Metabolome-Informed Microbiome Analysis Refines Metadata Classifications and Reveals Unexpected Medication Transfer in Captive Cheetahs.

Even high-quality collection and reporting of study metadata in microbiome studies can lead to various forms of inadvertently missing or mischaracterized information that can alter the interpretation or outcome of the studies, especially with nonmodel organisms. Metabolomic profiling of fecal microbiome samples can provide empirical insight into unanticipated confounding factors that are not possible to obtain even from detailed care records. We illustrate this point using data from cheetahs from the San Diego Zoo Safari Park. The metabolomic characterization indicated that one cheetah had to be moved from the non-antibiotic-exposed group to the antibiotic-exposed group. The detection of the antibiotic in this second cheetah was likely due to grooming interactions with the cheetah that was administered antibiotics. Similarly, because transit time for stool is variable, fecal samples within the first few days of antibiotic prescription do not all contain detected antibiotics, and the microbiome is not yet affected. These insights significantly altered the way the samples were grouped for analysis (antibiotic versus no antibiotic) and the subsequent understanding of the effect of the antibiotics on the cheetah microbiome. Metabolomics also revealed information about numerous other medications and provided unexpected dietary insights that in turn improved our understanding of the molecular patterns on the impact on the community microbial structure. These results suggest that untargeted metabolomic data provide empirical evidence to correct records and aid in the monitoring of the health of nonmodel organisms in captivity, although we also expect that these methods may be appropriate for other social animals, such as cats.IMPORTANCE Metabolome-informed analyses can enhance omics studies by enabling the correct partitioning of samples by identifying hidden confounders inadvertently misrepresented or omitted from carefully curated metadata. We demonstrate here the utility of metabolomics in a study characterizing the microbiome associated with liver disease in cheetahs. Metabolome-informed reinterpretation of metagenome and metabolome profiles factored in an unexpected transfer of antibiotics, preventing misinterpretation of the data. Our work suggests that untargeted metabolomics can be used to verify, augment, and correct sample metadata to support improved grouping of sample data for microbiome analyses, here for nonmodel organisms in captivity. However, the techniques also suggest a path forward for correcting clinical information in microbiome studies more broadly to enable higher-precision analyses

Theoretical and experimental investigation of the equation of state of boron plasmas

We report a theoretical equation of state (EOS) table for boron across a wide range of temperatures (5.1$\times$10$^4$-5.2$\times$10$^8$ K) and densities (0.25-49 g/cm$^3$), and experimental shock Hugoniot data at unprecedented high pressures (5608$\pm$118 GPa). The calculations are performed with full, first-principles methods combining path integral Monte Carlo (PIMC) at high temperatures and density functional theory molecular dynamics (DFT-MD) methods at lower temperatures. PIMC and DFT-MD cross-validate each other by providing coherent EOS (difference $<$1.5 Hartree/boron in energy and $<$5% in pressure) at 5.1$\times$10$^5$ K. The Hugoniot measurement is conducted at the National Ignition Facility using a planar shock platform. The pressure-density relation found in our shock experiment is on top of the shock Hugoniot profile predicted with our first-principles EOS and a semi-empirical EOS table (LEOS 50). We investigate the self diffusivity and the effect of thermal and pressure-driven ionization on the EOS and shock compression behavior in high pressure and temperature conditions We study the performance sensitivity of a polar direct-drive exploding pusher platform to pressure variations based on comparison of the first-principles calculations with LEOS 50 via 1D hydrodynamic simulations. The results are valuable for future theoretical and experimental studies and engineering design in high energy density research. (LLNL-JRNL-748227)Comment: 12 pages, 9 figures, 2 table

Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus

<p>Abstract</p> <p>Background</p> <p>Low serum paraoxonase (PON) activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE). Our prior studies have shown that the <it>PON1</it>/rs662 (p.Gln192Arg), <it>PON1</it>/rs854560 (p.Leu55Met), <it>PON3</it>/rs17884563 and <it>PON3</it>/rs740264 SNPs (single nucleotide polymorphisms) significantly affect serum PON activity. Since <it>PON1, PON2 </it>and <it>PON3 </it>share high degree of structural and functional properties, in this study, we examined the role of <it>PON2 </it>genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample.</p> <p>Methods</p> <p><it>PON2 </it>SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen <it>PON2 </it>SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP) or TaqMan allelic discrimination methods.</p> <p>Results</p> <p>Our pair-wise linkage disequilibrium (LD) analysis, using an <it>r</it>^{<it>2 </it>}cutoff of 0.7, identified 14 <it>PON2 </it>tagSNPs that captured all 19 <it>PON2 </it>variants in our sample, 12 of which were not in high LD with known <it>PON1 </it>and <it>PON3 </it>SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five <it>PON2 </it>SNPs [rs6954345 (p.Ser311Cys), rs13306702, rs987539, rs11982486, and rs4729189; <it>P </it>= 0.005 to 2.1 × 10^-6] that were significantly associated with PON activity. We found no association of <it>PON2 </it>SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183) and immunologic disorder (rs11981433) in SLE patients (<it>P </it>= 0.013 to 0.042).</p> <p>Conclusions</p> <p>Our data indicate that <it>PON2 </it>genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.</p

Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus

Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non-Europeans (including Asians) has a genetic basis

Oxygen–osmium isotope systematics of West Maui lavas: A record of shallow-level magmatic processes

New δ^(18)O and ^(187)Os/^(188)Os data from late shield-building stage lavas from West Maui volcano, Hawai'i, indicate that a range of distinct shallow-level processes can affect compositions of plume-generated ocean island magmas. The relative ages of the samples studied were determined either on the basis of field relationships, or from collection depth in a water well. The stratigraphically lower lavas have [Os] = 61–399 ppt, initial ^(187)Os/^(188)Os = 0.1311–0.1324 and δ^(18)O_(olivine) = 4.53–4.88‰. The stratigraphically higher lavas have [Os] = 20–273 ppt, initial ^(187)Os/^(188)Os = 0.1323–0.1390 (with the exception of one low [Os] sample with ^(187)Os/^(188)Os = 0.1517), and δ^(18)O_(olivine) = 4.73–5.21‰. These compositions are generally similar to those of Kea-type Hawaiian lavas from Mauna Kea and Kilauea volcanoes, but in detail, there are some significant differences between the West Maui lavas and other Kea-type lavas. The stratigraphically lower lavas have ^(187)Os/^(188)Os similar to those previously observed for Mauna Kea and Kilauea lavas, and define a nearly flat ^(87)Sr/^(86)Sr vs. ^(187)Os/^(188)Os trend that is consistent with assimilation by these magmas of small degree melts of Pacific oceanic crustal gabbros. The stratigraphically higher West Maui lavas extend to ^(187)Os/^(188)Os higher than observed at Mauna Kea or Kilauea. This probably results from interaction of these magmas with the hydrothermally altered volcanic edifice during the waning phases of the shield building stage. This process is likely to affect the isotope systematics of Os and O, but will have little effect on those of Hf, Nd, Pb or Sr

Rb-Sr, Sm-Nd and Lu-Hf isotope systematics of the lunar Mg-suite: the age of the lunar crust and its relation to the time of Moon formation

International audienceNew Rb-Sr, 146,147Sm-142,143Nd and Lu-Hf isotopic analyses of Mg-suite lunar crustal rocks 67667, 76335, 77215 and 78238, including an internal isochron for norite 77215, were undertaken to better define the time and duration of lunar crust formation and the history of the source materials of the Mg-suite. Isochron ages determined in this study for 77215 are: Rb-Sr=4450 ± 270 Ma, 147Sm-143Nd =4283 ± 23Ma and Lu-Hf=4421 ± 68 Ma. The data define an initial 146Sm/144Sm ratio of 0.00193 ± 0.00092 corresponding to ages between 4348 and 4413Ma depending on the halflife and initial abundance used for 146Sm. The initial Nd and Hf isotopic compositions of all samples indicate a source region with slight enrichment in the incompatible elements in accord with previous suggestions that the Mg-suite crustal rocks contain a component of KREEP. The Sm/Nd—142Nd/144Nd correlation shown by both ferroan anorthosite and Mg-suite rocks is coincident with the trend defined by mare and KREEP basalts, the slope of which corresponds to ages between 4.35 and 4.45 Ga. These data, along with similar ages for various early Earth differentiation events, are in accord with the model of lunar formation via giant impact into Earth at ca 4.4 Ga

Big Rubrics and Weird Genres: The Futility of Using Generic Assessment Tools Across Diverse Instructional Contexts

Interest "all-purpose" assessment of students' writing and/or speaking appeals to many teachers and administrators because it seems simple and efficient, offers a single set of standards that can inform pedagogy, and serves as a benchmark for institutional improvement. This essay argues, however, that such generalized standards are unproductive and theoretically misguided. Drawing on situated approaches to the assessment of writing and speaking, as well as many years of collective experience working with faculty, administrators, and students on communication instruction in highly specific curricular contexts, we demonstrate the advantages of shaping assessment around local conditions, including discipline-based genres and contexts, specific and varied communicative goals, and the embeddedness of communication instruction in particular "ways of knowing" within disciplines and subdisciplines. By sharing analyses of unique genres of writing and speaking at our institutions, and the processes that faculty and administrators have used to create assessment protocols for those genres, we support contextually-based approaches to assessment and argue for the abandonment of generic rubrics