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The ability to design lateral gap-plasmon modes for enhanced frequency conversion may hold the potential to develop on-chip, background-free molecular sensors and low-threshold upconversion lasers.A vortex is a universal and significant phenomenon that has been known for centuries. However, creating vortices to the atomic limit has remained elusive. Very recently, it was demonstrated that intervalley scattering induced by the single carbon defect of graphene leads to phase winding over a closed path surrounding the defect. Motivated by this, we demonstrate that the single carbon defects at A and B sublattices of graphene can be regarded as pseudospin-mediated atomic-scale vortices with angular momenta l = +2 and -2, respectively. The quantum interference measurements of the vortices indicate that the vortices cancel each other, resulting in zero total angular momentum, in the |A| = |B| case, and they show aggregate chirality and angular momenta similar to a single vortex of the majority in the |A| ≠ |B| case, where |A| (|B|) is the number of vortices with angular momenta l = +2 (l = -2).Inducing immune tolerance through repeated administration of self-antigens is a promising strategy for treating rheumatoid arthritis (RA), and current research indicates that coadministration of immunomodulators can further orchestrate the tolerogenic response. However, most of the clinical trials based on tolerance induction have negligible therapeutic effects. Peripheral lymphoid organs play critical roles in immunotherapy. A-366 nmr Here, we design an engineered nanoemulsion for targeted codelivery of self-antigens and an immunomodulator to ectopic lymphoid structures (ELSs) in inflamed joints of RA. Namely, a citrullinated multiepitope self-antigen (CitP) and rapamycin are incorporated into the nanoemulsions (NEs@CitP/Rapa), which are fabricated by a facial method using commercialized pharmaceutical excipients. After intravenous administration, the nanoemulsion shows satisfactory accumulation in the inflamed paws and provides enhanced anti-inflammatory effect in various experimental murine models of RA. Our study provides a promising targeting strategy to induce immune tolerance for the treatment of RA.Earlier experiments suggest that the evolutionary information (conservation and coevolution) encoded in protein sequences is necessary and sufficient to specify the fold of a protein family. However, there is no computational work to quantify the effect of such evolutionary information on the folding process. Here we explore the role of early folding steps for sequences designed using coevolution and conservation through a combination of computational and experimental methods. We simulated a repertoire of native and designed WW domain sequences to analyze early local contact formation and found that the N-terminal β-hairpin turn would not form correctly due to strong non-native local contacts in unfoldable sequences. Through a maximum likelihood approach, we identified five local contacts that play a critical role in folding, suggesting that a small subset of amino acid pairs can be used to solve the “needle in the haystack” problem to design foldable sequences. Thus, using the contact probability of those five local contacts that form during the early stage of folding, we built a classification model that predicts the foldability of a WW sequence with 81% accuracy. This classification model was used to redesign WW domain sequences that could not fold due to frustration and make them foldable by introducing a few mutations that led to the stabilization of these critical local contacts. The experimental analysis shows that a redesigned sequence folds and binds to polyproline peptides with a similar affinity as those observed for native WW domains. Overall, our analysis shows that evolutionary-designed sequences should not only satisfy the folding stability but also ensure a minimally frustrated folding landscape.The addition reaction of halogens to alkenes is important in organic synthesis, but the reaction intermediate has rarely been detected. Whether the structure of the intermediate bromoethyl (C2H4Br•) radical is a bridged form or an open form is unclear. We took advantage of the diminished cage effect of solid p-H2 and employed infrared (IR) absorption to record the IR spectrum of C2H4Br• after photolysis of a C2H4/Br2/p-H2 matrix at 254 nm, followed by annealing. New spectral features at 676.9, 776.7, 1068.5, 1148.0, 3041.8, and 3126.8 cm-1 are assigned to the open-form 2-bromoethyl radical, according to their photolytic behavior and comparison with scaled harmonic vibrational wavenumbers and IR intensities calculated with the B2PLYPD3/6-311++G(2df,2p) method.Circulating extracellular vesicles (EVs)-biological nanomaterials shed from most mammalian cells-have emerged as promising biomarkers, drug delivery vesicles, and treatment modulators. While different types of vesicles are being explored for these applications, it is becoming clear that human EVs are quite heterogeneous even in homogeneous or monoclonal cell populations. Since it is the surface EV protein composition that will largely dictate their biological behavior, high-throughput single EV profiling methods are needed to better define EV subpopulations. Here, we present an antibody-based immunosequencing method that allows multiplexed measurement of protein molecules from individual nanometer-sized EVs. We use droplet microfluidics to compartmentalize and barcode individual EVs. The barcodes/antibody-DNA are then sequenced to determine protein composition. Using this highly sensitive technology, we detected specific proteins at the single EV level. We expect that this technology can be further adapted for multiplexed protein analysis of any nanoparticle.Halogen bonds (XBs) are noncovalent interactions where halogen atoms act as electrophilic species interacting with Lewis bases. These interactions are relevant in biochemical systems being increasingly explored in drug discovery, mainly to modulate protein-ligand interactions, but are also found in engineered protein or nucleic acid systems. In this work, we report direct evidence for the existence of XBs in the context of biological membrane systems, thus expanding the scope of application of these interactions. Indeed, our molecular dynamics simulations show the presence of favorable interactions between halobenzene derivatives and both phosphate or ester oxygen acceptors from a model phospholipid bilayer, thus supporting the existence of XB-mediated phospholipid-halogen recognition phenomena influencing the membrane insertion profile of the ligands and their orientational preferences. This represents a relevant interaction, previously overlooked, eventually determining the pharmacological or toxicological activity of halogenated compounds and hence with potential implications in drug discovery and development, a place where such species account for a significant part of the chemical space.