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Shilong Yang

Publications and source records attributed to Shilong Yang.

8 recordsLinked to original sources
PubMed2026

Functional chimeric mRNAs encode proteins in mammalian immunity.

Individual mammalian mRNAs and proteins are typically believed to originate from single genomic loci, with isoform diversity arising through cis-splicing of pre-mRNA. Whether mRNA from distant genes can undergo trans-splicing to generate functionally relevant chimeric transcripts has remained unclear. Here we develop a pipeline combining long-read direct RNA sequencing with non-targeted and targeted validation to identify chimeric transcripts in macrophages. Chromatin conformation capture studies reveal that inflammation induces interchromosomal DNA interactions, positioning parent genes proximally to facilitate the formation of chimeric mRNA. Notably, we identify a protein-coding chimeric mRNA representing a fusion between the pore-forming protein gasdermin D (GSDMD)1,2 and a C-terminal domain translated out of frame from Tmem106a (Gsdmd-Tmem106a) in mice. We show that inflammasome priming upregulates Gsdmd-Tmem106a, with the protein localizing to the plasma membrane. After activation of the inflammasome, GSDMD-TMEM106A directly interacts with canonical GSDMD N termini to accelerate and enhance pore formation and IL-1β release. Finally, we show that GSDMD-TMEM106A balances host defence and immunopathology in vivo: its loss protects against lethal sepsis but compromises antibacterial defence, whereas overexpression enhances host protection while increasing sepsis lethality. We establish that protein-coding chimeric mRNAs formed by regulated transcript fusion events are operative during inflammation and immunity.

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PubMed2005

Stationary phase evaluations of quantum rate constants.

We compute the quantum rate constant based on two extended stationary phase approximations to the imaginary-time formulation of the quantum rate theory. The optimized stationary phase approximation to the imaginary-time flux-flux correlation function employs the optimized quadratic reference system to overcome the inaccuracy of the quadratic expansion in the standard stationary phase approximation, and yields favorable agreements with instanton results for both adiabatic and nonadiabatic processes in dissipative and nondissipative systems. The integrated stationary phase approximation to the two-dimensional barrier free energy is particularly useful for adiabatic processes and demonstrates consistent results with the imaginary-time flux-flux correlation function approach. Our stationary phase methods do not require calculation of tunneling paths or stability matrices, and work equally well in the high-temperature and the low-temperature regimes. The numerical results suggest their general applicability for calibration of imaginary-time methods and for the calculation of quantum rate constants in systems with a large number of degrees of freedom.

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PubMed2004

Nonperturbative vibrational energy relaxation effects on vibrational line shapes.

A general formulation of nonperturbative quantum dynamics of solutes in a condensed phase is proposed to calculate linear and nonlinear vibrational line shapes. In the weak solute-solvent interaction limit, the temporal absorption profile can be approximately factorized into the population relaxation profile from the off-diagonal coupling and the pure-dephasing profile from the diagonal coupling. The strength of dissipation and the anharmonicity-induced dephasing rate are derived in Appendix A. The vibrational energy relaxation (VER) rate is negligible for slow solvent fluctuations, yet it does not justify the Markovian treatment of off-diagonal contributions to vibrational line shapes. Non-Markovian VER effects are manifested as asymmetric envelops in the temporal absorption profile, or equivalently as side bands in the frequency domain absorption spectrum. The side bands are solvent-induced multiple-photon effects which are absent in the Markovian VER treatment. Exact path integral calculations yield non-Lorentzian central peaks in absorption spectrum resulting from couplings between population relaxations of different vibrational states. These predictions cannot be reproduced by the perturbative or the Markovian approximations. For anharmonic potentials, the absorption spectrum shows asymmetric central peaks and the asymmetry increases with anharmonicity. At large anharmonicities, all the approximation schemes break down and a full nonperturbative path integral calculation that explicitly accounts for the exact VER effects is needed. A numerical analysis of the O-H stretch of HOD in D(2)O solvent reveals that the non-Markovian VER effects generate a small recurrence of the echo peak shift around 200 fs, which cannot be reproduced with a Markovian VER rate. In general, the nonperturbative and non-Markovian VER contributions have a stronger effect on nonlinear vibrational line shapes than on linear absorption.

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PubMed2004

A semiclassical study of wave packet dynamics in anharmonic potentials.

Classical and semiclassical methods are developed to calculate and invert the wave packet motion measured in pump-probe experiments. With classical propagation of the Wigner distribution of the initial wave packet created by the pump pulse, we predict the approximate probe signal with slightly displaced recurrence peaks, and derive a set of first-order canonical perturbation expressions to relate the temporal features of the signal to the characteristics of the potential surface. A reduced dynamics scheme based on the Gaussian assumption leads to the correct center of mass motion but does not describe the evolution of the shape of the wave packet accurately. To incorporate the quantum interference into classical trajectories, we propose a final-value representation semiclassical method, specifically designed for the purpose of computing pump-probe signals, and demonstrate its efficiency and accuracy with a Morse oscillator and two kinetically coupled Morse oscillators. For the case of one-color pump probe, a simple phase-space quantization scheme is devised to reproduce the temporal profile at the left-turning point without actual wave packet propagation, revealing a quantum mechanical perspective of the nearly classical pump-probe signal.

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PubMed2004

Theoretical analysis and computer simulation of fluorescence lifetime measurements. I. Kinetic regimes and experimental time scales.

The configuration-controlled regime and the diffusion-controlled regime of conformation-modulated fluorescence emission are systematically studied for Markovian and non-Markovian dynamics of the reaction coordinate. A path integral simulation is used to model fluorescence quenching processes on a semiflexible chain. First-order inhomogeneous cumulant expansion in the configuration-controlled regime defines a lower bound for the survival probability, while the Wilemski-Fixman approximation in the diffusion-controlled regime defines an upper bound. Inclusion of the experimental time window of the fluorescence measurement adds another dimension to the two kinetic regimes and provides a unified perspective for theoretical analysis and experimental investigation. We derive a rigorous generalization of the Wilemski-Fixman approximation [G. Wilemski and M. Fixman, J. Chem. Phys. 60, 866 (1974)] and recover the 1/D expansion of the average lifetime derived by Weiss [G. H. Weiss, J. Chem. Phys. 80, 2880 (1984)].

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PubMed2004

Theoretical analysis and computer simulation of fluorescence lifetime measurements. II. Contour length dependence of single polymers.

Fluorescence lifetime measurements in a polymer chain are modeled using a memory function expansion, computer simulations, and simple scaling arguments. Unless the quenching rate is localized and infinitely fast, the fluorescence lifetime is generally not equivalent to the first passage time. The fluorescence lifetime distribution is decomposed into memory functions that can be measured separately in single-molecule experiments. The leading order of the expansion gives the Wilemski-Fixman (WF) approximation, and the convergence of higher order terms determines its validity. Simulations of the fluorescence quenching on a Rouse chain verify the accuracy of the WF approximation at small contact radii, short contour lengths, and small quenching rates. Detailed investigation of the average fluorescence lifetime reveals two competing mechanisms: the independent motion of end-to-end vector, which dominates at small contact radius, and the slowest relaxation of polymer, which dominates at large contact radius. The Wilemski-Fixman rate is used in combination with scaling arguments to predict the dependence of fluorescence lifetime on the contour length. Our predictions for the scaling of the average lifetime with the contour length are in good agreement with both simulations and recent experiments by Eaton and his group [L. J. Lapidus, W. A. Eaton, and J. Hofrichter, Proc. Natl. Acad. Sci. U.S.A. 97, 7220 (2000)].

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PubMed2002

Brownian motion in dynamically disordered media.

The motion of Brownian test particles in a model random potential with time dependent correlations is investigated using four methods: renormalized perturbation, perturbation using Martin, Siggia, and Rose functional formalism (MSR), the Edwards variational method on the MSR functional, and renormalization group with the MSR function. The disorder averaged one-particle propagators determined by the renormalized perturbation expansion and MSR perturbation expansion are identical to the second and possibly higher order, and the two-particle propagators determined by these perturbation methods are identical at the first and possibly higher order. The one-particle propagator determined by the Edwards method is identical to the perturbation expansions at the first order, but the second-order analogue of the Edwards method has a more complex expression, which reduces to the second-order perturbation expression with additional higher-order terms. The diffusion constant and two-particle correlations are calculated from these propagators and are used to determine the effects of the random potential on the Brownian particles. Generally, the diffusion rate decreases with the disorder strength and increases with the temporal decay rate. The two competing mechanisms result in an enhancement of the diffusion constant for weak potentials with fast temporal fluctuations. The system exhibits two-particle correlations that are inherently non-Gaussian and indicate clustering behavior. The diffusion constant is also determined from a simple one-loop renormalization group calculation. In the static limit, the diffusion constant calculated by the renormalization group recovers the results of Deem and Chandler [M.W. Deem and D. Chandler, J. Stat. Phys. 76, 911 (1994)].

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