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Guanine-rich nucleic acid sequences can adopt G-quadruplex (G4) structures, which pose barriers to DNA replication and repair. The FANCJ helicase contributes to genome stability by resolving these structures, a function linked to its G4-binding site that features an AKKQ amino acid motif. This site is thought to recognize oxidatively damaged G4, specifically those containing 8-oxoguanine (8oxoG) modifications. We hypothesize that FANCJ AKKQ recognition of 8oxoG-modified G4s (8oxoG4s) depends on the sequence context, the position of the lesion within the G4, and overall structural stability. Using fluorescence spectroscopy, we measured the binding affinities of a FANCJ AKKQ peptide for G4s formed by (GGGT)4, (GGGTT)4, and (TTAGGG)4 sequences. G4 conformation and thermal stability were assessed by circular dichroism spectroscopy. Each sequence was modified to include a single 8oxoG at the first (8oxo1), third (8oxo3), or fifth (8oxo5) guanine position. In potassium chloride (KCl), the most destabilized structures were (GGGT)4 8oxo1, (GGGTT)4 8oxo1, and (TTAGGG)4 8oxo5. In sodium chloride (NaCl), the most destabilized were (GGGT)4 8oxo1, (GGGTT)4 8oxo5, and (TTAGGG)4 8oxo5. FANCJ AKKQ binding affinities varied according to damage position and sequence context, with notable differences for (GGGT)4 in KCl and (TTAGGG)4 in NaCl. These findings support a model in which FANCJ binding to G4 and 8oxoG4 structures is modulated by both the oxidative damage position and the G4 local sequence environment.more » « lessFree, publicly-accessible full text available August 1, 2026
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Free, publicly-accessible full text available November 19, 2026
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Coastal wetlands can store carbon by sequestering more carbon through primary production than they release though biogenic greenhouse gas production. The joint effects of saltwater intrusion and sea level rise (SWISLR) and changing precipitation patterns alter sulfate and oxygen availability, challenging estimates of biogenic greenhouse gas emissions. Iron-rich soils have been shown to buffer soil sulfidization by sequestering sulfide into iron-sulfide. But as SWISLR increases soil sulfate concentrations, sulfide produced via sulfate reduction will likely exceed the buffering capacity of soil iron, allowing toxic sulfide levels to accumulate. We used a soil mesocosm approach to examine the influence of hydrology (wet, dry, interim) and plant presence (with or without plants) on wetland soils sourced from different hydrologic histories at a restored coastal wetland. We hypothesized that reducing conditions (i.e., flooded, no plants) impact anaerobic metabolisms similarly, whereas oxidizing conditions (i.e., dry, plant presence) disrupt coupled sulfate reduction and iron reduction. Over eight weeks of hydrologic manipulation, 16S rRNA amplicon sequencing and shotgun metagenomic sequencing were used to characterize microbial communities, while greenhouse gas fluxes, soil redox potential, and physicochemical properties were measured. Results showed that contemporary hydrologic treatment affected assimilatory sulfate reduction gene composition, and hydrologic history influenced dissimilatory sulfate reduction and iron reduction gene composition. Sulfate and iron reduction genes were correlated, and dissimilatory sulfate reduction genes explained variance in methane fluxes. These findings highlight the role of historical hydrology, potential saltwater exposure, and soil iron in shaping microbial responses to future changes in soil moisture and salinity.more » « lessFree, publicly-accessible full text available March 5, 2026
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Abstract Phototherapy approaches include photodynamic therapy (PDT), which utilizes chemically stable photocatalysts to sensitize the conversion of endogenous molecules such as oxygen (O2) to form transient reactive species such as1O2, and photopharmacology, a complementary approach that relies on molecules that undergo self‐modifying photochemistry, such as bond cleavage reactions or isomerization, for the creation of biologically active products. While Ru(II) polypyridyl systems have demonstrated utility for both approaches, related organometallic systems are relatively less explored. Here, the photochemistry and photobiological responses were compared for five Ru(II) arene compounds containing photolabile monodentate azine ligands and the π‐expansive bidentate ligands dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz), 4,5,9,16‐tetraaza‐dibenzo[a,c]naphthacene (dppn), and α‐terthienyl‐appended imidazo[4,5‐f][1,10]phenanthroline (IP‐3T). The compounds demonstrated significant light‐mediated photocytotoxicity in lung cancer and melanoma cell lines, with up to 6000‐fold increases in cytotoxicity upon irradiation. The arene systems were capable of partitioning between different excited state relaxation pathways, both releasing the monodentate ligand and generating1O2, but with notably low yields that did not correlate with the photocytotoxicity of the systems. The organometallic compounds exhibit less mixing of the metal‐associated and ligand‐centered excited states than analogous polypyridyl coordination compounds, providing a structurally, photochemically, and photobiologically distinct class of compounds that can support both metal‐ and ligand‐centered reactivity.more » « lessFree, publicly-accessible full text available October 16, 2026
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Biolayer interferometry (BLI) is a powerful tool that enables direct observations of protein-G4 interactions in real-time. In this article, we discuss the crucial aspects in conducting a BLI experiment by using the TAR DNA-binding protein (TDP43) and a G4 DNA formed by (GGGGCC)4 as a sample application. We also describe the necessary precautions in designing the DNA substrate and evaluating the signal contributions arising from nonspecific binding interactions. A comprehensive guide is included that details the necessary materials and reagents, experimental procedures, and data analysis methods for researchers who are interested in using BLI for similar studies. The insights provided in this article will allow researchers to harness the potential of BLI and unravel the complexities of protein-G4 interactions with precision and confidence.more » « less
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Linking neurobiology to relatively stable individual differences in cognition, emotion, motivation, and behavior can require large sample sizes to yield replicable results. Given the nature of between-person research, sample sizes at least in the hundreds are likely to be necessary in most neuroimaging studies of individual differences, regardless of whether they are investigating the whole brain or more focal hypotheses. However, the appropriate sample size depends on the expected effect size. Therefore, we propose four strategies to increase effect sizes in neuroimaging research, which may help to enable the detection of replicable between-person effects in samples in the hundreds rather than the thousands: (1) theoretical matching between neuroimaging tasks and behavioral constructs of interest; (2) increasing the reliability of both neural and psychological measurement; (3) individualization of measures for each participant; and (4) using multivariate approaches with cross-validation instead of univariate approaches. We discuss challenges associated with these methods and highlight strategies for improvements that will help the field to move toward a more robust and accessible neuroscience of individual differences.more » « less
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