Author Correction: Environment and host as large-scale controls of ectomycorrhizal fungi.

Change history: In the HTML version of this Article, author 'Filipa Cox' had no affiliation in the author list, although she was correctly associated with affiliation 3 in the PDF. In addition, the blue circles for 'oak' were missing from Extended Data Fig. 1. These errors have been corrected online.

Environment and host as large-scale controls of ectomycorrhizal fungi.

Explaining the large-scale diversity of soil organisms that drive biogeochemical processes-and their responses to environmental change-is critical. However, identifying consistent drivers of belowground diversity and abundance for some soil organisms at large spatial scales remains problematic. Here we investigate a major guild, the ectomycorrhizal fungi, across European forests at a spatial scale and resolution that is-to our knowledge-unprecedented, to explore key biotic and abiotic predictors of ectomycorrhizal diversity and to identify dominant responses and thresholds for change across complex environmental gradients. We show the effect of 38 host, environment, climate and geographical variables on ectomycorrhizal diversity, and define thresholds of community change for key variables. We quantify host specificity and reveal plasticity in functional traits involved in soil foraging across gradients. We conclude that environmental and host factors explain most of the variation in ectomycorrhizal diversity, that the environmental thresholds used as major ecosystem assessment tools need adjustment and that the importance of belowground specificity and plasticity has previously been underappreciated.

Elevated procalcitonin and C-reactive protein as potential biomarkers of sepsis in a subpopulation of thrombotic microangiopathy patients.

Thrombotic microangiopathy (TMA) comprises a group of microvascular thrombosis syndromes associated with multiple pathogenic factors. Deficient activity of ADAMTS13 is a pathogenic factor in a subset of TMA patients that provides a strong rationale for plasma exchange treatment. However, the subset of TMA patients with normal ADAMTS13 activity remains a heterogeneous group of patients in which the appropriate treatment is not well understood. In addition to the common forms of TMA thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome, the differential diagnosis of TMA may include sepsis, autoimmune disorders, and disseminated intravascular coagulation. Optimal treatment of TMA depends on timely recognition of treatable pathogenic factors. We hypothesized that sepsis is a rapidly identifiable pathogenic factor in a subset of TMA patients. To test this hypothesis, we retrospectively measured the rapid biomarkers of sepsis C-reactive protein (CRP) and procalcitonin (PCT), in a repository of pretreatment plasma samples from 61 TMA patients treated with plasma exchange. Levels were analyzed in 31 severely ADAMTS13-deficient and 30 ADAMTS13-normal patients. None of the 31 patients with severe deficiency of ADAMTS13 had elevated PCT. However, 11 of 30 (37%) non-ADAMTS13-deficient patient samples were strongly positive for PCT. These patient samples also had a >10-fold higher median CRP level than patients with normal PCT. We conclude that rapid assays may help identify sepsis in a subset of TMA patients.

Leukocyte proteases cleave von Willebrand factor at or near the ADAMTS13 cleavage site.

The function of von Willebrand factor (VWF) is regulated by proteolysis, which limits its multimeric size and ability to tether platelets. The importance of ADAMTS13 metalloprotease in VWF regulation is demonstrated by the association between severe deficiency of ADAMTS13 and thrombotic thrombocytopenic purpura (TTP). However, ADAMTS13 activity levels do not always correlate with the clinical course of TTP, suggesting that other proteases could be important in regulating VWF. We identified 4 leukocyte proteases that cleave the synthetic VWF substrate FRETS-VWF73 and multimeric VWF. Elastase and proteinase 3 (PR3) cleave multimeric VWF and FRETS-VWF73 at the V(1607)-T(1608) peptide bond; cathepsin G and matrix metalloprotease 9 cleave VWF substrates at the Y(1605)-M(1606) and M(1606)-V(1607) bonds, respectively. Isolated intact human neutrophils cleave FRETS-VWF73 at the V(1607)-T(1608) peptide bond, suggesting that elastase or PR3 expressed on leukocyte surfaces might cleave VWF. In the presence of normal or ADAMTS13-deficient plasma, cleavage of FRETS-VWF73 by resting neutrophils is abolished. However, activated neutrophils retain proteolytic activity toward FRETS-VWF73 in the presence of plasma. Although the in vivo relevance remains to be established, these studies suggest the existence of a "hot spot" of VWF proteolysis in the VWF A2 domain, and support the possibility that activated leukocytes may participate in the proteolytic regulation of VWF.

Severe deficiency of VWF-cleaving protease (ADAMTS13) activity defines a distinct population of thrombotic microangiopathy patients.

BACKGROUND: Severe deficiency of ADAMTS13 activity is a biologic risk factor for thrombotic microangiopathy (TMA). It was hypothesized that severe ADAMTS13 deficiency is associated with a distinct TMA subpopulation. STUDY DESIGN AND METHODS: ADAMTS13 activity before treatment was determined retrospectively in 107 adult TMA patients treated with plasma exchange. Patients were not clinically categorized, but divided between severely deficient (n = 50) and nonseverely deficient (n = 57) ADAMTS13 activity. Laboratory and clinical factors before treatment were compared between the groups. RESULTS: Median PLT counts were 44,000 per micro L in nonseverely deficient ADAMTS13 patients and 13,000 per micro L in severely deficient ADAMTS13 patients (p < 0.001). Median serum creatinine levels were 2.7 mg per dL in nonseverely deficient patients and 1.2 mg per dL in severely deficient patients (p < 0.001). In surviving patients, median plasma exchange procedures were 9 in nonseverely deficient patients and 14.5 in severely deficient patients (p < 0.01). Rates of relapse following remission were 4 of 47 in nonseverely deficient patients and 16 of 46 in severely deficient patients (p < 0.01). Among analyzed factors only mortality rates were not significantly different. CONCLUSION: In a heterogeneous population of TMA patients treated with plasma exchange, ADAMTS13 activity defined two subpopulations with distinct clinical and laboratory features. These results suggest that TMA with severe ADAMTS13 deficiency is a distinct pathologic process.

The degradation of the natural pyrethrins in crop storage.

Prolonged storage of harvested Tasmanian pyrethrum crop from Tanacetum cinerariaefolium has resulted in substantial losses of the pyrethrin esters due to the environmental conditions in the storage shed. The generation of heat, the presence of moisture and oxygen, and the microbial activity were identified as possible causes. A pyrethrum crop sample was divided up and stored in different conditions relating to these variables, and the pyrethrins content was monitored over time using a standard method. Temperature was determined to be a critical factor in the rate of the degradation of the natural pyrethrins. Moisture, oxygen, and microbial activity unexpectedly did not play a major role in the degradation. An initial rapid loss of the natural pyrethrins was observed before the pyrethrins content stabilized at a loss of around 65%. This suggests that the plant structure may provide chemical or physical protection to the pyrethrins. In all cases, the majority of the loss was attributed to the pyrethrin I and pyrethrin II esters.

Factor V Leiden: a genetic risk factor for thrombotic microangiopathy in patients with normal von Willebrand factor-cleaving protease activity.

Thrombotic microangiopathy (TM) is associated with abnormalities of von Willebrand factor-cleaving protease (VWCP) and other hemostatic factors. This study hypothesized that TM patients might have genetically determined thrombotic risk factors that predispose them to aberrant microvascular thrombosis. DNA samples from 30 white and 12 African American adult TM patients were analyzed for genetic alleles associated with vascular thrombosis, and plasma samples were analyzed for levels of VWCP activity. DNA was analyzed by using allele-specific polymerase chain reaction for factor V 1691A (Leiden), factor II 20 210A, methylenetetrahydrofolate reductase 667T, type 1 plasminogen activator inhibitor 4G/5G, and platelet GPIa 807T. Patients were segregated by race (white or African American) and plasma level of VWCP activity (normal or deficient). The prevalence of factor V Leiden was significantly increased among the white TM patients that had normal VWCP activity: 4 (36%) of 11 patients compared with 6 (3%) of 186 white control subjects possessed the factor V Leiden allele (P <.001; odds ratio, 17.1; 95% confidence interval, 5.4-54.0). No factor V Leiden alleles were detected in 19 white TM patients with intermediate or deficient levels of VWCP activity or in any of 12 African American patients. The prevalence of other thrombosis-associated alleles did not differ between TM patients and control subjects. These findings suggest that factor V Leiden may be a pathogenic risk factor in TM patients that have normal VWCP activity.