Fertilizing and Seeding Oil-damaged Arctic Tundra to Effect Vegetation Recovery Prudhoe Bay, Alaska

Vegetational recovery from an accidental oil spill on a wet tundra site at Prudhoe Bay, Alaska, was studied during six growing seasons. The spilled oil consisted of 22° API gravity, Prudhoe Bay crude from which diesel and heating oil fractions had been removed by a topping process. Damages from the winter spill ranged from killing the moss layer and above-grounds parts of vascular plants to killing all the macroflora. Damage to the oil sensitive mosses persisted throughout the study even in lightly oiled areas. Test plots where commercial phosphorus fertilizers had been applied were an exception to this. Moss cover began re-establishing during the first growing season with phosphorus fertilization and continued to improve thereafter. Growth of sedges and grasses, not killed by the oil, was significantly enhanced by phosphorus fertilizations, even though oil persisted in the soil. Revegetation attempts in a barren area during the fourth growing season after the spill resulted in establishing Puccinellia borealis (alkaligrass) seedlings and mosses in phosphorus-fertilized plots. Neither nitrogen nor potassium fertilizers alone and combined with each other improved growth of either resident or seeded plant species on the spill area. The more significant response was to phosphorus

Effects of Burning Crude Oil Spilled Onto Six Habitat Types in Alaska

The effects on vegetational recovery of removing spilled Prudhoe Bay crude oil from terrestrial sites by burning were observed at three Alaskan locations; Palmer, Fairbanks, and Prudhoe Bay. Five habitat types were studied: 1) abandoned agricultural grass field, 2) the high-brush stage in the secondary succession of interior Alaskan spruce forests, 3) sedge meadow, 4) spruce forest, and 5) wet and mesic arctic tundra. Oil burning was carried out on snow during winter, during the summer growing season and in autumn as soils were freezing. Burning in summer during the growing season was much more detrimental to plant survival than winter burning. Significant amounts of dormant or near dormant vegetation survived hot burns in September where the soil was frozen to a depth of at least four centimeters. Burning spilled oils on frozen soil surfaces at all three locations affected subsequent plant survival less than when soil surfaces were thawed. Plant dormancy, reduced soil permeability, high soil moisture levels and low soil temperatures were the most probable factors contributing to plants surviving oil spills and burns. Heating during the burn failed to raise soil temperatures to levels in the upper soil zone lethal to the perennating buds of grasses and forbs. Spilled oil, permitted to stand (aged), ignited with difficulty or not at all, suggesting the effects of volatilization on combustion potential. Oil that soaked into surface mats of organic matter was also impossible to burn. Attempts to ignite oil spilled on snow during winter at Prudhoe Bay were unsuccessful, possibly because strong winds were rapidly removing volatile fractions. Certain herbaceous plants were relatively unharmed, either by the oil or burning when dormant. Limited damage occurred in winter if the oil was burned immediately after spilling. Delaying burning of oil either 48 hrs or one month after spilling significantly decreased plant survival. In woody vegetation types, plant survival improved slightly where oil was removed by burning. Woody species apparently survived burning and oiling and regrew from stump sprouts. There were two extremes and no intermediate burning situations. Fires either burned rapidly and hot or were impossible to ignite. Heavy black smoke produced during the rapid burns was soon dissipated by light breezes

The Effect of Topical Fluoride on Dental Caries Experience in Adult Females of a Military Population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66668/2/10.1177_00220345550340011801.pd

Teaching abductive reasoning for use as a problem-solving tool in organic chemistry and beyond

The second-year undergraduate Organic Chemistry course sequence is often cited as one of the most, if not the most, challenging for students in the US. Thus, a persistent question remains: What is it about Organic Chemistry that makes the course so difficult for students? Herein, we put forward the hypothesis that a new mode of thinking and problem solving is expected of the students; these skills have not yet been developed in their prior scientific coursework and are often not deliberately taught in Organic Chemistry. This form of reasoning and problem solving, known as abductive reasoning, is highlighted for its connection to medical diagnosis and scientific thinking. We provide examples to showcase how instructors could explicitly foreground the reasoning process in their classroom. Ultimately, we argue that teaching how to reason using abduction may benefit students in both the short term (in the course) and the long term (in their careers as scientists and medical practitioners)

Do Electronic Health Records Help or Hinder Medical Education?

Many countries worldwide are digitizing patients' medical records. What impact will these electronic health records have upon medical education? This debate examines the threats and opportunities

The Actin-Binding Protein Capulet Genetically Interacts with the Microtubule Motor Kinesin to Maintain Neuronal Dendrite Homeostasis

BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease

Designing Bioactive Delivery Systems for Tissue Regeneration

The direct infusion of macromolecules into defect sites generally does not impart adequate physiological responses. Without the protection of delivery systems, inductive molecules may likely redistribute away from their desired locale and are vulnerable to degradation. In order to achieve efficacy, large doses supplied at interval time periods are necessary, often at great expense and ensuing detrimental side effects. The selection of a delivery system plays an important role in the rate of re-growth and functionality of regenerating tissue: not only do the release kinetics of inductive molecules and their consequent bioactivities need to be considered, but also how the delivery system interacts and integrates with its surrounding host environment. In the current review, we describe the means of release of macromolecules from hydrogels, polymeric microspheres, and porous scaffolds along with the selection and utilization of bioactive delivery systems in a variety of tissue-engineering strategies

Complex SUMO-1 Regulation of Cardiac Transcription Factor Nkx2-5

Reversible post-translational protein modifications such as SUMOylation add complexity to cardiac transcriptional regulation. The homeodomain transcription factor Nkx2-5/Csx is essential for heart specification and morphogenesis. It has been previously suggested that SUMOylation of lysine 51 (K51) of Nkx2-5 is essential for its DNA binding and transcriptional activation. Here, we confirm that SUMOylation strongly enhances Nkx2-5 transcriptional activity and that residue K51 of Nkx2-5 is a SUMOylation target. However, in a range of cultured cell lines we find that a point mutation of K51 to arginine (K51R) does not affect Nkx2-5 activity or DNA binding, suggesting the existence of additional Nkx2-5 SUMOylated residues. Using biochemical assays, we demonstrate that Nkx2-5 is SUMOylated on at least one additional site, and this is the predominant site in cardiac cells. The second site is either non-canonical or a “shifting” site, as mutation of predicted consensus sites and indeed every individual lysine in the context of the K51R mutation failed to impair Nkx2-5 transcriptional synergism with SUMO, or its nuclear localization and DNA binding. We also observe SUMOylation of Nkx2-5 cofactors, which may be critical to Nkx2-5 regulation. Our data reveal highly complex regulatory mechanisms driven by SUMOylation to modulate Nkx2-5 activity

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Phenotypic Characterization of <i>EIF2AK4</i> Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 ( BMPR2 ) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene ( EIF2AK4 ) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. Methods: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource–Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of &lt;1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. Results: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (K co ; 33% [interquartile range, 30%–35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23–38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. Conclusions: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low K co and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation. </jats:sec