Critical review of the impacts of grazing intensity on soil organic carbon storage and other soil quality indicators in extensively managed grasslands.

Livestock grazing intensity (GI) is thought to have a major impact on soil organic carbon (SOC) storage and soil quality indicators in grassland agroecosystems. To critically investigate this, we conducted a global review and meta-analysis of 83 studies of extensive grazing, covering 164 sites across different countries and climatic zones. Unlike previous published reviews we normalized the SOC and total nitrogen (TN) data to a 30 cm depth to be compatible with IPCC guidelines. We also calculated a normalized GI and divided the data into four main groups depending on the regional climate (dry warm, DW; dry cool, DC; moist warm, MW; moist cool, MC). Our results show that taken across all climatic zones and GIs, grazing (below the carrying capacity of the systems) results in a decrease in SOC storage, although its impact on SOC is climate-dependent. When assessed for different regional climates, all GI levels increased SOC stocks under the MW climate (+7.6%) whilst there were reductions under the MC climate (-19%). Under the DW and DC climates, only the low (+5.8%) and low to medium (+16.1%) grazing intensities, respectively, were associated with increased SOC stocks. High GI significantly increased SOC for C4-dominated grassland compared to C3-dominated grassland and C3-C4 mixed grasslands. It was also associated with significant increases in TN and bulk density but had no effect on soil pH. To protect grassland soils from degradation, we recommend that GI and management practices should be optimized according to climate region and grassland type (C3, C4 or C3-C4 mixed).

Low risk management intervention: Limited impact of remedial tillage on net ecosystem carbon balance at a commercial Miscanthus plantation.

Perennial bioenergy crops are a key tool in decarbonizing global energy systems, but to ensure the efficient use of land resources, it is essential that yields and crop longevity are maximized. Remedial shallow surface tillage is being explored in commercial Miscanthus plantations as an approach to reinvigorate older crops and to rectify poor establishment, improving yields. There are posited links, however, between tillage and losses in soil carbon (C) via increased ecosystem C fluxes to the atmosphere. As Miscanthus is utilized as an energy crop, changes in field C fluxes need to be assessed as part of the C balance of the crop. Here, for the first time, we quantify the C impacts of remedial tillage at a mature commercial Miscanthus plantation in Lincolnshire, United Kingdom. Net ecosystem C production based on eddy covariance flux observations and exported yield totalled 12.16 Mg C ha-1 over the 4.6 year period after tillage, showing the site functioned as a net sink for atmospheric carbon dioxide (CO2). There was no indication of negative tillage induced impacts on soil C stocks, with no difference 3 years post tillage in the surface (0-30 cm) or deep (0-70 cm) soil C stocks between the tilled Miscanthus field and an adjacent paired untilled Miscanthus field. Comparison to historic samples showed surface soil C stocks increased by 11.16 ± 3.91 Mg C ha-1 between pre (October 2011) and post tillage sampling (November 2016). Within the period of the study, however, the tillage did not result in the increased yields necessary to "pay back" the tillage induced yield loss. Rather the crop was effectively re-established, with progressive yield increases over the study period, mirroring expectations of newly planted sites. The overall impacts of remedial tillage will depend therefore, on the longer-term impacts on crop longevity and yields.

Safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the monoclonal antibody ASK8007 blocking osteopontin in patients with rheumatoid arthritis: a randomised, placebo controlled, proof-of-concept study.

OBJECTIVES: Osteopontin is an extracellular matrix protein with diverse immunomodulatory functions. The authors assessed the safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks osteopontin. METHODS: In this double-blind, multicentre, combined first-in-man, single-dose escalation (phase I, part A) and proof-of-concept, multiple-dose (phase IIA, part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. The expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in the number of CD68 synovial sublining macrophages, both assessed on day 43 (part B). RESULTS: ASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 sublining macrophages between ASK8007 and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers. CONCLUSIONS: Osteopontin blockade is well tolerated and not related to safety concerns. These results consistently show that osteopontin blockade is unlikely to induce robust clinical improvement in RA patients.

Near-patient platelet function testing in patients undergoing coronary artery surgery: a pilot study.

Platelet dysfunction after cardiopulmonary bypass contributes to microvascular bleeding and is associated with blood transfusion and resternotomy. Platelet count can be readily performed, but currently there are no standardised, reproducible, rapidly available platelet function tests. We studied platelet function as measured by multiple electrode platelet aggregometery (multiplate) and light transmission aggregometry in 44 patients undergoing routine coronary artery surgery. Platelet aggregation as measured by multiplate was reduced during and after cardiopulmonary bypass compared with baseline with evidence of partial recovery by the time of transfer to ITU. In patients transfused blood, platelet aggregation measured by multiplate was reduced during chest closure with adenosine diphosphate (18 U vs 29 U, p = 0.01) and thrombin receptor agonist peptide-6 agonist (65 U vs 88 U, p = 0.01) compared with patients not transfused. This suggests that multiplate, a new point of care analyser, can detect platelet dysfunction in this setting.

Measurement of intermodulation distortion in high-linearity photodiodes.

Accurately characterizing third order intermodulation distortion (IMD3) in high-linearity photodiodes is challenging. Two measurement techniques are evaluated-a standard two-tone measurement and a more complicated three-tone measurement technique to measure IMD3. A model of the measurement system is developed and used to analyze the limitations of the two techniques in determining the distortion of highly linear photodiodes. Experimental validation is provided by comparing the simulation trends with IMD3 results measured on two types of waveguide photodiodes: 1) an InP based uni-traveling-carrier (UTC) photodiode and 2) a Ge n-i-p waveguide photodetector on Silicon-on-Insulator (SOI) substrate.

Ecosystem engineers: feedback and population dynamics.

All organisms alter their abiotic environment, but ecosystem engineers are species with abiotic effects that may have to be explicitly accounted for when making predictions about population and community dynamics. The goal of this analysis is to identify those conditions in which engineering leads to population dynamics that are qualitatively different than one would predict using models that incorporate only biotic interactions. We present a simple model coupling an ecosystem engineer and the abiotic environment. We assume that the engineer alters environmental conditions at a rate dependent on engineer density and that the environment decays back to original conditions at an exponential rate. We determine when the feedback to population dynamics through environmental state can lead to altered equilibrium densities, bistability, or runaway growth of the engineer population. The conditions leading to changes in dynamics, such as susceptibility of a system to engineering or alteration of density-dependent and density-independent controls, define cases in which the engineering concept is essential for ecological understanding.

Ecology. The lion and the lamb find closure.

Interactions between enemies and their victims are found in all ecological communities. But what has puzzled ecologists is how victims and enemies coexist together for long periods of time without all of the victims being killed off. In a Perspective, Hastings explains a new model (Keeling et al.), which shows that variation in the distribution of victim and enemy species acts as a stabilizing factor in interactions between them.

Persistence of transients in spatially structured ecological models.

Simple discrete-time ecological models for a species with alternating reproduction and dispersal are shown to have complex transient dynamics. If the density dependence (nonlinearity) is strong enough, then the time required to reach the final dynamics is usually very long, approaching thousands of generations, and there are typically very sudden changes in the form of the dynamics. Apparent chaos can change to cycles or vice versa. These results are consistent with observed sudden changes in the form of the dynamics of a single species and imply that transient dynamics of ecological models may be more relevant than long-term behavior.

Mathematical and computational challenges in population biology and ecosystems science.

Mathematical and computational approaches provide powerful tools in the study of problems in population biology and ecosystems science. The subject has a rich history intertwined with the development of statistics and dynamical systems theory, but recent analytical advances, coupled with the enhanced potential of high-speed computation, have opened up new vistas and presented new challenges. Key challenges involve ways to deal with the collective dynamics of heterogeneous ensembles of individuals, and to scale from small spatial regions to large ones. The central issues-understanding how detail at one scale makes its signature felt at other scales, and how to relate phenomena across scales-cut across scientific disciplines and go to the heart of algorithmic development of approaches to high-speed computation. Examples are given from ecology, genetics, epidemiology, and immunology.

Production and characterization of a murine/human chimeric anti-idiotype antibody that mimics ganglioside.

The VL and VH from a murine anti-idiotypic antibody that mimics ganglioside have been cloned, sequenced, and expressed as a chimeric mouse/human IgG1 antibody. The chimeric antibody retained a binding specificity indistinguishable from the original murine antibody. The VH was a member of Vgam 3.8 family. The sequences are discussed in terms of ways in which proteins may mimic ganglioside epitopes.

Disequilibrium, selection, and recombination: limits in two-locus, two-allele models.

All possible combinations of equilibria and fitnesses in two-locus, two-allele, deterministic, discrete-generation selection models are enumerated. This knowledge is used to obtain limits (which can be calculated to arbitrary precision) to the relationships among disequilibrium, selection and recombination for fixed values of allele frequencies. In all cases, the inequality magnitude of rD less than s/10 holds, where r is recombination and D is disequilibrium, and all selection coefficients lie between 1 - s and 1 + s times that of the double heterozygote. Linear programming techniques are used to observed nonzero values of D reported in the literature. One conclusion is that the failure to observe nonzero values of D is not surprising.

Limits to the relationship among recombination, disequilibrium and epistasis in two-locus models.

I determine limits to the equilibrium relationship among epistasis, recombination and disequilibrium in two-locus, two-allele models using linear programming techniques. I show that when allele frequencies are one-half at each locus, the symmetric model is the fitness pattern that generates the most disequilibrium for the smallest level of epistasis. When allele frequencies deviate from one-half much larger levels of epistasis are required to generate similar levels of disequilibrium. I determine the level of epistasis required to generate observed significant levels of disequilibrium in natural populations. The overall implication is that disequilibrium will be large at equilibrium only between strongly interacting, closely linked loci.

Four simultaneously stable polymorphic equilibria in two-locus two-allele models.

The existence of four simultaneously stable equilibria with both loci polymorphic is shown for the Lewontin-Kojima version of the two-locus two-allele symmetric viability model, using bifurcation theory. This exceeds the previously claimed bound of two stable polymorphisms. Biological implications of the result are discussed.

Multilocus population genetics with weak epistasis. II. Equilibrium properties of multilocus models: what is the unit of selection?

Using perturbation techniques, I study the equilibrium of deterministic discrete time multilocus models with weak epistasis. The most important results are on the relationship between epistasis and disequilibrium. Disequilibrium involving a particular set of loci reflects only epistasis simultaneously involving those loci. Moreover, all the disequilibria of all orders vary approximately as the inverse of the probability of at least one recombination event among the loci involved. Finally, higher order disequilibria among loci will be lower than lower order ones, even if the level of epistasis is the same at all orders. In this sense, the unit of selection is small. However, given the larger number of higher order disequilibria, these higher order disequilibria may play an important role in the computation of gametic frequencies from allelic frequencies in models with a large number of loci. Finally, I show that epistasis between blocks of loci will be averages of epistatic effects, not additions of epistatic effects. Thus, failure to find significant epistasis on a chromosomal basis does not rule out the importance of epistatic effects.

Multilocus population genetics with weak epistasis. I. Equilibrium properties of two-locus two-allele models.

Using perturbation techniques, I determine the equilibrium of two-locus two-allele models with overdominance and weak epistasis. To lowest order, the allele frequencies, the mean fitness and the covariance between heterokaryotic and homokaryotic flies arising in the Sturtevant experimental design are independent of the recombination rate, r. The disequilibrium varies as one divided by the recombination rate, in contrast to neutral models. Although the disequilibrium generated by weak epistasis is small, too small to be experimentally detected, it can be large enough to have biological importance.

Stable equilibria at two loci in populations with large selfing rates.

The equilibrium structure of two-locus, two-allele models with very large selfing rates is found using perturbation techniques. For free recombination, r = 1/2, the following results hold. If the heterozygotes do not have at least an approximate 30% advantage in fitness relative to homozygotes, a stable equilibrium with all alleles present is possible only if all of the homozygote fitnesses differ at most by approximately the outcrossing rate, t, and all stable polymorphic equilibria have disequilibrium values, D, that are at most on the order of the outcrossing rate. Once the heterozygote fitnesses are above the threshold, there are stable equilibria possible with D near its maximum possible value. The results show that the observed disequilibria in highly selfed plant populations are not likely to result from selection leading to an equilibrium.

Unexpected behavior in two locus genetic systems: an analysis of marginal underdominance at a stable equilibrium.

The phenomenon of marginal underdominance at a stable equilibrium in a two-locus-two-allele deterministic selection model is studied analytically using bifurcation theory. This technique and additional numerical studies indicate several new aspects of the phenomenon that are of biological importance. Marginal underdominance can occur at both loci simultaneously and can be present in a model with small fitness differentials. This can occur for a fitness scheme that is a one parameter generalization of the classical symmetric fitness model.

Substitution rates under stabilizing selection.

Allelic substitutions under stabilizing phenotypic selection on quantitative traits are studied in Monte Carlo simulations of 8 and 16 loci. The results are compared and contrasted to analytical models based on work of M. Kimura for two and "infinite" loci. Selection strengths of S = 4Nes approximately four (which correspond to reasonable strengths of selection for quantitative characters) can retard substitution rates tenfold relative to rates under neutrality. An important finding is a strong dependence of per locus substitution rates on the number of loci.

Monotonic change of the mean phenotype in two-locus models.

It is shown that the mean phenotype monotonically approaches the optimum in a class of symmetric, two-locus, two-allele models with stabilizing selection. In this model, mean fitness does not change monotonically. Thus, Fisher's fundamental theorem does not hold, even though another quantity of evolutionary interest, the mean phenotype, can be shown to change monotonically. Using this quantity, it is proven that global stability results for this model.

Linkage disequilibrium and genetic variances under mutation-selection balance.

I determine the contribution of linkage disequilibrium to genetic variances using results for two loci and for induced or marginal systems. The analysis allows epistasis and dominance, but assumes that mutation is weak relative to selection. The linkage disequilibrium component of genetic variance is shown to be unimportant for unlinked loci if the gametic mutation rate divided by the harmonic mean of the pairwise recombination rates is much less than one. For tightly linked loci, linkage disequilibrium is unimportant if the gametic mutation rate divided by the (induced) per locus selection is much less than one.