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Spaceborne microwave remote sensing is widely used to monitor global environmental changes for understanding hydrological, ecological, and climate processes. A new global land parameter data record (LPDR) was generated using similar calibrated, multifrequency brightness temperature (Tb) retrievals from the Advanced Microwave Scanning Radiometer for EOS (AMSR-E) and the Advanced Microwave Scanning Radiometer 2 (AMSR2). The resulting LPDR provides a long-term (June 2002–December 2015) global record of key environmental observations at a 25 km grid cell resolution, including surface fractional open water (FW) cover, atmosphere precipitable water vapor (PWV), daily maximum and minimum surface air temperatures (Tmx and Tmn), vegetation optical depth (VOD), and surface volumetric soil moisture (VSM). Global mapping of the land parameter climatology means and seasonal variability over the full-year records from AMSR-E (2003–2010) and AMSR2 (2013–2015) observation periods is consistent with characteristic global climate and vegetation patterns. Quantitative comparisons with independent observations indicated favorable LPDR performance for FW (R ≥ 0.75; RMSE  ≤  0.06), PWV (R ≥ 0.91; RMSE  ≤  4.94 mm), Tmx and Tmn (R ≥ 0.90; RMSE  ≤  3.48 °C), and VSM (0.63 ≤ R ≤ 0.84; bias-corrected RMSE  ≤  0.06 cm3 cm−3). The LPDR-derived global VOD record is also proportional to satellite-observed NDVI (GIMMS3g) seasonality (R ≥ 0.88) due to the synergy between canopy biomass structure and photosynthetic greenness. Statistical analysis shows overall LPDR consistency but with small biases between AMSR-E and AMSR2 retrievals that should be considered when evaluating long-term environmental trends. The resulting LPDR and potential updates from continuing AMSR2 operations provide for effective global monitoring of environmental parameters related to vegetation activity, terrestrial water storage, and mobility and are suitable for climate and ecosystem studies. The LPDR dataset is publicly available at http://files.ntsg.umt.edu/data/LPDR_v2/.

Despite the success of chimeric antigen receptor T (CART) cell therapy in hematological malignancies, durable remissions remain low. Here, we report CART senescence as a potential resistance mechanism in 41BB-costimulated CART cell therapy. To mimic cancer relapse, we utilized an in vitro model with repeated CART cell activation cycles followed by rest periods. Using CD19-targeted CART cells with costimulation via 4-1BB-CD3ζ (BBζ) or CD28-CD3ζ (28ζ), we showed that CART cells undergo functional, phenotypical, and transcriptomic changes of senescence, which is more prominent in BBζ. We then utilized two additional independent strategies to induce senescence through MYC activation and irradiation. Induction of senescence impaired BBζ activity but improved 28ζ activity in preclinical studies. These findings were supported by analyses of independent patient data sets; senescence signatures in CART cell products were associated with non-response to BBζ but with improved clinical outcomes in 28ζ treatment. In summary, our study identifies senescence as a potential mechanism of failure predominantly in 41BB-costimulated CART cells. Significance We identified senescence as a cause of failure in CART cell therapy, predominantly in 4-1BB-costimulated CART cells.

Hydrologic cycle intensification is an expected manifestation of a warming climate. Although positive trends in several global average quantities have been reported, no previous studies have documented broad intensification across elements of the Arctic freshwater cycle (FWC). In this study we examine the character and quantitative significance of changes in annual precipitation, evapotranspiration, and river discharge across the terrestrial pan-Arctic over the past several decades from observations and a suite of coupled general circulation models (GCMs). Trends in freshwater flux and storage derived from observations across the Arctic Ocean and surrounding seas are also described. With few exceptions, precipitation, evapotranspiration, and river discharge fluxes from observations and the GCMs exhibit positive trends. Significant positive trends above the 90% confidence level, however, are not present for all of the observations. Greater confidence in the GCM trends arises through lower inter-annual variability relative to trend magnitude. Put another way, intrinsic variability in the observations limits our confidence in the robustness of their increases. Ocean fluxes are less certain, due primarily to the lack of long-term observations. Where available, salinity and volume flux data suggest some decrease in salt-water inflow to the Barents Sea (i.e., a decrease in freshwater outflow) in recent decades. A decline in freshwater storage across the central Arctic Ocean and suggestions that large-scale circulation plays a dominant role in freshwater trends raise questions as to whether Arctic Ocean freshwater flows are intensifying. Although oceanic fluxes of freshwater are highly variable and consistent trends are difficult to verify, the other components of the Arctic FWC do show consistent positive trends over recent decades. The broad-scale increases provide evidence that the Arctic FWC is experiencing intensification. Efforts which aim to develop an adequate observation system are needed to reduce uncertainties and to detect and document ongoing changes in all system components for further evidence of Arctic FWC intensification.

Bacteria and fungi drive the decomposition of dead plant biomass (litter), an important step in the terrestrial carbon cycle. Here we investigate the sensitivity of litter microbial communities to simulated global change (drought and nitrogen addition) in a California annual grassland. Using 16S and 28S rDNA amplicon pyrosequencing, we quantify the response of the bacterial and fungal communities to the treatments and compare these results to background, temporal (seasonal and interannual) variability of the communities. We found that the drought and nitrogen treatments both had significant effects on microbial community composition, explaining 2–6% of total compositional variation. However, microbial composition was even more strongly influenced by seasonal and annual variation (explaining 14–39%). The response of microbial composition to drought varied by season, while the effect of the nitrogen addition treatment was constant through time. These compositional responses were similar in magnitude to those seen in microbial enzyme activities and the surrounding plant community, but did not correspond to a consistent effect on leaf litter decomposition rate. Overall, these patterns indicate that, in this ecosystem, temporal variability in the composition of leaf litter microorganisms largely surpasses that expected in a short-term global change experiment. Thus, as for plant communities, future microbial communities will likely be determined by the interplay between rapid, local background variability and slower, global changes.

In a randomized, placebo-controlled trial involving children 6 months to 5 years of age, the mRNA-1273 vaccine was shown to be safe, and the elicited antibody responses were similar to those in young adults.

The authors assessed transmission of SARS-CoV-2 and evaluated the adequacy of symptom-based screening in a skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission.

Preventable vitamin D deficiency (VDD) is a global health concern. The prevention, early detection, and treatment of vitamin D deficiency aligning with serum 25-hydroxyvitamin D concentration recommendations of 40–60 ng/mL (100–150 nmol/L), provided by an international panel of 48 vitamin D researchers, would result in significant health benefits and cost savings to individuals and society. However, research shows that healthcare professionals lack knowledge and confidence in best practices with respect to vitamin D. A vitamin D toolkit was developed that included a model for decision-making support, e-tools, and accompanying resources and was implemented using an online, asynchronous learning management system. This pre-test, post-test, and follow-up survey study design aimed to increase nurses’ and dietitians’ levels of knowledge and confidence regarding vitamin D, aid in their translation of evidence into spheres of practice and influence, and help them identify translation barriers. The completion of the toolkit increased the participants’ (n = 119) knowledge from 31% to 65% (p < 0.001) and their confidence from 2.0 to 3.3 (p < 0.001) on a scale of 1–5. Respondents reported using the model (100%) as a framework to successfully guide the translation of vitamin D knowledge into their sphere of influence or practice (94%) and identifying translation barriers. The toolkit should be included in interdisciplinary continuing education, research/quality improvement initiatives, healthcare policy, and institutions of higher learning to increase the movement of research into practice.

Global climate models suggest that many ecosystems will experience reduced precipitation over the next century and the consequences for invasive plant performance are largely unknown. Annual invasive species may be able to quickly evolve traits associated with drought escape or tolerance through rapid genetic changes. We investigated the influence of 5 years of water and nitrogen manipulations on trait values in a southern California grassland system. Seeds from two annual grass species (Avena barbata and Bromus madritensis) were collected from experimental plots and grown in a common environment over two generations. We measured 14 physiological, morphological, phenological and reproductive traits. Both species displayed phenotypic differences depending on the water treatment from which they were collected, but not depending on the nitrogen treatment. Both species displayed trait values characteristic of drought escape (e.g. earlier flowering in A. barbata and B. madritensis, lower water‐use efficiency in B. madritensis) when grown from the seeds collected from plots that experienced five years of reduced precipitation. Furthermore, A. barbata individuals grown from the seeds collected from drought plots had higher reproductive output and higher photosynthetic performance than individuals grown from water addition plots, with individuals grown from ambient plots displaying intermediate trait values. Notably, we found no phenotypic variation among treatments for six root traits. Synthesis. Trait differences were observed following two generations in a common garden, suggesting that treatment differences were genetically based. This suggests that populations were responding to selection over the 5 years of water manipulations, a remarkably short time period. The rapid evolutionary responses observed here may help these two widespread invasive grass species thrive under reduced precipitation scenarios, which could have important implications for fire dynamics, invasive species management and native plant restoration in communities invaded by annual grasses.

Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect ( ) demonstrated delayed early healing (days 1-3) and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D), Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in and was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect ( on a high-fat diet), improved wound healing was seen at late time points (days 6-7). These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.

One primary goal at the intersection of community ecology and global change biology is to identify functional traits that are useful for predicting plant community response to global change. We used observations of community composition from a long‐term field experiment in two adjacent plant communities (grassland and coastal sage shrub) to investigate how nine key plant functional traits were related to altered water and nitrogen availability following fire. We asked whether the functional responses of species found in more than one community type were context dependent and whether community‐weighted mean and functional diversity were significantly altered by water and nitrogen input. Our results suggest varying degrees of context dependency. We found that plants with high leaf nitrogen concentration (specifically nitrogen fixers), shallow roots, and low leaf mass per unit area and plant‐level transpiration were similarly negatively influenced by added nitrogen across community types. In contrast, responses to water manipulations exhibited greater context dependency; plants with high water‐use efficiency, lower plant‐level transpiration rates, and shallower roots were negatively impacted by simulated drought in the shrub‐dominated community, but there was no significant relationship between these traits and changes in water inputs in the grassland community. Similarly, we found context dependency in community‐wide trait responses to global change. Functional diversity tended to be higher in plots with reduced water as compared to those with added water in grassland, while the opposite trend was observed in coastal sage scrub. Our results indicate that some traits are strong predictors of species and community response to altered water and nitrogen availability, but the magnitude and direction of the response may be modulated by the abiotic and biotic context.