106 research outputs found

    Clearance kinetics and matrix binding partners of the receptor for advanced glycation end products

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    Elucidating the sites and mechanisms of sRAGE action in the healthy state is vital to better understand the biological importance of the receptor for advanced glycation end products (RAGE). Previous studies in animal models of disease have demonstrated that exogenous sRAGE has an anti-inflammatory effect, which has been reasoned to arise from sequestration of pro-inflammatory ligands away from membrane-bound RAGE isoforms. We show here that sRAGE exhibits in vitro binding with high affinity and reversibly to extracellular matrix components collagen I, collagen IV, and laminin. Soluble RAGE administered intratracheally, intravenously, or intraperitoneally, does not distribute in a specific fashion to any healthy mouse tissue, suggesting against the existence of accessible sRAGE sinks and receptors in the healthy mouse. Intratracheal administration is the only effective means of delivering exogenous sRAGE to the lung, the organ in which RAGE is most highly expressed; clearance of sRAGE from lung does not differ appreciably from that of albumin. Copyright: © 2014 Milutinovic et al

    Ecosystem Overfishing in the Ocean

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    Fisheries catches represent a net export of mass and energy that can no longer be used by trophic levels higher than those fished. Thus, exploitation implies a depletion of secondary production of higher trophic levels (here the production of mass and energy by herbivores and carnivores in the ecosystem) due to the removal of prey. The depletion of secondary production due to the export of biomass and energy through catches was recently formulated as a proxy for evaluating the ecosystem impacts of fishing–i.e., the level of ecosystem overfishing. Here we evaluate the historical and current risk of ecosystem overfishing at a global scale by quantifying the depletion of secondary production using the best available fisheries and ecological data (i.e., catch and primary production). Our results highlight an increasing trend in the number of unsustainable fisheries (i.e., an increase in the risk of ecosystem overfishing) from the 1950s to the 2000s, and illustrate the worldwide geographic expansion of overfishing. These results enable to assess when and where fishing became unsustainable at the ecosystem level. At present, total catch per capita from Large Marine Ecosystems is at least twice the value estimated to ensure fishing at moderate sustainable levels

    Regional Decline of Coral Cover in the Indo-Pacific: Timing, Extent, and Subregional Comparisons

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    A number of factors have recently caused mass coral mortality events in all of the world's tropical oceans. However, little is known about the timing, rate or spatial variability of the loss of reef-building corals, especially in the Indo-Pacific, which contains 75% of the world's coral reefs.We compiled and analyzed a coral cover database of 6001 quantitative surveys of 2667 Indo-Pacific coral reefs performed between 1968 and 2004. Surveys conducted during 2003 indicated that coral cover averaged only 22.1% (95% CI: 20.7, 23.4) and just 7 of 390 reefs surveyed that year had coral cover >60%. Estimated yearly coral cover loss based on annually pooled survey data was approximately 1% over the last twenty years and 2% between 1997 and 2003 (or 3,168 km(2) per year). The annual loss based on repeated measures regression analysis of a subset of reefs that were monitored for multiple years from 1997 to 2004 was 0.72 % (n = 476 reefs, 95% CI: 0.36, 1.08).The rate and extent of coral loss in the Indo-Pacific are greater than expected. Coral cover was also surprisingly uniform among subregions and declined decades earlier than previously assumed, even on some of the Pacific's most intensely managed reefs. These results have significant implications for policy makers and resource managers as they search for successful models to reverse coral loss

    Conservation of Forest Birds: Evidence of a Shifting Baseline in Community Structure

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    Quantifying changes in forest bird diversity is an essential task for developing effective conservation actions. When subtle changes in diversity accumulate over time, annual comparisons may offer an incomplete perspective of changes in diversity. In this case, progressive change, the comparison of changes in diversity from a baseline condition, may offer greater insight because changes in diversity are assessed over longer periods of times. Our objectives were to determine how forest bird diversity has changed over time and whether those changes were associated with forest disturbance.We used North American Breeding Bird Survey data, a time series of Landsat images classified with respect to land cover change, and mixed-effects models to associate changes in forest bird community structure with forest disturbance, latitude, and longitude in the conterminous United States for the years 1985 to 2006. We document a significant divergence from the baseline structure for all birds of similar migratory habit and nest location, and all forest birds as a group from 1985 to 2006. Unexpectedly, decreases in progressive similarity resulted from small changes in richness (<1 species per route for the 22-year study period) and modest losses in abundance (-28.7 - -10.2 individuals per route) that varied by migratory habit and nest location. Forest disturbance increased progressive similarity for Neotropical migrants, permanent residents, ground nesting, and cavity nesting species. We also documented highest progressive similarity in the eastern United States.Contemporary forest bird community structure is changing rapidly over a relatively short period of time (e.g., approximately 22 years). Forest disturbance and forest regeneration are primary factors associated with contemporary forest bird community structure, longitude and latitude are secondary factors, and forest loss is a tertiary factor. Importantly, these findings suggest some regions of the United States may already fall below the habitat amount threshold where fragmentation effects become important predictors of forest bird community structure

    Co-expression of nuclear and cytoplasmic HMGB1 is inversely associated with infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer

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    <p>Abstract</p> <p>Background</p> <p>The intratumoral infiltration of T cells, especially memory T cells, is associated with a favorable prognosis in early colorectal cancers. However, the mechanism underlying this process remains elusive. This study examined whether high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, is involved in the infiltration of T cells and disease progression in locally advanced colon cancer.</p> <p>Methods</p> <p>Seventy-two cases of pathologically-confirmed specimens were obtained from patients with stage IIIB (T3N1M0) colon cancer who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University. The density of tumor-infiltrating lymphocytes (TILs) within the tumor tissue and the expression of HMGB1 in the cancer cells were examined via immunohistochemical analysis. The phenotype of CD45RO+ cells was confirmed using a flow cytometric assay. The association between HMGB1 expression, the density of TILs, and the 5-year survival rate were analyzed.</p> <p>Results</p> <p>The density of CD45RO+ T cells within the tumor was independently prognostic, although a higher density of CD3+ T cells was also associated with a favorable prognosis. More importantly, the expression of HMGB1 was observed in both the nucleus and the cytoplasm (co-expression pattern) in a subset of colon cancer tissues, whereas nuclear-only expression of HMGB1 (nuclear expression pattern) existed in most of the cancer tissues and normal mucosa. The co-expression pattern of HMGB1 in colon cancer cells was inversely associated with the infiltration of both CD3+ and CD45RO+ T cells and 5-year survival rates.</p> <p>Conclusions</p> <p>This study revealed that the co-expression of HMGB1 is inversely associated with the infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer, indicating that the distribution patterns of HMGB1 might contribute to the progression of colon cancer via modulation of the local immune response.</p

    Cancer treatment: the combination of vaccination with other therapies

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    Harnessing of the immune system by the development of ‘therapeutic’ vaccines, for the battle against cancer has been the focus of tremendous research efforts over the past two decades. As an illustration of the impressive amounts of data gathered over the past years, numerous antigens expressed on the surface of cancer cells, have been characterized. To this end, recent years research has focussed on characterization of antigens that play an important role for the growth and survival of cancer cells. Anti-apoptotic molecules like survivin that enhance the survival of cancer cells and facilitate their escape from cytotoxic therapies represent prime vaccination candidates. The characterization of a high number of tumor antigens allow the concurrent or serial immunological targeting of different proteins associated with such cancer traits. Moreover, while vaccination in itself is a promising new approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending on the specific chemotherapeutics. Also, chemotherapy represents one of several options available for clearance of CD4+ Foxp3+ regulatory T cells. Moreover, therapies based on monoclonal antibodies may have synergistic potential in combination with vaccination, both when used for targeting of tumor cells and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system

    The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

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    The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

    Multi-messenger observations of a binary neutron star merger

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    On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

    Audiotactile interactions in temporal perception

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