BIOMONITORING OF CONTAMINANTS IN BIRDS FROM TWO TROPHIC LEVELS IN THE NORTH PACIFIC

Abstract-The presence and accumulation of persistent contaminants at high latitudes from long-range transport is an important environmental issue. Atmospheric transport has been identified as the source of pollutants in several arctic ecosystems and has the potential to severely impact high-latitude populations. Elevated levels of contaminants in Aleutian Island avifauna have been documented, but the great distance from potential industrial sources and the region's complex military history have confounded identification of contaminant origins. We sampled bird species across the natural longitudinal transect of the Aleutian Archipelago to test three contaminant source hypotheses. We detected patterns in some polychlorinated biphenyl congeners and mercury that indicate abandoned military installations as likely local point sources. Carbon isotopes were distinct among island groups, enabling us to rule out transfer through migratory prey species as a contaminant source. The long-range transport hypothesis was supported by significant west-to-east declines in contaminant concentrations for most detected organochlorines and some trace metals. Although relatively low at present, concentrations may increase in Aleutian fauna as Asian industrialization increases and emitted contaminants are atmospherically transported into the region, necessitating continued monitoring in this unique ecosystem

Prevalence of Influenza A viruses in wild migratory birds in Alaska: Patterns of variation in detection at a crossroads of intercontinental flyways

<p>Abstract</p> <p>Background</p> <p>The global spread of the highly pathogenic avian influenza H5N1 virus has stimulated interest in a better understanding of the mechanisms of H5N1 dispersal, including the potential role of migratory birds as carriers. Although wild birds have been found dead during H5N1 outbreaks, evidence suggests that others have survived natural infections, and recent studies have shown several species of ducks capable of surviving experimental inoculations of H5N1 and shedding virus. To investigate the possibility of migratory birds as a means of H5N1 dispersal into North America, we monitored for the virus in a surveillance program based on the risk that wild birds may carry the virus from Asia.</p> <p>Results</p> <p>Of 16,797 birds sampled in Alaska between May 2006 and March 2007, low pathogenic avian influenza viruses were detected in 1.7% by rRT-PCR but no highly pathogenic viruses were found. Our data suggest that prevalence varied among sampling locations, species (highest in waterfowl, lowest in passerines), ages (juveniles higher than adults), sexes (males higher than females), date (highest in autumn), and analytical technique (rRT-PCR prevalence = 1.7%; virus isolation prevalence = 1.5%).</p> <p>Conclusion</p> <p>The prevalence of low pathogenic avian influenza viruses isolated from wild birds depends on biological, temporal, and geographical factors, as well as testing methods. Future studies should control for, or sample across, these sources of variation to allow direct comparison of prevalence rates.</p

Avian Communities in Bayheads, Willowheads, and Sawgrass Marshes of the Central Everglades

Volume: 110Start Page: 45End Page: 5

How family caregivers of persons with advanced cancer assist with upstream healthcare decision-making: A qualitative study.

AimsNumerous healthcare decisions are faced by persons with advanced cancer from diagnosis to end-of-life. The family caregiver role in these decisions has focused on being a surrogate decision-maker, however, little is known about the caregiver's role in supporting upstream patient decision-making. We aimed to describe the roles of family caregivers in assisting community-dwelling advanced cancer patients with healthcare decision-making across settings and contexts.MethodsQualitative study using one-on-one, semi-structured interviews with community-dwelling persons with metastatic cancer (n = 18) and their family caregivers (n = 20) recruited from outpatient oncology clinics of a large tertiary care academic medical center, between October 2016 and October 2017. Transcribed interviews were analyzed using a thematic analysis approach.FindingsCaregivers averaged 56 years and were mostly female (95%), white (85%), and the patient's partner/spouse (70%). Patients averaged 58 years and were mostly male (67%) in self-reported "fair" or "poor" health (50%) with genitourinary (33%), lung (17%), and hematologic (17%) cancers. Themes describing family member roles in supporting patients' upstream healthcare decision-making were: 1) seeking information about the cancer, its trajectory, and treatments options; 2) ensuring family and healthcare clinicians have a common understanding of the patient's treatment plan and condition; 3) facilitating discussions with patients about their values and the framing of their illness; 5) posing "what if" scenarios about current and potential future health states and treatments; 6) addressing collateral decisions (e.g., work arrangements) resulting from medical treatment choices; 6) originating healthcare-related decision points, including decisions about seeking emergency care; and 7) making healthcare decisions for patients who preferred to delegate healthcare decisions to their family caregivers.ConclusionsThese findings highlight a previously unreported and understudied set of critical decision partnering roles that cancer family caregivers play in patient healthcare decision-making. Optimizing these roles may represent novel targets for early decision support interventions for family caregivers

Characterization and selective inhibition of myristoyl-CoA:protein N-myristoyltransferase from Trypanosoma brucei and Leishmania major

The eukaryotic enzyme NMT (myristoyl-CoA:protein N-myristoyltransferase) has been characterized in a range of species from Saccharomyces cerevisiae to Homo sapiens. NMT is essential for viability in a number of human pathogens, including the fungi Candida albicans and Cryptococcus neoformans, and the parasitic protozoa Leishmania major and Trypanosoma brucei. We have purified the Leishmania and T. brucei NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and specific peptide substrates. A number of inhibitory compounds that target NMT in fungal species have been tested against the parasite enzymes in vitro and against live parasites in vivo. Two of these compounds inhibit TbNMT with IC(50) values of <1 μM and are also active against mammalian parasite stages, with ED(50) (the effective dose that allows 50% cell growth) values of 16–66 μM and low toxicity to murine macrophages. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against infectious diseases including African sleeping sickness and Nagana

N-myristoyltransferase is a cell wall target in <i>Aspergillus fumigatus</i>

Treatment of filamentous fungal infections relies on a limited repertoire of antifungal agents. Compounds possessing novel modes of action are urgently required. <i>N</i>-myristoylation is a ubiquitous modification of eukaryotic proteins. The enzyme <i>N</i>-myristoyltransferase (NMT) has been considered a potential therapeutic target in protozoa and yeasts. Here, we show that the filamentous fungal pathogen <i>Aspergillus fumigatus</i> possesses an active NMT enzyme that is essential for survival. Surprisingly, partial repression of the gene revealed downstream effects of <i>N</i>-myristoylation on cell wall morphology. Screening a library of inhibitors led to the discovery of a pyrazole sulphonamide compound that inhibits the enzyme and is fungicidal under partially repressive <i>nmt</i> conditions. Together with a crystallographic complex showing the inhibitor binding in the peptide substrate pocket, we provide evidence of NMT being a potential drug target in <i>A. fumigatus</i>