Generalized Langevin Mode Analysis (GLMA) for Local Density Fluctuation of Water in an Inhomogeneous Field of a Biomolecule

An idea to analyze the fluctuational mode or/and spectrum of water molecules in an inhomogeneous environment around a biomolecule such as protein and DNA is proposed based on the generalized Langevin equation (GLE) for water interacting with a biomolecule. The idea is to solve an eigen-value problem of the collective frequency matrix of water, which has a physical meaning similar to the Hessian matrix in the case of a connected harmonic-oscillator. The diagonalization of the matrix gives the mode and frequency of the density fluctuation of water around the biomolecule. The treatment is a natural extension of that made for water in a homogeneous environment by Chong and Hirata in 2008, in which the authors have found the four modes for density fluctuation; one for an acoustic mode, and the other three for optical modes. It is the point of the new approach how the mode and frequency of the density fluctuation are modulated by the field from the biomolecule. The method provides a way to distinguish the mode of fluctuation with color. A few possible applications of the theoretical approach to problems of the life science including medicine are also proposed

Design of teleoperation system with a force-reflecting real-time simulator

We developed a force-reflecting teleoperation system that uses a real-time graphic simulator. This system eliminates the effects of communication time delays in remote robot manipulation. The simulator provides the operator with predictive display and feedback of computed contact forces through a six-degree of freedom (6-DOF) master arm on a real-time basis. With this system, peg-in-hole tasks involving round-trip communication time delays of up to a few seconds were performed at three support levels: a real image alone, a predictive display with a real image, and a real-time graphic simulator with computed-contact-force reflection and a predictive display. The experimental results indicate the best teleoperation efficiency was achieved by using the force-reflecting simulator with two images. The shortest work time, lowest sensor maximum, and a 100 percent success rate were obtained. These results demonstrate the effectiveness of simulated-force-reflecting teleoperation efficiency

Site-site memory equation approach in study of density/pressure dependence of translational diffusion coefficient and rotational relaxation time of polar molecular solutions: acetonitrile in water, methanol in water, and methanol in acetonitrile

We present results of theoretical study and numerical calculation of the dynamics of molecular liquids based on combination of the memory equation formalism and the reference interaction site model - RISM. Memory equations for the site-site intermediate scattering functions are studied in the mode-coupling approximation for the first order memory kernels, while equilibrium properties such as site-site static structure factors are deduced from RISM. The results include the temperature-density(pressure) dependence of translational diffusion coefficients D and orientational relaxation times t for acetonitrile in water, methanol in water and methanol in acetonitrile, all in the limit of infinite dilution. Calculations are performed over the range of temperatures and densities employing the SPC/E model for water and optimized site-site potentials for acetonitrile and methanol. The theory is able to reproduce qualitatively all main features of temperature and density dependences of D and t observed in real and computer experiments. In particular, anomalous behavior, i.e. the increase in mobility with density, is observed for D and t of methanol in water, while acetonitrile in water and methanol in acetonitrile do not show deviations from the ordinary behavior. The variety exhibited by the different solute-solvent systems in the density dependence of the mobility is interpreted in terms of the two competing origins of friction, which interplay with each other as density increases: the collisional and dielectric frictions which, respectively, increase and decrease with increasing density.Comment: 13 pages, 8 eps-figures, 3 tables, RevTeX4-forma

Statistical-mechanical theory of ultrasonic absorption in molecular liquids

We present results of theoretical description of ultrasonic phenomena in molecular liquids. In particular, we are interested in the development of microscopical, i.e., statistical-mechanical framework capable to explain the long living puzzle of the excess ultrasonic absorption in liquids. Typically, ultrasonic wave in a liquid can be generated by applying the periodically alternating external pressure with the angular frequency that corresponds to the ultrasound. If the perturbation introduced by such process is weak - its statistical-mechanical treatment can be done with the use of the linear response theory. We treat the liquid as a system of interacting sites, so that all the response/aftereffect functions as well as the energy dissipation and generalized (wave-vector and frequency dependent) ultrasonic absorption coefficient are obtained in terms of familiar site-site static and time correlation functions such as static structure factors or intermediate scattering functions. To express the site-site intermediate scattering functions we refer to the site-site memory equations in the mode-coupling approximation for the first-order memory kernels, while equilibrium properties such as site-site static structure factors, direct and total correlation functions are deduced from the integral equation theory of molecular liquids known as RISM or one of its generalizations. All the formalism is phrased in a general manner, hence the obtained results are expected to work for arbitrary type of molecular liquid including simple, ionic, polar, and non-polar liquids.Comment: 14 pages, 1 eps-figure, RevTeX4-forma

Mutual Effects of Orexin and Bone Morphogenetic Proteins on Gonadotropin Expression by Mouse Gonadotrope Cells

Orexin plays a key role in the regulation of sleep and wakefulness and in feeding behavior in the central nervous system, but its receptors are expressed in various peripheral tissues including endocrine tissues. In the present study, we elucidated the effects of orexin on pituitary gonadotropin regulation by focusing on the functional involvement of bone morphogenetic proteins (BMPs) and clock genes using mouse gonadotrope L beta T2 cells that express orexin type 1 (OX1R) and type 2 (OX2R) receptors. Treatments with orexin A enhanced LH beta and FSH beta mRNA expression in a dose-dependent manner in the absence of GnRH, whereas orexin A in turn suppressed GnRH-induced gonadotropin expression in L beta T2 cells. Orexin A downregulated GnRH receptor expression, while GnRH enhanced OX1R and OX2R mRNA expression. Treatments with orexin A as well as GnRH increased the mRNA levels of Bmal1 and Clock, which are oscillational regulators for gonadotropin expression. Of note, treatments with BMP-6 and -15 enhanced OX1R and OX2R mRNA expression with upregulation of clock gene expression. On the other hand, orexin A enhanced BMP receptor signaling of Smad1/5/9 phosphorylation through upregulation of ALK-2/BMPRII among the BMP receptors expressed in L beta T2 cells. Collectively, the results indicate that orexin regulates gonadotropin expression via clock gene expression by mutually interacting with GnRH action and the pituitary BMP system in gonadotrope cells

Structural basis of Sec-independent membrane protein insertion by YidC

[プレスリリース]バイオサイエンス研究科膜分子複合機能学研究室の塚崎智也准教授らの研究グループが、タンパク質を細胞膜に組み込むメカニズムを解明しました（2014/04/17）Newly synthesized membrane proteins must be accurately inserted into the membrane, folded and assembled for proper functioning. The protein YidC inserts its substrates into the membrane, thereby facilitating membrane protein assembly in bacteria; the homologous proteins Oxa1 and Alb3 have the same function in mitochondria and chloroplasts, respectively1, 2. In the bacterial cytoplasmic membrane, YidC functions as an independent insertase and a membrane chaperone in cooperation with the translocon SecYEG3, 4, 5. Here we present the crystal structure of YidC from Bacillus halodurans, at 2.4 Å resolution. The structure reveals a novel fold, in which five conserved transmembrane helices form a positively charged hydrophilic groove that is open towards both the lipid bilayer and the cytoplasm but closed on the extracellular side. Structure-based in vivo analyses reveal that a conserved arginine residue in the groove is important for the insertion of membrane proteins by YidC. We propose an insertion mechanism for single-spanning membrane proteins, in which the hydrophilic environment generated by the groove recruits the extracellular regions of substrates into the low-dielectric environment of the membrane

Identification of a novel uterine leiomyoma GWAS locus in a Japanese population

Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P = 6.12 × 10−25 with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma