Effects of ownership patterns on cross-boundary wildfires.

Understanding ownership effects on large wildfires is a precursor to the development of risk governance strategies that better protect people and property and restore fire-adapted ecosystems. We analyzed wildfire events in the Pacific Northwest from 1984 to 2018 to explore how area burned responded to ownership, asking whether particular ownerships burned disproportionately more or less, and whether these patterns varied by forest and grass/shrub vegetation types. While many individual fires showed indifference to property lines, taken as a whole, we found patterns of disproportionate burning for both forest and grass/shrub fires. We found that forest fires avoided ownerships with a concentration of highly valued resources-burning less than expected in managed US Forest Service forested lands, private non-industrial, private industrial, and state lands-suggesting the enforcement of strong fire protection policies. US Forest Service wilderness was the only ownership classification that burned more than expected which may result from the management of natural ignitions for resource objectives, its remoteness or both. Results from this study are relevant to inform perspectives on land management among public and private entities, which may share boundaries but not fire management goals, and support effective cross-boundary collaboration and shared stewardship across all-lands.

Impacts of the Northwest Forest Plan on forest composition and bird populations.

The Northwest Forest Plan (NWFP) initiated one of the most sweeping changes to forest management in the world, affecting 10 million hectares of federal land. The NWFP is a science-based plan incorporating monitoring and adaptive management and provides a unique opportunity to evaluate the influence of policy. We used >25 years of region-wide bird surveys, forest data, and land-ownership maps to test this policy's effect on biodiversity. Clearcutting decreased rapidly, and we expected populations of older-forest-associated birds to stabilize on federal land, but to continue declining on private industrial lands where clearcutting continued. In contrast, we expected declines in early-seral-associated species on federal land because of reduced anthropogenic disturbance since the NWFP. Bayesian hierarchical models revealed that bird species' population trends tracked changes in forest composition. However, against our expectations, declines of birds associated with older forests accelerated. These declines are partly explained by losses of older forests due to fire on federal land and continued clearcutting elsewhere. Indeed, the NWFP anticipated that reversing declines of older forests would take time. Overall, the early-seral ecosystem area was stable, but declined in two ecoregions-the Coast Range and Cascades-along with early-seral bird populations. Although the NWFP halted clearcutting on federal land, this has so far been insufficient to reverse declines in older-forest-associated bird populations. These findings underscore the importance of continuing to prioritize older forests under the NWFP and ensuring that the recently proposed creation of early-seral ecosystems does not impede the conservation and development of older-forest structure.

Fire deficits have increased drought sensitivity in dry conifer forests: Fire frequency and tree-ring carbon isotope evidence from Central Oregon.

A century of fire suppression across the Western United States has led to more crowded forests and increased competition for resources. Studies of forest thinning or stand conditions after mortality events have provided indirect evidence for how competition can promote drought stress and predispose forests to severe fire and/or bark beetle outbreaks. Here, we demonstrate linkages between fire deficits and increasing drought stress through analyses of annually resolved tree-ring growth, fire scars, and carbon isotope discrimination (Δ13 C) across a dry mixed-conifer forest landscape. Fire deficits across the study area have increased the sensitivity of leaf gas exchange to drought stress over the past >100 years. Since 1910, stand basal area in these forests has more than doubled and fire-return intervals have increased from 25 to 140 years. Meanwhile, the portion of interannual variation in tree-ring Δ13 C explained by the Palmer Drought Severity Index has more than doubled in ca. 300-500-year-old Pinus ponderosa as well as in fire-intolerant, ca. 90-190-year-old Abies grandis. Drought stress has increased in stands with a basal area of ≥25 m2 /ha in 1910, as indicated by negative temporal Δ13 C trends, whereas stands with basal area ≤25 m2 /ha in 1910, due to frequent or intense wildfire activity in decades beforehand, were initially buffered from increased drought stress and have benefited more from rising ambient carbon dioxide concentrations, [CO2 ], as demonstrated by positive temporal Δ13 C trends. Furthermore, the average Δ13 C response across all P. ponderosa since 1830 indicates that photosynthetic assimilation rates and stomatal conductance have been reduced by ~10% and ~20%, respectively, compared to expected trends due to increasing [CO2 ]. Although disturbance legacies contribute to local-scale intensity of drought stress, fire deficits have reduced drought resistance of mixed-conifer forests and made them more susceptible to challenges by pests and pathogens and other disturbances.

Cumulative effects of wildfires on forest dynamics in the eastern Cascade Mountains, USA.

Wildfires pose a unique challenge to conservation in fire-prone regions, yet few studies quantify the cumulative effects of wildfires on forest dynamics (i.e., changes in structural conditions) across landscape and regional scales. We assessed the contribution of wildfire to forest dynamics in the eastern Cascade Mountains, USA from 1985 to 2010 using imputed maps of forest structure (i.e., tree size and canopy cover) and remotely sensed burn severity maps. We addressed three questions: (1) How do dynamics differ between the region as a whole and the unburned portion of the region? (2) How do dynamics vary among vegetation zones differing in biophysical setting and historical fire frequency? (3) How have forest structural conditions changed in a network of late successional reserves (LSRs)? Wildfires affected 10% of forests in the region, but the cumulative effects at this scale were primarily slight losses of closed-canopy conditions and slight gains in open-canopy conditions. In the unburned portion of the region (the remaining 90%), closed-canopy conditions primarily increased despite other concurrent disturbances (e.g., harvest, insects). Although the effects of fire were largely dampened at the regional scale, landscape scale dynamics were far more variable. The warm ponderosa pine and cool mixed conifer zones experienced less fire than the region as a whole despite experiencing the most frequent fire historically. Open-canopy conditions increased slightly in the mixed conifer zone, but declined across the ponderosa pine zone even with wildfires. Wildfires burned 30% of the cold subalpine zone, which experienced the greatest increase in open-canopy conditions and losses of closed-canopy conditions. LSRs were more prone to wildfire than the region as a whole, and experienced slight declines in late seral conditions. Despite losses of late seral conditions, wildfires contributed to some conservation objectives by creating open habitats (e.g., sparse early seral and woodland conditions) that otherwise generally decreased in unburned landscapes despite management efforts to increase landscape diversity. This study demonstrates the potential for wildfires to contribute to regional scale conservation objectives, but implications for management and biodiversity at landscape scales vary geographically among biophysical settings, and are contingent upon historical dynamics and individual species habitat preferences.

Soluble MICB in Plasma and Urine Explains Population Expansions of NKG2D+CD4 T Cells Inpatients with Juvenile-Onset Systemic Lupus Erythematosus.

Abnormal NKG2D ligand expression has been implicated in the initiation and maintenance of various auto-inflammatory disorders including systemic lupus erythematosus (SLE). This study's goal was to identify the cellular contexts providing NKG2D ligands for stimulation of the immunosuppressive NKG2D+CD4 T cell subset that has been implicated in modulating juvenile-onset SLE disease activity. Although previous observations with NKG2D+CD4 T cells in healthy individuals pointed towards peripheral B cell and myeloid cell compartments as possible sites of enhanced NKG2DL presence, we found no evidence for a disease-associated increase of NKG2DL-positivity among juvenile-onset SLE B cells and monocytes. However, juvenile-onset SLE patient plasma and matched urine samples were positive by ELISA for the soluble form of the NKG2D ligands MICA and MICB, suggesting that kidney and/or peripheral blood may constitute the NKG2DL positive microenvironments driving NKG2D+CD4 T cell population expansions in this disease.

Control of Tumor Initiation by NKG2D Naturally Expressed on Ovarian Cancer Cells.

Cancer cells may co-opt the NKG2D lymphocyte receptor to complement the presence of its ligands for autonomous stimulation of oncogenic signaling. Previous studies raise the possibility that cancer cell NKG2D may induce high malignancy traits, but its full oncogenic impact is unknown. Using epithelial ovarian cancer as model setting, we show here that ex vivo NKG2D+ cancer cells have stem-like capacities, and provide formal in vivo evidence linking NKG2D stimulation with the development and maintenance of these functional states. NKG2D+ ovarian cancer cell populations harbor substantially greater capacities for self-renewing in vitro sphere formation and in vivo tumor initiation in immunodeficient (NOD scid gamma) mice than NKG2D- controls. Sphere formation and tumor initiation are impaired by NKG2D silencing or ligand blockade using antibodies or a newly designed pan ligand-masking NKG2D multimer. In further support of pathophysiological significance, a prospective study of 47 high-grade serous ovarian cancer cases revealed that the odds of disease recurrence were significantly greater and median progression-free survival rates higher among patients with above and below median NKG2D+ cancer cell frequencies, respectively. Collectively, our results define cancer cell NKG2D as an important regulator of tumor initiation in ovarian cancer and presumably other malignancies and thus challenge current efforts in immunotherapy aimed at enhancing NKG2D function.

Historical harvests reduce neighboring old-growth basal area across a forest landscape.

While advances in remote sensing have made stand, landscape, and regional assessments of the direct impacts of disturbance on forests quite common, the edge influence of timber harvesting on the structure of neighboring unharvested forests has not been examined extensively. In this study, we examine the impact of historical timber harvests on basal area patterns of neighboring old-growth forests to assess the magnitude and scale of harvest edge influence in a forest landscape of western Oregon, USA. We used lidar data and forest plot measurements to construct 30-m resolution live tree basal area maps in lower and middle elevation mature and old-growth forests. We assessed how edge influence on total, upper canopy, and lower canopy basal area varied across this forest landscape as a function of harvest characteristics (i.e., harvest size and age) and topographic conditions in the unharvested area. Upper canopy, lower canopy, and total basal area increased with distance from harvest edge and elevation. Forests within 75 m of harvest edges (20% of unharvested forests) had 4% to 6% less live tree basal area compared with forest interiors. An interaction between distance from harvest edge and elevation indicated that elevation altered edge influence in this landscape. We observed a positive edge influence at low elevations (<800 m) and a negative edge influence at moderate to high elevations (>800 m). Surprisingly, we found no or weak effects of harvest age (13-60 yr) and harvest area (0.2-110 ha) on surrounding unharvested forest basal area, implying that edge influence was relatively insensitive to the scale of disturbance and multi-decadal recovery processes. Our study indicates that the edge influence of past clearcutting on the structure of neighboring uncut old-growth forests is widespread and persistent. These indirect and diffuse legacies of historical timber harvests complicate forest management decision-making in old-growth forest landscapes by broadening the traditional view of stand boundaries. Furthermore, the consequences of forest harvesting may reach across ownership boundaries, highlighting complex governance issues surrounding landscape management of old-growth forests.

A cross-continental comparison of plant and beetle responses to retention of forest patches during timber harvest.

Timber harvest can adversely affect forest biota. Recent research and application suggest that retention of mature forest elements (retention forestry), including unharvested patches (or aggregates) within larger harvested units, can benefit biodiversity compared to clearcutting. However, it is unclear whether these benefits can be generalized among the diverse taxa and biomes in which retention forestry is practiced. Lack of comparability in methods for sampling and analyzing responses to timber harvest and edge creation presents a challenge to synthesis. We used a consistent methodology (similarly spaced plots or traps along transects) to investigate responses of vascular plants and ground-active beetles to aggregated retention at replicate sites in each of four temperate and boreal forest types on three continents: Douglas-fir forests in Washington, USA; aspen forests in Minnesota, USA; spruce forests in Sweden; and wet eucalypt forests in Tasmania, Australia. We assessed (1) differences in local (plot-scale) species richness and composition between mature (intact) and regenerating (previously harvested) forest; (2) the lifeboating function of aggregates (capacity to retain species of unharvested forest); and whether intact forests and aggregates (3) are susceptible to edge effects and (4) influence the adjacent regenerating forest. Intact and harvested forests differed in composition but not richness of plants and beetles. The magnitude of this difference was generally similar among regions, but there was considerable heterogeneity of composition within and among replicate sites. Aggregates within harvest units were effective at lifeboating for both plant and beetle communities. Edge effects were uncommon even within the aggregates. In contrast, effects of forest influence on adjacent harvested areas were common and as strong for aggregates as for larger blocks of intact forest. Our results provide strong support for the widespread application of aggregated retention in boreal and temperate forests. The consistency of pattern in four very different regions of the world suggests that, for forest plants and beetles, responses to aggregated retention are likely to apply more widely. Our results suggest that through strategic placement of aggregates, it is possible to maintain the natural heterogeneity and biodiversity of mature forests managed for multiple objectives.

Evaluating carbon storage, timber harvest, and habitat possibilities for a Western Cascades (USA) forest landscape.

Forest policymakers and managers have long sought ways to evaluate the capability of forest landscapes to jointly produce timber, habitat, and other ecosystem services in response to forest management. Currently, carbon is of particular interest as policies for increasing carbon storage on federal lands are being proposed. However, a challenge in joint production analysis of forest management is adequately representing ecological conditions and processes that influence joint production relationships. We used simulation models of vegetation structure, forest sector carbon, and potential wildlife habitat to characterize landscape-level joint production possibilities for carbon storage, timber harvest, and habitat for seven wildlife species across a range of forest management regimes. We sought to (1) characterize the general relationships of production possibilities for combinations of carbon storage, timber, and habitat, and (2) identify management variables that most influence joint production relationships. Our 160 000-ha study landscape featured environmental conditions typical of forests in the Western Cascade Mountains of Oregon (USA). Our results indicate that managing forests for carbon storage involves trade-offs among timber harvest and habitat for focal wildlife species, depending on the disturbance interval and utilization intensity followed. Joint production possibilities for wildlife species varied in shape, ranging from competitive to complementary to compound, reflecting niche breadth and habitat component needs of species examined. Managing Pacific Northwest forests to store forest sector carbon can be roughly complementary with habitat for Northern Spotted Owl, Olive-sided Flycatcher, and red tree vole. However, managing forests to increase carbon storage potentially can be competitive with timber production and habitat for Pacific marten, Pileated Woodpecker, and Western Bluebird, depending on the disturbance interval and harvest intensity chosen. Our analysis suggests that joint production possibilities under forest management regimes currently typical on industrial forest lands (e.g., 40- to 80-yr rotations with some tree retention for wildlife) represent but a small fraction of joint production outcomes possible in the region. Although the theoretical boundaries of the production possibilities sets we developed are probably unachievable in the current management environment, they arguably define the long-term potential of managing forests to produce multiple ecosystem services within and across multiple forest ownerships.

Complex mountain terrain and disturbance history drive variation in forest aboveground live carbon density in the western Oregon Cascades, USA.

Forest carbon (C) density varies tremendously across space due to the inherent heterogeneity of forest ecosystems. Variation of forest C density is especially pronounced in mountainous terrain, where environmental gradients are compressed and vary at multiple spatial scales. Additionally, the influence of environmental gradients may vary with forest age and developmental stage, an important consideration as forest landscapes often have a diversity of stand ages from past management and other disturbance agents. Quantifying forest C density and its underlying environmental determinants in mountain terrain has remained challenging because many available data sources lack the spatial grain and ecological resolution needed at both stand and landscape scales. The objective of this study was to determine if environmental factors influencing aboveground live carbon (ALC) density differed between young versus old forests. We integrated aerial light detection and ranging (lidar) data with 702 field plots to map forest ALC density at a grain of 25 m across the H.J. Andrews Experimental Forest, a 6369 ha watershed in the Cascade Mountains of Oregon, USA. We used linear regressions, random forest ensemble learning (RF) and sequential autoregressive modeling (SAR) to reveal how mapped forest ALC density was related to climate, topography, soils, and past disturbance history (timber harvesting and wildfires). ALC increased with stand age in young managed forests, with much greater variation of ALC in relation to years since wildfire in old unmanaged forests. Timber harvesting was the most important driver of ALC across the entire watershed, despite occurring on only 23% of the landscape. More variation in forest ALC density was explained in models of young managed forests than in models of old unmanaged forests. Besides stand age, ALC density in young managed forests was driven by factors influencing site productivity, whereas variation in ALC density in old unmanaged forests was also affected by finer scale topographic conditions associated with sheltered sites. Past wildfires only had a small influence on current ALC density, which may be a result of long times since fire and/or prevalence of non-stand replacing fire. Our results indicate that forest ALC density depends on a suite of multi-scale environmental drivers mediated by complex mountain topography, and that these relationships are dependent on stand age. The high and context-dependent spatial variability of forest ALC density has implications for quantifying forest carbon stores, establishing upper bounds of potential carbon sequestration, and scaling field data to landscape and regional scales.

Searching for resilience: addressing the impacts of changing disturbance regimes on forest ecosystem services.

1. The provisioning of ecosystem services to society is increasingly under pressure from global change. Changing disturbance regimes are of particular concern in this context due to their high potential impact on ecosystem structure, function and composition. Resilience-based stewardship is advocated to address these changes in ecosystem management, but its operational implementation has remained challenging. 2. We review observed and expected changes in disturbance regimes and their potential impacts on provisioning, regulating, cultural and supporting ecosystem services, concentrating on temperate and boreal forests. Subsequently, we focus on resilience as a powerful concept to quantify and address these changes and their impacts, and present an approach towards its operational application using established methods from disturbance ecology. 3. We suggest using the range of variability concept - characterizing and bounding the long-term behaviour of ecosystems - to locate and delineate the basins of attraction of a system. System recovery in relation to its range of variability can be used to measure resilience of ecosystems, allowing inferences on both engineering resilience (recovery rate) and monitoring for regime shifts (directionality of recovery trajectory). 4. It is important to consider the dynamic nature of these properties in ecosystem analysis and management decision-making, as both disturbance processes and mechanisms of resilience will be subject to changes in the future. Furthermore, because ecosystem services are at the interface between natural and human systems, the social dimension of resilience (social adaptive capacity and range of variability) requires consideration in responding to changing disturbance regimes in forests. 5.Synthesis and applications. Based on examples from temperate and boreal forests we synthesize principles and pathways for fostering resilience to changing disturbance regimes in ecosystem management. We conclude that future work should focus on testing and implementing these pathways in different contexts to make ecosystem services provisioning more robust to changing disturbance regimes and advance our understanding of how to cope with change and uncertainty in ecosystem management.

A conceptual framework for characterizing forest areas with high societal values: experiences from the Pacific Northwest of USA and Central Europe.

In recent decades, much work has been invested to describe forest allocations with high societal values. Yet, few comparative analyses have been conducted on their importance and differences across the regions of the globe. This paper introduces a conceptual framework to characterize forest priority areas defined as areas with identified higher importance of societal values in the context of multi-objective forest management. The six dimensions of the framework (designation objective, prioritization of objectives, governance, permanency, spatial scale, and management regime) characterize the general approach (integrative vs. segregative) to multi-objective forest management and explain the form and role of priority areas for providing forest services. The framework was applied in two case study regions--Pacific Northwest of USA (PNW) and Central Europe (CE). Differences between the regions exist in all dimensions. Late-successional and riparian reserves are specific to the PNW, while protection against natural hazards is specific to CE. In PNW, priority areas are mainly focused on public lands whereas in CE they include public and private lands. Priority areas in PNW are designated in a much larger spatial context and have longer time commitments. In CE, integration of management objectives on priority areas prevails, whereas in PNW priority areas tend to be designated for single objectives. In CE, greater tolerance of timber management within priority areas compared to PNW is allowed. Convergent trends in application of priority areas between the regions indicate mixing of segregation and integration approaches to forest management.

Autonomous stimulation of cancer cell plasticity by the human NKG2D lymphocyte receptor coexpressed with its ligands on cancer cells.

The stimulatory NKG2D receptor on lymphocytes promotes tumor immune surveillance by targeting ligands selectively induced on cancer cells. Progressing tumors counteract by employing tactics to disable lymphocyte NKG2D. This negative dynamic is escalated as some human cancer cells co-opt expression of NKG2D, thereby complementing the presence of its ligands for autonomous stimulation of oncogenic signaling. Clinical association data imply relationships between cancer cell NKG2D and metastatic disease. Here we show that NKG2D promotes cancer cell plasticity by induction of phenotypic, molecular, and functional signatures diagnostic of the epithelial-mesenchymal transition, and of stem-like traits via induction of Sox9, a key transcriptional regulator of breast stem cell maintenance. These findings obtained with model breast tumor lines and xenotransplants were recapitulated by ex vivo cancer cells from primary invasive breast carcinomas. Thus, NKG2D may have the capacity to drive high malignancy traits underlying metastatic disease.

Disturbance legacies increase the resilience of forest ecosystem structure, composition, and functioning.

Disturbances are key drivers of forest ecosystem dynamics, and forests are well adapted to their natural disturbance regimes. However, as a result of climate change, disturbance frequency is expected to increase in the future in many regions. It is not yet clear how such changes might affect forest ecosystems, and which mechanisms contribute to (current and future) disturbance resilience. We studied a 6364-ha landscape in the western Cascades of Oregon, USA, to investigate how patches of remnant old-growth trees (as one important class of biological legacies) affect the resilience of forest ecosystems to disturbance. Using the spatially explicit, individual-based, forest landscape model iLand, we analyzed the effect of three different levels of remnant patches (0%, 12%, and 24% of the landscape) on 500-year recovery trajectories after a large, high-severity wildfire. In addition, we evaluated how three different levels of fire frequency modulate the effects of initial legacies. We found that remnant live trees enhanced the recovery of total ecosystem carbon (TEC) stocks after disturbance, increased structural complexity of forest canopies, and facilitated the recolonization of late-seral species (LSS). Legacy effects were most persistent for indicators of species composition (still significant 500 years after disturbance), while TEC (i.e., a measure of ecosystem functioning) was least affected, with no significant differences among legacy scenarios after 236 years. Compounding disturbances were found to dampen legacy effects on all indicators, and higher initial legacy levels resulted in elevated fire severity in the second half of the study period. Overall, disturbance frequency had a stronger effect on ecosystem properties than the initial level of remnant old-growth trees. A doubling of the historically observed fire frequency to a mean fire return interval of 131 years reduced TEC by 10.5% and lowered the presence of LSS on the landscape by 18.1% on average, demonstrating that an increase in disturbance frequency (a potential climate change effect) may considerably alter the structure, composition, and functioning of forest landscapes. Our results indicate that live tree legacies are an important component of disturbance resilience, underlining the potential of retention forestry to address challenges in ecosystem management.

Mixed-conifer forests of central Oregon: effects of logging and fire exclusion vary with environment.

Twentieth-century land management has altered the structure and composition of mixed-conifer forests and decreased their resilience to fire, drought, and insects in many parts of the Interior West. These forests occur across a wide range of environmental settings and historical disturbance regimes, so their response to land management is likely to vary across landscapes and among ecoregions. However, this variation has not been well characterized and hampers the development of appropriate management and restoration plans. We identified mixed-conifer types in central Oregon based on historical structure and composition, and successional trajectories following recent changes in land use, and evaluated how these types were distributed across environmental gradients. We used field data from 171 sites sampled across a range of environmental settings in two subregions: the eastern Cascades and the Ochoco Mountains. We identified four forest types in the eastern Cascades and four analogous types with lower densities in the Ochoco Mountains. All types historically contained ponderosa pine, but differed in the historical and modern proportions of shade-tolerant vs. shade-intolerant tree species. The Persistent Ponderosa Pine and Recent Douglas-fir types occupied relatively hot­dry environments compared to Recent Grand Fir and Persistent Shade Tolerant sites, which occupied warm­moist and cold­wet environments, respectively. Twentieth-century selective harvesting halved the density of large trees, with some variation among forest types. In contrast, the density of small trees doubled or tripled early in the 20th century, probably due to land-use change and a relatively cool, wet climate. Contrary to the common perception that dry ponderosa pine forests are the most highly departed from historical conditions, we found a greater departure in the modern composition of small trees in warm­moist environments than in either hot­dry or cold­wet environments. Furthermore, shade-tolerant trees began infilling earlier in cold­wet than in hot­dry environments and also in topographically shaded sites in the Ochoco Mountains. Our new classification could be used to prioritize management that seeks to restore structure and composition or create resilience in mixed-conifer forests of the region.

Fire-mediated pathways of stand development in Douglas-fir/ western hemlock forests of the Pacific Northwest, USA.

Forests dominated by Douglas-fir and western hemlock in the Pacific Northwest of the United States have strongly influenced concepts and policy concerning old-growth forest conservation. Despite the attention to their old-growth characteristics, a tendency remains to view their disturbance ecology in relatively simple terms, emphasizing infrequent, stand-replacing (SR) fire and an associated linear pathway toward development of those old-growth characteristics. This study uses forest stand- and age-structure data from 124 stands in the central western Cascades of Oregon to construct a conceptual model of stand development under the mixed-severity fire regime that has operated extensively in this region. Hierarchical clustering of variables describing the age distributions of shade-intolerant and shade-tolerant species identified six groups, representing different influences of fire frequency and severity on stand development. Douglas-fir trees > 400 years old were found in 84% of stands, yet only 18% of these stands (15% overall) lack evidence of fire since the establishment of these old trees, whereas 73% of all stands show evidence of at least one non-stand-replacing (NSR) fire. Differences in fire frequency and severity have contributed to multiple development pathways and associated variation in contemporary stand structure and the successional roles of the major tree species. Shade-intolerant species form a single cohort following SR fire, or up to four cohorts per stand in response to recurring NSR fires that left living trees at densities up to 45 trees/ha. Where the surviving trees persist at densities of 60-65 trees/ha, the postfire cohort is composed only of shade-tolerant species. This study reveals that fire history and the development of old-growth forests in this region are more complex than characterized in current stand-development models, with important implications for maintaining existing old-growth forests and restoring stands subject to timber management.

Immunobiology and conflicting roles of the human NKG2D lymphocyte receptor and its ligands in cancer.

Cancers adopt diverse strategies to safeguard their survival, which often involve blinding or incapacitating the immune response, thereby gaining battleground advantage against the host. In immune responses against cancer, an important stimulatory lymphocyte receptor is NKG2D because the tumor-associated expression of its ligands promotes destruction of malignant cells. However, with advanced human cancers profound changes unfold wherein NKG2D and its ligands are targeted or exploited for immune evasion and suppression. This negative imprinting on the immune system may be accompanied by another functional state wherein cancer cells coopt expression of NKG2D to complement the presence of its ligands for self-stimulation of tumor growth and presumably malignant progression. This review emphasizes these conflicting functional dynamics at the immunity-cancer biology interface in humans, within an overview of the immunobiology of NKG2D and mechanisms underlying the regulation of its ligands in cancer, with reference to instructive clinical observations and translational approaches.

Expression of ERp5 and GRP78 on the membrane of chronic lymphocytic leukemia cells: association with soluble MICA shedding.

MICA is a ligand of the activating receptor NKG2D, expressed by NK and T cells. MICA expression is induced in cancer cells favoring their elimination by the immune system; however, many advanced tumors shed soluble MICA (sMICA), which impairs NKG2D-mediated cytotoxicity. ERp5 and GRP78 are endoplasmic reticulum-resident proteins that are translocated to the surface of epithelial tumor cells where they interact with MICA and are involved in sMICA shedding. In this study, we analyze the role of ERp5 and GRP78 in sMICA shedding in chronic lymphocytic leukemia (CLL). Immunofluorescence and flow cytometry analyses showed that ERp5 and GRP78 were significantly expressed on the surface of B cells and leukemia cells, but they were not expressed on T cells. The expression of ERp5 and GRP78 was significantly higher in leukemia cells than in B cells from controls. ERp5 and GRP78 co-localized with MICA on the surface of leukemia cells and the levels of expression of ERp5 and GRP78 correlated with the level of expression of membrane-bound MICA in CLL patients. Associated with higher expression of membrane-bound ERp5 and GRP78, serum sMICA levels were approximately threefold higher in patients than in controls. Elevated sMICA levels in CLL patients were associated with the down-modulation of NKG2D surface expression on CD8 T cells. Finally, pharmacological inhibition of B cell lines and stimulated leukemia cells showed that ERp5 activity is involved in sMICA shedding in CLL. In conclusion, these results uncover a molecular mechanism which regulates MICA protein shedding and immune evasion in CLL.

Major histocompatibility complex class I-related chain A/B (MICA/B) expression in tumor tissue and serum of pancreatic cancer: role of uric acid accumulation in gemcitabine-induced MICA/B expression.

BACKGROUND: Major histocompatibility complex class I-related chain A and B (MICA/B) are two stress-inducible ligands that bind the immunoreceptor NKG2D and play an important role in mediating the cyotoxicity of NK and T cells. In this study, we sought to study MICA/B expression in pancreatic cancer and to determine whether and how genotoxic drugs such as gemcitabine can affect MICA/B expression and natural killer cytotoxity. METHODS: Seven pancreatic cancer cell lines were analyzed for MICA/B expression by flow cytometry and for their sensitivity to NK-92 cell killing by a 51Cr release assay. MICA/B expression in tumor tissues and sera of pancreatic cancer was analyzed by immunohistochemical staining (IHC) and ELISA, respectively. RESULTS: Two MICA/B-positive cell lines were sensitive to the cytotoxic activity of NK-92 cells. Other two MICA/B-positive cell lines and three MICA/B-negative cell lines were resistant to NK-92 cell killing. MICA/B expression was positive in 17 of 25 (68%) pancreatic ductal adenocarcinomas but not in normal pancreatic ductal epithelial cells. Serum MICA/B levels were significantly elevated in patients with pancreatic adenocarcinomas but did not correlate with the stage of pancreatic cancer and patient survival. Gemcitabine therapy led to increased serum MICA levels in 6 of 10 patients with detectable serum MICA. Allopurinol, an inhibitor of xanthine oxidoreductase that converts xanthine to uric acid, blocked uric acid production, MICA/B expression, and sensitivity to NK-92 cell killing toward a PANC-1 cancer cell line exposed to radiation and two genotoxic drugs, gemcitabine and 5-fluorouracil. CONCLUSIONS: The levels of MICA/B expression in serum and tissue of pancreatic cancer are elevated. DNA damage-induced MICA/B expression is mediated through increased uric acid production.