A disrupted circumstellar torus inside eta Carinae's Homunculus Nebula

We present thermal infrared images of the bipolar nebula surrounding eta Carinae at six wavelengths from 4.8 to 24.5 microns. These were obtained with the MIRAC3 camera system at the Magellan Observatory. Our images reveal new intricate structure in the bright core of the nebula, allowing us to re-evaluate interpretations of morphology seen in images with lower resolution. Complex structures in the core might not arise from a pair of overlapping rings or a cool (110 K) and very massive dust torus, as has been suggested recently. Instead, it seems more likely that the arcs and compact knots comprise a warm (350 K) disrupted torus at the intersection of the larger polar lobes. Some of the arcs appear to break out of the inner core region, and may be associated with equatorial features seen in optical images. The torus could have been disrupted by a post-eruption stellar wind, or by ejecta from the Great Eruption itself if the torus existed before that event. Kinematic data are required to rule out either possibility.Comment: 8 pages, 3 figures (Fig. 1 in color); to appear in ApJ Letter

Atrial Natriuretic Peptide Protects against Histamine-Induced Endothelial Barrier Dysfunction in Vivo

Endothelial barrier dysfunction is a hallmark of many severe pathologies, including sepsis or atherosclerosis. The cardiovascular hormone atrial natriuretic peptide (ANP) has increasingly been suggested to counteract endothelial leakage. Surprisingly, the precise in vivo relevance of these observations has never been evaluated. Thus, we aimed to clarify this issue and, moreover, to identify the permeability-controlling subcellular systems that are targeted by ANP. Histamine was used as important pro-inflammatory, permeability-increasing stimulus. Measurements of fluorescein isothiocyanate (FITC)-dextran extravasation from venules of the mouse cremaster muscle and rat hematocrit values were performed to judge changes of endothelial permeability in vivo. It is noteworthy that ANP strongly reduced the histamine-evoked endothelial barrier dysfunction in vivo. In vitro, ANP blocked the breakdown of transendothelial electrical resistance (TEER) induced by histamine. Moreover, as judged by immunocytochemistry and Western blot analysis, ANP inhibited changes of vascular endothelial (VE)-cadherin, β-catenin, and p120ctn morphology; VE-cadherin and myosin light chain 2 (MLC2) phosphorylation; and F-actin stress fiber formation. These changes seem to be predominantly mediated by the natriuretic peptide receptor (NPR)-A, but not by NPR-C. In summary, we revealed ANP as a potent endothelial barrier protecting agent in vivo and identified adherens junctions and the contractile apparatus as subcellular systems targeted by ANP. Thus, our study highlights ANP as an interesting pharmacological compound opening new therapeutic options for preventing endothelial leakage

Mammals of the Northern Great Plains

For the purposes of this book, the Northern Great Plains are defined as the states of Nebraska, North Dakota, and South Dakota. As a physiographic concept, the northern part of the great interior grasslands of North America is, of course, much broader in geographic extent than the Dakotas and Nebraska, but the three states lie in the heart of the region, and thus the title for this work seems appropriate. Our expectations in writing Mammals of the Northern Great Plains were to provide a comprehensive, yet semitechnical, treatmeat of free-living mammals that would prove useful to specialist and nonspecialist alike. The content and style therefore were developed in a way we hope will interest the inquiring high-school student, on the one hand, and provide a point of reference for the professional mammalogist on the other. Between these extremes, wildlife biologists, conservationists, environmental specialists, college students of vertebrate zoology, and others interested in mammalian natural history should find the present treatment useful for their needs as well. In the accounts that follow, species of each genus are listed in alphabetical order. Genera, families, and orders are arranged in conventional phylogenetic sequence, and treatment of these higher taxa is deliberately brief. Readers desiring more detail should consult the synopsis by Anderson and Jones (1967) for orders and families and that of Walker et al. (1964 and subsequent editions) for genera. Both scientific and vernacular names of species generally follow Jones, Carter, and Genoways (1979). Information in the accounts of species is organized under five headings: Name, Distribution, Description, Natural History, and Selected References. In the first section, comment is made on the derivation of the scientific name of the species; often, alternative vernacular names are provided. The section on distribution describes the general geographic and ecological range of a species. Subspecies (if recognized) are listed in this section. The geographic ranges of most species are mapped, based on the currently known distribution; the maps, however, are deliberately conservative, and additional fieldwork in various parts of the region certainly will extend the known limits of many mammals. In several cases where too few specimens of a species have been reported to allow the distribution in the tristate region to be shaded with confidence, only the actual localities of record are indicated

The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepatica

BACKGROUND:Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni (blood fluke) and Fasciola hepatica (liver fluke). These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis, respectively. As no vaccine is currently available for anti-flukicidal immunoprophylaxis, current treatment is mediated by mono-chemical chemotherapy in the form of mass drug administration (MDA) (praziquantel for schistosomiasis) or drenching (triclabendazole for fascioliasis) programmes. This overreliance on single chemotherapeutic classes has dramatically limited the number of novel chemical entities entering anthelmintic drug discovery pipelines, raising significant concerns for the future of sustainable blood and liver fluke control. METHODOLOGY/ PRINCIPLE FINDINGS:Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated from Lycium chinense, has dual anthelmintic activity against related S. mansoni and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent bioassay (HFB), this activity is specific (Therapeutic index = 4.2, when compared to HepG2 cell lines) and moderately potent (LD50 = 19.1 μM) against S. mansoni schistosomula cultured in vitro. This anti-schistosomula effect translates into activity against both adult male and female schistosomes cultured in vitro where 7-keto-sempervirol negatively affects motility/behaviour, surface architecture (inducing tegumental holes, tubercle swelling and spine loss/shortening), oviposition rates and egg morphology. As assessed by the HFB and microscopic phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 μM). Scanning electron microscopy (SEM) evaluation of adult F. hepatica liver flukes co-cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic abnormalities including breaches in tegumental integrity and spine loss. CONCLUSIONS/ SIGNIFICANCE:7-keto-sempervirol negatively affects the viability and phenotype of two related pathogenic trematodes responsible for significant human and animal infectious diseases. This plant-derived, natural product is also active against both larval and adult developmental forms. As such, the data collectively indicate that 7-keto-sempervirol is an important starting point for anthelmintic drug development. Medicinal chemistry optimisation of more potent 7-keto-sempervirol analogues could lead to the identification of novel chemical entities useful for future combinatorial or replacement anthelmintic control

Sleep‐disordered breathing in major depressive disorder

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99077/1/jsr12029.pd

The Growth Response of Two Diatom Species to Atmospheric Dust from the Last Glacial Maximum

Relief of iron (Fe) limitation in the surface Southern Ocean has been suggested as one driver of the regular glacial-interglacial cycles in atmospheric carbon dioxide (CO2). The proposed cause is enhanced deposition of Fe-bearing atmospheric dust to the oceans during glacial intervals, with consequent effects on export production and the carbon cycle. However, understanding the role of enhanced atmospheric Fe supply in biogeochemical cycles is limited by knowledge of the fluxes and ‘bioavailability’ of atmospheric Fe during glacial intervals. Here, we assess the effect of Fe fertilization by dust, dry-extracted from the Last Glacial Maximum portion of the EPICA Dome C Antarctic ice core, on the Antarctic diatom species Eucampia antarctica and Proboscia inermis. Both species showed strong but differing reactions to dust addition. E. antarctica increased cell number (3880 vs. 786 cells mL-1), chlorophyll a (51 vs. 3.9 μg mL-1) and particulate organic carbon (POC; 1.68 vs. 0.28 μg mL-1) production in response to dust compared to controls. P. inermis did not increase cell number in response to dust, but chlorophyll a and POC per cell both strongly increased compared to controls (39 vs. 15 and 2.13 vs. 0.95 ng cell-1 respectively). The net result of both responses was a greater production of POC and chlorophyll a, as well as decreased Si:C and Si:N incorporation ratios within cells. However, E, antarctica decreased silicate uptake for the same nitrate and carbon uptake, while P. inermis increased carbon and nitrate uptake for the same silicate uptake. This suggests that nutrient utilization changes in response to Fe addition could be driven by different underlying mechanisms between different diatom species. Enhanced supply of atmospheric dust to the surface ocean during glacial intervals could therefore have driven nutrient-utilization changes which could permit greater carbon fixation for lower silica utilization. Additionally, both species responded more strongly to lower amounts of direct Fe chloride addition than they did to dust, suggesting that not all the Fe released from dust was in a bioavailable form available for uptake by diatoms

Magnetic Resonance Imaging-Guided Focused Ultrasound Treatment of Symptomatic Uterine Fibroids Impact of Technology Advancement on Ablation Volumes in 115 Patients

Objectives: The aim of this study was to assess the impact of the advanced technology of the new ExAblate 2100 system (Insightec Ltd, Haifa, Israel) for magnetic resonance imaging (MRI)-guided focused ultrasound surgery on treatment outcomes in patients with symptomatic uterine fibroids, as measured by the nonperfused volume ratio. Materials and Methods: This is a retrospective analysis of 115 women (mean age, 42 years; range, 27-54 years) with symptomatic fibroids who consecutively underwent MRI-guided focused ultrasound treatment in a single center with the new generation ExAblate 2100 system from November 2010 to June 2011. Mean +/- SD total volume and number of treated fibroids (per patient) were 89 +/- 94 cm(3) and 2.2 +/- 1.7, respectively. Patient baseline characteristics were analyzed regarding their impact on the resulting nonperfused volume ratio. Results: Magnetic resonance imaging-guided focused ultrasound treatment was technically successful in 115 of 123 patients (93.5%). In 8 patients, treatment was not possible because of bowel loops in the beam pathway that could not be mitigated (n = 6), patient movement (n = 1), and system malfunction (n = 1). Mean nonperfused volume ratio was 88% +/- 15% (range, 38%-100%). Mean applied energy level was 5400 +/- 1200 J, and mean number of sonications was 74 +/- 27. No major complications occurred. Two cases of first-degree skin burn resolved within 1 week after the intervention. Of the baseline characteristics analyzed, only the planned treatment volume had a statistically significant impact on nonperfused volume ratio. Conclusions: With technological advancement, the outcome of MRI-guided focused ultrasound treatment in terms of the nonperfused volume ratio can be enhanced with a high safety profile, markedly exceeding results reported in previous clinical trials

Antischistosomal Properties of Sclareol and Its Heck-Coupled Derivatives:Design, Synthesis, Biological Evaluation and Untargeted Metabolomics

Sclareol, a plant-derived diterpenoid widely used as a fragrance and flavoring substance, is well-known for its promising antimicrobial and anticancer properties. However, its activity on helminth parasites has not been previously reported. Here, we show that sclareol is active against larval (IC50 ≈ 13 μM), juvenile (IC50 = 5.0 μM), and adult (IC50 = 19.3 μM) stages of Schistosoma mansoni, a parasitic trematode responsible for the neglected tropical disease schistosomiasis. Microwave-assisted synthesis of Heck-coupled derivatives improved activity, with the substituents choice guided by the Matsy decision tree. The most active derivative 12 showed improved potency and selectivity on larval (IC50 ≈ 2.2 μM, selectivity index (SI) ≈ 22 in comparison to HepG2 cells), juvenile (IC50 = 1.7 μM, SI = 28.8), and adult schistosomes (IC50 = 9.4 μM, SI = 5.2). Scanning electron microscopy studies revealed that compound 12 induced blebbing of the adult worm surface at sublethal concentration (12.5 μM); moreover, the compound inhibited egg production at the lowest concentration tested (3.13 μM). The observed phenotype and data obtained by untargeted metabolomics suggested that compound 12 affects membrane lipid homeostasis by interfering with arachidonic acid metabolism. The same methodology applied to praziquantel (PZQ)-treated worms revealed sugar metabolism alterations that could be ascribed to the previously reported action of PZQ on serotonin signaling and/or effects on glycolysis. Importantly, our data suggest that compound 12 and PZQ exert different antischistosomal activities. More studies will be necessary to confirm the generated hypothesis and to progress the development of more potent antischistosomal sclareol derivatives

230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Costa, K. M., Hayes, C. T., Anderson, R. F., Pavia, F. J., Bausch, A., Deng, F., Dutay, J., Geibert, W., Heinze, C., Henderson, G., Hillaire-Marcel, C., Hoffmann, S., Jaccard, S. L., Jacobel, A. W., Kienast, S. S., Kipp, L., Lerner, P., Lippold, J., Lund, D., Marcantonio, F., McGee, D., McManus, J. F., Mekik, F., Middleton, J. L., Missiaen, L., Not, C., Pichat, S., Robinson, L. F., Rowland, G. H., Roy-Barman, M., Alessandro, Torfstein, A., Winckler, G., & Zhou, Y. 230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean. Paleoceanography and Paleoclimatology, 35(2), (2020): e2019PA003820, doi:10.1029/2019PA003820.230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (>1,000 m water depth).We thank Zanna Chase and one anonymous reviewer for valuable feedback. K. M. C. was supported by a Postdoctoral Scholarship at WHOI. L. M. acknowledges funding from the Australian Research Council grant DP180100048. The contribution of C. T. H., J. F. M., and R. F. A. were supported in part by the U.S. National Science Foundation (US‐NSF). G. H. R. was supported by the Natural Environment Research Council (grant NE/L002434/1). S. L. J. acknowledges support from the Swiss National Science Foundation (grants PP002P2_144811 and PP00P2_172915). This study was supported by the Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and the US‐NSF. This work grew out of a 2018 workshop in Aix‐Marseille, France, funded by PAGES, GEOTRACES, SCOR, US‐NSF, Aix‐Marseille Université, and John Cantle Scientific. All data are publicly available as supporting information to this document and on the National Center for Environmental Information (NCEI) at https://www.ncdc.noaa.gov/paleo/study/28791