Hydrogen sulfide (H(2)S) is a synaptic modulator as well as a neuroprotectant. Currently, pyridoxal-5'-phosphate (PLP)-dependent cystathionine beta-synthase (CBS) is thought to be the major H(2)S-producing enzyme in the brain. We recently found that brain homogenates of CBS-knockout mice, even in the absence of PLP, produce H(2)S at levels similar to those of wild-type mice, suggesting the presence of another H(2)S-producing enzyme. Here we show that 3-mercaptopyruvate sulfurtransferase (3MST) in combination with cysteine aminotransferase (CAT) produces H(2)S from cysteine. In addition, 3MST is localized to neurons, and the levels of bound sulfane sulfur, the precursor of H(2)S, are greatly increased in the cells expressing 3MST and CAT but not increased in cells expressing functionally defective mutant enzymes. These data present a new perspective on H(2)S production and storage in the brain.
In eukaryotes, hydrogen sulphide acts as a signalling molecule and cytoprotectant. Hydrogen sulphide is known to be produced from L-cysteine by cystathionine b-synthase, cystathionine g-lyase and 3-mercaptopyruvate sulfurtransferase coupled with cysteine aminotransferase. Here we report an additional biosynthetic pathway for the production of hydrogen sulphide from D-cysteine involving 3-mercaptopyruvate sulfurtransferase and D-amino acid oxidase. Unlike the L-cysteine pathway, this D-cysteine-dependent pathway operates predominantly in the cerebellum and the kidney. Our study reveals that administration of D-cysteine protects primary cultures of cerebellar neurons from oxidative stress induced by hydrogen peroxide and attenuates ischaemia-reperfusion injury in the kidney more than L-cysteine. This study presents a novel pathway of hydrogen sulphide production and provides a new therapeutic approach to deliver hydrogen sulphide to specific tissues.
Despite such very appealing features of the radial basis function (RBF) as inherent meshfree and independent of dimension and geometry, the various RBF-based schemes [1] of solving partial differential equations (PDE's) still confront some deficiencies. For instances, the lack of easy-to-use spectral convergent RBFs, ill-conditioning and costly evaluation of full interpolation matrix. The purpose of this study is a combined use of radial basis function and the other approximation methods to cure these drawbacks.Atkinson [2] developed a strategy which splits solution of a PDE system into homogeneous and particular solutions, where the former have to satisfy the boundary and governing equation, while the latter only need to satisfy the governing equation without concerning geometry. Since the particular solution can be solved irrespective of boundary shape, we can use a readily available fast Fourier or orthogonal polynomial technique O(NlogN) to evaluate it in a regular box or sphere surrounding physical domain.The distinction of this study is that we approximate homogeneous solution with nonsingular general solution RBF as in the boundary knot method [3]. The collocation method using general solution RBF has very high accuracy and spectral convergent speed and is a simple, truly meshfree approach for any complicated geometry. More importantly, the use of nonsingular general solution avoids the controversial artificial boundary in the method of fundamental solution [4] due to the singularity of fundamental solution.Due to the fact that the present scheme is a combination of the RBF and other approximation techniques, we call it the quasi-RBF method (QRM) compared with a pure RBF method. Experimenting the QRM with typical Laplace, Helmholtz and convection-diffusion problems shows that the method produces very accurate solutions with a relatively small number of nodes. It is worth stressing that the QRM converges very fast and is quite easy to learn and program, especially for high-dimensional complicated-shape problems. REFERENCES1.E.J. Kansa, Multiquadrics: A scattered data approximation scheme with applications to computational fluid-dynamics.
This review article deals with the regularization of the boundary element formulations for solution of boundary value problems of continuum mechanics. These formulations may be singular owing to the use of two-point singular fundamental solutions. When the physical interpretation is irrelevant for this topic of computational mechanics, we consider various mechanical problems simultaneously within particular sections selected according to the main topic. In spite of such a structure of the paper, applications of the regularization techniques to many mechanical problems are described. There are distinguished two main groups of regularization techniques according to their application to singular formulations either before or after the discretization. Further subclassification of each group is made with respect to basic principles employed in individual regularization techniques. This paper summarizes the substances of the regularization procedures which are illustrated on the boundary element formulation for a scalar potential field. We discuss the regularizations of both the strongly singular and hypersingular integrals, occurring in the boundary integral equations, as well as those of nearly singular and nearly hypersingular integrals arising when the source point is near the integration element (as compared to its size) but not on this element. The possible dimensional inconsistency (or scale dependence of results) of the regularization after discretization is pointed out. Finally, we discuss the numerical approximations in various boundary element formulations, as well as the implementations of solutions of some problems for which derivative boundary integral equations are required.
A free-base cofacial bisporphyrin, H(4)DPOx, forms a pi-complex with acridinium ion (AcH(+)) by pi-pi interaction in benzonitrile (PhCN). Formation of the H(4)DPOx-AcH(+) pi-complex was probed by UV-vis and NMR spectroscopy. The binding constant between AcH(+) and H(4)DPOx is determined as 9.7 x 10(4) M(-)(1). Photoinduced electron transfer (ET) from the H(4)DPOx to the AcH(+) moiety occurred efficiently in the pi-complex to form the ET state (H(4)DPOx(*)(+)-AcH(*)). The ET state is successfully detected by laser flash photolysis. The lifetime of the ET state is 18 mus in PhCN at 298 K, and the quantum yield of the ET state is 90%. The temperature dependence of the ET state lifetime has been examined in the range from 273 to 353 K. The ET state lifetime exhibited a large temperature dependence, and the linear plot of ln(k(BET)T(1/2)) vs T(-)()(1), in accordance with the Marcus equation, affords the ET reorganization energy (0.54 eV). As a result, a remarkably long-lived ET state has been attained at low temperature, and virtually no decay of the ET state was observed at 77 K. Such an extremely long-lived ET state is indeed detected by steady-state UV-vis absorption spectroscopy.
Efficient chromosomal movements are important for the fidelity of chromosome segregation during mitosis; however, movements are constrained during interphase by tethering of multiple domains to the nuclear envelope (NE). Higher eukaryotes undergo open mitosis accompanied by NE breakdown, enabling chromosomes to be released from the NE, whereas lower eukaryotes undergo closed mitosis, in which NE breakdown does not occur. Although the chromosomal movements in closed mitosis are thought to be restricted compared to open mitosis, the cells overcome this problem by an unknown mechanism that enables accurate chromosome segregation. Here, we report the spatiotemporal regulation of telomeres in Schizosaccharomyces pombe closed mitosis. We found that the telomeres, tethered to the NE during interphase, are transiently dissociated from the NE during mitosis. This dissociation from the NE is essential for accurate chromosome segregation because forced telomere tethering to the NE causes frequent chromosome loss. The phosphorylation of the telomere protein Rap1 during mitosis, primarily by Cdc2, impedes the interaction between Rap1 and Bqt4, a nuclear membrane protein, thereby inducing telomere dissociation from the NE. We propose that the telomere dissociation from the NE promoted by Rap1 phosphorylation is critical for the fidelity of chromosome segregation in closed mitosis.
This paper has made some significant advances in the boundary-only and domain-type RBF techniques. The proposed boundary knot method (BKM) is different from the standard boundary element method in a number of important aspects. Namely, it is truly meshless, exponential convergence, integration-free (of course, no singular integration), boundary-only for general problems, and leads to symmetric matrix under certain conditions (able to be extended to general cases after further modified). The BKM also avoids the artificial boundary in the method of fundamental solution. An amazing finding is that the BKM can formulate linear modeling equations for nonlinear partial differential systems with linear boundary conditions. This merit makes it circumvent all perplexing issues in the iteration solution of nonlinear equations. On the other hand, by analogy with Green's second identity, we also presents a general solution RBF (GSR) methodology to construct efficient RBFs in the domain-type RBF collocation method and dual reciprocity method. The GSR approach first establishes an explicit relationship between the BEM and RBF itself on the ground of the potential theory. This paper also discusses some essential issues relating to the RBF computing, which include time-space RBFs, direct and indirect RBF schemes, finite RBF method, and the application of multipole and wavelet to the RBF solution of the PDEs.
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