifluoroacetate, [P]CFCOO, in the water-rich region. The mixture shows phase separation with a lower critical solution temperature. To learn how the solute [P]CFCOO species interact with each other in the dilute region, the third derivative quantities of Gibbs energy in terms of enthalpy, H, and volume, V, are evaluated.

Comprehensive Conformational and Rotational Analyses of the Butyl Group in Cyclic Cations: DFT Calculations for Imidazolium, Pyridinium, Pyrrolidinium, and Piperidinium.

The flexibility and conformational variety of the butyl group in cations of ionic liquids (ILs) play an important role in dictating the macroscopic and microscopic properties of ILs. Here we calculate potential energy surfaces for the dihedral angles of the butyl group in four different types of cyclic cations, imidazolium, pyridinium, pyrrolidinium, and piperidinium, using the density functional theory method. The calculation results highlight the role of the butyl group in these cations by comparison of five-membered and six-membered rings, and of aromatic and alicyclic rings, in terms of stable conformations and rotational barriers.

NMR Study on Ion Dynamics and Phase Behavior of a Piperidinium-Based Room-Temperature Ionic Liquid: 1-Butyl-1-methylpiperidinium Bis(fluorosulfonyl)amide.

By use of pulse NMR methods, the temperature dependences of the longitudinal and transverse relaxation times for (1)H and (19)F were measured for the three phases of 1-butyl-1-methylpiperidinium bis(fluorosulfonyl)amide ([Pip1,4][FSA]), i.e., liquid or supercooled liquid, Cryst-α, and Cryst-β, to investigate the ion dynamics and phase behavior related to the dynamics.

Anion and cation effects on the size control of Au nanoparticles prepared by sputter deposition in imidazolium-based ionic liquids.

The sputter deposition of metals in an ionic liquid (IL) capture medium is a simple and elegant method for preparing nanoparticles without any chemical reaction. Although there have been some reports on the size determination factors for Au nanoparticles (AuNPs) prepared using this method, the effects with respect to the type of IL used have not been clearly elucidated. This is because there are some complicating factors, some of which have been revealed by our previous systematic studies.

Phase Behavior of a Piperidinium-Based Room-Temperature Ionic Liquid Exhibiting Scanning Rate Dependence.

The structural flexibility and conformational variety of the ions in room-temperature ionic liquids (RTILs) have significant effects on their physicochemical properties. To begin a systematic study of the thermodynamic properties of nonaromatic RTILs, 1-methyl-1-butylpiperidinium bis(fluorosulfonyl)amide ([Pip1,4][FSA]) was selected as the first sample. In addition to the rotational flexibility of the alkyl group, the [Pip1,4](+) cation has characteristic ring-flipping flexibility, which is very different from the behavior of the well-studied imidazolium-based cations.

Structure and dynamics of room temperature ionic liquids with bromide anion: results from 81Br NMR spectroscopy.

We report the results of a comprehensive (81)Br NMR spectroscopic study of the structure and dynamics of two room temperature ionic liquids (RTILs), 1-butyl-3-methylimidazolium bromide ([C(4)mim]Br) and 1-butyl-2,3-dimethylimidazolium bromide ([C(4)C(1)mim]Br), in both liquid and crystalline states. NMR parameters in the gas phase are also simulated for stable ion pairs using quantum chemical calculations. The combination of (81)Br spin-lattice and spin-spin relaxation measurements in the motionally narrowed region of the stable liquid state provides information on the correlation time of the translational motion of the cation.

Anion and cation dynamics of sulfonylamide-based ionic liquids and the solid-liquid transitions.

Some of the important factors that characterise room-temperature ionic liquids (RTILs) are the variety of conformations adopted by the constituent ions and their flexibility. Using 1,3-dimethylimidazolium bis(fluorosulfonyl)amide ([C1mim][FSA]) and 1,3-dimethylimidazolium bis(trifluoromethylsulfonyl)amide ([C1mim][NTf2]) as samples, the longitudinal and transverse relaxation times (T1 and T2) for (19)F and (1)H were determined as a function of temperature and were correlated with the dynamics of the phase behaviours of the two RTILs. Because the anions and cations in the two compounds have (19)F and (1)H nuclei, respectively, their dynamics can be independently investigated and the relationships between them can be discussed.

Model-potential-free analysis of small angle scattering of proteins in solution: insights into solvent effects on protein-protein interaction.

To extract protein-protein interaction from experimental small-angle scattering of proteins in solutions using liquid state theory, a model potential consisting of a hard-sphere repulsive potential and the excess interaction potential has been introduced. In the present study, we propose a model-potential-free integral equation method that extracts the excess interaction potential by using the experimental small-angle scattering data without specific model potential such as the Derjaguin-Landau-Verwey-Overbeek (DLVO)-type model. Our analysis of experimental small-angle X-ray scattering data for lysozyme solution shows both the stabilization of contact configurations of protein molecules and a large activation barrier against the formation of the contact configurations in addition to the screened Coulomb repulsion.

IL-6 signal blockade ameliorates the enhanced osteoclastogenesis and the associated joint destruction in a novel FcγRIIB-deficient rheumatoid arthritis mouse model.

Objective: We earlier found that TNFα but not interleukin (IL)-17 is indispensable in the pathogenesis of spontaneously occurring rheumatoid arthritis (RA)-like disease in our newly established FcγRIIB-deficient C57BL/6 (B6) mouse model, designated KO1. Here, we examined the role of IL-6 in the pathogenesis of RA features in KO1, with particular reference to cartilage and bone destruction in arthritic joints.

Methods: To evaluate the preventive effect of MR16-1, a rat anti-mouse IL-6 receptor (IL-6R) mAb, 4-month-old preclinical KO1 mice were divided into three groups: the first treated with MR16-1 for 6 months, the second treated with normal rat IgG, as a control, and the third left untreated.

How much weaker are the effects of cations than those of anions? The effects of K+ and Cs+ on the molecular organization of liquid H2O.

We characterized the effects of K(+) and Cs(+) ions on the molecular organization of H2O by the 1-propanol probing methodology, previously developed by us (Phys. Chem. Chem.

TNFα but not IL-17 is critical in the pathogenesis of rheumatoid arthritis spontaneously occurring in a unique FcγRIIB-deficient mouse model.

Objective: TNFα and IL-17 have been shown to be the major inflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA). Here, we examined the effect of these cytokines on spontaneously occurring RA in our newly established arthritis-prone FcγRIIB- deficient C57BL/6 (B6) mice, designated KO1, by introducing genetic deficiency of TNFα and IL-17 into KO1 mice.

Methods: KO1.

Modulation of the intermolecular interaction of myoglobin by removal of the heme.

Toward understanding intermolecular interactions governing self-association of proteins, the present study investigated a model protein, myoglobin, using a small-angle X-ray scattering technique. It has been known that removal of the heme makes myoglobin aggregation-prone. The interparticle interferences of the holomyoglobin and the apomyoglobin were compared in terms of the structure factor.

Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Yaa mutation into FcγRIIB-deficient C57BL/6 mice.

We previously established an IgG Fc receptor IIB (FcγRIIB)-deficient C57BL/6 (B6)-congenic mouse strain (KO1), which spontaneously develops rheumatoid arthritis (RA), but not systemic lupus erythematosus (SLE). Here, we show that when Y chromosome-linked autoimmune acceleration (Yaa) mutation was introduced in KO1 strain (KO1.Yaa), the majority of KO1.

Effects of tetramethyl- and tetraethylammonium chloride on H2O: calorimetric and near-infrared spectroscopic study.

The effect of tetraethylammonium chloride (TEAC) on H(2)O was investigated by the 1-propanol (1P) probing thermodynamic methodology developed by us earlier. It was found that TEAC is an amphiphile with a small hydrophobic and a dominant hydrophilic contribution. An earlier application of the same 1P-probing methodology to tetramethylammonium chloride (TMAC) indicated that the latter is as hydrophilic as urea without any hydrophobic contribution.

A comparative study of the rotational dynamics of PF6(-) anions in the crystals and liquid states of 1-butyl-3-methylimidazolium hexafluorophosphate: results from 31P NMR spectroscopy.

The rotational dynamics of the hexafluorophosphate anion (PF(6)(-)) in the crystalline and liquid states of the archetypal room temperature ionic liquid (RTIL) 1-butyl-3-methylimidazolium hexafluorophosphate ([C(4)mim]PF(6)) are investigated using (31)P NMR spectroscopy line shape analyses and spin-lattice relaxation time measurements. The PF(6)(-) anion performs isotropic rotation in all three polymorphic crystals phases α, β, and γ as well as in the liquid state with a characteristic time scale that ranges from a few ps to a few hundred ps over a temperature range of 180-280 K. The rotational correlation time τ(c) for PF(6)(-) rotation follows the sequence γ-phase < α-phase ≈ liquid < β-phase.

Determination of sphingoid bases from hydrolyzed glucosylceramide in rice and wheat by online post-column high-performance liquid chromatography with O-phthalaldehyde derivatization.

We developed a determination method for sphingoid bases using online post-column high-performance liquid chromatography (HPLC) with O-phthalaldehyde (OPA) derivatization. Good separation was achieved using a reversed-phase column and eluting with 50% acetonitrile containing formic acid and heptafluorobutyric acid. Using these conditions, an excellent linearity (R² > 0.