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[This corrects the article DOI: 10.1371/journal.pone.0159909.].

Seedling establishment is a critical step that may ultimately govern tree species' distribution shifts under environmental change. Annual variation in the location of seed rain and microclimates results in transient "windows of opportunity" for tree seedling establishment across the landscape. These establishment windows vary at fine spatiotemporal scales that are not considered in most assessments of climate change impacts on tree species range dynamics and habitat displacement. We integrate field seedling establishment trials conducted in the southern Sierra Nevada and western Tehachapi Mountains of southern California with spatially downscaled grids of modeled water-year climatic water deficit (CWDwy) and mean August maximum daily temperature (Tmax) to map historical and projected future microclimates suitable for establishment windows of opportunity for Quercus douglasii, a dominant tree species of warm, dry foothill woodlands, and Q. kelloggii, a dominant of cooler, more mesic montane woodlands and forests. Based on quasi-binomial regression models, Q. douglasii seedling establishment is significantly associated with modeled CWDwy and to a lesser degree with modeled Tmax. Q. kelloggii seedling establishment is most strongly associated with Tmax and best predicted by a two-factor model including CWDwy and Tmax. Establishment niche models are applied to explore recruitment window dynamics in the western Tehachapi Mountains, where these species are currently widespread canopy dominants. Establishment windows are projected to decrease by 50-95%, shrinking locally to higher elevations and north-facing slopes by the end of this century depending on the species and climate scenario. These decreases in establishment windows suggest the potential for longer-term regional population declines of the species. While many additional processes regulate seedling establishment and growth, this study highlights the need to account for topoclimatic controls and interannual climatic variation when assessing how seedling establishment and colonization processes could be affected by climate change.

Refugia have long been studied from paleontological and biogeographical perspectives to understand how populations persisted during past periods of unfavorable climate. Recently, researchers have applied the idea to contemporary landscapes to identify climate change refugia, here defined as areas relatively buffered from contemporary climate change over time that enable persistence of valued physical, ecological, and socio-cultural resources. We differentiate historical and contemporary views, and characterize physical and ecological processes that create and maintain climate change refugia. We then delineate how refugia can fit into existing decision support frameworks for climate adaptation and describe seven steps for managing them. Finally, we identify challenges and opportunities for operationalizing the concept of climate change refugia. Managing climate change refugia can be an important option for conservation in the face of ongoing climate change.

Radiotherapy (RT) treatment is an important strategy for the management of non-small cell lung cancer (NSCLC). Local recurrence amongst patients with late-stage NSCLC remains a challenge. The loss of PTEN has been associated with radio-resistance. This study aimed to examine the efficacy of RT combined with ataxia telangiectasia-mutated Rad3-related (ATR) inhibition using Ceralasertib in phosphatase and tensin homolog (PTEN)-depleted NSCLC cells and to assess early inflammatory responses indicative of radiation pneumonitis (RP) after combined-modality treatment. Small hairpin RNA (shRNA) transfections were used to generate H460 and A549 PTEN-depleted models. Ceralasertib was evaluated as a single agent and in combination with RT in vitro and in vivo. Histological staining was used to assess immune cell infiltration in pneumonitis-prone C3H/NeJ mice. Here, we report that the inhibition of ATR in combination with RT caused a significant reduction in PTEN-depleted NSCLC cells, with delayed DNA repair and reduced cell viability, as shown by an increase in cells in Sub G1. Combination treatment in vivo significantly inhibited H460 PTEN-depleted tumour growth in comparison to H460 non-targeting PTEN-expressing (NT) cell-line-derived xenografts (CDXs). Additionally, there was no significant increase in infiltrating macrophages or neutrophils except at 4 weeks, whereby combination treatment significantly increased macrophage levels relative to RT alone. Overall, our study demonstrates that ceralasertib and RT combined preferentially sensitises PTEN-depleted NSCLC models in vitro and in vivo, with no impact on early inflammatory response indicative of RP. These findings provide a rationale for evaluating ATR inhibition in combination with RT in NSCLC patients with PTEN mutations. [ABSTRACT FROM AUTHOR]

Review of the climate science for severe convective storms, extreme precipitation, hurricanes and typhoons, and severe snowstorms and ice storms in the US shows that the ability to detect and attribute trends varies, depending on the phenomenon. A specific subset of extreme weather and climate types affecting the country is discussed to examine these extreme weather conditions. The categories of storms described were selected as they caused property damage and loss of life. The identification of an extreme occurrence was based on meteorological properties in place of the destructiveness. The primary purpose was to examine the scientific evidence for the prevailing capability to detect trends and understand their causes for certain weather types, including severe convective storms and hurricanes and typhoons.

Blue oak tree-ring chronologies correlate highly with winter–spring precipitation totals over California, with Sacramento and San Joaquin river stream flow, and with seasonal variations in the salinity gradient in San Francisco Bay. The convergence of fresh and saline currents can influence turbidity, sediment accumulation, and biological productivity in the estuary. Three selected blue oak chronologies were used to develop a 625-year-long reconstruction of the seasonal salinity gradient, or low salinity zone (LSZ), which provides a unique perspective on the interannual-to-decadal variability of this important estuarine habitat indicator. The reconstruction was calibrated with instrumental LSZ data for the winter–spring season, and explains 73% of the variance in the February–June position of the LSZ from 1956 to 2003. Because this calibration period post-dates the sweeping changes that have occurred to land cover, channel morphology, and natural streamflow regimes in California, the reconstruction provides an idealized estimate for how the LSZ might have fluctuated under the seasonal precipitation variations of the past 625 years, given the modern geometry and bathymetry of the estuary and land cover across the drainage basin. The February–June season integrates precipitation and runoff variability during the cool season, and does not extend into the late-summer dry season when LSZ extremes can negatively affect Sacramento–San Joaquin Delta (Delta) agriculture and some aquatic organisms. However, there is such strong inter-seasonal persistence in the instrumental LSZ data that precipitation totals during the cool season can strongly pre-condition LSZ position in late summer. The 625-year-long reconstruction indicates strong interannual and decadal variability, the frequent recurrence of consecutive 2-year LSZ maxima and minima, large-scale ocean atmospheric forcing, and an interesting asymmetrical influence of warm El Niño–Southern Oscillation (ENSO) events.

Long-term variations in climate (temperature and precipitation) in portions of California are not sufficiently well sampled in some remote areas lacking meteorological or hydrological stations. A combined strategy of small clusters of climate stations arranged from the coast to the mountains was adopted to guide the deployment of a network of new long-term monitoring sites. This strategy for the stations installed as part of this project was suggested through consultation with research and operational entities throughout the state but priority was given to stations located in the coastal environment and high elevations above the average winter snow line. A set of 15 sites had instruments installed to become a part of this study; they provide on-going measurements with 10-minute resolution, at elevations ranging from sea level to over 14,000 feet. Almost the entire range of elevation in California is now sampled for climate monitoring as a result of this project. Most stations are located where future site disruption is judged to be unlikely. A few sites were established to monitor particular climate elements such as wind, temperature or humidity. Coastal sites have shown very large differences in short vertical and horizontal distances, confirming the rationale for close spacing in certain settings. Measure data are posted immediately to the web. Methods to graph, summarize, and download the data have been working very well. Experimental techniques are showing that higher elevations appear to have begun warming significantly over the last 1-2 decades in comparison with lower elevation areas. The project motivated the development of the California Climate Tracker, a method for showing the climate history of the state and 11 subregions for the past 115 years. This tool is intended for a wide audience and can be accessed through the California Climate Data Archive and the Western Regional Climate Center.

Introduction: Radium-223 (223Ra) has been shown to have an overall survival benefit in metastatic castration-resistant prostate cancer (mCRPC) involving bone. Despite its increased clinical usage, relatively little is known regarding the mechanism of action of 223Ra at the cellular level. Methods: We evaluated the effects of 223Ra irradiation in a panel of cell lines and then compared them with standard X-ray and external alpha-particle irradiation, with a particular focus on cell survival and DNA damage repair kinetics. Results: 223Ra exposures had very high, cell-type-dependent RBE50% ranging from 7 to 15. This was significantly greater than external alpha irradiations (RBE50% from 1.4 to 2.1). These differences were shown to be partially related to the volume of 223Ra solution added, independent of the alpha-particle dose rate, suggesting a radiation-independent mechanism of effect. Both external alpha particles and 223Ra exposure were associated with delayed DNA repair, with similar kinetics. Additionally, the greater treatment efficacy of 223Ra was associated with increased levels of residual DNA damage and cell death by mitotic catastrophe. Conclusions: These results suggest that 223Ra exposure may be associated with greater biological effects than would be expected by direct comparison with a similar dose of external alpha particles, highlighting important challenges for future therapeutic optimization. [ABSTRACT FROM AUTHOR]