42 research outputs found

    Transformation induced by Ewing's sarcoma associated EWS/FLI-1 is suppressed by KRAB/FLI-1

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    Ewing's sarcoma is a childhood bone tumour with poor prognosis, most commonly associated with a t(11;22)(q24;q12) reciprocal translocation that fuses the EWS and FLI-1 genes, resulting in the production of an aberrant chimeric transcription factor EWS/FLI-1. To erucidate the mechanisms by which EWS/FLI-1 mediates transformation in mouse models, we have generated a murine Ews/Fli-1 fusion protein. We demonstrate that this protein transforms fibroblast celrs in vitro similar to human EWS/FLI-1 as demonstrated by serum and anchorage-independent growth, the formation of tumours in nude mice and elevation of the oncogenic marker c-myc. Furthermore, transformation of these cells was inhibited by a specific represser, KRAB/FLI-1. The KRAB/FLI-1 repressor also suppressed the tumorigenic phenotype of a human Ewing's sarcoma cell line. These findings suggest that the transformed phenotype of Ewing's sarcoma cells can be reversed by using the sequence-specific FLI-1-DNA-binding domain to target a gone repressor domain. The inhibition of EWS/FLI-1 is the first demonstration of the KRAB domain suppressing the action of an ETS factor. This approach provides potential avenues for the elucidation of the biological mechanisms of EWS/FLI-1 oncogenesis and the development of novel therapeutic strategies. © 2003 Cancer Research UK.link_to_subscribed_fulltex

    Frequent and Recent Human Acquisition of Simian Foamy Viruses Through Apes' Bites in Central Africa

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    Human infection by simian foamy viruses (SFV) can be acquired by persons occupationally exposed to non-human primates (NHP) or in natural settings. This study aimed at getting better knowledge on SFV transmission dynamics, risk factors for such a zoonotic infection and, searching for intra-familial dissemination and the level of peripheral blood (pro)viral loads in infected individuals. We studied 1,321 people from the general adult population (mean age 49 yrs, 640 women and 681 men) and 198 individuals, mostly men, all of whom had encountered a NHP with a resulting bite or scratch. All of these, either Pygmies (436) or Bantus (1085) live in villages in South Cameroon. A specific SFV Western blot was used and two nested PCRs (polymerase, and LTR) were done on all the positive/borderline samples by serology. In the general population, 2/1,321 (0.2%) persons were found to be infected. In the second group, 37/198 (18.6%) persons were SFV positive. They were mostly infected by apes (37/39) FV (mainly gorilla). Infection by monkey FV was less frequent (2/39). The viral origin of the amplified sequences matched with the history reported by the hunters, most of which (83%) are aged 20 to 40 years and acquired the infection during the last twenty years. The (pro)viral load in 33 individuals infected by a gorilla FV was quite low (<1 to 145 copies per 105 cells) in the peripheral blood leucocytes. Of the 30 wives and 12 children from families of FV infected persons, only one woman was seropositive in WB without subsequent viral DNA amplification. We demonstrate a high level of recent transmission of SFVs to humans in natural settings specifically following severe gorilla bites during hunting activities. The virus was found to persist over several years, with low SFV loads in infected persons. Secondary transmission remains an open question

    Molecular Ecology and Natural History of Simian Foamy Virus Infection in Wild-Living Chimpanzees

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    Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) and Ebola virus. Simian foamy viruses (SFVs) are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic exposure risks. Surprisingly, no information exists concerning the prevalence, geographic distribution, and genetic diversity of SFVs in wild-living monkeys and apes. Here, we report the first comprehensive survey of SFVcpz infection in free-ranging chimpanzees (Pan troglodytes) using newly developed, fecal-based assays. Chimpanzee fecal samples (n = 724) were collected at 25 field sites throughout equatorial Africa and tested for SFVcpz-specific antibodies (n = 706) or viral nucleic acids (n = 392). SFVcpz infection was documented at all field sites, with prevalence rates ranging from 44% to 100%. In two habituated communities, adult chimpanzees had significantly higher SFVcpz infection rates than infants and juveniles, indicating predominantly horizontal rather than vertical transmission routes. Some chimpanzees were co-infected with simian immunodeficiency virus (SIVcpz); however, there was no evidence that SFVcpz and SIVcpz were epidemiologically linked. SFVcpz nucleic acids were recovered from 177 fecal samples, all of which contained SFVcpz RNA and not DNA. Phylogenetic analysis of partial gag (616 bp), pol-RT (717 bp), and pol-IN (425 bp) sequences identified a diverse group of viruses, which could be subdivided into four distinct SFVcpz lineages according to their chimpanzee subspecies of origin. Within these lineages, there was evidence of frequent superinfection and viral recombination. One chimpanzee was infected by a foamy virus from a Cercopithecus monkey species, indicating cross-species transmission of SFVs in the wild. These data indicate that SFVcpz (i) is widely distributed among all chimpanzee subspecies; (ii) is shed in fecal samples as viral RNA; (iii) is transmitted predominantly by horizontal routes; (iv) is prone to superinfection and recombination; (v) has co-evolved with its natural host; and (vi) represents a sensitive marker of population structure that may be useful for chimpanzee taxonomy and conservation strategies

    Political Effects of Environmental Regulation - Evidence from the Clean Air Act

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    This Senior Thesis explores the effects of regulations under the Clean Air Act on turnout and party vote shares in federal elections between 1992 and 2018. We construct a new data set on the county level, allowing us to exploit variation in the level of air pollution regulation over time to investigate whether increased regulation leads to changes in voting behavior. In particular, we test whether possible political reactions indicate discontent with the level of environmental regulation. Using event-study models as well as difference-in-differences estimators, we find that non-attainment designation has no measurable effect on turnout but is linked to an increase of around 2 percentage points in the Democrats’ vote share. Exploring the underlying mechanism behind this effect, our models suggest that most of the increasing vote shares for Democratic candidates are driven by a loss of vote shares for Independent candidates, and that education levels in a county better explain political reactions than the potential economic vulnerability to environmental regulation does. We interpret these findings as evidence for the increasing importance of environmental policy in voting decisions. In addition, our study provides preliminary support for a model in which environmental policy can affect political outcomes not just by imposing economic costs on voters but also by signalling to voters that environmental regulation is needed

    Effects of Currents on Waves

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    Source: https://erdc-library.erdc.dren.mil/jspui/This report presents ways in which a horizontal current influences surface gravity waves and their measurement. Relatively simple hand-calculation methods are described which provide a means to estimate (a) the wavelength modification due to a current, ( b) whether a current can prevent waves from reaching a particular location, (c) the correction needed to compensate for a current when observed bottom pressure fluctuations are used to estimate wave heights, and (d) the range of periods (if any) where the effects of currents can be neglected when wave heights are estimated from bottom pressure fluctuations

    Products from Two Computer Programs which Process Digital Bathymetric Data

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    Source: https://erdc-library.erdc.dren.mil/jspui/A description is given of products from two computer programs which process digital bathymetric data. One program generates regularly spaced bathymetric data from irregularly spaced data. The other uses regularly spaced data to determine and draw contours. A large set of irregularly spaced bathymetric data available on magnetic tape for U.S. coastal regions is also described. Examples of output from each program are displayed for two coastal areas

    Effects of currents on waves /

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    THE EFFECTS OF RACKET INERTIA TENSOR ON ELBOW LOADINGS AND RACKET BEHAVIOR FOR CENTRAL AND ECCENTRIC IMPACTS

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    This paper discusses the inertia tensors of tennis rackets and their influence on the elbow swing torques in a forehand motion, the loadings transmitted to the elbow from central and eccentric impacts, and the racket acceleration responses from central and eccentric impacts. Inertia tensors of various rackets with similar mass and mass center location were determined by an inertia pendulum and were found to vary considerably in all three orthogonal directions. Tennis swing mechanics and impact analyses were performed using a computer model comprised of a full-body model of a human, a parametric model of the racket, and an impact function. The swing mechanics analysis of a forehand motion determined that inertia values had a moderate linear effect on the pronation-supination elbow torques required to twist the racket, and a minor effect on the flexion-extension and valgus-varus torques. The impact analysis found that mass center inertia values had a considerable effect on the transmitted torques for both longitudinal and latitudinal eccentric impacts and significantly affected all elbow torque components. Racket acceleration responses to central and eccentric impacts were measured experimentally and found to be notably sensitive to impact location and mass center inertia value
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