Zhu et al. report the identification of CD112R as a new coinhibitory receptor of the TIGIT–DNAM-1 family for human T cells.
Adenosine-to-inosine (A-to-I) editing of eukaryotic cellular RNAs is essential for protection against auto-immune disorders. Editing is carried out by ADAR1, whose innate immune response-specific cytoplasmic isoform possesses a Z-DNA binding domain (Zα) of unknown function. Zα also binds to CpG repeats in RNA, which are a hallmark of Z-RNA formation. Unexpectedly, Zα has been predicted — and in some cases even shown — to bind to specific regions within mRNA and rRNA devoid of such repeats. Here, we use NMR, circular dichroism, and other biophysical approaches to demonstrate and characterize the binding of Zα to mRNA and rRNA fragments. Our results reveal a broad range of RNA sequences that bind to Zα and adopt Z-RNA conformations. Binding is accompanied by destabilization of neighboring A-form regions which is similar in character to what has been observed for B-Z-DNA junctions. The binding of Zα to non-CpG sequences is specific, cooperative and occurs with an affinity in the low micromolar range. This work allows us to propose a model for how Zα could influence the RNA binding specificity of ADAR1.
We have designed de novo and synthesized ten 26-residue D-conformation amphipathic α-helical cationic antimicrobial peptides (AMPs), seven with “specificity determinants”, which provide specificity for prokaryotic cells over eukaryotic cells. The ten AMPs contain five or six positively charged residues (D-Arg, D-Lys, D-Orn, L-Dab, or L-Dap) on the polar face to understand their role in hemolytic activity against human red blood cells and antimicrobial activity against seven Acinetobacter baumannii strains, resistant to polymyxin B and colistin, and 20 A. baumannii worldwide isolates from 2016 and 2017 with antibiotic resistance to 18 different antibiotics. AMPs with specificity determinants and with L-Dab and L-Dap residues on the polar face have essentially no hemolytic activity at 1000 μg/mL (380 μM), showing for the first time the importance of these unusual amino acid residues in solving longstanding hemolysis issues of AMPs. Specificity determinants maintained excellent antimicrobial activity in the presence of human sera.
The recent expansion in the use of nanomaterials in consumer and industrial applications has led to a growing concern over their behavior, fate, and impacts in environmental systems. However, engineered nanoparticles comprise only a small fraction of the total nanoparticle mass in aquatic systems. Human activities, particularly in urban watersheds, are increasing the population of incidental nanoparticles and are likely altering the cycling of more abundant natural nanoparticles. Accurate detection, quantification, characterization, and tracking of these different populations is important for assessing both the ecological risks of anthropogenic particles, and their impact on environmental health. The urban portion of the South Platte watershed in Denver, Colorado (United States) was sampled for zinc to identify and quantify different nanomaterial sources. Single particle ICP-QMS was employed, to provide single elemental (Zn) signals arising from particle detection events. Coupling spICP-QMS to sample pre-fractionation (sedimentation, filtration) provided some insights into Zn association with nanoparticulate, colloidal, and suspended sediment phases. Single particle ICP-TOFMS (spICP-TOFMS) provided quantification across a large atomic mass range, yielding an even more detailed characterization (elemental ratios) on a particleby-particle basis, providing some delineation of multiple sources of particles. Across the watershed, on average, 21% of zinc mass was present as zinc-only particles with a rather uniform mean size of 40.2 nm. Zinc that was detected with one or more other elements, primarily Al, Fe, and Si, is likely to be present as heteroagglomerates or within mineral colloids. Although spICP-TOFMS provides a substantial amount of information, it is still in its early stages as an analytical technique and currently lacks the requisite sensitivity to study the smallest of nanoparticles. As this technique continues to develop, it is anticipated that this methodology can be broadly applied to study sources, behavior and effects of a disparate variety of nanoparticles from both geogenic and anthropogenic origins.
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