The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries

Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI) involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO) would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury

Biomass Production of Herbaceous Energy Crops in the United States: Field Trial Results and Yield Potential Maps from the Multiyear Regional Feedstock Partnership

Current knowledge of yield potential and best agronomic management practices for perennial bioenergy grasses is primarily derived from small‐scale and short‐term studies, yet these studies inform policy at the national scale. In an effort to learn more about how bioenergy grasses perform across multiple locations and years, the U.S. Department of Energy (US DOE)/Sun Grant Initiative Regional Feedstock Partnership was initiated in 2008. The objectives of the Feedstock Partnership were to (1) provide a wide range of information for feedstock selection (species choice) and management practice options for a variety of regions and (2) develop national maps of potential feedstock yield for each of the herbaceous species evaluated. The Feedstock Partnership expands our previous understanding of the bioenergy potential of switchgrass, Miscanthus, sorghum, energycane, and prairie mixtures on Conservation Reserve Program land by conducting long‐term, replicated trials of each species at diverse environments in the U.S. Trials were initiated between 2008 and 2010 and completed between 2012 and 2015 depending on species. Field‐scale plots were utilized for switchgrass and Conservation Reserve Program trials to use traditional agricultural machinery. This is important as we know that the smaller scale studies often overestimated yield potential of some of these species. Insufficient vegetative propagules of energycane and Miscanthus prohibited farm‐scale trials of these species. The Feedstock Partnership studies also confirmed that environmental differences across years and across sites had a large impact on biomass production. Nitrogen application had variable effects across feedstocks, but some nitrogen fertilizer generally had a positive effect. National yield potential maps were developed using PRISM‐ELM for each species in the Feedstock Partnership. This manuscript, with the accompanying supplemental data, will be useful in making decisions about feedstock selection as well as agronomic practices across a wide region of the country

Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes

Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons(1,2). Several groups have attributed this apparent plasticity to 'transdifferentiation'(3-5). Others, however, have suggested that cell fusion could explain these results(6-9). Using a simple method based on Cre/lox recombination to detect cell fusion events, we demonstrate that bone-marrow-derived cells (BMDCs) fuse spontaneously with neural progenitors in vitro. Furthermore, bone marrow transplantation demonstrates that BMDCs fuse in vivo with hepatocytes in liver, Purkinje neurons in the brain and cardiac muscle in the heart, resulting in the formation of multinucleated cells. No evidence of transdifferentiation without fusion was observed in these tissues. These observations provide the first in vivo evidence for cell fusion of BMDCs with neurons and cardiomyocytes, raising the possibility that cell fusion may contribute to the development or maintenance of these key cell types.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62789/1/nature02069.pd

Biomass production of herbaceous energy crops in the United States: field trial results and yield potential maps from the multiyear regional feedstock partnership

Current knowledge of yield potential and best agronomic management practices for perennial bioenergy grasses is primarily derived from small-scale and short-term studies, yet these studies inform policy at the national scale. In an effort to learn more about how bioenergy grasses perform across multiple locations and years, the U.S. Department of Energy (US DOE)/Sun Grant Initiative Regional Feedstock Partnership was initiated in 2008. The objectives of the Feedstock Partnership were to (1) provide a wide range of information for feedstock selection (species choice) and management practice options for a variety of regions and (2) develop national maps of potential feedstock yield for each of the herbaceous species evaluated. The Feedstock Partnership expands our previous understanding of the bioenergy potential of switchgrass, Miscanthus, sorghum, energycane, and prairie mixtures on Conservation Reserve Program land by conducting long-term, replicated trials of each species at diverse environments in the U.S. Trials were initiated between 2008 and 2010 and completed between 2012 and 2015 depending on species. Field-scale plots were utilized for switchgrass and Conservation Reserve Program trials to use traditional agricultural machinery. This is important as we know that the smaller scale studies often overestimated yield potential of some of these species. Insufficient vegetative propagules of energycane and Miscanthus prohibited farm-scale trials of these species. The Feedstock Partnership studies also confirmed that environmental differences across years and across sites had a large impact on biomass production. Nitrogen application had variable effects across feedstocks, but some nitrogen fertilizer generally had a positive effect. National yield potential maps were developed using PRISM-ELM for each species in the Feedstock Partnership. This manuscript, with the accompanying supplemental data, will be useful in making decisions about feedstock selection as well as agronomic practices across a wide region of the country

Mediators of alkalosis-induced relaxation in pulmonary arteries from normoxic and chronically hypoxic piglets Downloaded from

. Mediators of alkalosis-induced relaxation in pulmonary arteries from normoxic and chronically hypoxic piglets. Am. J. Physiol. 276 (Lung Cell. Mol. Physiol. 20): L155-L163, 1999.-Alkalosis-induced relaxation was measured in precontracted arterial rings from 1-wk-old piglets exposed to normoxia or to 3 days of chronic hypoxia. In normoxic piglet arteries, alkalosis-induced relaxation was blunted in arteries without functional endothelium and in arteries treated with nitric oxide synthase or guanylate cyclase inhibitors but not in arteries treated with cyclooxygenase inhibitors or Ca 2ϩ -and ATP-dependent K ϩ -channel inhibitors. Inhibition of voltage-dependent K ϩ channels with 10 Ϫ3 M 4-aminopyridine also failed to block alkalosis-induced relaxation. 4-Aminopyridine at 10 Ϫ2 M did block the response, but this may have been due to sustained vascular smooth muscle depolarization. Arteries from hypoxic piglets exhibited greater contraction to the thromboxane mimetic U-46619, decreased endothelium-dependent relaxation, and blunted alkalosis-induced relaxation. The residual relaxation was eliminated by nitric oxide synthase but not by cyclooxygenase or voltage-dependent K ϩ -channel inhibition. Alkalosisinduced relaxation of newborn piglet pulmonary arteries appears to be mediated by the nitric oxide-cGMP pathway and is attenuated after 3 days of hypoxia, likely because of decreased nitric oxide activity. pulmonary hypertension; newborn; endothelium-derived relaxing factors; potassium channels HYPOCAPNIC ALKALOSIS is widely used in treating severe neonatal and pediatric pulmonary hypertension In some studies, alkalosis-induced pulmonary vasodilation appeared to be mediated by endothelium-derived modulators such as prostacyclin (18, 41) and nitric oxide (2). However, others METHODS Preparation. This study was approved by the Institutional Animal Care and Use Committees of the Medical College of Wisconsin and the Zablocki Veterans Affairs Medical Center (Milwaukee, WI). Responses to alkalosis were measured in 186 rings from 35 Norm piglets and 55 rings from 7 Hyp piglets. The Hyp piglets were maintained in 12% O 2 for 3 days before study, and all piglets were euthanized at 1 wk of age. Fike and Kaplowitz (10, 11) previously showed that this relatively brief chronic Hyp exposure leads to reactive pulmonary hypertension At the time of study, fourth-to fifth-generation pulmonary arterial segments (Ϸ0.5-mm diameter) were identified and gently dissected from the lungs. The segments were cut into 2-mm-long rings, and small stainless steel hooks were inserted through the lumen. The upper hook was suspended from an isometric force transducer (model 52-9529, Harvard Apparatus, South Natick, MA), and the lower hook was attached to the base of a 10-ml organ chamber (Harvard Apparatus). The organ baths were filled with MKS maintained at 37.5°C and initially bubbled with 6% CO 2 and 21% O 2 to achieve a pH of 7.40. The transducer was mounted on a micromanipulator (model 55020, Stoelting, Chicago, IL), allowing adjustment of resting tension as needed. Vessel tension was constantly measured and recorded on flatbed recorders (model L6514-4, Linseis, Princeton Junction, NJ). Protocol. In preliminary KCl length-tension experiments (data not shown), we found that the optimal resting tension for 0.5-mm-diameter piglet pulmonary arteries was 1 g. Therefore, the resting tension was set at 1 g in all subsequent experiments. The arteries were allowed to equilibrate at the resting tension for 60-90 min, then responses to three successive challenges with 40 mM KCl were measured to assess vascular smooth muscle integrity. The arteries were The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked ''advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact

Paradoxical relationship between Mn superoxide dismutase deficiency and radiation-induced cognitive defects.

Radiation therapy of the CNS, even at low doses, can lead to deficits in neurocognitive functions. Reduction in hippocampal neurogenesis is usually, but not always, associated with cognitive deficits resulting from radiation therapy. Generation of reactive oxygen species is considered the main cause of radiation-induced tissue injuries, and elevated levels of oxidative stress persist long after the initial cranial irradiation. Consequently, mutant mice with reduced levels of the mitochondrial antioxidant enzyme, Mn superoxide dismutase (MnSOD or Sod2), are expected to be more sensitive to radiation-induced changes in hippocampal neurogenesis and the related functions. In this study, we showed that MnSOD deficiency led to reduced generation of immature neurons in Sod2-/+ mice even though progenitor cell proliferation was not affected. Compared to irradiated Sod2+/+ mice, which showed cognitive defects and reduced differentiation of newborn cells towards the neuronal lineage, irradiated Sod2-/+ mice showed normal hippocampal-dependent cognitive functions and normal differentiation pattern for newborn neurons and astroglia. However, we also observed a disproportional decrease in newborn neurons in irradiated Sod2-/+ following behavioral studies, suggesting that MnSOD deficiency may render newborn neurons more sensitive to stress from behavioral trainings following cranial irradiation. A positive correlation between normal cognitive functions and normal dendritic spine densities in dentate granule cells was observed. The data suggest that maintenance of synaptic connections, via maintenance of dendritic spines, may be important for normal cognitive functions following cranial irradiation