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Ten new ruthenium compounds based on the N,N,N,N-chelate Me2bpbMe2 (bpb = 1,2-bis(pyridine-2-carboximido)benzene) have prepared and characterized by 1H NMR and IR spectroscopy. The monocarbonyl compound (Me2bpbMe2)Ru(CO)(H2O) compound was generated from the reaction of the free base Me2bpbMe2H2 with Ru3(CO)12 in refluxing DMF. Isoamyl nitrite reacts with this compound to yield the trans-addition nitrosyl alkoxide (Me2bpbMe2)Ru(NO)(O-i-C5H11). Nitrosothiols similarly add in a formal trans-addition manner to yield (Me2bpbMe2)Ru(NO)(SR/Ar) (SR/Ar = S-i-C5H11, SPh, SC6F4H, SC(Me)2CHNHC(O)Me) derivatives. The (Me2bpbMe2)Ru(NO)(O-i-C5H11) compound undergoes alkoxide exchange reactions with PhOH and HOC6F4H to generate (Me2bpbMe2)Ru(NO)(OPh) and (Me2bpbMe2)Ru(NO)(OC6F4H), respectively. The neutral alkoxide/aryloxide nitrosyl compounds exhibit higher NO bands (1809–1842 cm-1) relative to their thiolate analogues (1755–1823 cm-1). The X-ray crystal structures of (Me2bpbMe2)Ru(NO)(OPh), (Me2bpbMe2)Ru(NO)(OC6F4H), and (Me2bpbMe2)Ru(NO)(SPh), have been determined, and reveal linear axial (O)N–Ru–O/S linkages consistent with trans positioning of the NO and aryloxide and -thiolate groups, and near-linear Ru–N–O moieties (164–174°) consistent with these complexes being formulated as {RuNO}6 species. The electrooxidation behavior of (Me2bpbMe2)Ru(NO)(OC6F4H), (Me2bpbMe2)Ru(NO)(SC6F4H), and (Me2bpbMe2)Ru(NO)(SPh) were examined by cyclic voltammetry and IR spectroelectrochemistry in CH2Cl2. (Me2bpbMe2)Ru(NO)(OC6F4H) and (Me2bpbMe2)Ru(NO)(SC6F4H) display reversible first oxidations, whereas (Me2bpbMe2)Ru(NO)(SPh) displays an irreversible first oxidation with likely loss of the thiolate ligand. Chemical reactivity of (Me2bpbMe2)Ru(NO)(SPh) with H+ and Me+ results in the generation of the free thiol PhSH and thioether PhSMe, respectively. 

The electrochemistry and spectroelectrochemistry of Ru(porphyrin)(NO)(phenoxide) complexes indicate that initial one-electron oxidation results in structure-dependent net reactivity at the phenoxide ligand. 

Abstract Several studies have now described instances where G-rich sequences in promoters and enhancers regulate gene expression through forming G-quadruplex (G4) structures. Relatedly, our group recently identified 301 long genomic stretches significantly enriched for minimal G4 motifs (LG4s) in humans and found the majority of these overlap annotated enhancers, and furthermore, that the promoters regulated by these LG4 enhancers are similarly enriched with G4-capable sequences. While the generally accepted model for enhancer:promoter specificity maintains that interactions are dictated by enhancer- and promoter-bound transcriptional activator proteins, the current study tested an alternative hypothesis: that LG4 enhancers interact with cognate promoters via a direct G4:G4 DNA-based mechanism. This work establishes the nuclear proximity of LG4 enhancer:promoter pairs, biochemically demonstrates the ability of individual LG4 single-stranded DNAs (ssDNAs) to directly interact target promoter ssDNAs, and confirms that these interactions, as well as the ability of LG4 enhancers to activate target promoters in culture, are mediated by G4 DNA. 

Immune checkpoint inhibitors can stimulate antitumor immunity but can also induce toxicities termed immune-related adverse events (irAEs). Colitis is a common and severe irAE that can lead to treatment discontinuation. Mechanistic understanding of gut irAEs has been hampered because robust colitis is not observed in laboratory mice treated with checkpoint inhibitors. We report here that this limitation can be overcome by using mice harboring the microbiota of wild-caught mice, which develop overt colitis following treatment with anti-CTLA-4 antibodies. Intestinal inflammation is driven by unrestrained activation of IFNγ-producing CD4⁺T cells and depletion of peripherally induced regulatory T cells through Fcγ receptor signaling. Accordingly, anti-CTLA-4 nanobodies that lack an Fc domain can promote antitumor responses without triggering colitis. This work suggests a strategy for mitigating gut irAEs while preserving antitumor stimulating effects of CTLA-4 blockade. 

ABSTRACT MotivationSNAPSHOT USA is an annual, multicontributor camera trap survey of mammals across the United States. The growing SNAPSHOT USA dataset is intended for tracking the spatial and temporal responses of mammal populations to changes in land use, land cover and climate. These data will be useful for exploring the drivers of spatial and temporal changes in relative abundance and distribution, as well as the impacts of species interactions on daily activity patterns. Main Types of Variables ContainedSNAPSHOT USA 2019–2023 contains 987,979 records of camera trap image sequence data and 9694 records of camera trap deployment metadata. Spatial Location and GrainData were collected across the United States of America in all 50 states, 12 ecoregions and many ecosystems. Time Period and GrainData were collected between 1st August and 29th December each year from 2019 to 2023. Major Taxa and Level of MeasurementThe dataset includes a wide range of taxa but is primarily focused on medium to large mammals. Software FormatSNAPSHOT USA 2019–2023 comprises two .csv files. The original data can be found within the SNAPSHOT USA Initiative in the Wildlife Insights platform. 

Michelmore, R.W., Coaker, G. et 38 al. (2017). Foundational and translational research opportunities to improve plant health. Molec. Plant-Microbe Interact. 30:515-516. Full article on line: https://doi.org/10.1094/MPMI-01-17-0010-CR.