886 research outputs found

    Building Better Conservation Easements for America the Beautiful

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    In January 2021, the Biden Administration endorsed the goal of protecting 30% of the nation’s lands and waters by 2030 to conserve biodiversity and help curb greenhouse gas emissions. The Administration’s initial report on this “America the Beautiful” initiative, issued in May, indicates that federally-deductible conservation easements are likely to play an important role in its implementation. This essay addresses whether and how such easements should be counted in this process. This matter is of great importance. Donations of conservation easements, by which landowners receive generous federal tax deductions if they restrict the use of their properties in perpetuity in the interest of conservation, cost American taxpayers billions of dollars annually in foregone revenue. In addition, growing reports of abuse and other developments raise serious questions about the effectiveness of deductible easements in achieving durable conservation outcomes. This essay outlines the fundamental problems plaguing the deductible conservation easement program. It compares practices regarding deductible conservation easements with the protocols employed in various government conservation easement purchase programs. It concludes with specific suggestions for making deductible easements an effective tool for achieving the America the Beautiful goal. Simply accelerating the pace of conservation easement donations is not enough— to achiev[e] durable outcomes that meaningfully improve the lives of Americans,” better conservation easements need to be built

    Kinetic analysis of an efficient DNA-dependent TNA polymerase.

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    alpha-l-Threofuranosyl nucleoside triphosphates (tNTPs) are tetrafuranose nucleoside derivatives and potential progenitors of present-day beta-d-2'-deoxyribofuranosyl nucleoside triphosphates (dNTPs). Therminator DNA polymerase, a variant of the 9 degrees N DNA polymerase, is an efficient DNA-directed threosyl nucleic acid (TNA) polymerase. Here we report a detailed kinetic comparison of Therminator-catalyzed TNA and DNA syntheses. We examined the rate of single-nucleotide incorporation for all four tNTPs and dNTPs from a DNA primer-template complex and carried out parallel experiments with a chimeric DNA-TNA primer-DNA template containing five TNA residues at the primer 3'-terminus. Remarkably, no drop in the rate of TNA incorporation was observed in comparing the DNA-TNA primer to the all-DNA primer, suggesting that few primer-enzyme contacts are lost with a TNA primer. Moreover, comparison of the catalytic efficiency of TNA synthesis relative to DNA synthesis at the downstream positions reveals a difference of no greater than 5-fold in favor of the natural DNA substrate. This disparity becomes negligible when the TNA synthesis reaction mixture is supplemented with 1.25 mM MnCl(2). These results indicate that Therminator DNA polymerase can recognize both a TNA primer and tNTP substrates and is an effective catalyst of TNA polymerization despite changes in the geometry of the reactants

    Adaptive immunity alters distinct host feeding pathways during nematode induced inflammation, a novel mechanism in parasite expulsion

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    Gastrointestinal infection is often associated with hypophagia and weight loss; however, the precise mechanisms governing these responses remain poorly defined. Furthermore, the possibility that alterations in feeding during infection may be beneficial to the host requires further study. We used the nematode Trichinella spiralis, which transiently inhabits the small intestine before migrating to skeletal muscle, as a biphasic model of infection to determine the cellular and molecular pathways controlling feeding during enteric and peripheral inflammation. Through the infection of genetically modified mice lacking cholecystokinin, Tumor necrosis factor α receptors and T and B-cells, we observed a biphasic hypophagic response to infection resulting from two separate immune-driven mechanisms. The enteroendocrine I-cell derived hormone cholecystokinin is an essential mediator of initial hypophagia and is induced by CD4+ T-cells during enteritis. In contrast, the second hypophagic response is extra-intestinal and due to the anorectic effects of TNFα during peripheral infection of the muscle. Moreover, via maintaining naive levels of the adipose secreted hormone leptin throughout infection we demonstrate a novel feedback loop in the immunoendocrine axis. Immune driven I-cell hyperplasia and resultant weight loss leads to a reduction in the inflammatory adipokine leptin, which in turn heightens protective immunity during infection. These results characterize specific immune mediated mechanisms which reduce feeding during intestinal or peripheral inflammation. Importantly, the molecular mediators of each phase are entirely separate. The data also introduce the first evidence that I-cell hyperplasia is an adaptively driven immune response that directly impinges on the outcome to infection

    Consistency of use of plant stanol ester margarine in Finland

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    Abstract Objective: The aims of this study were to investigate the consistency of use of plant stanol ester margarine and to characterise consistent and inconsistent users. Design: A cohort of plant stanol ester margarine users was established based on 14 national surveys conducted by the National Public Health Institute in Finland between 1996 and 1999. A follow-up study questionnaire was developed and sent to 1294 users in 2000. Setting: Subjects who reported using plant stanol ester margarine in both the original survey and the follow-up study were classified as consistent users, and the rest as inconsistent users. Subjects: The study population consisted of 1094 subjects aged 18-87 years, 590 men and 504 women. Results: There were 357 (33%) consistent and 737 (67%) inconsistent users of plant stanol ester margarine in the study population. Consistent users were more likely to be men and to have a higher household income than inconsistent users. Both consistent and inconsistent users were predominantly middle-aged persons with a healthy lifestyle and diet as well as a history of cardiovascular disease. Healthfulness was the main factor affecting bread spread choice among 94% of the consistent users and 59% of the inconsistent users. Conclusions: The use of plant stanol ester margarine is more often inconsistent than consistent. There is nevertheless a relatively large subgroup of long-term users of plant stanol ester margarine. It is important to examine the health effects especially among these regular user

    Knockdown of the schizophrenia susceptibility gene TCF4 alters gene expression and proliferation of progenitor cells from the developing human neocortex

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    BACKGROUND: Common variants in the TCF4 gene are among the most robustly supported genetic risk factors for schizophrenia. Rare TCF4 deletions and loss-of-function point mutations cause Pitt-Hopkins syndrome, a developmental disorder associated with severe intellectual disability. METHODS: To explore molecular and cellular mechanisms by which TCF4 perturbation could interfere with human cortical development, we experimentally reduced the endogenous expression of TCF4 in a neural progenitor cell line derived from the developing human cerebral cortex using RNA interference. Effects on genome-wide gene expression were assessed by microarray, followed by Gene Ontology and pathway analysis of differentially expressed genes. We tested for genetic association between the set of differentially expressed genes and schizophrenia using genome-wide association study data from the Psychiatric Genomics Consortium and competitive gene set analysis (MAGMA). Effects on cell proliferation were assessed using high content imaging. RESULTS: Genes that were differentially expressed following TCF4 knockdown were highly enriched for involvement in the cell cycle. There was a nonsignificant trend for genetic association between the differentially expressed gene set and schizophrenia. Consistent with the gene expression data, TCF4 knockdown was associated with reduced proliferation of cortical progenitor cells in vitro. LIMITATIONS: A detailed mechanistic explanation of how TCF4 knockdown alters human neural progenitor cell proliferation is not provided by this study. CONCLUSION: Our data indicate effects of TCF4 perturbation on human cortical progenitor cell proliferation, a process that could contribute to cognitive deficits in individuals with Pitt-Hopkins Syndrome and risk for schizophrenia

    Mouse TEX15 is essential for DNA double-strand break repair and chromosomal synapsis during male meiosis

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    During meiosis, homologous chromosomes undergo synapsis and recombination. We identify TEX15 as a novel protein that is required for chromosomal synapsis and meiotic recombination. Loss of TEX15 function in mice causes early meiotic arrest in males but not in females. Specifically, TEX15-deficient spermatocytes exhibit a failure in chromosomal synapsis. In mutant spermatocytes, DNA double-strand breaks (DSBs) are formed, but localization of the recombination proteins RAD51 and DMC1 to meiotic chromosomes is severely impaired. Based on these data, we propose that TEX15 regulates the loading of DNA repair proteins onto sites of DSBs and, thus, its absence causes a failure in meiotic recombination

    Opioid growth factor modulates angiogenesis

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    AbstractObjective: Induced angiogenesis has recently been attempted as a therapeutic modality in patients with occlusive arterial atherosclerotic disease. We investigated the possible role of endogenous opioids in the modulation of angiogenesis. Methods: Chick chorioallantoic membrane was used as an in vivo model to study angiogenesis. Fertilized chick eggs were incubated for 3 days, explanted, and incubated for an additional 2 days. Three-millimeter methylcellulose disks were placed on the surface of the chorioallantoic membrane; each disk contained opioid growth factor ([Met5]-enkephalin; 5 μg), the short-acting opioid receptor antagonist naloxone (5 μg), opioid growth factor and naloxone together (5 μg of each), the long-acting opioid antagonist naltrexone (5 μg), or distilled water (control). A second series of experiments was performed with distilled water, the angiogenic inhibitor retinoic acid (1 μg), and vascular endothelial growth factor (1 μg) to further evaluate our model. The developing vasculature was imaged 2 days later with a digital camera and exported to a computer for image analysis. Total number of blood vessels, total vessel length, and mean vessel length were measured within a 100-mm2 region surrounding each applied disk. Immunocytochemical analysis was performed with antibodies directed against opioid growth factor and its receptor (OGFr). Results: Opioid growth factor had a significant inhibitory effect on angiogenesis, both the number of blood vessels and the total vessel length being decreased (by 35% and 20%, respectively) in comparison with control levels (P <.005). The simultaneous addition of naloxone and opioid growth factor had no effect on blood vessel growth, nor did naloxone alone. Chorioallantoic membranes exposed to naltrexone displayed increases of 51% and 24% in blood vessel number and length, respectively, in comparison with control specimens (P <.005). These results indicate that the opioid growth factor effects are receptor mediated and tonically active. Immunocytochemistry demonstrated the presence of both opioid growth factor and OGFr within the endothelial cells and mesenchymal cells of the developing chorioallantoic membrane vessel wall. Retinoic acid significantly reduced the number and the total length of blood vessels, whereas vascular endothelial growth factor increased both the number and the length of blood vessels in comparison with the controls (P <.0001). The magnitude of opioid growth factor's effects were comparable to those seen with retinoic acid, whereas inhibition of opioid growth factor with naltrexone induced an increase in total vessel length comparable to that for vascular endothelial growth factor. Conclusions: These results demonstrate for the first time that endogenous opioids modulate in vivo angiogenesis. Opioid growth factor is a tonically active peptide that has a receptor-mediated action in regulating angiogenesis in developing endothelial and mesenchymal vascular cells. (J Vasc Surg 2000;32:364-73.

    Structural Parameters of Seven SMC Intermediate-Age and Old Star Clusters

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    We present structural parameters for the seven intermediate-age and old star clusters NGC121, Lindsay 1, Kron 3, NGC339, NGC416, Lindsay 38, and NGC419 in the Small Magellanic Cloud. We fit King profiles and Elson, Fall, and Freeman profiles to both surface-brightness and star count data taken with the Advanced Camera for Surveys aboard the Hubble Space Telescope. Clusters older than 1 Gyr show a spread in cluster core radii that increases with age, while the youngest clusters have relatively compact cores. No evidence for post core collapse clusters was found. We find no correlation between core radius and distance from the SMC center, although consistent with other studies of dwarf galaxies, some relatively old and massive clusters have low densities. The oldest SMC star cluster, the only globular NGC121, is the most elliptical object of the studied clusters. No correlation is seen between ellipticity and distance from the SMC center. The structures of these massive intermediate-age (1-8 Gyr) SMC star clusters thus appear to primarily result from internal evolutionary processes.Comment: 16 pages, 13 figure
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