Michael J. Schuster

Immunoglobulin M-to-Immunoglobulin G Anti-Human Leukocyte Antigen Class II Antibody Switching in Cardiac Transplant Recipients Is Associated With an Increased Risk of Cellular Rejection and Coronary Artery Disease

Background— Activation of T cells induces immunoglobulin (Ig)M-to-IgG B-cell isotype switching via costimulatory regulatory pathways. Because rejection of transplanted organs is preceded by alloantigen-dependent T-cell activation, we investigated whether B-cell isotype switching could predict acute cellular rejection and the subsequent development of transplantation-related coronary artery disease (TCAD) in cardiac transplant recipients. Methods and Results— Among 267 nonsensitized heart transplant recipients, switching from IgM to IgG anti-human leukocyte antigens (HLA) antibodies directed against class II but not against class I antigens was associated with a shorter duration to high-grade rejection, defined as International Society for Heart and Lung Transplantation grade 3A or higher (P<0.001), a higher cumulative rejection frequency (P=0.002), accelerated development of TCAD (P=0.04), and decreased late survival (P=0.03). Conversely, the persistence of IgM anti-HLA antibodies against class II but not against class I antigens for >30 days and the lack of IgG isotype switching were associated with protection against both acute rejection (P=0.02) and TCAD (P=0.05). Alloisotype switching coincided with T-cell activation, as evidenced by increased serum levels of soluble CD40 ligand costimulatory molecules. Finally, a case-control study showed that reduction of cardiac allograft rejection by mycophenolic acid was accompanied by reduced CD40 ligand serum levels and the prevention of IgM-to-IgG anti-HLA class II antibody switching. Conclusions— T-cell-dependent B-cell isotype switching and the consequent production of IgG anti-HLA class II antibodies are strongly correlated with acute cellular rejection, a high incidence of recurrent rejections, TCAD, and poor long-term survival. Detecting this isotype switch is a clinically useful surrogate marker for in vivo T-cell activation and may provide a noninvasive approach for monitoring the efficacy of T-cell targeted immunosuppressive therapy in heart transplant recipients.

Rainfall variability and nitrogen addition synergistically reduce plant diversity in a restored tallgrass prairie

Summary 1. Climate change is expected to bring fewer, larger rainfall events and prolonged droughts (i.e. increased rainfall variability). Concurrently, the burning of fossil fuels and reliance on nitrogen (N) fertilizers are expected to continue to increase N availability in many ecosystems. These changes in water and N availability have the potential to alter plant community composition and structure. 2. We manipulated rainfall variability and N inputs in a restored tallgrass prairie over the course of two growing seasons. 3. Greater rainfall variability led to wetter soils throughout the majority of both growing seasons and provided punctuated relief from a severe drought that occurred during the first three months of the experiment. 4. Both rainfall variability- and fertilization-induced increases in resource availability favoured fast-growing, deeply rooted C3 forbs, particularly the dominant Solidago canadensis, at the expense of species adapted to low resource conditions, particularly C4 grasses and N-fixing forbs. 5. This change in community composition decreased plant community diversity and evenness in plots receiving both supplemental N and more variable rainfall. 6. Synthesis and applications. These results suggest that future increases in rainfall variability and nitrogen (N) deposition could synergistically alter the structure of prairie restorations and jeopardize restoration targets related to increasing floral diversity. Mitigating N availability in restoration sites may help to maintain prairie diversity as rainfall patterns become more variable.

Increased rainfall variability and N addition accelerate litter decomposition in a restored prairie

Anthropogenic nitrogen deposition and projected increases in rainfall variability (the frequency of drought and heavy rainfall events) are expected to strongly influence ecosystem processes such as litter decomposition. However, how these two global change factors interact to influence litter decomposition is largely unknown. I examined how increased rainfall variability and nitrogen addition affected mass and nitrogen loss of litter from two tallgrass prairie species, Schizachyrium scoparium and Solidago canadensis, and isolated the effects of each during plant growth and during litter decomposition. I increased rainfall variability by consolidating ambient rainfall into larger events and simulated chronic nitrogen deposition using a slow-release urea fertilizer. S. scoparium litter decay was more strongly regulated by the treatments applied during plant growth than by those applied during decomposition. During plant growth, increased rainfall variability resulted in S. scoparium litter that subsequently decomposed more slowly and immobilized more nitrogen than litter grown under ambient conditions, whereas nitrogen addition during plant growth accelerated subsequent mass loss of S. scoparium litter. In contrast, S. canadensis litter mass and N losses were enhanced under either N addition or increased rainfall variability both during plant growth and during decomposition. These results suggest that ongoing changes in rainfall variability and nitrogen availability are accelerating nutrient cycling in tallgrass prairies through their combined effects on litter quality, environmental conditions, and plant community composition.

A DNA enzyme against plasminogen activator inhibitor- type 1 (PAI-1) limits neointima formation after angioplasty in an obese diabetic rodent model.

We investigated whether targeted cleavage of PAI-1 mRNA might prevent post-angioplasty neointima formation in diabetic JCR:LA-cp/cp rats with naturally elevated PAI-1 levels. Catalytic DNA enzymes targeting rat PAI-1 mRNA (PAI-1 DNA enzyme, n = 12) or a random sequence as control (scrambled DNA enzyme, n = 12) were infused at the site of arterial damage. Control animals demonstrated prominent PAI-1 protein expression in the arterial endothelium at 48 hours, and robust neointimal proliferation by two weeks, with 60 ± 10% mean occlusion of the artery lumen. The neointimal lesion consisted of dense fibrin deposition and numerous proliferating smooth muscle cells, as determined by dual α-smooth muscle actin/Ki67 expression. Treatment with PAI-1 DNA enzyme resulted in marked early (48 hour) reduction of endothelial PAI-1 protein expression, which persisted for the next two weeks as well as a two fold reduction of expression of PAI-1 mRNA by RT-PCR at the same time point, (P < 0.05). By two weeks, PAI-1 DNA enzyme treated animals demonstrated significantly reduced levels of fibrin deposition and 5-fold lower levels of proliferating smooth muscle cells at the site of arterial injury compared to controls (P < 0.01), and a 2-fold lower neointima/media ratio (0.67 ± 0.11 vs 1.39 ± 0.12) (P < 0.05). Treatment with a catalytic PAI-1 DNA enzyme successfully prevents neointimal proliferation after balloon injury in diabetic animals.

Responses of aboveground C and N pools to rainfall variability and nitrogen deposition are mediated by seasonal precipitation and plant community dynamics

Plant productivity and tissue chemistry in temperate ecosystems are largely driven by water and nitrogen (N) availability. Although changes in rainfall patterns may influence nutrient limitation, few studies have considered how these two global change factors could interact to influence terrestrial ecosystem productivity and stoichiometry. Here, we examined the influence of experimentally-increased intra-annual rainfall variability and low-level nitrogen addition on aboveground productivity, C and N pools, and C:N ratios in a restored tallgrass prairie across two growing seasons. In the drier first year of the experiment, increased rainfall variability boosted productivity and C pools. In the wetter second year, aboveground productivity and C pools increased with N addition, suggesting a switch in primary resource limitation from water to N. Increased rainfall variability also reduced aboveground N pools in the second year. Community-level C:N increased under increased rainfall variability in the wetter second year and N addition slightly reduced community C:N in both years. These changes in element pools and stoichiometry were mostly a result of increased forb dominance in response to both treatments. Overall, our findings from a restored prairie indicate that increased rainfall variability and N addition can enhance aboveground productivity and C pools, but that N pools may not have a consistent response to either global change factor. Our study also suggests that these effects are dependent on growing season precipitation patterns and are mediated by shifts in plant community composition.

Categorization of literature pertaining to the use of revegetation in suppressing invasive plant species

A search strategy was developed to identify literature on the use of revegetation as a strategy to suppress reinvasion of invasive species in grasslands and forests. This dataset summarizes the data points for each article included in the literature analysis.

Amur maple ( Acer ginnala ): an emerging invasive plant in North America

Acer ginnala Maxim. (Amur maple) is a growing threat to woodland systems in North America. Despite this, Amur maple has been largely ignored by ecologists, and scientific understanding of the species is mostly limited to anecdotal evidence from land managers. We evaluated the cover and richness of native and exotic understory plant communities under Amur maple canopies, native tree canopies, and nearby open areas near St. Paul, Minnesota, USA. Overall, Amur maple created dense canopies that only allowed 2% canopy light penetration, strongly reducing cover of all plants except Amur maple. With this critical first step in understanding the impacts of Amur maple complete, we suggest key research priorities related to the distribution of Amur maple, its mechanisms and impacts of invasion, and how best to control its spread in order to encourage future research into Amur maple and mitigate the species’ potential for ecological and economic harm.