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The conservation of a rare species requires an understanding of its habitat requirements, including its response to different light levels. Accordingly, we conducted a study of the light requirements of Pycnanthemum verticillatum var. verticillatum, a New York State S1S2-Endangered perennial forb found on Staten Island, Richmond County, NY. Much of its present habitat in this urban county is along disturbed roadsides and is undergoing increased shading due to woody encroachment. We grew plants in full sunlight (no shade cloth), medium sunlight (30% shade cloth), and low sunlight (60% shade cloth), and measured their growth, reproductive, and morphological responses. Plants were largest and most likely to produce flowers in the full and medium sunlight treatments. Plants exhibited typical shade-avoidant responses such as stem elongation and increased secondary ramet production in the low sunlight treatment. We conclude that Pycnanthemum verticillatum var. verticillatum may survive in deep shade, but partial and full sun result in more vigorous growth and reproduction. Canopy thinning to maintain no more than 30–50% shade is necessary for the plants to thrive. Managing for sunny habitats, such as meadows and open-canopy forests, would have broad conservation benefits for this species and other native plants that require high-light environments in the region. [ABSTRACT FROM AUTHOR]

Creating, restoring, and sustaining forests in urban areas are complicated by habitat fragmentation, invasive species, and degraded soils. Although there is some research on the outcomes of urban reforestation plantings during the first 5 years, there is little research on longer term outcomes. Here, we compare the successional trajectories of restored and unrestored forest sites 20 years after initiating restoration. The sites are located within the Rodman's Neck area of Pelham Bay Park, in the northeast corner of the Bronx in New York City ( NYC), U.S.A. Compared with unrestored sites, we saw improvements in species diversity, greater forest structure complexity, and evidence of the regeneration and retention of native tree species in restored sites. In addition, we found differences in restoration outcomes depending on the level of intervention: clearing exotic shrubs and vines and planting native trees and shrubs improved tree diversity and canopy closure to a greater extent than clearing exotics alone, and the mechanical removal of invasive plants after the native plantings further improved some measures of restoration, such as tree species diversity and native tree regeneration. The results of this study suggest that the goal of a sustainable forest ecosystem dominated by native trees and other plant species may not be achievable without continued human intervention on site. In addition, these results indicate that the restoration approach adopted by NYC's reforestation practitioners is moving the site toward a more desirable vegetative community dominated by native species. [ABSTRACT FROM AUTHOR]

Forests are vital components of the urban landscape because they provide ecosystem services such as carbon sequestration, storm-water mitigation, and air-quality improvement. To enhance these services, cities are investing in programs to create urban forests. A major unknown, however, is whether planted trees will grow into the mature, closed-canopied forest on which ecosystem service provision depends. We assessed the influence of biotic and abiotic land management on planted tree performance as part of urban forest restoration in New York City, U.S.A. Biotic treatments were designed to improve tree growth, with the expectation that higher tree species composition (six vs. two) and greater stand complexity (with shrubs vs. without) would facilitate tree performance. Similarly, the abiotic treatment (compost amendment vs. without) was expected to increase tree performance by improving soil conditions. Growth and survival was measured for approximately 1,300 native saplings across three growing seasons. The biotic and abiotic treatments significantly improved tree performance, where shrub presence increased tree height for five of the six tree species, and compost increased basal area and stem volume of all species. Species-specific responses, however, highlighted the difficulty of achieving rapid growth with limited mortality. Pioneer species had the highest growth in stem volume over 3 years (up to 3,500%), but also the highest mortality (up to 40%). Mid-successional species had lower mortality (<16%), but also the slowest growth in volume (approximately 500% in volume). Our results suggest that there will be trade-offs between optimizing tree growth versus survival when implementing urban tree planting initiatives. [ABSTRACT FROM AUTHOR]

In healthy blood vessels, albumin crosses the endothelium to leave the circulation by transcytosis. However, little is known about the regulation of albumin transcytosis or how it differs in different tissues; its physiological purpose is also unclear. Using total internal reflection fluorescence microscopy, we quantified transcytosis of albumin across primary human microvascular endothelial cells from both lung and skin. We then validated our in vitro findings using a tissue-specific knockout mouse model. We observed that albumin transcytosis was saturable in the skin but not the lung microvascular endothelial cells, implicating a receptor-mediated process. We identified the scavenger receptor CD36 as being both necessary and sufficient for albumin transcytosis across dermal microvascular endothelium, in contrast to the lung where macropinocytosis dominated. Mutations in the apical helical bundle of CD36 prevented albumin internalization by cells. Mice deficient in CD36 specifically in endothelial cells exhibited lower basal permeability to albumin and less basal tissue edema in the skin but not in the lung. Finally, these mice also exhibited a smaller subcutaneous fat layer despite having identical total body weights and circulating fatty acid levels as wild-type animals. In conclusion, CD36 mediates albumin transcytosis in the skin but not the lung. Albumin transcytosis may serve to regulate fatty acid delivery from the circulation to tissues.

The primary target organ for uptake of systemically administered phosphorothioate oligonucleotides is the kidney cortex and the proximal tubular epithelium in particular. To determine the effect of oligonucleotide uptake on renal function, a detailed renal physiology study was performed in cynomolgus monkeys treated with 10-40 mg/kg/week ISIS 113715 for 4 weeks. The concentrations of oligonucleotide in the kidney cortex ranged from 1400 to 2600 μg/g. These concentrations were associated with histologic changes in proximal tubular epithelial cells that ranged from the appearance of cytoplasmic basophilic granules to atrophic and degenerative changes at higher concentrations. However, there were no renal functional abnormalities as determined by the typical measurements of blood urea nitrogen, serum creatinine, creatinine clearance, or urine specific gravity. Nor were there changes in glomerular filtration rate, or renal blood flow. Specific urinary markers of tubular epithelial cell damage, such as N-acetyl-glucosaminidase, and α-glutathione-s-transferase were not affected. Tubular function was further evaluated by monitoring the urinary excretion of amino acids, β(2)-microglobulin, or glucose. Renal function was challenged by administering a glucose load and by examining concentrating ability after a 4-h water deprivation. Neither challenge produced any evidence of change in renal function. The only change observed was a low incidence of increased urine protein/creatinine ratio in monkeys treated with ≥40 mg/kg/week which was rapidly reversible. Collectively, these data indicate that ISIS 113715-uptake by the proximal tubular epithelium has little or no effect on renal function at concentrations of 2600 μg/g., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: The purpose of train-the-trainer (TTT) programs within the context of continuing medical education (CME) is to help facilitators acquire and/or enhance their skills at leading CME sessions. The provision of follow-up is one feature of successful CME workshops over which CME providers have some control. Follow-up is defined as any encounter between participants and workshop leaders, following an initial workshop or other development session, and is designed to enhance, maintain, reinforce, transfer, extend, or support the learning from the original workshop. In this article, we elaborate on the use of audio teleconferences to provide follow-up for a TTT workshop in Saskatchewan, a largely rural province in western Canada., Methods: The teleconferences began 6 weeks after the workshop and were held at approximately 6-week intervals, with five conference calls in total. Each lasted about 45 minutes. Participants were interviewed to determine their view of the value of the teleconferences., Results: Participants reported learning from the teleconferences and feeling more prepared to conduct CME sessions due to their participation in the teleconferences. Participants missed teleconferences only for extenuating circumstances (e.g., emergency deliveries)., Findings: We have found that audio teleconferences allow for and encourage professional discussion that is crucial to changing practices. They are an effective way to incorporate follow-up to TTT workshops when participants travel great distances to attend.

UDP-glucuronosyltransferase 1A6 (UGT1A6), a key enzyme catalyzing the glucuronidation of small planar phenols and amines, is expressed in a tissue- and inducer-dependent manner. Expression is high in kidney, gastrointestinal tract, and induced liver, with low expression in spleen, lung, and ovary. Exposure to certain chemicals, such as 3-methylcholanthrene, benzo[a]pyrene, beta-naphthoflavone, and oltipraz elevates UGT1A6 mRNA in liver and to a lesser extent gastrointestinal tract and kidney, but not in other tissues. The mechanisms underlying this complex pattern of expression have been elusive. We have identified a new type of UGT1A6 mRNA (class 2) that differs in its 5' untranslated sequence. The class 2 transcript is the more abundant type expressed in liver, gastrointestinal tract, and kidney. Transcription of the class 2 mRNA is initiated 107 bases 5' of the UGT1A6 coding exon. The promoter region flanking the transcription start site contains an HNF1-like binding site identical to that in the human UGT1A6 gene. Both class 1 and class 2 mRNAs were elevated in liver by 3-methylcholanthrene, benzo[a]pyrene, beta-naphthoflavone, and oltipraz, with preferential elevation of class 1 occurring after 3-methylcholanthrene and benzo[a]pyrene treatment. These data suggest that transcription from a second promoter contributes to tissue- and inducer-specific expression of rat UGT1A6., (Copyright 2001 Academic Press.)

One of the most important mechanisms involved in host defense against xenobiotic chemicals and endogenous toxins is the glucuronidation catalysed by UDP-glucuronosyltransferase enzymes (UGT). The role of genetic factors in determining variable rates of glucuronidation is not well understood, but phenotypic evidence in support of such variation has been reported. In the present study, six single nucleotide polymorphisms were discovered in the first exon of the UGT1A7 gene, which codes for the putative substrate-binding domain, revealing a high structural heterogeneity at the UGT1 gene locus. The new UGT1A7 proteins differ in their primary structure at amino acid positions 129, 131 and 208, creating four distinct UGT1A7 allelic variants in the human population: UGT1A7*1 (N129 R131 W208), *2 (K129 K131 W208), *3 (K129 K131 R208), and *4 (N129 R131 R208). In functional studies, HEK cells stably transfected to express the four allelic UGT1A7 variants exhibited significant differences in catalytic activity towards 3-, 7-, and 9-hydroxy-benzo(a)pyrene. UGT1A7*3 exhibited a 5.8-fold lower relative Vmax compared to wild-type *1, whereas *2 and *4 had a 2.6- and 2.8-fold lower relative Vmax than *1, respectively, suggesting that these mutations confer slow glucuronidation phenotype. Kinetic characterization suggested that these differences were primarily attributable to altered Vmax. Additionally, it suggested that each amino acid substitutions can independently affect the UGT1A7 catalytic activity, and that their effects are additive. The expression pattern of UGT1A7 studied herein and its catalytic activity profile suggest a possible role of UGT1A7 in the detoxification and elimination of carcinogenic products in lung. A population study demonstrated that a considerable proportion of the population (15.3%) was found homozygous for the low activity allele containing all three missense mutations, UGT1A7*3. These findings suggest that further studies are needed to investigate the impact of the low UGT1A7 conjugator genotype on individual susceptibility to chemical-induced diseases and responses to therapeutic drugs.

UDP-glucuronosyltransferase 1A7 (UGT1A7) is a major UGT contributing to the glucuronidation of xenobiotic phenols in rats. Its expression in rat liver is tightly regulated, with low constitutive and high inducible expression in response to aryl hydrocarbon receptor ligands and oltipraz. Previously, we reported the absence of 3-methylcholanthrene- or oltipraz-responsive elements in the 1.6-kbp region flanking the UGT1A7 promoter. However, potential binding sites were noted for several liver-enriched transcription factors. Here we show that deletion of the hepatic nuclear factor (HNF)3, HNF4, and CCAAT-enhancer binding protein-like binding sites had no effect on the expression of a UGT1A7 reporter plasmid, p(-965/+56)1A7-Luc, in primary rat hepatocytes. The full activity of the promoter was contained in the region between bases -157 and +76. Two sites of binding by rat liver nuclear proteins were detected in this region by DNase footprinting. PR-1 corresponded to the HNF1-like binding site between bases -52 and -38, whereas PR-2 was located between -30 to -6. Gel retardation studies supported the presence of HNF1alpha in the PR-1 DNA-liver nuclear protein complex. Mutation of PR-1 inhibited binding in the gel shift assay, prevented activation by overexpressed HNF1 in human embryonic kidney cells, and reduced by >80% the maximal luciferase activities expressed from basal and 3-methylcholanthrene-responsive UGT1A7 gene reporter constructs in primary rat hepatocytes. These data provide evidence for an important stimulatory role of HNF1 in promoting UGT1A7 gene expression in rat liver.

In Crigler-Najjar type II patients and, recently, in Crigler-Najjar type I patients treated with human hepatocyte cell therapy, phenobarbital has been used for reducing the serum bilirubin load. Its effect is attributed to induction of the enzyme required for hepatic bilirubin elimination, UDP-glucuronosyltransferase, UGT1A1. This study investigated the expression and inducibility of UGT1A1 in human donor livers and their corresponding primary hepatocyte cultures. Immunoblot analysis using a specific antibody directed against the amino terminal of the human UGT1A1 isoform showed that 5 hepatocyte donors exhibited a >50-fold difference in UGT1A1 level. UGT1A1 protein level correlated strongly with both liver microsomal bilirubin UGT activity and liver UGT1A1 mRNA level (r(2) =.82 and.72, respectively). Of the 4 patients with the lowest UGT1A1 levels, 3 were homozygotes for the UGT1A1 promoter variant sequence associated with Gilbert's syndrome, and the fourth was a heterozygote. The 3 donors with the highest levels had a history of phenytoin exposure. Hepatocytes isolated from the phenytoin-exposed donors exhibited marked declines in UGT1A1 mRNA levels during culturing. Induction studies using hepatocytes treated for 48 hours with phenobarbital (2 mmol/L), oltipraz (50 micromol/L), or 3-methylcholanthrene (2.5 micromol/L) revealed UGT1A1-inducing effects of phenobarbital, oltipraz, and, in particular, 3-methylcholanthrene. Our data suggest that both genetic and environmental factors play an important role in the marked interindividual variability in UGT1A1 expression. An understanding of these mechanisms could lead to advances in the pharmacological therapy of life-threatening unconjugated hyperbilirubinemia.