Genome-wide profiling of chromosome interactions in Plasmodium falciparum characterizes nuclear architecture and reconfigurations associated with antigenic variation.

Spatial relationships within the eukaryotic nucleus are essential for proper nuclear function. In Plasmodium falciparum, the repositioning of chromosomes has been implicated in the regulation of the expression of genes responsible for antigenic variation, and the formation of a single, peri-nuclear nucleolus results in the clustering of rDNA. Nevertheless, the precise spatial relationships between chromosomes remain poorly understood, because, until recently, techniques with sufficient resolution have been lacking. Here we have used chromosome conformation capture and second-generation sequencing to study changes in chromosome folding and spatial positioning that occur during switches in var gene expression. We have generated maps of chromosomal spatial affinities within the P. falciparum nucleus at 25 Kb resolution, revealing a structured nucleolus, an absence of chromosome territories, and confirming previously identified clustering of heterochromatin foci. We show that switches in var gene expression do not appear to involve interaction with a distant enhancer, but do result in local changes at the active locus. These maps reveal the folding properties of malaria chromosomes, validate known physical associations, and characterize the global landscape of spatial interactions. Collectively, our data provide critical information for a better understanding of gene expression regulation and antigenic variation in malaria parasites

Spitzer and z' Secondary Eclipse Observations of the Highly Irradiated Transiting Brown Dwarf KELT-1b

We present secondary eclipse observations of the highly irradiated transiting brown dwarf KELT-1b. These observations represent the first constraints on the atmospheric dynamics of a highly irradiated brown dwarf, and the atmospheres of irradiated giant planets at high surface gravity. Using the Spitzer Space Telescope, we measure secondary eclipse depths of 0.195+/-0.010% at 3.6um and 0.200+/-0.012% at 4.5um. We also find tentative evidence for the secondary eclipse in the z' band with a depth of 0.049+/-0.023%. These measured eclipse depths are most consistent with an atmosphere model in which there is a strong substellar hotspot, implying that heat redistribution in the atmosphere of KELT-1b is low. While models with a more mild hotspot or even with dayside heat redistribution are only marginally disfavored, models with complete heat redistribution are strongly ruled out. The eclipse depths also prefer an atmosphere with no TiO inversion layer, although a model with TiO inversion is permitted in the dayside heat redistribution case, and we consider the possibility of a day-night TiO cold trap in this object. For the first time, we compare the IRAC colors of brown dwarfs and hot Jupiters as a function of effective temperature. Importantly, our measurements reveal that KELT-1b has a [3.6]-[4.5] color of 0.07+/-0.11, identical to that of isolated brown dwarfs of similarly high temperature. In contrast, hot Jupiters generally show redder [3.6]-[4.5] colors of ~0.4, with a very large range from ~0 to ~1. Evidently, despite being more similar to hot Jupiters than to isolated brown dwarfs in terms of external forcing of the atmosphere by stellar insolation, KELT-1b has an atmosphere most like that of other brown dwarfs. This suggests that surface gravity is very important in controlling the atmospheric systems of substellar mass bodies.Comment: 14 pages, 3 tables, 11 figures. Accepted by ApJ. Updated to reflect the accepted versio

Errors and Improvements in the Use of Archived Meteorological Data for Chemical Transport Modeling: An Analysis Using GEOS-Chem V11-01 Driven by GEOS-5 Meteorology

Global simulations of atmospheric chemistry are commonly conducted with off-line chemical transport models (CTMs) driven by archived meteorological data from general circulation models (GCMs). The off-line approach has the advantages of simplicity and expediency, but it incurs errors due to temporal averaging in the meteorological archive and the inability to reproduce the GCM transport algorithms exactly. The CTM simulation is also often conducted at coarser grid resolution than the parent GCM. Here we investigate this cascade of CTM errors by using (exp 222)Rn(exp 210)Pb(exp 7)Be chemical tracer simulations off-line in the GEOS-Chem CTM at rectilinear 0.250.3125 (25km) and 22.5 (200km) resolutions and online in the parent GEOS-5 GCM at cubed-sphere c360 (25km) and c48 (200km) horizontal resolutions. The c360 GEOS-5 GCM meteorological archive, updated every 3h and remapped to 0.250.3125, is the standard operational product generated by the NASA Global Modeling and Assimilation Office (GMAO) and used as input by GEOS-Chem. We find that the GEOS-Chem (exp 222)Rn simulation at native 0.250.3125 resolution is affected by vertical transport errors of up to 20% relative to the GEOS-5 c360 online simulation, in part due to loss of transient organized vertical motions in the GCM (resolved convection) that are temporally averaged out in the 3h meteorological archive. There is also significant error caused by operational remapping of the meteorological archive from a cubed-sphere to a rectilinear grid. Decreasing the GEOS-Chem resolution from 0.250.3125 to 22.5 induces further weakening of vertical transport as transient vertical motions are averaged out spatially and temporally. The resulting (exp 222)Rn concentrations simulated by the coarse-resolution GEOS-Chem are overestimated by up to 40% in surface air relative to the online c360 simulations and underestimated by up to 40% in the upper troposphere, while the tropospheric lifetimes of (exp 210)Pb and (exp 7)Be against aerosol deposition are affected by 510%. The lost vertical transport in the coarse-resolution GEOS-Chem simulation can be partly restored by recomputing the convective mass fluxes at the appropriate resolution to replace the archived convective mass fluxes and by correcting for bias in the spatial averaging of boundary layer mixing depths

Validation of Aura Microwave Limb Sounder O-3 and CO observations in the upper troposphere and lower stratosphere

International audienceGlobal satellite observations of ozone and carbon monoxide from the Microwave Limb Sounder (MLS) on the EOS Aura spacecraft are discussed with emphasis on those observations in the 215–100 hPa region (the upper troposphere and lower stratosphere). The precision, resolution and accuracy of the data produced by the MLS “version 2.2” processing algorithms are discussed and quantified. O3 accuracy is estimated at ~40 ppbv +5% (~20 ppbv +20% at 215 hPa) while the CO accuracy is estimated at ~30 ppbv +30% for pressures of 147 hPa and less. Comparisons with expectations and other observations show good agreements for the O3 product, generally consistent with the systematic errors quoted above. In the case of CO, a persistent factor of ~2 high bias is seen at 215 hPa. However, the morphology is shown to be realistic, consistent with raw MLS radiance data, and useful for scientific study. The MLS CO data at higher altitudes are shown to be consistent with other observations

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (−)-2(S)-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening

Factors Driving Mercury Variability in the Arctic Atmosphere and Ocean over the Past 30 Years

[1] Long-term observations at Arctic sites (Alert and Zeppelin) show large interannual variability (IAV) in atmospheric mercury (Hg), implying a strong sensitivity of Hg to environmental factors and potentially to climate change. We use the GEOS-Chem global biogeochemical Hg model to interpret these observations and identify the principal drivers of spring and summer IAV in the Arctic atmosphere and surface ocean from 1979–2008. The model has moderate skill in simulating the observed atmospheric IAV at the two sites (r ~ 0.4) and successfully reproduces a long-term shift at Alert in the timing of the spring minimum from May to April (r = 0.7). Principal component analysis indicates that much of the IAV in the model can be explained by a single climate mode with high temperatures, low sea ice fraction, low cloudiness, and shallow boundary layer. This mode drives decreased bromine-driven deposition in spring and increased ocean evasion in summer. In the Arctic surface ocean, we find that the IAV for modeled total Hg is dominated by the meltwater flux of Hg previously deposited to sea ice, which is largest in years with high solar radiation (clear skies) and cold spring air temperature. Climate change in the Arctic is projected to result in increased cloudiness and strong warming in spring, which may thus lead to decreased Hg inputs to the Arctic Ocean. The effect of climate change on Hg discharges from Arctic rivers remains a major source of uncertainty.Earth and Planetary SciencesEngineering and Applied Science

Follow-up observations of PTFO 8-8695: a 3 MYR old T Tauri star hosting a Jupiter-mass planetary candidate

We present Spitzer 4.5 μm light curve observations, Keck NIRSPEC radial velocity observations, and LCOGT optical light curve observations of PTFO 8-8695, which may host a Jupiter-sized planet in a very short orbital period (0.45 days). Previous work by van Eyken et al. and Barnes et al. predicts that the stellar rotation axis and the planetary orbital plane should precess with a period of 300-600 days. As a consequence, the observed transits should change shape and depth, disappear, and reappear with the precession. Our observations indicate the long-term presence of the transit events ( years), and that the transits indeed do change depth, disappear and reappear. The Spitzer observations and the NIRSPEC radial velocity observations (with contemporaneous LCOGT optical light curve data) are consistent with the predicted transit times and depths for the precession model and demonstrate the disappearance of the transits. An LCOGT optical light curve shows that the transits do reappear approximately 1 year later. The observed transits occur at the times predicted by a straight-forward propagation of the transit ephemeris. The precession model correctly predicts the depth and time of the Spitzer transit and the lack of a transit at the time of the NIRSPEC radial velocity observations. However, the precession model predicts the return of the transits approximately 1 month later than observed by LCOGT. Overall, the data are suggestive that the planetary interpretation of the observed transit events may indeed be correct, but the precession model and data are currently insufficient to confirm firmly the planetary status of PTFO 8-8695b

Transits of Known Planets Orbiting a Naked-Eye Star

© 2020 The American Astronomical Society. All rights reserved.Some of the most scientifically valuable transiting planets are those that were already known from radial velocity (RV) surveys. This is primarily because their orbits are well characterized and they preferentially orbit bright stars that are the targets of RV surveys. The Transiting Exoplanet Survey Satellite (TESS) provides an opportunity to survey most of the known exoplanet systems in a systematic fashion to detect possible transits of their planets. HD 136352 (Nu2 Lupi) is a naked-eye (V = 5.78) G-type main-sequence star that was discovered to host three planets with orbital periods of 11.6, 27.6, and 108.1 days via RV monitoring with the High Accuracy Radial velocity Planet Searcher (HARPS) spectrograph. We present the detection and characterization of transits for the two inner planets of the HD 136352 system, revealing radii of 1.482-0.056+0.058 R ⊕ and 2.608-0.077+0.078 R ⊕ for planets b and c, respectively. We combine new HARPS observations with RV data from the Keck/High Resolution Echelle Spectrometer and the Anglo-Australian Telescope, along with TESS photometry from Sector 12, to perform a complete analysis of the system parameters. The combined data analysis results in extracted bulk density values of ρb = 7.8-1.1+1.2 g cm-3 and ρc = 3.50-0.36+0.41 g cm-3 for planets b and c, respectively, thus placing them on either side of the radius valley. The combination of the multitransiting planet system, the bright host star, and the diversity of planetary interiors and atmospheres means this will likely become a cornerstone system for atmospheric and orbital characterization of small worlds.Peer reviewe