760 research outputs found

    \u3ci\u3eHoplistoscelis Sordidus\u3c/i\u3e (Heteroptera: Nabidae) in Canada

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    Hoplistoscelis sordidus is recorded for the first time from Canada. The distribution of the species, its establishment in Canada, and its bionomics are discussed. Characters are given that distinguish Hoplistoscelis from all other eastern Canadian genera of Nabinae. The potential role of the genus as a biological control agent is also briefly outlined

    Arsenic alters the function of the glucocorticoid receptor as a transcription factor.

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    Chronic human exposure to nonovertly toxic doses of arsenic is associated with an increased risk of cancer. Although its carcinogenic mechanism is still unknown, arsenic does not directly cause DNA damage or mutations and is therefore thought to act principally as a co-mutagen, co-carcinogen, and/or tumor promoter. Previous studies in our laboratory demonstrated that effects of low-dose arsenic (III) (arsenite) on expression of the hormone-regulated phosphoenolpyruvate carboxykinase (PEPCK) gene were strongly associated with the glucocorticoid receptor (GR)-mediated regulatory pathway. We therefore examined specifically the effects of arsenite on the biochemical function of GR in hormone-responsive H4IIE rat hepatoma cells. Completely noncytotoxic arsenite treatments (0.3-3.3 microM) significantly decreased dexamethasone-induced expression of transiently transfected luciferase constructs containing either an intact hormone-responsive promoter from the mammalian PEPCK gene or two tandem glucocorticoid response elements (GRE). Western blotting and confocal microscopy of a green fluorescent protein-tagged-GR fusion protein demonstrated that arsenite pretreatment did not block the normal dexamethasone-induced nuclear translocation of GR. These data indicate that nontoxic doses of arsenite can interact directly with GR complexes and selectively inhibit GR-mediated transcription, which is associated with altered nuclear function rather than a decrease in hormone-induced GR activation or nuclear translocation

    Synergistic Combination of Hyperoxygenation and Radiotherapy by Repeated Assessments of Tumor pO2 with EPR Oximetry

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    The effect of hyperoxygenation with carbogen (95% O2 + 5% CO2) inhalation on RIF-1 tumor pO2and its consequence on growth inhibition with fractionated radiotherapy is reported. The temporal changes in the tumor pO2 were assessed by in vivo Electron Paramagnetic Resonance (EPR) oximetry in mice breathing 30% O2 or carbogen and the tumors were irradiated with 4 Gy/day for 5 consecutive days; a protocol that emulates the clinical application of carbogen. The RIF-1 tumors were hypoxic with a tissue pO2 of 5–9 mmHg. Carbogen (CB) breathing significantly increased tumor pO2, with a maximum increase at 22.9–31.2 min on days 1–5, however, the magnitude of increase in pO2 declined on day 5. Radiotherapy during carbogen inhalation (CB/RT) resulted in a significant tumor growth inhibition from day 3 to day 6 as compared to 30%O2/RT and carbogen (CB/Sham RT) groups. The results provide unambiguous quantitative information on the effect of carbogen inhalation on tumor pO2 over the course of 5 days. Tumor growth inhibition in the CB/RT group confirms that the tumor oxygenation with carbogen was radiobiologically significant. Repeated tumor pO2 measurements by EPR oximetry can provide temporal information that could be used to improve therapeutic outcomes by scheduling doses at times of improved tumor oxygenation

    Design and update of a classification system: The UCSD map of science

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    Global maps of science can be used as a reference system to chart career trajectories, the location of emerging research frontiers, or the expertise profiles of institutes or nations. This paper details data preparation, analysis, and layout performed when designing and subsequently updating the UCSD map of science and classification system. The original classification and map use 7.2 million papers and their references from Elsevier's Scopus (about 15,000 source titles, 2001-2005) and Thomson Reuters' Web of Science (WoS) Science, Social Science, Arts & Humanities Citation Indexes (about 9,000 source titles, 2001-2004)-about 16,000 unique source titles. The updated map and classification adds six years (2005-2010) of WoS data and three years (2006-2008) from Scopus to the existing category structure-increasing the number of source titles to about 25,000. To our knowledge, this is the first time that a widely used map of science was updated. A comparison of the original 5-year and the new 10-year maps and classification system show (i) an increase in the total number of journals that can be mapped by 9,409 journals (social sciences had a 80% increase, humanities a 119% increase, medical (32%) and natural science (74%)), (ii) a simplification of the map by assigning all but five highly interdisciplinary journals to exactly one discipline, (iii) a more even distribution of journals over the 554 subdisciplines and 13 disciplines when calculating the coefficient of variation, and (iv) a better reflection of journal clusters when compared with paper-level citation data. When evaluating the map with a listing of desirable features for maps of science, the updated map is shown to have higher mapping accuracy, easier understandability as fewer journals are multiply classified, and higher usability for the generation of data overlays, among others

    TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation

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    <p>Abstract</p> <p>Background</p> <p>The discovery of heat-sensitive Transient Receptor Potential Vanilloid (TRPV) ion channels provided a potential molecular explanation for the perception of innocuous and noxious heat stimuli. TRPV1 has a significant role in acute heat nociception and inflammatory heat hyperalgesia. Yet, substantial innocuous and noxious heat sensitivity remains in TRPV1 knockout animals. Here we investigated the role of two related channels, TRPV3 and TRPV4, in these capacities. We studied TRPV3 knockout animals on both C57BL6 and 129S6 backgrounds, as well as animals deficient in both TRPV3 and TRPV4 on a C57BL6 background. Additionally, we assessed the contributions of TRPV3 and TRPV4 to acute heat nociception and inflammatory heat hyperalgesia during inhibition of TRPV1.</p> <p>Results</p> <p>TRPV3 knockout mice on the C57BL6 background exhibited no obvious alterations in thermal preference behavior. On the 129S6 background, absence of TRPV3 resulted in a more restrictive range of occupancy centered around cooler floor temperatures. TRPV3 knockout mice showed no deficits in acute heat nociception on either background. Mice deficient in both TRPV3 and TRPV4 on a C57BL6 background showed thermal preference behavior similar to wild-type controls on the thermal gradient, and little or no change in acute heat nociception or inflammatory heat hyperalgesia. Masking of TRPV1 by the TRPV1 antagonist JNJ-17203212 did not reveal differences between C57BL6 animals deficient in TRPV3 and TRPV4, compared to their wild-type counterparts.</p> <p>Conclusions</p> <p>Our results support the notion that TRPV3 and TRPV4 likely make limited and strain-dependent contributions to innocuous warm temperature perception or noxious heat sensation, even when TRPV1 is masked. These findings imply the existence of other significant mechanisms for heat perception.</p

    Molecular basis for effects of carcinogenic heavy metals on inducible gene expression.

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    Certain forms of the heavy metals arsenic and chromium are considered human carcinogens, although they are believed to act through very different mechanisms. Chromium(VI) is believed to act as a classic and mutagenic agent, and DNA/chromatin appears to be the principal target for its effects. In contrast, arsenic(III) is considered nongenotoxic, but is able to target specific cellular proteins, principally through sulfhydryl interactions. We had previously shown that various genotoxic chemical carcinogens, including chromium (VI), preferentially altered expression of several inducible genes but had little or no effect on constitutive gene expression. We were therefore interested in whether these carcinogenic heavy metals might target specific but distinct sites within cells, leading to alterations in gene expression that might contribute to the carcinogenic process. Arsenic(III) and chromium(VI) each significantly altered both basal and hormone-inducible expression of a model inducible gene, phosphoenolpyruvate carboxykinase (PEPCK), at nonovertly toxic doses in the chick embryo in vivo and rat hepatoma H411E cells in culture. We have recently developed two parallel cell culture approaches for examining the molecular basis for these effects. First, we are examining the effects of heavy metals on expression and activation of specific transcription factors known to be involved in regulation of susceptible inducible genes, and have recently observed significant but different effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding. Second, we have developed cell lines with stably integrated PEPCK promoter-luciferase reporter gene constructs to examine effects of heavy metals on promoter function, and have also recently seen profound effects induced by both chromium(VI) and arsenic(III) in this system. These model systems should enable us to be able to identify the critical cis (DNA) and trans (protein) cellular targets of heavy metal exposure leading to alterations in expression of specific susceptible genes. It is anticipated that such information will provide valuable insight into the mechanistic basis for these effects as well as provide sensitive molecular biomarkers for evaluating human exposure

    Convection enhanced delivery and \u3ci\u3ein vivo\u3c/i\u3e imaging of polymeric nanoparticles for the treatment of malignant glioma

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    A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells demonstrated. Convection enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma

    Growth factor release from a chemically modified elastomeric poly(1,8‐octanediol‐co‐citrate) thin film promotes angiogenesis in vivo

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    The ultimate success of in vivo organ formation utilizing ex vivo expanded “starter” tissues relies heavily upon the level of vascularization provided by either endogenous or artificial induction of angiogenic or vasculogenic events. To facilitate proangiogenic outcomes and promote tissue growth, an elastomeric scaffold previously shown to be instrumental in the urinary bladder regenerative process was modified to release proangiogenic growth factors. Carboxylic acid groups on poly(1,8‐octanediol‐co‐citrate) films (POCfs) were modified with heparan sulfate creating a heparan binding POCf (HBPOCf). Release of proangiogenic growth factors vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and insulin‐like growth factor 1 (IGF‐1) from HBPOCfs demonstrated an approximate threefold increase over controls during a 30‐day time course in vitro . Atomic force microscopy demonstrated significant topological differences between films. Subcutaneous implantation of POCf alone, HBPOCf, POCf‐VEGF, and HBPOCf‐VEGF within the dorsa of nude rats yielded increased vascular growth in HBPOCf‐VEGF constructs. Vessel quantification studies revealed that POCfs alone contained 41.1 ± 4.1 vessels/mm 2 , while HBPOCf, POCf‐VEGF, and HBPOCF‐VEGF contained 41.7 ± 2.6, 76.3 ± 9.4, and 167.72 ± 15.3 vessels/mm 2 , respectively. Presence of increased vessel growth was demonstrated by CD31 and vWF immunostaining in HBPOCf‐VEGF implanted areas. Data demonstrate that elastomeric POCfs can be chemically modified and possess the ability to promote angiogenesis in vivo . © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90248/1/33306_ftp.pd
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