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Biomedical subjects

Ji Wang

Publications and source records attributed to Ji Wang.

At least 19 recordsLinked to original sources

Programmed ribosomal frameshifting during PLEKHM2 mRNA decoding generates a constitutively active proteoform that supports myocardial function.

Programmed ribosomal frameshifting is a process where a proportion of ribosomes change their reading frame on an mRNA. While frameshifting is commonly used by viruses, very few phylogenetically conserved examples are known in nuclear encoded genes. Here, we report a +1 frameshifting event during decoding of the human gene PLEKHM2 that provides access to a second internally overlapping ORF. The new carboxyl-terminal domain of this frameshift protein forms an α helix, which relieves PLEKHM2 from autoinhibition and allows it to move to the tips of cells without activation by ARL8. Reintroducing both the canonically translated and frameshifted protein are necessary to restore normal contractile function of PLEKHM2 knockout cardiomyocytes, demonstrating the necessity of frameshifting for normal cardiac activity.

Frameshifting, Ribosomal↗

Negative regulation of ISG15 E3 ligase EFP through its autoISGylation.

The function of ubiquitin-like protein ISG15 and protein modification by ISG15 (ISGylation) has been an enigma for many years. Recently, the research of ISGylation has been accelerated by the identification of the enzymes involved in the ISG15 conjugation process. Our previous study identified the interferon inducible protein EFP as an ISG15 isopeptide ligase (E3) for 14-3-3sigma. In this study, we show that ISG15 E3 ligase EFP can be modified by ISG15. Two ubiquitin E2 conjugating enzymes, UbcH6 and UbcH8, can support ISGylation of EFP. The Ring-finger domain of EFP is important for its ISGylation. Full-length EFP can enhance the ISGylation of Ring domain deleted EFP, indicating EFP can function as an ISG15 E3 ligase for itself. We also determined the ISGylation site of EFP and created its ISGylation resistant mutant EFP-K117R. Compared to the wild-type EFP, this mutant further increases the ISGylation of 14-3-3sigma. Thus we propose that autoISGylation of EFP negatively regulates its ISG15 E3 ligase activity for 14-3-3sigma.

Binding Sites↗

MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stress.

c-Jun, a major transcription factor in the activating protein 1 family of regulatory proteins, is activated by many physiologic and pathological stimuli. We show here that c-Jun was downregulated in response to osmotic stress via ubiquitination-dependent degradation by the PHD/RING finger domain of MEKK1, which exhibited E3 ubiquitin ligase activity toward c-Jun in vitro and in vivo. The reduced c-Jun protein level resulting from exogenous expression of wild-type MEKK1 and the opposite effect induced by expression of a MEKK1 PHD/RING finger domain mutant were consistent with a higher level of c-Jun protein in MEKK1(-/-) cells than in corresponding wild-type cells. The deficiency of MEKK1 blocked posttranslational downregulation of c-Jun in response to osmotic stress. Furthermore, apoptosis induced by osmotic stress was suppressed by overexpression of c-Jun, indicating that the downregulation of c-Jun promotes apoptosis.

Animals↗

Molecular dynamics investigation of bent-core molecules on a water surface.

Molecular dynamics simulations are carried out for bent-core molecules at water surfaces. The water surface is shown to alter the equilibrium molecular structure significantly by causing a different class of torsional states to become more favorable. The equilibrium structure is also altered by the substitution of chlorine atoms for hydrogen atoms on the central phenyl ring in that this substitution forces the bent core to remain in a single torsional state rather than be delocalized among several torsional states. The consequences of these structural changes on the chirality and packing of these molecules on water surfaces are discussed.

Journal Article↗

Love wave propagation in functionally graded piezoelectric material layer.

An exact approach is used to investigate Love waves in functionally graded piezoelectric material (FGPM) layer bonded to a semi-infinite homogeneous solid. The piezoelectric material is polarized in z-axis direction and the material properties change gradually with the thickness of the layer. We here assume that all material properties of the piezoelectric layer have the same exponential function distribution along the x-axis direction. The analytical solutions of dispersion relations are obtained for electrically open or short circuit conditions. The effects of the gradient variation of material constants on the phase velocity, the group velocity, and the coupled electromechanical factor are discussed in detail. The displacement, electric potential, and stress distributions along thickness of the graded layer are calculated and plotted. Numerical examples indicate that appropriate gradient distributing of the material properties make Love waves to propagate along the surface of the piezoelectric layer, or a bigger electromechanical coupling factor can be obtained, which is in favor of acquiring a better performance in surface acoustic wave (SAW) devices.

Manufactured Materials↗

Two-dimensional analysis of the effect of an electrode layer on surface acoustic waves in a finite anisotropic plate.

The effect of a metal layer over an elastic substrate on surface acoustic wave propagating in the structure can be evaluated precisely for semi-infinite solids and infinite plates, but there is no accurate analytical solution if the finite size of the plate has to be considered. By expanding displacements with eigensolutions of surface acoustic waves in a semi-inifite solid, a set of two-dimensional equations similar to the Mindlin plate theory are obtained. Then for a thin electrode layer, the effect is considered through the approximation of displacements in the metal layer with the ones in the substrate, and an integration over the thickness incorporated the properties of the metal layer into equations through the modification of material properties with the decaying indices of surface acoustic waves and the thickness of the metal layer. Using AT-cut quartz crystal as the substrate, we present the effect of silver electrode layers of finite thickness on the phase velocity of propagating surface acoustic waves.

Journal Article↗

The determination of electrical parameters of quartz crystal resonators with the consideration of dissipation.

Recently, as the dissipation of quartz crystal through material viscosity is being considered in vibrations of piezoelectric plates, we have the opportunity to obtain electrical parameters from vibration solutions of a crystal plate representing an ideal resonator. Since the solutions are readily available with complex elastic constants from Mindlin plate equations for thickness-shear vibrations, the calculation of resistance and other parameters related to both mechanical deformation and electrical potential is straightforward. We start with the first-order Mindlin plate equations of a piezoelectric plate for the thickness-shear vibration analysis of a simple resonator model. The electrical parameters are derived with emphasis on the resistance that is related to the imaginary part of complex elastic constants, or the viscosity. All the electrical parameters are frequency dependent, enabling the study of the frequency behavior of crystal resonators with a direct formulation. Through the full consideration of complications like partial electrodes and supporting structures, we should be able obtain electrical parameters for practical applications in resonator design.

Journal Article↗

Exact and approximate analysis of surface acoustic waves in an infinite elastic plate with a thin metal layer.

For an accurate approximation of the effect of a thin layer over a finite substrate, we consider the displacements are continuous across the interface, while the stress components are obtained from derivatives of displacements. As a result, the stress boundary conditions are transformed to a relationship between stresses in the vicinity of the interface of two layers and density of the metal layer. Through this approximation, we eventually have four equations to solve for the surface acoustic wave dispersion relation of the two-layer structure. The approximate and accurate results are compared with good agreement for small thickness of the metal layer. These results are intended for periodic structures with separate solutions for electroded and unelectroded regions, which can be connected by the continuity boundary conditions for the analysis of the complete structure of typical surface acoustic wave resonators.

Acoustics↗

Dynamic interaction of anti-plane shear waves with arc-shaped interfacial crack in piezoelectric media.

The dynamic interaction between anti-plane shear waves with arc-shaped interfacial crack of piezoelectric media is considered here. The region of the debonding is modeled as an arc-shaped interfacial crack with non-contacting faces. The electric permeable and impermeable boundary conditions are adopted to get the disturbed solution, respectively. The crack opening displacement and the electric potential are represented by Chebyshev polynomials and a system of equations is derived. The calculation results show that the piezoelectric coefficient has remarkable effect on the crack opening displacement.

Journal Article↗

Anisotropy in Langmuir layers of a bent-core liquid crystal.

Langmuir layers of a symmetric bent-core molecule with hydrocarbon end chains and two chlorine atoms substituted on the central phenyl ring of the bent core were characterized by a combination of surface pressure isotherms, Brewster angle microscopy, and surface potential measurements. These layers were found to be optically anisotropic, in contrast to Langmuir layers of similar molecules with different substitutions on the core. After compression, the orientation of the optical axis was essentially uniform over the film. Upon decompression, the film broke into uniform islands or domains. Measuring domain reflectivity while changing the domain orientation allowed the determination of the tilt angle with respect to both domain features and the film normal, as well as the refractive index anisotropy. The tilt angle, near 90 degrees, suggests that the bent-core molecules lie quite flat on the surface.

Journal Article↗

Consideration of stiffness and mass effects of relatively thicker electrodes with Mindlin plate theory.

Mindlin plate theory has been widely used in the high-frequency vibrations of piezoelectric crystal plates with emphasis on its applications in crystal resonator analysis and design. The plate equations were derived without considering the effect of electrodes from the beginning. But continuing efforts have been made to include the mechanical effect, or the mass loading, through the consideration of the mass ratio of the electrodes and crystal blank. Such a consideration has been effective for relatively thin electrodes before, but the ever-increasing mass ratio has been pressing further improvement to take into account relatively thicker electrodes. To extend Mindlin plate equations for these applications, we derive the plate equations systematically with the approximation of displacements in electrodes with those in the crystal blank. As a result, both mass and stiffness effects of electrodes are considered through ratios of the thickness, density, and elastic constants of the electrodes to those of the crystal blank, respectively, and the plate equations are modified accordingly. A practical design of the electrodes and crystal blank are analyzed to demonstrate the necessity of such modifications to Mindlin plate equations.

Computer Simulation↗

A novel thermoacidophilic endoglucanase, Ba-EGA, from a new cellulose-degrading bacterium, Bacillus sp.AC-1.

A newly discovered bacterium, strain AC1, containing cellulase was isolated from the gastric juice of the mollusca, Ampullaria crosseans. Analysis of the 16S rDNA sequence and carbon sources revealed that the bacterium belonged to the genus Bacillus. A novel endoglucanase (Ba-EGA) was purified from culture supernatants of the bacterium growing in CMC-Na (low viscosity) induction medium. The cellulase was purified about 150-fold by ammonium sulfate fractionation, ion exchange, hydrophobic, and gel filtration chromatography, with a specific activity of 35.0 IU/mg. The molecular mass of the enzyme was 67 kDa. N-terminal amino acid sequencing revealed a sequence of SDYNYVEVLQKSILF, which had high homology with endoglucanases from the Bacillus and Clostridium species. The maximal activity of the enzyme with the substrate of CM-cellulose is at pH 4.5-6.5 and 70 degrees C, respectively. The studies on pH and temperature stability showed that the Ba-EGA is stable enough between pH 7.5 and 10.5 at 30 degrees C for 2 h, and more than 80% of the activity still remains when incubation was prolonged to 1 h at 50 degrees C. The activity of the enzyme was significantly inhibited by Fe(2+), Cu(2+) (5.0 mM of each), and sodium dodecyl sulfate (SDS) (0.5%) and obviously activated by Tween 20 and Triton X-100 (0.25% each). Binding studies revealed that the Ba-EGA had cellulose-binding domain.

Amino Acid Sequence↗

The determination of the optimal length of crystal blanks in quartz crystal resonators.

It is well understood that the strong coupling of thickness-shear and flexural vibrations in piezoelectric crystal plates only occurs at specific length at which the vibration mode conversion, like the flexural mode gradually converting to thickness-shear mode while the thickness-shear mode converting to higher-order flexural mode, happens. It is important to avoid the strong coupling of modes in a crystal resonator that uses thickness-shear vibrations to enhance the energy trapping. To achieve such a design goal, the length of a crystal blank should be carefully chosen such that the coupling is at its weakest, which usually is in the middle of two strong coupling points. Through a closer examination of the frequency spectra, or the frequency-length relationship in this study, we can see that the strong coupling points appear periodically. This implies that we can find exact locations with the plate theory that predicts the resonance frequency. Based on this observation, we first use the first-order Mindlin plate theory with the precise thickness-shear frequency, which is normalized to one, to find corresponding wavenumbers. Then the length as a variable is solved from the coupled frequency equation for exact coupling points in a crystal plate of AT-cut quartz. The optimal length of a crystal blank in the simplest resonator model is calculated for the coupled thickness-shear, flexural, and extensional vibrations. The solutions and the method will be important in the determination of optimal length of a crystal blank in the resonator design process.

Computer Simulation↗

ERS1 encodes a functional homologue of the human lysosomal cystine transporter.

Cystinosis is a lysosomal storage disease caused by an accumulation of insoluble cystine in the lumen of the lysosome. CTNS encodes the lysosomal cystine transporter, mutations in which manifest as a range of disorders and are the most common cause of inherited renal Fanconi syndrome. Cystinosin, the CTNS product, is highly conserved among mammals. Here we show that the yeast Ers1 protein and cystinosin are functional orthologues, despite sharing only limited sequence homology. Ers1 is a vacuolar protein whose loss of function results in growth sensitivity to hygromycin B. This phenotype can be complemented by the human CTNS gene but not by mutant ctns alleles that were previously identified in cystinosis patients. A genetic screen for multicopy suppressors of an ers1Delta yeast strain identified a novel gene, MEH1, which is implicated in regulating Ers1 function. Meh1 localizes to the vacuolar membrane and loss of MEH1 results in a defect in vacuolar acidification, suggesting that the vacuolar environment is critical for normal ERS1 function. This genetic system has also led us to identify Gtr1 as an Meh1 interacting protein. Like Meh1 and Ers1, Gtr1 associates with vacuolar membranes in an Meh1-dependent manner. These results demonstrate the utility of yeast as a model system for the study of CTNS and vacuolar function.

Amino Acid Sequence↗

Langmuir monolayers of bent-core molecules.

A systematic study of five different, symmetric bent-core liquid crystals in Langmuir thin films at the air/water interface is presented. Both the end chains (siloxane vs hydrocarbon) and the core (more or less amphiphilic) are varied, to allow an exploration of different possible layer structures at the interface. The characterization includes systematic surface pressure isotherms, Brewster angle microscopy, and surface potential measurements. The properties of these layers are strongly dependent on the individual type of molecule: the molecules with amphiphilic end chains lie quite flat on the surface, while the molecules with hydrophobic end chains construct multilayer structures. In both cases, the three-dimensional collapse structure is reversible.

Air↗

pH-dependent stability of EGX, a multi-functional cellulase from mollusca, Ampullaria crossean.

The cellulase activity and stability of EGX, a multi-functional cellulase previously purified from the mollusca Ampullaria crossean, was systematically studied under different pH. The pH induced con-formation and stability change of EGX have been investigated by using the intrinsic fluorescence, ANS fluorescence and CD spectrum. It has been found that the conformation and activity of this cellulase were strongly dependent on the pH. EGX was stable for both the enzyme activity and the conformation from pH 5.6 to pH 7.4. As shown by intrinsic and ANS fluorescence, no red shift of emission maximum occurred and a negligible intensity change was observed at pH 5.6-7.4. The activity of EGX remained about 80% in pH 5.6-7.4 and obviously decreased out of side the pH range. Urea-induced changes in EGX at pH 5.4 and pH 8.0 were measured by intrinsic fluorescence and CD spectrum. At pH 5.4, a significantly red shift of emission maximum occurred when the concentration of urea was 5 M compared to the concentration was 3 M at pH 8.0. The alpha-helix at pH 5.4 was 40.51% in the absence of urea and 31.04% in the presence of 4 M urea. At pH 8.0 the alpha-helix was 7.23% in the presence of 4 M urea. The data indicated that EGX was much susceptible to urea-induced unfolding at pH 8.0 and much stable at pH 5.4. The greater pH dependent stability of EGX may allow the enzyme to adequately catalyze the hydrolysis of cellulosic materials under natural or industrial extreme conditions.

Animals↗