Summary• Availability of growth limiting resources may alter root dynamics in forest ecosystems, possibly affecting the land-atmosphere exchange of carbon. This was evaluated for a commercially important southern timber species by installing a factorial experiment of fertilization and irrigation treatments in an 8-yr-old loblolly pine ( Pinus taeda ) plantation.• After 3 yr of growth, production and turnover of fine, coarse and mycorrhizal root length was observed using minirhizotrons, and compared with stem growth and foliage development.• Fertilization increased net production of fine roots and mycorrhizal roots, but did not affect coarse roots. Fine roots had average lifespans of 166 d, coarse roots 294 d and mycorrhizal roots 507 d. Foliage growth rate peaked in late spring and declined over the remainder of the growing season, whereas fine roots experienced multiple growth flushes in the spring, summer and fall.• We conclude that increased nutrient availability might increase carbon input to soils through enhanced fine root turnover. However, this will depend on the extent to which mycorrhizal root formation is affected, as these mycorrhizal roots have much longer average lifespans than fine and coarse roots.

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Conflict of interest:FC consults for Fate Therapeutics and has received research funds from this relationship. JSM serves on the Scientific Advisory Board (SAB) and consults for GT BioPharma and Fate Therapeutics. He has received research funds from these relationships. JSM also serves on the SAB for CytoSen and Onkimmune. BRB declares a financial conflict with Tmunity and Kadmon Corporation. He also serves on the SAB for GT Biopharma, Magenta Therapeutics, and Five Prime Therapeutics. He consults for Regeneron and Equillium Inc. None of these companies had a role in funding this research. All conflicts are managed according to institutional policies. Figure 1. Chronic stimulation through NKG2C expands adaptive NK cells. CD3/CD19-depleted PBMCs from HCMV-seropositive donors were cultured for 7 days with 10 ng/ml IL-15 and PBS, IgG2b isotype Ab, anti-NKG2A/C Ab, or anti-NKG2C Ab. (A) Representative FACS plots and summary data showing the percentages of NK cell subsets defined by expression of CD57 and NKG2C before and after a 7-day culture (n = 7). Results are from 3 independent experiments. (B) NK cells were labeled with CellTrace dye prior to culturing. Shown are FACS plots of representative donor cells stratified by CD57 and NKG2C expression and summary data (n = 6). Results are from 3 independent experiments. *P ≤ 0.05 by paired t test. P values for multiple group comparisons (A, each group vs. PBS; B, each group vs. IgG2b isotype Ab) were adjusted using the Hommel method.Study approval. The present studies involving the use of human peripheral blood products were reviewed and approved by the IRB of the University of Minnesota under protocol 9709M00134. All blood donors provided informed consent prior to donation according to Memorial Blood Bank policies. All blood samples were deidentified prior to arrival in the laboratory.

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Natural killer (NK) cells with adaptive immunological properties expand and persist in response to human cytomegalovirus. Here, we explored the metabolic processes unique to these cells. Adaptive CD3CD56CD57NKG2C NK cells exhibited metabolic hallmarks of lymphocyte memory, including increased oxidative mitochondrial respiration, mitochondrial membrane potential, and spare respiratory capacity. Mechanistically, we found that a short isoform of the chromatin-modifying transcriptional regulator, AT-rich interaction domain 5B (ARID5B), was selectively induced through DNA hypomethylation in adaptive NK cells. Knockdown and overexpression studies demonstrated that ARID5B played a direct role in promoting mitochondrial membrane potential, expression of genes encoding electron transport chain components, oxidative metabolism, survival, and IFN-γ production. Collectively, our data demonstrate that ARID5B is a key regulator of metabolism in human adaptive NK cells, which, if targeted, may be of therapeutic value.

Maturation of human natural killer cells (NK cells) as defined by accumulation of cell surface expression of CD57 is associated with increased cytotoxic character and TNF and IFN-γ production upon target cell recognition. Notably, multiple studies point to a unique role for CD57+ NK cells in cancer immunosurveillance, yet there is scant information about how they mature. In this study, we show that pharmacological inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL-15 greatly enhances CD57 upregulation and late-stage maturation. GSK3 inhibition elevated the expression of several transcription factors associated with late-stage NK cell maturation including T-BET, ZEB2 and BLIMP-1 without affecting viability or proliferation. When exposed to human cancer cells, NK cell expanded ex vivo in the presence of a GSK3 inhibitor exhibited significantly higher production of TNF and IFN-γ, elevated natural cytotoxicity, and increased antibody-dependent cellular cytotoxicity (ADCC). In an established mouse xenograft model of ovarian cancer, adoptive transfer of NK cells conditioned in the same way also displayed more robust and durable tumor control. Our findings show how GSK3 kinase inhibition can greatly enhance the mature character of NK cells most desired for effective cancer immunotherapy.

We used estimates of autotrophic respiration (R A ), net primary productivity (NPP) and soil CO 2 evolution (S ff ), to develop component carbon budgets for 12-year-old loblolly pine plantations during the fifth year of a fertilization and irrigation experiment. Annual carbon use in R A was 7.5, 9.0, 15.0, and 15.1 Mg C ha À1 in control (C), irrigated (I), fertilized (F) and irrigated and fertilized (IF) treatments, respectively. Foliage, fine root and perennial woody tissue (stem, branch, coarse and taproot) respiration accounted for, respectively, 37%, 24%, and 39% of R A in C and I treatments and 38%, 12% and 50% of R A in F and IF treatments. Annual gross primary production (GPP 5 NPP 1 R A ) ranged from 13.1 to 26.6 Mg C ha À1 . The I, F, and IF treatments resulted in a 21, 94, and 103% increase in GPP, respectively, compared to the C treatment. Despite large treatment differences in NPP, R A , and carbon allocation, carbon use efficiency (CUE 5 NPP/GPP) averaged 0.42 and was unaffected by manipulating site resources.Ecosystem respiration (R E ), the sum of S ff , and above ground R A , ranged from 12.8 to 20.2 Mg C ha À1 yr À1 . S ff contributed the largest proportion of R E , but the relative importance of S ff decreased from 0.63 in C treatments to 0.47 in IF treatments because of increased aboveground R A . Aboveground woody tissue R A was 15% of R E in C and I treatments compared to 25% of R E in F and IF treatments. Net ecosystem productivity (NEP 5 GPP-R E ) was roughly 0 in the C and I treatments and 6.4 Mg C ha À1 yr À1 in F and IF treatments, indicating that non-fertilized treatments were neither a source nor a sink for atmospheric carbon while fertilized treatments were carbon sinks. In these young stands, NEP is tightly linked to NPP; increased ecosystem carbon storage results mainly from an increase in foliage and perennial woody biomass.