304 research outputs found

    FORESTLAND OWNERSHIP IN ONEIDA AND VILAS COUNTIES, WISCONSIN, 1975-1994

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    Privately owned forests in the United States are being divided, roaded, and developed by increasing numbers of second-home buyers, retirees, and recreation enthusiasts. Forested parcels adjacent to or embedded in public land are considered especially desirable and a premium is being paid for the aesthetic or recreational amenities associated with such properties. However, virtually all information on variations in forestland prices in northern Wisconsin is anecdotal. One objective of this study was to identify parcel characteristics that influenced forestland prices in Vilas and Oneida counties, Wisconsin, between 1975 and 1994. A second objective was to ascertain what impact the creation and expansion of the Northern Highland-American Legion State Forest (NHALSF) had on the forestland market in Vilas and Oneida counties during this time period. Several trends suggest that the drive to acquire forestland for the construction of second homes in Vilas and Oneida counties is strong and that the NHALSF continues to impact forestland prices. Forestland in Vilas and Oneida counties was shown to react to macroeconomic forces as if it were a luxury good (that is, declining sales during a recession, increasing sales during an economic upturn) and not simply a timber resource. Positive relationships were identified between the per-acre price of forestland, the presence of highway frontage, and parcel size for the years 1975, 1980, and 1990. Forested parcels adjacent to the NHALSF were shown to have higher per-acre prices than parcels without frontage on the NHALSF. The acquisition of land by the Wisconsin Department of Natural Resources (WDNR) to expand the NHALSF has continued in recent decades, taking large quantities of land off the "open market." The reduced supply of available parcels in and near the NHALSF, as well as the highly desirable nature of owning forestland with frontage on public land, has caused the price of the remaining privately owned forestland in Vilas and Oneida counties to increase faster than similar forestland in other northern counties of Wisconsin.Forests and forestry--Wisconsin--Oneida County, Forests and forestry--Wisconsin-- Vilas County, Forest landowners--Wisconsin, Real property--Wisconsin, Real property--Prices--Wisconsin, Land prices--United States--Wisconsin, Resource /Energy Economics and Policy,

    State policy innovation and transfer: The role of bureaucratic professional communication networks

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    The central question of this research is, what is the role of state administrative agencies in the innovation and transfer of public policy? One of the theoretical perspectives of the study of public policy examines the borrowing of one nation or U.S. state\u27s policy by another followed by adaptation to the new jurisdiction. The past focus of most of this research has been on legislative policy adoptions. This study draws upon a different perspective, bureaucratic adoptions of public policy.;A two-fold approach is employed, using both quantitative and qualitative research techniques. Information was gathered on both state agencies and their lead officials by telephone, in person, and through written survey instruments. Further documentary data were drawn from a variety of sources on state public health agencies and other political and economic characteristics of individual U.S. states. This information was used in two ways.;First, a detailed depiction describes the professional communication networks of state public health agency officials. The literature on policy transfer assumes the use of such a network, but past research has neither described the network and its mechanisms of communication nor substantiated its existence. The primary finding of this section is that such a communication network exists but that it occurs on an ad hoc rather than systematic basis. This research also demonstrates the importance of various specific communication mechanisms to state public health officials for the transfer of policy and programmatic information.;Secondly, this research addresses the possible differences between legislative and bureaucratic policy adoption. Using OLS regression, two different models of the determinants of policy innovation are tested. A comparison is made between legislative adoption of policy and bureaucratic adoption of policy. The central finding is that the determinants of legislative policy adoption do different from the determinants of bureaucratic policy adoption.;This research demonstrates the importance of examining policy innovation and transfer from the perspective of multiple political and policymaking institutions, in particular, the bureaucracy. It also broadens our understanding of the coalitions of policymakers that exist that create U.S. state public policy

    Deep sequencing of virus-infected cells reveals HIV-encoded small RNAs

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    Small virus-derived interfering RNAs (viRNAs) play an important role in antiviral defence in plants, insects and nematodes by triggering the RNA interference (RNAi) pathway. The role of RNAi as an antiviral defence mechanism in mammalian cells has been obscure due to the lack of viRNA detection. Although viRNAs from different mammalian viruses have recently been identified, their functions and possible impact on viral replication remain unknown. To identify viRNAs derived from HIV-1, we used the extremely sensitive SOLiDTM 3 Plus System to analyse viRNA accumulation in HIV-1-infected T lymphocytes. We detected numerous small RNAs that correspond to the HIV-1 RNA genome. The majority of these sequences have a positive polarity (98.1%) and could be derived from miRNAs encoded by structured segments of the HIV-1 RNA genome (vmiRNAs). A small portion of the viRNAs is of negative polarity and most of them are encoded within the 3′-UTR, which may represent viral siRNAs (vsiRNAs). The identified vsiRNAs can potently repress HIV-1 production, whereas suppression of the vsiRNAs by antagomirs stimulate virus production. These results suggest that HIV-1 triggers the production of vsiRNAs and vmiRNAs to modulate cellular and/or viral gene expression

    A peptide-loaded dendritic cell based cytotoxic T-lymphocyte (CTL) vaccination strategy using peptides that span SIV Tat, Rev, and Env overlapping reading frames

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    CTL based vaccine strategies in the macaque model of AIDS have shown promise in slowing the progression to disease. However, rapid CTL escape viruses can emerge rendering such vaccination useless. We hypothesized that such escape is made more difficult if the immunizing CTL epitope falls within a region of the virus that has a high density of overlapping reading frames which encode several viral proteins. To test this hypothesis, we immunized macaques using a peptide-loaded dendritic cell approach employing epitopes in the second coding exon of SIV Tat which spans reading frames for both Env and Rev. We report here that autologous dendritic cells, loaded with SIV peptides from Tat, Rev, and Env, induced a distinct cellular immune response measurable ex vivo. However, conclusive in vivo control of a challenge inoculation of SIVmac239 was not observed suggesting that CTL epitopes within densely overlapping reading frames are also subject to escape mutations

    The identification of unique serum proteins of HIV-1 latently infected long-term non-progressor patients

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    <p>Abstract</p> <p>Background</p> <p>The search for disease biomarkers within human peripheral fluids has become a favorable approach to preventative therapeutics throughout the past few years. The comparison of normal versus disease states can identify an overexpression or a suppression of critical proteins where illness has directly altered a patient's cellular homeostasis. In particular, the analysis of HIV-1 infected serum is an attractive medium with which to identify altered protein expression due to the ease and non-invasive methods of collecting samples as well as the corresponding insight into the <it>in vivo </it>interaction of the virus with infected cells/tissue. The utilization of proteomic techniques to globally identify differentially expressed serum proteins in response to HIV-1 infection is a significant undertaking that is complicated due to the innate protein profile of human serum.</p> <p>Results</p> <p>Here, the depletion of 12 of the most abundant serum proteins, followed by two-dimensional gel electrophoresis coupled with identification of these proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, has allowed for the identification of differentially expressed, low abundant serum proteins. We have analyzed and compared serum samples from HIV-1 infected subjects who are being treated using highly active antiretroviral therapy (HAART) to those who are latently infected but have not progressed to AIDS despite the absence of treatment, i.e. long term non-progressors (LTNPs). Here we have identified unique serum proteins that are differentially expressed in LTNP HIV-1 patients and may contribute to the ability of these patients to combat HIV-1 infection in the absence of HAART. We focused on the cdk4/6 cell cycle inhibitor p16<sup>INK4A </sup>and found that the treatment of HIV-1 latently infected cell lines with p16<sup>INK4A </sup>decreases viral production despite it not being expressed endogenously in these cells.</p> <p>Conclusions</p> <p>Identification of these unique proteins may serve as an indication of altered viral states in response to infection as well as a natural phenotypic variability in response to HIV-1 infection in a given population.</p

    HIV-1 TAR element is processed by Dicer to yield a viral micro-RNA involved in chromatin remodeling of the viral LTR

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    <p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) is a regulatory mechanism conserved in higher eukaryotes. The RNAi pathway generates small interfering RNA (siRNA) or micro RNA (miRNA) from either long double stranded stretches of RNA or RNA hairpins, respectively. The siRNA or miRNA then guides an effector complex to a homologous sequence of mRNA and regulates suppression of gene expression through one of several mechanisms. The suppression of gene expression through these mechanisms serves to regulate endogenous gene expression and protect the cell from foreign nucleic acids. There is growing evidence that many viruses have developed in the context of RNAi and express either a suppressor of RNAi or their own viral miRNA.</p> <p>Results</p> <p>In this study we investigated the possibility that the HIV-1 TAR element, a hairpin structure of ~50 nucleotides found at the 5' end of the HIV viral mRNA, is recognized by the RNAi machinery and processed to yield a viral miRNA. We show that the protein Dicer, the enzyme responsible for cleaving miRNA and siRNA from longer RNA sequences, is expressed in CD4+ T-cells. Interestingly, the level of expression of Dicer in monocytes is sub-optimal, suggesting a possible role for RNAi in maintaining latency in T-cells. Using a biotin labeled TAR element we demonstrate that Dicer binds to this structure. We show that recombinant Dicer is capable of cleaving the TAR element in vitro and that TAR derived miRNA is present in HIV-1 infected cell lines and primary T-cell blasts. Finally, we show that a TAR derived miRNA is capable of regulating viral gene expression and may be involved in repressing gene expression through transcriptional silencing.</p> <p>Conclusion</p> <p>HIV-1 TAR element is processed by the Dicer enzyme to create a viral miRNA. This viral miRNA is detectable in infected cells and appears to contribute to viral latency.</p

    Two specific drugs, BMS-345541 and purvalanol A induce apoptosis of HTLV-1 infected cells through inhibition of the NF-kappaB and cell cycle pathways

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    Human T-cell leukemia virus type-1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATL/L), a fatal lymphoproliferative disorder, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic progressive disease of the central nervous system after a long period of latent infection. Although the mechanism of transformation and leukemogenesis is not fully elucidated, there is evidence to suggest that the viral oncoprotein Tax plays a crucial role in these processes through the regulation of several pathways including NF-κB and the cell cycle pathways. The observation that NF-κB, which is strongly induced by Tax, is indispensable for the maintenance of the malignant phenotype of HTLV-1 by regulating the expression of various genes involved in cell cycle regulation and inhibition of apoptosis provides a possible molecular target for these infected cells. To develop potential new therapeutic strategies for HTLV-1 infected cells, in this present study, we initially screened a battery of NF-κB and CDK inhibitors (total of 35 compounds) to examine their effects on the growth and survival of infected T-cell lines. Two drugs namely BMS-345541 and Purvalanol A exhibited higher levels of growth inhibition and apoptosis in infected cell as compared to uninfected cells. BMS-345541 inhibited IKKβ kinase activity from HTLV-1 infected cells with an IC50 (the 50% of inhibitory concentration) value of 50 nM compared to 500 nM from control cells as measured by in vitro kinase assays. The effects of Purvalanol A were associated with suppression of CDK2/cyclin E complex activity as previously shown by us. Combination of both BMS-345541 and Purvalanol A showed a reduced level of HTLV-1 p19 Gag production in cell culture. The apparent apoptosis in these infected cells were associated with increased caspase-3 activity and PARP cleavage. The potent and selective apoptotic effects of these drugs suggest that both BMS-345541 and Purvalanol A, which target both NF-κB and CDK complex and the G1/S border, might be promising new agents in the treatment of these infected patients
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