The fate of carbon in a mature forest under carbon dioxide enrichment.

Atmospheric carbon dioxide enrichment (eCO2) can enhance plant carbon uptake and growth1-5, thereby providing an important negative feedback to climate change by slowing the rate of increase of the atmospheric CO2 concentration6. Although evidence gathered from young aggrading forests has generally indicated a strong CO2 fertilization effect on biomass growth3-5, it is unclear whether mature forests respond to eCO2 in a similar way. In mature trees and forest stands7-10, photosynthetic uptake has been found to increase under eCO2 without any apparent accompanying growth response, leaving the fate of additional carbon fixed under eCO2 unclear4,5,7-11. Here using data from the first ecosystem-scale Free-Air CO2 Enrichment (FACE) experiment in a mature forest, we constructed a comprehensive ecosystem carbon budget to track the fate of carbon as the forest responded to four years of eCO2 exposure. We show that, although the eCO2 treatment of +150 parts per million (+38 per cent) above ambient levels induced a 12 per cent (+247 grams of carbon per square metre per year) increase in carbon uptake through gross primary production, this additional carbon uptake did not lead to increased carbon sequestration at the ecosystem level. Instead, the majority of the extra carbon was emitted back into the atmosphere via several respiratory fluxes, with increased soil respiration alone accounting for half of the total uptake surplus. Our results call into question the predominant thinking that the capacity of forests to act as carbon sinks will be generally enhanced under eCO2, and challenge the efficacy of climate mitigation strategies that rely on ubiquitous CO2 fertilization as a driver of increased carbon sinks in global forests.

Testing the link between community structure and function for ectomycorrhizal fungi involved in a global tripartite symbiosis.

Alnus trees associate with ectomycorrhizal (ECM) fungi and nitrogen-fixing Frankia bacteria and, although their ECM fungal communities are uncommonly host specific and species poor, it is unclear whether the functioning of Alnus ECM fungal symbionts differs from that of other ECM hosts. We used exoenzyme root tip assays and molecular identification to test whether ECM fungi on Alnus rubra differed in their ability to access organic phosphorus (P) and nitrogen (N) when compared with ECM fungi on the non-Frankia host Pseudotsuga menziesii. At the community level, potential acid phosphatase (AP) activity of ECM fungal root tips from A. rubra was significantly higher than that from P. menziesii, whereas potential leucine aminopeptidase (LA) activity was significantly lower for A. rubra root tips at one of the two sites. At the individual species level, there was no clear relationship between ECM fungal relative root tip abundance and relative AP or LA enzyme activities on either host. Our results are consistent with the hypothesis that ECM fungal communities associated with Alnus trees have enhanced organic P acquisition abilities relative to non-Frankia ECM hosts. This shift, in combination with the chemical conditions present in Alnus forest soils, may drive the atypical structure of Alnus ECM fungal communities.

Little evidence for niche partitioning among ectomycorrhizal fungi on spruce seedlings planted in decayed wood versus mineral soil microsites.

Ectomycorrhizal fungal (EMF) communities vary among microhabitats, supporting a dominant role for deterministic processes in EMF community assemblage. EMF communities also differ between forest and clearcut environments, responding to this disturbance in a directional manner over time by returning to the species composition of the original forest. Accordingly, we examined EMF community composition on roots of spruce seedlings planted in three different microhabitats in forest and clearcut plots: decayed wood, mineral soil adjacent to downed wood, or control mineral soil, to determine the effect of retained downed wood on EMF communities over the medium and long term. If downed and decayed wood provide refuge habitat distinct from that of mineral soil, we would expect EMF communities on seedlings in woody habitats in clearcuts to be similar to those on seedlings planted in the adjacent forest. As expected, we found EMF species richness to be higher in forests than clearcuts (P ≤ 0.01), even though soil nutrient status did not differ greatly between the two plot types (P ≥ 0.05). Communities on forest seedlings were dominated by Tylospora spp., whereas those in clearcuts were dominated by Amphinema byssoides and Thelephora terrestris. Surprisingly, while substrate conditions varied among microsites (P ≤ 0.03), especially between decayed wood and mineral soil, EMF communities were not distinctly different among microhabitats. Our data suggest that niche partitioning by substrate does not occur among EMF species on very young seedlings in high elevation spruce-fir forests. Further, dispersal limitations shape EMF community assembly in clearcuts in these forests.

Living donor kidney paired donation transplantation: experience as a founding member center of the National Kidney Registry.

Kidney paired donation (KPD) is a safe and effective means of transplantation for transplant candidates with willing but incompatible donors. We report our single-center experience with KPD through participation in the National Kidney Registry. Patient demographics, transplant rates, and clinical outcomes including delayed graft function (DGF), rejection, and survival were analyzed. We also review strategies employed by our center to maximize living donor transplantation through KPD. We entered 44 incompatible donor/recipient pairs into KPD from 9/2007 to 1/2011, enabling 50 transplants. Incompatibility was attributable to blood type (54.4%) and donor-specific sensitization (43.2%). Thirty-six candidates (81.8%) were transplanted after 157 d (median), enabling pre-emptive transplantation in eight patients. Fourteen candidates on the deceased donor waiting list also received transplants. More than 50% of kidneys were received from other transplant centers. DGF occurred in 6%; one-yr rejection rate was 9.1%. One-yr patient and graft survival was 98.0% and 94.8%. KPD involving participation of multiple transplant centers can provide opportunities for transplantation, with potential to expand the donor pool, minimize waiting times, and enable pre-emptive transplantation. Our experience demonstrates promising short-term outcomes; however, longer follow-up is needed to assess the impact of KPD on the shortage of organs available for transplantation.

A prospective trial of a steroid-free/calcineurin inhibitor minimization regimen in human leukocyte antigen (HLA)-identical live donor renal transplantation.

BACKGROUND: Few prospective trials in human leukocyte antigen (HLA) identical living donor (LD) renal transplantation exist. This prospective study evaluated a corticosteroid (CS)-free, calcineurin inhibitor (CNI) minimization immunosuppressive regimen in HLA-identical LD renal transplant recipients. METHODS: Twenty HLA-identical LD recipients were prospectively enrolled. Immunosuppression included mycophenolate mofetil (MMF) (2 g/day), tacrolimus (target trough 4-8 ng/mL), sirolimus (target trough 6-10 ng/mL), and no pre- or postoperative steroids. In the absence of prior rejection, tacrolimus was discontinued at posttransplant day 120 and sirolimus at 1 year, leaving patients on MMF monotherapy. RESULTS: Tacrolimus was successfully withdrawn in 94% of patients (16/17). One hundred percent (15/15) of patients who reached 1-year posttransplant had sirolimus discontinued. Ninety-four percent (17/18) of patients remain off CSs. Mean serum creatinine at 6, 12, and 24 months were 1.38+/-0.32, 1.35+/-0.37, and 1.25+/-0.29 mg/dL; corresponding mean calculated creatinine clearance estimates were 70+/-18, 73+/-17, and 72+/-15 mL/min. Acute cellular rejection, chronic allograft nephropathy, and CNI toxicity were not observed. Death-censored graft survival was 100% at last follow-up. CONCLUSIONS: A CS-free, CNI minimization immunosuppressive regimen with weaning to MMF monotherapy provides excellent renal function, graft survival, and patient survival in HLA-identical LD renal transplant recipients.

Long-term experimental warming alters nitrogen-cycling communities but site factors remain the primary drivers of community structure in high arctic tundra soils.

Arctic air temperatures are expected to rise significantly over the next century. Experimental warming of arctic tundra has been shown to increase plant productivity and cause community shifts and may also alter microbial community structure. Hence, the objective of this study was to determine whether experimental warming caused shifts in soil microbial communities by measuring changes in the frequency, relative abundance and/or richness of nosZ and nifH genotypes. Five sites at a high arctic coastal lowland were subjected to a 13-year warming experiment using open-top chambers (OTCs). Sites differed by dominant plant community, soil parent material and/or moisture regimen. Six soil cores were collected from each of four replicate OTC and ambient plots at each site and subdivided into upper and lower samples. Differences in frequency and relative abundance of terminal restriction fragments were assessed graphically by two-way cluster analysis and tested statistically with permutational multivariate analysis of variance (ANOVA). Genotypic richness was compared using factorial ANOVA. The genotype frequency, relative abundance and genotype richness of both nosZ and nifH communities differed significantly by site, and by OTC treatment and/or depth at some sites. The site that showed the most pronounced treatment effect was a wet sedge meadow, where community structure and genotype richness of both nosZ and nifH were significantly affected by warming. Although warming was an important factor affecting these communities at some sites at this high arctic lowland, overall, site factors were the main determinants of community structure.

Medication use in the neonatal intensive care unit: current patterns and off-label use of parenteral medications.

OBJECTIVES: To study the current patterns of medication use, assess the extent of off-label parenteral medication use, and evaluate evidence for efficacy and safety of parenteral medications used off-label in neonates. STUDY DESIGN: We collected information on all medications dispensed for infants admitted to an urban tertiary care neonatal intensive care unit over a 3-year period. Parenteral drugs were reviewed for off-label use, and medications not approved for use in neonates were evaluated for evidence of efficacy and safety in neonates. RESULTS: The ranges of gestational age, length of stay, and number of medications per infant were 23 to 42 weeks, 1 to 190 days, and 1 to 62, respectively, for 2304 admissions during the study period. Infants with lower birth weight and shorter gestational age received more medications compared with more mature infants. Of 61 parenteral medications evaluated, 27 (45%) were used off-label in neonates. Food and Drug Administration (FDA) approval for use in neonatal period was highest for antibiotics (14/16); the parenteral medications most frequently used off-label were analgesics, vasopressors, and hematologic agents. CONCLUSIONS: Critically ill neonates are exposed to numerous medications, a significant proportion of which are not yet FDA-approved for use in this vulnerable group of patients.

Leukopenia complicates cytomegalovirus prevention after renal transplantation with alemtuzumab induction.

BACKGROUND: Cytomegalovirus (CMV) is a major cause of morbidity after transplantation. Valganciclovir (VGCV) is commonly utilized for CMV prophylaxis but can cause leukopenia, with risk compounded by the use of myelosuppressive immunosuppression. By utilizing a preemptive therapeutic strategy with VGCV targeted only toward patients at risk for developing CMV disease, the rate and extent of leukopenia may be reduced. METHODS: VGCV prophylactic and preemptive strategies were compared in renal transplant recipients receiving alemtuzumab induction and prednisone-free maintenance with tacrolimus and mycophenolate mofetil (MMF). Patients were risk-stratified by CMV serologic status. All donor seropositive/recipient seronegative (D+/R-) patients, February 2002-January 2004 (n=32), received prophylaxis with VGCV 450 mg daily for 3 months. Outcomes of D+/-/R+ patients were compared. Patients in the first cohort, February 2002-October 2002 (n=61), received prophylaxis as described. In the second cohort, October 2002-January 2004 (n=110), patients were monitored by quantitative CMV-polymerase chain reaction (PCR) every 2 weeks for 3 months. If the CMV load was above laboratory threshold, VGCV 450 mg daily was initiated for 1 month or until viremia cleared. RESULTS: Comparing preemptive therapy versus prophylaxis in D+/-/R+ patients, there was a lower incidence of leukopenia (67% vs. 82%, P=0.039) and trend toward less granulocyte-colony stimulating factor (G-CSF) use (24% vs. 33%, P=0.196), but higher CMV disease rate (15% vs. 3%, P=0.02). One limitation was strategy compliance: 41% (7 of 17) of preemptive patients who developed CMV missed at least 1 CMV-PCR before diagnosis. One-year patient (98.2% vs. 98.4%) and death-censored graft (100% vs. 98.4%) survival was similar. CONCLUSIONS: Antiviral toxicity may be decreased with preemptive therapy, but effectiveness for CMV prevention seems dependent upon monitoring compliance.

Homer2 is necessary for EtOH-induced neuroplasticity.

Homer proteins are integral to the assembly of proteins regulating glutamate signaling and synaptic plasticity. Constitutive Homer2 gene deletion [knock-out (KO)] and rescue with adeno-associated viral (AAV) transfection of Homer2b was used to demonstrate the importance of Homer proteins in neuroplasticity produced by repeated ethanol (EtOH) administration. Homer2 KO mice avoided drinking high concentrations of EtOH and did not develop place preference or locomotor sensitization after repeated EtOH administration. The deficient behavioral plasticity to EtOH after Homer2 deletion was paralleled by a lack of augmentation in the rise in extracellular dopamine and glutamate elicited by repeated EtOH injections. The genotypic differences in EtOH-induced change in behavior and neurochemistry were essentially reversed by AAV-mediated transfection of Homer2b into accumbens cells including, differences in EtOH preference, locomotor sensitization, and EtOH-induced elevations in extracellular glutamate and dopamine. These data demonstrate a necessary and active role for accumbens Homer2 expression in regulating EtOH-induced behavioral and cellular neuroplasticity.