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Previous studies of aging cynomolgus monkeys from our group identified spontaneous age-associated cognitive declines associated with biomarkers and brain lesions reminiscent of Alzheimer's Disease (AD), in a proportion of aged monkeys. However, the molecular mechanisms that underlie the spontaneous amyloid disorders and cognitive declines observed in these affected monkeys have yet to be investigated in detail. Using reverse transcriptase quantitative real time PCR techniques, normalized to the ACTB housekeeping gene, we analyzed the expression patterns of a number of genes which have been implicated in amyloid and tau abnormalities, in well-characterized aged cynomolgus monkeys with cognitive decline. A significantly increased expression of the genes coding for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), was found in aged-cognitive decline monkeys compared to age-matched healthy controls. GAPDH has been implicated in several neurodegenerative diseases and interacts with beta amyloid precursor proteins. These findings provide support for the utilization of cynomolgus macaques in translational preclinical research as valid spontaneous models in experimental investigations of the relationships among aging, cognitive decline, and the neuropathy of AD.

The US Midwest is the largest and most intensive corn (Zea mays, L.) production region in the world. However, N losses from corn systems cause serious environmental impacts including dead zones in coastal waters, groundwater pollution, particulate air pollution, and global warming. New approaches to reducing N losses are urgently needed. N surplus is gaining attention as such an approach for multiple cropping systems. We combined experimental data from 127 on-farm field trials conducted in seven US states during the 2011–2016 growing seasons with biochemical simulations using the PNM model to quantify the benefits of a dynamic location-adapted management approach to reduce N surplus. We found that this approach allowed large reductions in N rate (32%) and N surplus (36%) compared to existing static approaches, without reducing yield and substantially reducing yield-scaled N losses (11%). Across all sites, yield-scaled N losses increased linearly with N surplus values above ~48 kg ha−1. Using the dynamic model-based N management approach enabled growers to get much closer to this target than using existing static methods, while maintaining yield. Therefore, this approach can substantially reduce N surplus and N pollution potential compared to static N management.

Vegetation cover in dry regions is a key variable in determining desertification. Soils exposed to rainfall by desertification can form physical crusts that reduce infiltration, exacerbating water stress on the remaining vegetation. Paradoxically, field studies show that crust removal is associated with plant mortality in desert systems, while artificial biological crusts can improve plant regeneration. Here it is shown how physical crusts can act as either drivers of or buffers against desertification depending on their environmental context. The behavior of crusts is first explored using a simplified theory for water movement on a uniform, partly vegetated slope subject to stationary hydrologic conditions. Numerical model runs supplemented with field data from a semiarid Long-Term Ecological Research site are then applied to represent more realistic environmental conditions. When vegetation cover is significant, crusts can drive desertification, but this process is potentially self-limiting. For low vegetation cover, crusts mitigate against desertification by providing water subsidy to plant communities through a runoff-runon mechanism.

Vegetation cover in dry regions is a key variable in determining desertification. Soils exposed to rainfall by desertification can form physical crusts that reduce infiltration, exacerbating water stress on the remaining vegetation. Paradoxically, field studies show that crust removal is associated with plant mortality in desert systems, while artificial biological crusts can improve plant regeneration. Here it is shown how physical crusts can act as either drivers of or buffers against desertification depending on their environmental context. The behavior of crusts is first explored using a simplified theory for water movement on a uniform, partly vegetated slope subject to stationary hydrologic conditions. Numerical model runs supplemented with field data from a semiarid Long-Term Ecological Research site are then applied to represent more realistic environmental conditions. When vegetation cover is significant, crusts can drive desertification, but this process is potentially self-limiting. For low vegetation cover, crusts mitigate against desertification by providing water subsidy to plant communities through a runoff-runon mechanism.

Contains fulltext : 69914.pdf (publisher's version ) (Closed access), Patients on chronic hemodialysis (HD) are at high risk for developing atherosclerosis and cardiovascular complications. Heparanase, an endoglycosidase that cleaves heparan sulfate (HS) side chains of proteoglycans, is involved in extracellular matrix degradation and, as such, may be involved in the atherosclerotic lesion progression. We hypothesize that heparanase is elevated in HD patients, partly due to its release from primed circulating polymorphonuclear leukocytes (PMNLs), undergoing degranulation. Priming of PMNLs was assessed by levels of CD11b and the rate of superoxide release. Heparanase mRNA expression in PMNLs was determined by RT-PCR. PMNL and plasma levels of heparanase were determined by immunoblotting, immunofluorescence, and flow cytometry analyses. The levels of soluble HS in plasma were measured by a competition ELISA. This study shows that PMNLs isolated from HD patients have higher mRNA and protein levels of heparanase compared with normal control (NC) subjects and that heparanase levels correlate positively with PMNL priming. Plasma levels of heparanase were higher in HD patients than in NC subjects and were further elevated after the dialysis session. In addition, heparanase expression inversely correlates with plasma HS levels. A pronounced expression of heparanase was found in human atherosclerotic lesions. The increased heparanase activity in the blood of HD patients results at least in part from the degranulation of primed PMNLs and may contribute to the acceleration of the atherosclerotic process. Our findings highlight primed PMNLs as a possible source for the increased heparanase in HD patients, posing heparanase as a new risk factor for cardiovascular complications and atherosclerosis.

Contains fulltext : 69914.pdf (publisher's version ) (Closed access), Patients on chronic hemodialysis (HD) are at high risk for developing atherosclerosis and cardiovascular complications. Heparanase, an endoglycosidase that cleaves heparan sulfate (HS) side chains of proteoglycans, is involved in extracellular matrix degradation and, as such, may be involved in the atherosclerotic lesion progression. We hypothesize that heparanase is elevated in HD patients, partly due to its release from primed circulating polymorphonuclear leukocytes (PMNLs), undergoing degranulation. Priming of PMNLs was assessed by levels of CD11b and the rate of superoxide release. Heparanase mRNA expression in PMNLs was determined by RT-PCR. PMNL and plasma levels of heparanase were determined by immunoblotting, immunofluorescence, and flow cytometry analyses. The levels of soluble HS in plasma were measured by a competition ELISA. This study shows that PMNLs isolated from HD patients have higher mRNA and protein levels of heparanase compared with normal control (NC) subjects and that heparanase levels correlate positively with PMNL priming. Plasma levels of heparanase were higher in HD patients than in NC subjects and were further elevated after the dialysis session. In addition, heparanase expression inversely correlates with plasma HS levels. A pronounced expression of heparanase was found in human atherosclerotic lesions. The increased heparanase activity in the blood of HD patients results at least in part from the degranulation of primed PMNLs and may contribute to the acceleration of the atherosclerotic process. Our findings highlight primed PMNLs as a possible source for the increased heparanase in HD patients, posing heparanase as a new risk factor for cardiovascular complications and atherosclerosis.