Notes

Serine-linked PARP1 auto-modification settings PARP chemical reply.
Radiation-tolerant materials are in great demand for safe operation and advancement of nuclear and aerospace systems. Nanostructuring is a key strategy to improve the radiation tolerance of materials. SiOC polymer-derived ceramics (PDCs) are unique synthetic nanocomposites consisting of β-SiC nanocrystals and turbostratic graphite distributed in amorphous SiOC matrix, which are "all-rounder" materials for many advanced structural and functional applications. Radiation effects in the crystalline-amorphous system have been investigated in detail by experiments and molecular dynamics (MD) simulations. The results indicate that the amorphous SiOC structure retains amorphous accompanied by redistribution of the Si-containing tetrahedra. The graphite is shown to amorphize more easily than β-SiC nanocrystals under the same irradiation condition. The sample richer in oxygen, namely, containing more amorphous SiOC, shows less disordering of graphite, resulting from greater mitigation of radiation damage by the amorphous phase as efficient sinks. This study provides details of the microstructure evolution of SiOC PDCs under ion irradiation, as well as insights for the design and development of advanced ion damage-resistant materials.Membrane proteins participate in a broad range of cellular processes and represent more than 60% of drug targets. One approach to their structural analyses is mass spectrometry (MS)-based footprinting including hydrogen/deuterium exchange (HDX), fast photochemical oxidation of proteins (FPOP), and residue-specific chemical modification. Studying membrane proteins usually requires their isolation from the native lipid environment, after which they often become unstable. To overcome this problem, we are pursuing a novel methodology of incorporating membrane proteins into saposin A picodiscs for MS footprinting. We apply different footprinting approaches to a model membrane protein, mouse ferroportin, in picodiscs and achieve high coverage that enables the analysis of the ferroportin structure. FPOP footprinting shows extensive labeling of the extramembrane regions of ferroportin and protection at its transmembrane regions, suggesting that the membrane folding of ferroportin is maintained throughout the labeling process. In contrast, an amphipathic reagent, N-ethylmaleimide (NEM), efficiently labels cysteine residues in both extramembrane and transmembrane regions, thereby affording complementary footprinting coverage. Finally, optimization of sample treatment gives a peptic-map of ferroportin in picodiscs with 92% sequence coverage, setting the stage for HDX. These results, taken together, show that picodiscs are a new platform broadly applicable to mass spectrometry studies of membrane proteins.Colloidal inorganic nanostructures (metal, carbon, and silica) have been widely used as "nanoquenchers" for construction of nanosensors; however, inherent drawbacks such as insufficient fluorescence quenching efficiency, false positive signals, and uncertain long-term cytotoxicity have limited their further utility. Herein, by taking advantages of polymeric nanoparticles (PNPs) in terms of high loading capacity, facile surface modification chemistry, and good biocompatibility, we report a broad-spectrum (400-750 nm) polymeric fluorescence-quenching platform for sensor fabrication. Our newly developed polymeric nanoquenchers (qPNPs) were constructed by concurrently encapsulating various alkylated black-hole quenchers into nanoparticles made of poly(methyl methacrylate-co-methacrylic acid) and were found to have an excellent fluorescence quenching effect (>400-fold) on common fluorophores (FAM, TMR, and Cy5) together with high stability under physiological conditions. As a proof of concept, the feasibility of te construction of more complex biosensors in the future.Tight stacking between two-dimensional (2D) sheet-like materials, such as graphene, in the solid state is a major challenge hindering their applications, especially in the gas sensing field. Here, we report on a TiO2 nanoparticle-spaced reduced graphene oxide (RGO) assembly for the design of highly sensitive gas sensors. The TiO2 nanospacers are derived from a 2D MXene that is intercalated between RGO sheets. The produced TiO2-spaced RGO assembly exhibits a uniform nanoparticle distribution and highly wrinkled RGO sheets that interconnect in micrometer-scale pores. The space limitation between adjacent RGO sheets can restrict the particle growth and lead to the formation of TiO2 nanoparticles with uniform diameters of ca. 6.2 nm. The sensitivity of the TiO2-spaced RGO sensor to NO2 improved by over 400% in comparison with pure RGO due to the more available surface area and active adsorption sites. Furthermore, fast response and recovery, excellent selectivity and flexibility, and reliable workability in a humid environment (with the relative humidity ranging from 5 to 95%) were also simultaneously achieved, demonstrating great potential for next-generation wearable sensors.ConspectusRecently, alkene dicarbofunctionalization, i.e., the powerful organic synthesis method of alkene difunctionalization with two carbon sources, emerged as a formidable reaction with immense promise to synthesize complex molecules expeditiously from simple chemicals. This reaction is generally achieved with transition metals (TMs) through interception by carbon sources of an alkylmetal [β-H-C(sp3)-[M]] species, a key intermediate prone to undergo rapid β-H elimination. Related prior reports, since Paolo Chiusoli and Catellani's work in 1982 [ Tetrahedron Lett. 1982, 23, 4517], have used bicyclic and disubstituted terminal alkenes, wherein β-H elimination is avoided by geometric restriction or complete lack of β-H's. With reasoning that β-H-C(sp3)-[M] intermediates could be rendered amenable to interception with the use of first row late TMs and formation of coordination-assisted transient metallacycles, these two strategies were implemented to address the β-H elimination problem in alkene dicarbofunctil halides, and aryl halides to afford complex carbo- and heterocycles. In addition, forming coordination-assisted transient nickellacycles enabled regioselective performance of three-component dicarbofunctionalization of various alkenyl compounds. In situ reaction of [M]-H with alkenes generated after β-H elimination induced an unprecedented metallacycle contraction process, in which six-membered metal-containing rings shrank to five-membered cycles, allowing creation of new carbon-carbon bonds at allylic (1,3) positions. Applications of these regioselective alkene dicarbofunctionalization reactions are discussed.The white sturgeon (Acipenser transmontanus) is an endangered ancient fish species that is known to be particularly sensitive to certain environmental contaminants, partly because of the uptake and subsequent toxicity of lipophilic pollutants prone to bioconcentration as a result of their high lipid content. To better understand the bioconcentration of organic contaminants in this species, toxicokinetic (TK) models were developed for the embryo-larval and subadult life stages. The embryo-larval model was designed as a one-compartment model and validated using whole-body measurements of benzo[a]pyrene (B[a]P) metabolites from a waterborne exposure to B[a]P. A physiologically based TK (PBTK) model was used for the subadult model. The predictive power of the subadult model was validated with an experimental data set of four chemicals. Results showed that the TK models could accurately predict the bioconcentration of organic contaminants for both life stages of white sturgeon within 1 order of magnitude of measured values. These models provide a tool to better understand the impact of environmental contaminants on the health and the survival of endangered white sturgeon populations.The Aer2 receptor from Pseudomonas aeruginosa has an O2-binding PAS-heme domain that stabilizes O2 via a Trp residue in the distal heme pocket. Trp rotates ∼90° to bond with the ligand and initiate signaling. Although the isolated PAS domain is monomeric, both in solution and in a cyanide-bound crystal structure, an unliganded structure forms a dimer. An overlay of the two structures suggests possible signaling motions but also predicts implausible clashes at the dimer interface when the ligand is bound. Moreover, in a full-length Aer2 dimer, PAS is sandwiched between multiple N- and C-terminal HAMP domains, which would feasibly restrict PAS motions. To explore the PAS dimer interface and signal-induced motions in full-length Aer2, we introduced Cys substitutions and used thiol-reactive probes to examine in vivo accessibility and residue proximities under both aerobic and anaerobic conditions. In vivo, PAS dimers were retained in full-length Aer2 in the presence and absence of O2, and the dimer interface was consistent with the isolated PAS dimer structure. O2-mediated changes were also consistent with structural predictions in which the PAS N-terminal caps move apart and the C-terminal DxT region moves closer together. The DxT motif links PAS to the C-terminal HAMP domains and was critical for PAS-HAMP signaling. Removing the N-terminal HAMP domains altered the distal PAS dimer interface and prevented signaling, even after signal-on lesions were introduced into PAS. selleck products The N-terminal HAMP domains thus facilitate the O2-dependent shift of PAS to the signal-on conformation, clarifying their role upstream of the PAS-sensing domain.Photodynamic/photothermal therapy (PDT/PTT) that deploys a near-infrared responsive nanosystem is emerging to be a promising modality in cancer treatment. It is highly desirable to have a multifunctional nanosystem that can be used for efficient tumor targeting and inhibiting metastasis/recurrence of cancer. In the current study, self-assembled chlorophyll-rich fluorosomes derived from Spinacia oleracea were developed. These fluorosomes were co-assembled on a polydopamine core, forming camouflaged nanoparticles (SPoD NPs). The SPoD NPs exhibited a commingled PDT/PTT (i.e., interdependent PTT and PDT) that inhibited both normoxic and hypoxic cancer cell growth. These nanoparticles showed stealth properties with enhanced physiological stability and passive tumor targeting. SPoD NPs also exhibited tumor suppression by synergistic PTT and PDT. It also prevented lung metastasis and splenomegaly in tumor-bearing Balb/c mice. Interestingly, treatment with SPoD NPs also caused the suppression of secondary tumors by eliciting an anti-tumor immune response. In conclusion, a co-assembled multifunctional nanosystem derived from S. oleracea showed enhanced stability and tumor-targeting efficacy, resulting in a commingled PDT/PTT effect.Cell-free systems have become a compelling choice for the prototyping of synthetic circuits. Many robust protocols for preparing cell-free systems are now available along with toolboxes designed for a variety of applications. Thus far, the production of cell-free extracts has often been decoupled from the production of functionalized proteins. Here, we leveraged a recent protocol for producing an E. coli-based cell-free expression system with two CRISPR-associated proteins, Csy4 and dCas9, expressed prior to harvest. We found that pre-expression did not affect the resulting extract performance, and the final concentrations of the endonucleases matched the level required for synthetic circuit prototyping. We demonstrated the benefits and versatility of dCas9 and Csy4 through the use of RNA circuitry based on a combination of single guide RNAs, small transcriptional activator RNAs, and toehold switches. For instance, we show that Csy4 processing increased 4-fold the dynamic range of a previously published AND-logic gate.
Homepage: https://www.selleckchem.com/