Limited Activity Of Miltefosine In Murine Models Of Cryptococcal Meningoencephalitis And Disseminated Cryptococcosis

Miltefosine is an alkyl phosphocholine with good oral bioavailability and in vitro activity against Cryptococcus species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the in vivo efficacy of miltefosine in experimental in vivo models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either C. neoformans USC1597 or H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice daily) or amphotericin B deoxycholate (3 mg/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either C. neoformans isolate. There was a trend toward improved survival with miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and amphotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of C. neoformans infections.Pharmac

Cooler winters as a possible cause of mass extinctions at the eocene/oligocene boundary

The Eocene/Oligocene boundary, at about 33.7 Myr ago, marks one of the largest extinctions of marine invertebrates in the Cenozoic period(1). For example, turnover of mollusc species in the US Gulf coastal plain was over 90% at this time(2,3). A temperature change across this boundary-from warm Eocene climates to cooler conditions in the Oligocene-has been suggested as a cause of this extinction event(4), but climate reconstructions have not provided support for this hypothesis. Here we report stable oxygen isotope measurements of aragonite in fish otoliths-ear stones-collected across the Eocene/Oligocene boundary. Palaeotemperatures reconstructed from mean otolith oxygen isotope values show little change through this interval, in agreement with previous studies(5,6). From incremental microsampling of otoliths, however, we can resolve the seasonal variation in temperature, recorded as the otoliths continue to accrete new material over the life of the fish. These seasonal data suggest that winters became about 4 degrees C colder across the Eocene/Oligocene boundary. We suggest that temperature variability, rather than change in mean annual temperature, helped to cause faunal turnover during this transition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62707/1/407887a0.pd

QZ Serpentis: A Dwarf Nova with a 2-Hour Orbital Period and an Anomalously Hot, Bright Secondary Star

We present spectroscopy and time-series photometry of the dwarf nova QZ Ser. The spectrum shows a rich absorption line spectrum of type K4 +- 2. K-type secondary stars are generally seen in dwarf novae with orbital periods P-orb around 6 h, but in QZ Ser the absorption radial velocities show an obvious modulation (semi-amplitude 207(5) km/s) at P-orb = 119.752(2) min, much shorter than typical for such a relatively warm and prominent secondary spectrum. The H-alpha emission-line velocity is modulated at the same period and roughly opposite phase. Time-series photometry shows flickering superposed on a modulation with two humps per orbit, consistent with ellipsoidal variation of the secondary's light. QZ Ser is a second example of a relatively short-period dwarf nova with a surprisingly warm secondary. Model calculations suggest that the secondary is strongly enhanced in helium, and had already undergone significant nuclear evolution when mass transfer began. Several sodium absorption features in the secondary spectrum are unusually strong, which may indicate that the present-day surface was the site of CNO-cycle hydrogen burning in the past.Comment: 11 pages, 3 postscript figures, 1 jpeg greyscale figure. Accepted for publication in PAS

A millennium of trophic stability inAtlantic cod (Gadus morhua): transition to a lower and converging trophic niche in modern times

Stable isotope analyses of zooarchaeological material can be used to examine ecological variability in exploited species at centennial to millennial scales. Climate change is a notable driver of marine ecosystem change, although historical fishing is also likely to have impacted past marine systems. Fishing removes the oldest and largest individuals and may thereby result in shorter trophic pathways and reduced niche width of predatory fish species. In the current study we examine the trophic niche of Atlantic cod, haddock and Atlantic wolffish, in the last millennium using δ13C and δ15N values of bone collagen. We report a lower trophic level of Atlantic cod and haddock but higher level of wolffish in present times, following centuries at consistent and higher trophic levels of Atlantic cod. This results in a concurrent converging trophic niche of the demersal fish. We suggest that the current data set provides a valuable historical baseline facilitating interpretation of current variability in the trophic ecology of northern demersal fish.publishedVersio

Do Vertebral Chemical Signatures Distinguish Juvenile Blacktip Shark (Carcharhinus limbatus) Nursery Regions in the Northern Gulf of Mexico?

Identifying and protecting shark nurseries is a common management strategy used to help rebuild overfished stocks, yet we know little about connectivity between juvenile and adult populations. By analysing trace metals incorporated into vertebral cartilage, it may be possible to infer natal origin based on nursery-specific chemical signatures. To assess the efficacy of this approach, we collected juvenile blacktip sharks (Carcharhinus limbatus; n = 93) from four regions in the Gulf of Mexico in 2012 and 2013 and analysed their vertebral centra with laser ablation-inductively coupled plasma-mass spectrometry. We observed significant regional differences in six element : Ca ratios in both 2012 and 2013. Multi-element chemical signatures were significantly different among regions and between year-classes. Year-class-specific linear discriminant function analysis yielded regional classification accuracies of 81% for 2012 and 85% for 2013, although samples were not obtained from all four regions in 2012. Combining year-classes resulted in an overall classification accuracy of 84%, thus demonstrating the usefulness of this approach. These results are encouraging yet highlight a need for more research to better evaluate the efficacy of vertebral chemistry to study elasmobranch population connectivity

Using binary stars to bound the mass of the graviton

Interacting white dwarf binary star systems, including helium cataclysmic variable (HeCV) systems, are expected to be strong sources of gravitational radiation, and should be detectable by proposed space-based laser interferometer gravitational wave observatories such as LISA. Several HeCV star systems are presently known and can be studied optically, which will allow electromagnetic and gravitational wave observations to be correlated. Comparisons of the phases of a gravitational wave signal and the orbital light curve from an interacting binary white dwarf star system can be used to bound the mass of the graviton. Observations of typical HeCV systems by LISA could potentially yield an upper bound on the inverse mass of the graviton as strong as $h/m_{g} = \lambda_{g} > 1 \times 10^{15}$ km ($m_{g} < 1 \times 10^{-24}$ eV), more than two orders of magnitude better than present solar system derived bounds.Comment: 21 pages plus 4 figures; ReVTe

Paleosalinity History of Middle Holocene Lagoonal and Lacustrine Deposits in the Enriquillo Valley, Dominican Republic Based on Pore Morphometrics and Isotope Geochemistry of Ostracoda

The southwestern region of the Dominican Republic (Enriquillo Valley) contains exceptionally well-preserved, relict marine and saline lake deposits of mid-Holocne age. Abundant euryhaline ostracodes found in this deposit include Cyprideis salebrosa, C. mexicana, C. similis, and C. edentata. Morphometric and geochemical analyses performed on Cyprideis spp. provide high δ18O and δ13C values that are coincident with relative abundances of irregularly shaped pores that permeate the ostracode carapace. We recognize three stratigraphic intervals with distinct ostracode pore shape and stable isotope trends: (I) a 4.5-5.0m interval that contains ostracodes with highly irregular shaped pores (multiradiate) and high amplitude variability in δ18O and δ13C values; (II) a 5.0-5.6m interval comprised of ostracodes with circular pores and an overall trend towards low δ18O and δ13C values; and (III) a 5.6-6.5m interval containing ostracodes with an upward increasing abundance of circular pore shapes coincident with decreasing δ18O and δ13C values. When the Enriquillo lagoon was first separated from the Caribbean Sea approximately 4.3 ka, an arid and evaporative climate led to hypersaline water in a restricted lagoon environment. By the middle to late-Holocene, increased precipitation in the valley resulted in a coastal lake system that became progressively oligohaline. Moderate to small amplitude variability in the salinity proxy data (δ18O) suggest short-term oscillations in the precipitation-evaporation budgets at that time. At least two marine incursions likely contributed to the ob- served variability in ostracode δ18O and δ13C values. Evidence for abrupt changes in base level indicate that climatic factors or also tectonic activity may have contributed to the observed paleoenvironmental trends recorded in these deposits

Integrating Stomach Content and Stable Isotope Analyses to Quantify the Diets of Pygoscelid Penguins

Stomach content analysis (SCA) and more recently stable isotope analysis (SIA) integrated with isotopic mixing models have become common methods for dietary studies and provide insight into the foraging ecology of seabirds. However, both methods have drawbacks and biases that may result in difficulties in quantifying inter-annual and species-specific differences in diets. We used these two methods to simultaneously quantify the chick-rearing diet of Chinstrap (Pygoscelis antarctica) and Gentoo (P. papua) penguins and highlight methods of integrating SCA data to increase accuracy of diet composition estimates using SIA. SCA biomass estimates were highly variable and underestimated the importance of soft-bodied prey such as fish. Two-source, isotopic mixing model predictions were less variable and identified inter-annual and species-specific differences in the relative amounts of fish and krill in penguin diets not readily apparent using SCA. In contrast, multi-source isotopic mixing models had difficulty estimating the dietary contribution of fish species occupying similar trophic levels without refinement using SCA-derived otolith data. Overall, our ability to track inter-annual and species-specific differences in penguin diets using SIA was enhanced by integrating SCA data to isotopic mixing modes in three ways: 1) selecting appropriate prey sources, 2) weighting combinations of isotopically similar prey in two-source mixing models and 3) refining predicted contributions of isotopically similar prey in multi-source models