Understanding pre-structured motifs (PreSMos) in intrinsically unfolded proteins

Intrinsically unfolded proteins (IUPs) do not obey the golden rule of structural biology, 3D structure = function, as they manifest their inherent functions without resorting to three-dimensional structures. Absence of a compact globular topology in these proteins strongly implies that their ligand recognition processes should involve factors other than spatially well-defined binding pockets. Heteronuclear multidimensional (HetMulD) NMR spectroscopy assisted with a stable isotope labeling technology is a powerful tool for quantitatively investigating detailed structural features in IUPs. In particular, it allows us to delineate the presence and locations of pre-structured motifs (PreSMos) on a per-residue basis. PreSMos are the transient local structural elements that presage target-bound conformations and act as specificity determinants for IUP recognition by target proteins. Here, we present a brief chronicle of HetMulD NMR studies on IUPs carried out over the past two decades along with a discussion on the functional significance of PreSMos in IUPs.     

S-nitrosothiol detection via amperometric nitric oxide sensor with surface modified hydrogel layer containing immobilized organoselenium catalyst

A novel electrochemical device for the direct detection of S-nitrosothiol species (RSNO) is proposed by modifying an amperometric nitric oxide (NO) gas sensor with thin hydrogel layer containing an immobilized organoselenium catalyst. The diselenide, 3,3'-dipropionicdiselenide, is covalently coupled to primary amine groups in polyethylenimine (PEI), which is further cross-linked to form a hydrogel layer on a dialysis membrane support. Such a polymer film containing the organoselenium moiety is capable of decomposing S-nitrosothiols to generate NO(g) at the distal tip of the NO sensor. Under optimized conditions, various RSNOs (e.g., nitrosocysteine (CysNO), nitrosoglutathione (GSNO), etc.) are reversibly detected at 相似文献   

Tissue engineering of heart valves by recellularization of glutaraldehyde-fixed porcine valves using bone marrow-derived cells

To increase the biocompatibility and durability of glutaraldehyde (GA)-fixed valves, a biological coating with viable endothelial cells (ECs) has been proposed. However, stable EC layers have not been formed successfully on GA-fixed valves due to their inability to repopulate. In this study, to improve cellular adhesion and proliferation, the GA-fixed prostheses were detoxified by treatment with citric acid to remove free aldehyde groups. Canine bone marrow mononuclear cells (MNCs) were differentiated into EC-like cells and myofibroblast-like cells in vitro. Detoxified prostheses were seeded and recellularized with differentiated bone marrow- derived cells (BMCs) for seven days. Untreated GA-fixed prostheses were used as controls. Cell attachment, proliferation, metabolic activity, and viability were investigated and cell-seeded leaflets were histologically analyzed. On detoxified GA-fixed prostheses, BMC seeding resulted in uninhibited cell proliferation after seven days. In contrast, on untreated GA-fixed prostheses, cell attachment was poor and no viable cells were observed. Positive staining for smooth muscle a-actin, CD31, and proliferating cell nuclear antigen was observed on the luminal side of the detoxified valve leaflets, indicating differentiation and proliferation of the seeded BMCs. These results demonstrate that the treatment of GA-fixed valves with citric acid established a surface more suitable for cellular attachment and proliferation. Engineering heart valves by seeding detoxified GA-fixed biological valve prostheses with BMCs may increase biocompatibility and durability of the prostheses. This method could be utilized as a new approach for the restoration of heart valve structure and function in the treatment of end-stage heart valve disease.     

Caveolin-1 upregulation in senescent neurons alters amyloid precursor protein processing

Lipid rafts provide a platform for regulating cellular functions and participate in the pathogenesis of several diseases. However, the role of caveolin-1 in this process has not been elucidated definitely in neuron. Thus, this study was performed to examine whether caveolin-1 can regulate amyloid precursor protein (APP) processing in neuronal cells and to identify the molecular mechanisms involved in this regulation. Caveolin-1 is up-regulated in all parts of old rat brain, namely hippocampus, cerebral cortex and in elderly human cerebral cortex. Moreover, detergent-insoluble glycolipid (DIG) fractions indicated that caveolin-1 was co-localized with APP in caveolae-like structures. In DIG fractions, beta APP secretion was up-regulated by caveolin-1 over- expression, which was modulated via protein kinase C (PKC) in neuroblastoma cells. From these results we conclude that caveolin-1 is selectively expressed in senescent neurons and that it induces the processing of APP by beta-secretase via PKC downregulation.     

van der Waals interactions and dipole polarizabilities of lanthanides: Tm(2F)-He and Yb(1S)-He potentials

Anisotropic dipole polarizabilities of Tm(2F), Tm+2(2F), and Yb(1S) are calculated using the finite-field multireference averaged quadratic coupled cluster (MR-AQCC) (Tm and Tm+2) and RCCSD(T) (Yb) methods with small-core relativistic pseudopotentials ECP28MWB combined with the augmented ANO basis sets. The lanthanide atoms are strongly polarizable with the scalar part originating from the 6s electrons and the tensorial part from the open 4f shells. The adiabatic interaction potentials 2Sigma+, 2Pi, 2Delta, and 2Phi of Tm(2F)-He and Tm+2(2F)-He were examined by the multireference approaches, multireference configuration interaction and MR-AQCC, using the basis sets designed in the polarizability calculations. A closed-shell lanthanide system Yb(1S)-He was included for comparison. The Tm-He 2Sigma+, 2Pi, 2Delta, and 2Phi interaction potentials are very shallow and nearly degenerate (within 0.01 cm(-1)), with the well depths in the range of 2.35-2.36 cm(-1) at R=6.17 A. The basis-set saturated well depths are expected to be larger by ca. 25%, as estimated using the bond-function augmented basis set. The interactions of lanthanide atoms with He are one order of magnitude less anisotropic than those involving first-row transition metal atoms. The suppression of anisotropy is chiefly attributed to the screening effected by the 6s shell. When these electrons are removed as in the di-cation complex Tm+2(2F)-He, the potentials deepen to a thousand wave number range and their anisotropy is enhanced 500-fold.     

Interaction potentials for Br(-)-Rg (Rg=He-Rn): spectroscopy and transport coefficients

High-level ab initio CCSD(T) calculations are performed in order to obtain accurate interaction potentials for the Br(-) anion interacting with each rare gas (Rg) atom. For the Rg atoms from He to Ar, two approaches are taken. The first one implements a relativistic core potential and an aug-cc-pVQZ basis set for bromine, an aug-cc-pV5Z basis set for Rg, and a set of bond functions placed at the midpoint of the Rg-Br distance. The second one uses the all-electron approximation with aug-cc-pV5Z bases further augmented by an extra diffuse function in each shell. Comparison reveals close similarity between both sets of results, so for Rg atoms from Kr to Rn only the second approach is exploited. Calculated potentials are assessed against the previous empirical, semiempirical, and ab initio potentials, and against available beam scattering data, zero electron kinetic energy spectroscopic data, and various sets of the measured ion mobilities and diffusion coefficients. This multiproperty analysis leads to the conclusion that the present potentials are consistently good for the whole series of Br(-)-Rg pairs over the whole range of internuclear distances covered.     

Chaotic response and bifurcation analysis of a flexible rotor supported by porous and non-porous bearings with nonlinear suspension

This study presents numerical work investigating the dynamic responses of a flexible rotor supported by porous journal bearings. Both porous and non-porous bearing types are taken into consideration in this study. The rotating speed ratios and imbalance parameters are also presented and proved to be important control parameters. Many non-periodic responses to chaotic and quasi-periodic motions are found, too. From the bifurcation diagrams in this paper, it is also evidenced that the vibration behaviors would be improved by porous bearings. The modeling result obtained here can be employed to predict the dynamics of bearing–rotor systems, and undesirable behavior of the rotor and bearing orbits can be avoided. Also, this could help engineers and researchers in designing and studying bearing–rotor systems or some turbo-machinery in the future.     

Application of the differential transformation method to the free vibrations of strongly non-linear oscillators

This paper adopts the differential transformation method to obtain the free vibration behavior of an oscillator with fifth-order non-linearities. The principle of differential transformation is briefly introduced, and is then applied in the derivation of a set of difference equations for the free vibration oscillator problem. The solutions are subsequently solved by a process of inverse transformation. The time responses of the oscillator are presented under different parameter conditions, and the current results are then compared with those derived from the established Runge–Kutta method in order to verify the accuracy of the proposed method. It is shown that there is excellent agreement between the two sets of results. This finding confirms that the proposed differential transformation method is a powerful and efficient tool for solving non-linear problems.     

Numerical approach and experimental verification for interface shape determination between layered fluids subject to a magnetic field

Various applications of magnetic fluids involve interface phenomena. The analysis of the hydrostatic interface shape between two immiscible liquid layers, especially under magnetic field influence, is the first step to understand the accompanying complex dynamic phenomena as well as to providing reliable numerical capabilities for their accurate prediction. This study presents a relatively simple numerical approach, and the accompanying theory, to reliably define the meniscus shape in a two-layered fluid system in presence of a horizontal magnetic field with a vertical gradient. In the course of the study, two dimensionless parameters have been derived to describe the magnetic pressure jump at the interface and the magnetic body force throughout the volume. These parameters are used to interpret the results of the analysis and to show that a horizontal magnetic field tends to flatten the meniscus shape at the interface despite of the direction of its vertical gradient.     

脉冲爆震发动机尾焰温度测量与数值模拟

本文采用新型研制的脉冲温度和水蒸气浓度测量仪测量了吸气式脉冲爆震发动机多循环工作过程中的尾焰温度,结果表明该测量仪不仅能够很好地捕捉每一个脉冲温度,与热成像仪测量的结果比较证明其测量温度在误差范围内.并采用了三阶TVD迎风格式和 Strang-splitting 算子分裂法,C3H8/air单步反应机理对混合物爆震燃烧进行了二维数值计算.与测量结果对比,说明采用本文的计算方法能够很好地捕捉到爆震波的点火和传播过程.