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DNA methylation aberrancies are found in autosomal dominant polycystic kidney disease (ADPKD), which suggests the methylome to be a promising therapeutic target. However, the impact of combining DNA methylation inhibitors (DNMTi) and ADPKD drugs in treating ADPKD and on disease-associated methylation patterns has not been fully explored. To test this, ADPKD drugs, metformin and tolvaptan (MT), were delivered in combination with DNMTi 5-aza-2′-deoxycytidine (Aza) to 2D or 3D cystic Pkd1 heterozygous renal epithelial cells (PKD1-Het cells) as free drugs or within nanoparticles to enable direct delivery for future in vivo applications. We found Aza synergizes with MT to reduce cell viability and cystic growth. Reduced representation bisulfite sequencing (RRBS) was performed across four groups: PBS, Free-Aza (Aza), Free-Aza+MT (F-MTAza), and Nanoparticle-Aza+MT (NP-MTAza). Global methylation patterns showed that while Aza alone induces a unimodal intermediate methylation landscape, Aza+MT recovers the bimodality reminiscent of somatic methylomes. Importantly, site-specific methylation changes associated with F-MTAza and NP-MTAza were largely conserved including hypomethylation at ADPKD-associated genes. Notably, we report hypomethylation of cancer-associated genes implicated in ADPKD pathogenesis as well as new target genes that may provide additional therapeutic effects. Overall, this study motivates future work to further elucidate the regulatory mechanisms of observed drug synergy and apply these combination therapies in vivo. [ABSTRACT FROM AUTHOR]

We found that Drosophila species vary in their susceptibility to the broad-spectrum entomopathogen, Metarhizium anisopliae (strain Ma549). Generalist species were generally more resistant than dietary specialists, with the cactophilic Drosophila buzzatii and Drosophila sechellia, a specialist of the Morinda citrifolia (Morinda) fruit, being most susceptible. Morinda fruit is reported to be toxic to most herbivores because it contains Octanoic Acid (OA). We confirmed that OA is toxic to Drosophila spp., other than D. sechellia, and we also found that OA is highly toxic to entomopathogenic fungi including Ma549 and Beauveria bassiana. Drosophilasechellia fed a diet containing OA, even at levels much less than found in Morinda fruit, had greatly reduced susceptibility to Ma549. This suggests that specializing to Morinda may have provided an enemy-free space, reducing adaptive prioritization on a strong immune response. Our results demonstrate that M. anisopliae and Drosophila species with divergent lifestyles provide a versatile model system for understanding the mechanisms of host–pathogen interactions at different scales and in environmental context. [ABSTRACT FROM AUTHOR]

Climate change is amplifying both wildfire burned area and severity, as well as incidents of drought-induced tree mortality (dieback). Direct effects from climate change amplify wildfires and episodes of drought-induced dieback have well-known impacts on forest's ability to regulate climate, provide water, and store carbon. Less understood are how past disturbances produce interaction effects that can change subsequent disturbance occurrence and intensity, with implications for management decisions that can promote forest resistance and resilience. We constructed two parallel forest chrono-sequences by combining a geospatial database of historical fire with satellite and airborne observations of forests in the Sierra Nevada of California to assess the impact of fire history on vegetation recovery, water use (evapotranspiration), and drought-induced forest dieback. We used these data sets to assess two research questions: (1.) Does fire history amplify or reduce drought-dieback intensity? (2.) What mechanisms explain how fire-induced changes to forest structure and ET alter subsequent forest dieback intensity? We show that recent fire history decreased drought-induced forest dieback intensity, compared to unburned controls. These fire-affected forests were characterized by reduced tree cover and decreased evapotranspiration, which combined to increase drought resistance more than would be expected by either effect individually. Two decades post-fire, evapotranspiration returned to pre-fire conditions. Tree and shrub cover started to approach pre-fire conditions, except for high severity fires where decreased tree cover and increased shrub cover persisted. Field based research on fuels treatments suggests that fire history may also increase longer term forest resilience. In fire-prone conifer forests, interaction effects from recent low and moderate severity fires will increase drought resistance and perhaps longer-term forest stability. • Fire history reduced tree cover and water use and increased shrub cover. • Fire history decreased forest dieback intensity compared to unburned controls. • Reduced dieback intensity suggests an antagonistic interaction effect from fire history. • Prescribed fires and low and moderate severity wildfires increased forest resistance and perhaps resilience to drought. [ABSTRACT FROM AUTHOR]

Forest litterfall is pivotal for biogeochemical cycles and for assessing the impacts of perturbations on ecosystems. Typhoon occurrence is the primary mechanism for producing litterfall; Taiwan is situated in one of the most frequently disturbed regions. However, no typhoons were recorded in 2018, only occurring three times since 1911. This rare occasion, along with the regular (2017) and extreme typhoon (2016) years, provides an opportunity to investigate the responses of typhoon-prone forest ecosystems to a future climate scenario: Elevated temperatures amplify the intensity but reduce the frequency of typhoons. We compared three years (2016–2018) of summer typhoon season (July–October) mean monthly litterfall (MML) in the subtropical montane cloud forests of northeastern Taiwan, and investigated the relationships between MML/typhoon-induced MML (ΔMML) and 17 biophysical, bioclimatic and topographic attributes. More MML was produced in 2016, caused by strong winds and heavy rainfall. However, there was no statistical difference between 2017 and 2018 since forests may also produce substantial amounts of litterfall in summer without typhoons. The relationship between ΔMML and 17 variables was relatively insensitive to typhoon severity. Variables associated with succession and forest management were crucial for modeling MML in the presence of typhoons, but none of them were pivotal for MML without typhoons. The mean air temperature and elevation (related to forest productivity) were crucial for MML without typhoons; surface curvature may form shelters to prevent extreme typhoon with reduced MML. These outcomes may shed light on future ecosystem dynamics in typhoon-prone forests under a changing climate. [ABSTRACT FROM AUTHOR]

Nature‐based climate solutions are a vital component of many climate mitigation strategies, including California's, which aims to achieve carbon neutrality by 2045. Most carbon offsets in California's cap‐and‐trade program come from improved forest management (IFM) projects. Since 2012, various landowners have set up IFM projects following the California Air Resources Board's IFM protocol. As many of these projects approach their 10th year, we now have the opportunity to assess their effectiveness, identify best practices, and suggest improvements toward future protocol revisions. In this study, we used remote sensing‐based datasets to evaluate the carbon trends and harvest histories of 37 IFM projects in California. Despite some current limitations and biases, these datasets can be used to quantify carbon accumulation and harvest rates in offset project lands relative to nearby similar "control" lands before and after the projects began. Five lines of evidence suggest that the carbon accumulated in offset projects to date has generally not been additional to what might have otherwise occurred: (1) most forests in northwestern California have been accumulating carbon since at least the mid‐1980s and continue to accumulate carbon, whether enrolled in offset projects or not; (2) harvest rates were high in large timber company project lands before IFM initiation, suggesting they are earning carbon credits for forests in recovery; (3) projects are often located on lands with higher densities of low‐timber‐value species; (4) carbon accumulation rates have not yet increased on lands that enroll as offset projects, relative to their pre‐enrollment levels; and (5) harvest rates have not decreased on most project lands since offset project initiation. These patterns suggest that the current protocol should be improved to robustly measure and reward additionality. In general, our framework of geospatial analyses offers an important and independent means to evaluate the effectiveness of the carbon offsets program, especially as these data products continue improving and as offsets receive attention as a climate mitigation strategy. [ABSTRACT FROM AUTHOR]

Temperature increases across the circumpolar north have driven rapid increases in vegetation productivity, often described as 'greening'. These changes have been widespread, but spatial variation in their pattern and magnitude suggests that biophysical factors also influence the response of tundra vegetation to climate warming. In this study, we used field sampling of soils and vegetation and random forests modeling to identify the determinants of trends in Landsat-derived Enhanced Vegetation Index, a surrogate for productivity, in the Beaufort Delta region of Canada between 1984 and 2016. This region has experienced notable change, with over 71% of the Tuktoyaktuk Coastlands and over 66% of the Yukon North Slope exhibiting statistically significant greening. Using both classification and regression random forests analyses, we show that increases in productivity have been more widespread and rapid at low-to-moderate elevations and in areas dominated by till blanket and glaciofluvial deposits, suggesting that nutrient and moisture availability mediate the impact of climate warming on tundra vegetation. Rapid greening in shrub-dominated vegetation types and observed increases in the cover of low and tall shrub cover (4.8% and 6.0%) also indicate that regional changes have been driven by shifts in the abundance of these functional groups. Our findings demonstrate the utility of random forests models for identifying regional drivers of tundra vegetation change. To obtain additional fine-grained insights on drivers of increased tundra productivity, we recommend future research combine spatially comprehensive time series satellite data (as used herein) with samples of high spatial resolution imagery and integrated field investigations. [ABSTRACT FROM AUTHOR]