Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques

Dysregulated extracellular matrix (ECM) metabolism may contribute to vascular remodeling during the development and complication of human atherosclerotic lesions. We investigated the expression of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components in human atherosclerotic plaques (n = 30) and in uninvolved arterial specimens (n = 11). We studied members of all three MMP classes (interstitial collagenase, MMP-1; gelatinases, MMP-2 and MMP-9; and stromelysin, MMP-3) and their endogenous inhibitors (TIMPs 1 and 2) by immunocytochemistry, zymography, and immunoprecipitation. Normal arteries stained uniformly for 72-kD gelatinase and TIMPs. In contrast, plaques' shoulders and regions of foam cell accumulation displayed locally increased expression of 92-kD gelatinase, stromelysin, and interstitial collagenase. However, the mere presence of MMP does not establish their catalytic capacity, as the zymogens lack activity, and TIMPs may block activated MMPs. All plaque extracts contained activated forms of gelatinases determined zymographically and by degradation of 3H-collagen type IV. To test directly whether atheromata actually contain active matrix-degrading enzymes in situ, we devised a method which allows the detection and microscopic localization of MMP enzymatic activity directly in tissue sections. In situ zymography revealed gelatinolytic and caseinolytic activity in frozen sections of atherosclerotic but not of uninvolved arterial tissues. The MMP inhibitors, EDTA and 1,10-phenanthroline, as well as recombinant TIMP-1, reduced these activities which colocalized with regions of increased immunoreactive MMP expression, i.e., the shoulders, core, and microvasculature of the plaques. Focal overexpression of activated MMP may promote destabilization and complication of atherosclerotic plaques and provide novel targets for therapeutic intervention

Sub-sampling a large physical soil archive for additional analyses to support spatial mapping; a pre-registered experiment in the Southern Nations, Nationalities, and Peoples Region (SNNPR) of Ethiopia

The value of physical archives of soil material from field sampling activities has been widely recognized. If we want to use archive material for new destructive analyses to support a task, such as spatial mapping, then an efficient sub-sampling strategy is needed, both to manage analytical costs and to conserve the archive material. In this paper we present an approach to this problem when the objective is spatial mapping by ordinary kriging. Our objective was to subsample the physical archive from the Ethiopia Soil Information System (EthioSIS) survey of the Southern Nations, Nationalities and Peoples Region (SNNPR) for spatial mapping of two variables, concentrations of particular fractions of selenium and iodine in the soil, which had not been measured there. We used data from cognate parts of surrounding regions of Ethiopia to estimate variograms of these properties, and then computed prediction error variances for maps in SNNPR based on proposed subsets of the archive of different size, selected to optimize a spatial coverage criterion (with some close sample pairs included). On this basis a subsample was selected. This is a preregistered experiment in that we have proposed criteria for evaluating the success of our approach, and are publishing that in advance of receiving analytical data on the subsampled material from the laboratories where they are being processed. A subsequent short report will publish the outcome. The use of preregistered trials is widely recommended and used in areas of science including public health, and we believe that it is a sound strategy to promote reproducible research in soil science

Agronomic biofortification increases grain zinc concentration of maize grown under contrasting soil types in Malawi

Zinc (Zn) deficiency remains a public health problem in Malawi, especially among poor and marginalized rural populations, linked with low dietary intake of Zn due to consumption of staple foods that are low in Zn content. The concentration of Zn in staple cereal grain can be increased through application of Zn-enriched fertilizers, a process called agronomic biofortification or agro-fortification. Field experiments were conducted at three Agricultural Research Station sites to assess the potential of agronomic biofortification to improve Zn concentration in maize grain in Malawi as described in registered report published previously. The hypotheses of the study were (i) that application of Zn-enriched fertilizers would increase in the concentration of Zn in maize grain to benefit dietary requirements of Zn and (ii) that Zn concentration in maize grain and the effectiveness of agronomic biofortification would be different between soil types. At each site two different subsites were used, each corresponding to one of two agriculturally important soil types of Malawi, Lixisols and Vertisols. Within each subsite, three Zn fertilizer rates (1, 30, and 90 kg ha−1) were applied to experimental plots, using standard soil application methods, in a randomized complete block design. The experiment had 10 replicates at each of the three sites as informed by a power analysis from a pilot study, published in the registered report for this experiment, designed to detect a 10% increase in grain Zn concentration at 90 kg ha−1, relative to the concentration at 1 kg ha−1. At harvest, maize grain yield and Zn concentration in grain were measured, and Zn uptake by maize grain and Zn harvest index were calculated. At 30 kg ha−1, Zn fertilizer increased maize grain yields by 11% compared with nationally recommended application rate of 1 kg ha−1. Grain Zn concentration increased by 15% and uptake by 23% at the application rate of 30 kg ha−1 relative to the national recommendation rate. The effects of Zn fertilizer application rate on the response variables were not dependent on soil type. The current study demonstrates the importance of increasing the national recommendation rate of Zn fertilizer to improve maize yield and increase the Zn nutritional value of the staple crop

Sub-sampling a large physical soil archive for additional analyses to support spatial mapping; a pre-registered experiment in the Southern Nations, Nationalities, and Peoples Region (SNNPR) of Ethiopia

The value of physical archives of soil material from field sampling activities has been widely recognized. If we want to use archive material for new destructive analyses to support a task, such as spatial mapping, then an efficient sub-sampling strategy is needed, both to manage analytical costs and to conserve the archive material. In this paper we present an approach to this problem when the objective is spatial mapping by ordinary kriging. Our objective was to subsample the physical archive from the Ethiopia Soil Information System (EthioSIS) survey of the Southern Nations, Nationalities and Peoples Region (SNNPR) for spatial mapping of two variables, concentrations of particular fractions of selenium and iodine in the soil, which had not been measured there. We used data from cognate parts of surrounding regions of Ethiopia to estimate variograms of these properties, and then computed prediction error variances for maps in SNNPR based on proposed subsets of the archive of different size, selected to optimize a spatial coverage criterion (with some close sample pairs included). On this basis a subsample was selected. This is a preregistered experiment in that we have proposed criteria for evaluating the success of our approach, and are publishing that in advance of receiving analytical data on the subsampled material from the laboratories where they are being processed. A subsequent short report will publish the outcome. The use of preregistered trials is widely recommended and used in areas of science including public health, and we believe that it is a sound strategy to promote reproducible research in soil science

Non-Enzymatic Decomposition of Collagen Fibers by a Biglycan Antibody and a Plausible Mechanism for Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory and destructive joint disorder that affects tens of millions of people worldwide. Normal healthy joints maintain a balance between the synthesis of extracellular matrix (ECM) molecules and the proteolytic degradation of damaged ones. In the case of RA, this balance is shifted toward matrix destruction due to increased production of cleavage enzymes and the presence of (autoimmune) immunoglobulins resulting from an inflammation induced immune response. Herein we demonstrate that a polyclonal antibody against the proteoglycan biglycan (BG) causes tissue destruction that may be analogous to that of RA affected tissues. The effect of the antibody is more potent than harsh chemical and/or enzymatic treatments designed to mimic arthritis-like fibril de-polymerization. In RA cases, the immune response to inflammation causes synovial fibroblasts, monocytes and macrophages to produce cytokines and secrete matrix remodeling enzymes, whereas B cells are stimulated to produce immunoglobulins. The specific antigen that causes the RA immune response has not yet been identified, although possible candidates have been proposed, including collagen types I and II, and proteoglycans (PG's) such as biglycan. We speculate that the initiation of RA associated tissue destruction in vivo may involve a similar non-enzymatic decomposition of collagen fibrils via the immunoglobulins themselves that we observe here ex vivo

Natural climate solutions for the United States

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science Advances 4 (2018): eaat1869, doi:10.1126/sciadv.aat1869.Limiting climate warming to <2°C requires increased mitigation efforts, including land stewardship, whose potential in the United States is poorly understood. We quantified the potential of natural climate solutions (NCS)—21 conservation, restoration, and improved land management interventions on natural and agricultural lands—to increase carbon storage and avoid greenhouse gas emissions in the United States. We found a maximum potential of 1.2 (0.9 to 1.6) Pg CO2e year−1, the equivalent of 21% of current net annual emissions of the United States. At current carbon market prices (USD 10 per Mg CO2e), 299 Tg CO2e year−1 could be achieved. NCS would also provide air and water filtration, flood control, soil health, wildlife habitat, and climate resilience benefits.This study was made possible by funding from the Doris Duke Charitable Foundation. C.A.W. and H.G. acknowledge financial support from NASA’s Carbon Monitoring System program (NNH14ZDA001N-CMS) under award NNX14AR39G. S.D.B. acknowledges support from the DOE’s Office of Biological and Environmental Research Program under the award DE-SC0014416. J.W.F. acknowledges financial support from the Florida Coastal Everglades Long-Term Ecological Research program under National Science Foundation grant no. DEB-1237517