Site-selective protein modification via disulfide rebridging for fast tetrazine/trans-cyclooctene bioconjugation

An inverse electron demand Diels–Alder reaction between tetrazine and trans-cyclooctene (TCO) holds great promise for protein modification and manipulation. Herein, we report the design and synthesis of a tetrazine-based disulfide rebridging reagent, which allows the site-selective installation of a tetrazine group into disulfide-containing peptides and proteins such as the hormone somatostatin (SST) and the antigen binding fragment (Fab) of human immunoglobulin G (IgG). The fast and efficient conjugation of the tetrazine modified proteins with three different TCO-containing substrates to form a set of bioconjugates in a site-selective manner was successfully demonstrated for the first time. Homogeneous, well-defined bioconjugates were obtained underlining the great potential of our method for fast bioconjugation in emerging protein therapeutics. The formed bioconjugates were stable against glutathione and in serum, and they maintained their secondary structure. With this work, we broaden the scope of tetrazine chemistry for site-selective protein modification to prepare well-defined SST and Fab conjugates with preserved structures and good stability under biologically relevant conditions

Spectral properties and magneto-optical excitations in semiconductor double-rings under Rashba spin-orbit interaction

We have numerically solved the Hamiltonian of an electron in a semiconductor double ring subjected to the magnetic flux and Rashba spin-orbit interaction. It is found that the Aharonov-Bohm energy spectrum reveals multi-zigzag periodic structures. The investigations of spin-dependent electron dynamics via Rabi oscillations in two-level and three-level systems demonstrate the possibility of manipulating quantum states. Our results show that the optimal control of photon-assisted inter-ring transitions can be achieved by employing cascade-type and $\Lambda$-type transition mechanisms. Under chirped pulse impulsions, a robust and complete transfer of an electron to the final state is shown to coincide with the estimation of the Landau-Zener formula.Comment: RevTex, 9 pages, 5 figure

Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations

Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase) activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.We are grateful to an NIHR award of a Biomedical Research Centre to Addenbrookes Hospital and the University of Cambridge. We are also grateful to the Rosetrees Trust, the WT-MRC Stem Cell Institute and the Canadian Institutes of Health Research (CIHR) fellowship (358492) for the funding for this work

Mapping Monte Carlo to Langevin dynamics: A Fokker-Planck approach

We propose a general method of using the Fokker-Planck equation (FPE) to link the Monte-Carlo (MC) and the Langevin micromagnetic schemes. We derive the drift and disusion FPE terms corresponding to the MC method and show that it is analytically equivalent to the stochastic Landau-Lifshitz-Gilbert (LLG) equation of Langevin-based micromagnetics. Subsequent results such as the time quantification factor for the Metropolis MC method can be rigorously derived from this mapping equivalence. The validity of the mapping is shown by the close numerical convergence between the MC method and the LLG equation for the case of a single magnetic particle as well as interacting arrays of particles. We also found that our Metropolis MC is accurate for a large range of damping factors $\alpha$, unlike previous time-quantified MC methods which break down at low $\alpha$, where precessional motion dominates.Comment: 4 pages, 4 figures. Accepted for publication in Phys. Rev. Let

Growth of GaN films on porous SiC substrate by molecular-beam epitaxy

Porous SiC (PSiC) substrates were used for the growth of GaN by reactive molecular-beam epitaxy with ammonia as the nitrogen source. Improved quality of GaNfilms has been demonstrated for growth on PSiC substrates, as compared to that on standard 6H–SiC substrates. Cross-sectional transmission electron microscopy and electron diffraction showed a reduction in dislocation density and a higher degree of lattice and thermal relaxation in the GaNfilmsgrown on porous substrates. The submicron GaNfilms exhibit a rocking curve linewidth of 3.3 arcmin for (0002) diffraction and 13.7 arcmin for (101̄2) diffraction. Low-temperature photoluminescence showed an excitonic transition with a full width at half maximum of 9.5 meV at 15 K, as well as high quantum efficiency, on the GaN layer grown on PSiC when the thin skin layer on porous SiC was removed before growth

Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an,. I optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ads). Patchy dendrimers bound to the surface of Ads formed a synthetic polymer corona that greatly altered various host interactions of Ads as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ads to blood coagulation factor X, one of the most critical virus host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ads with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications

A Tracker Solution for a Holographic Dark Energy Model

We investigate a kind of holographic dark energy model with the future event horizon the IR cutoff and the equation of state -1. In this model, the constraint on the equation of state automatically specifies an interaction between matter and dark energy. With this interaction included, an accelerating expansion is obtained as well as the transition from deceleration to acceleration. It is found that there exists a stable tracker solution for the numerical parameter $d>1$, and $d$ smaller than one will not lead to a physical solution. This model provides another possible phenomenological framework to alleviate the cosmological coincidence problem in the context of holographic dark energy. Some properties of the evolution which are relevant to cosmological parameters are also discussed.Comment: 10 pages, 3 figures; accepted for publication in Int.J.Mod.Phys.