Investigations into the Genomes of Two Ascomyetes

Fusarium verticillioides is a filamentous ascomycete that is both a plant endophyte and pathogen, causing disease during any life stage of the plant. When F. verticillioides grows in maize the fungus can synthesis a number of mycotoxins including the fumonisins, which have been linked with human esophageal cancer and neural tube associated birth defects. In an attempt to control fumonisin production our lab is searching the genome of F. verticillioides for a selfish genetic element known as Spore killer. The plan is simple; we envision creating a bio-control strain capable of harnessing the genetic transmission-distorting properties of Spore killer to modify the genetic structure of agricultural populations of fungi by linking the Spore killer element with the gene cluster responsible for fumonisin production that has been deleted or is deficient in the ability to synthesize the mycotoxins. In the case of F. verticillioides, this could allow us to target fumonisin synthesis in an agricultural population and limit the contamination of agricultural products. Here I present the necessary steps toward cloning and characterizing the locus that causes spore killing in F. verticillioides

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

A Meiotic Drive Element in the Maize Pathogen Fusarium verticillioides Is Located Within a 102 kb Region of Chromosome V

Fusarium verticillioides is an agriculturally important fungus because of its association with maize and its propensity to contaminate grain with toxic compounds. Some isolates of the fungus harbor a meiotic drive element known as Spore killer (SkK) that causes nearly all surviving meiotic progeny from an SkK × Spore killer-susceptible (SkS) cross to inherit the SkK allele. SkK has been mapped to chromosome V but the genetic element responsible for meiotic drive has yet to be identified. In this study, we used cleaved amplified polymorphic sequence markers to genotype individual progeny from an SkK × SkS mapping population. We also sequenced the genomes of three progeny from the mapping population to determine their single nucleotide polymorphisms. These techniques allowed us to refine the location of SkK to a contiguous 102 kb interval of chromosome V, herein referred to as the Sk region. Relative to SkS genotypes, SkK genotypes have one extra gene within this region for a total of 42 genes. The additional gene in SkK genotypes, herein named SKC1 for Spore Killer Candidate 1, is the most highly expressed gene from the Sk region during early stages of sexual development. The Sk region also has three hyper-variable regions, the longest of which includes SKC1. The possibility that SKC1, or another gene from the Sk region, is an essential component of meiotic drive and spore killing is discussed

Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?

OBJECTIVE: To explore whether electrochemiluminescence (ECL) assays can help improve prediction of time to type 1 diabetes in the TrialNet autoantibody-positive population. RESEARCH DESIGN AND METHODS: TrialNet subjects who were positive for one or more autoantibodies (microinsulin autoantibody, GAD65 autoantibody [GADA], IA-2A, and ZnT8A) with available ECL-insulin autoantibody (IAA) and ECL-GADA data at their initial visit were analyzed; after a median follow-up of 24 months, 177 of these 1,287 subjects developed diabetes. RESULTS: Univariate analyses showed that autoantibodies by radioimmunoassays (RIAs), ECL-IAA, ECL-GADA, age, sex, number of positive autoantibodies, presence of HLA DR3/4-DQ8 genotype, HbA(1c), and oral glucose tolerance test (OGTT) measurements were all significantly associated with progression to diabetes. Subjects who were ECL positive had a risk of progression to diabetes within 6 years of 58% compared with 5% for the ECL-negative subjects (P < 0.0001). Multivariate Cox proportional hazards models were compared, with the base model including age, sex, OGTT measurements, and number of positive autoantibodies by RIAs. The model with positivity for ECL-GADA and/or ECL-IAA was the best, and factors that remained significantly associated with time to diabetes were area under the curve (AUC) C-peptide, fasting C-peptide, AUC glucose, number of positive autoantibodies by RIAs, and ECL positivity. Adding ECL to the Diabetes Prevention Trial risk score (DPTRS) improved the receiver operating characteristic curves with AUC of 0.83 (P < 0.0001). CONCLUSIONS: ECL assays improved the ability to predict time to diabetes in these autoantibody-positive relatives at risk for developing diabetes. These findings might be helpful in the design and eligibility criteria for prevention trials in the future

Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?

Photograph used for a story in the Oklahoma City Times newspaper. Caption: "Homestead Staked Out by the Mummers Theater is this square block on the west edge of the downtown urban renewal Project 1-A. Photographer Austin Traverse, using fisheye lens, aimed his camera south from a 10th-floor Black Hotel window. Twenty-one businesses will be relocated and 18 buildings will be torn down before the new theater can go up. The urban renewal authority is taking bids on the demolition in the site. Bids will be opened February 15, with demolition scheduled for completion May 1.

Leg 187: Mantle reservoirs and migration associated with Australian-Antarctic rifting (16 November 1999-10 January 2000)

Leg 187 undertook to trace the boundary between Indian and Pacific, ocean-scale mantle provinces across 10- to 30-Ma seafloor of the Southeast Indian Ocean between Australia and Antarctica. The boundary is sharply defined on young seafloor within the Australian Antarctic Discordance (AAD), where it is migrating to the west at ~40 mm/yr. The leg was built around a responsive drilling strategy in which real-time shipboard geochemical analyses from one site were used to guide the selection of subsequent sites from a slate of preapproved targets. This strategy proved highly effective, allowing us to maximize our time on site and to focus on sites that could potentially yield the best definition of the boundary configuration. Using Ba and Zr contents of basalt glasses referenced to our database of younger (0-7 Ma) lavas from the AAD and Zone A (east of the AAD), we were able to assign each of the 23 holes drilled at 13 sites to an Indian, Pacific, or Transitional-Pacific upper mantle type. At three sites we encountered lavas from two of these three mantle types, indicating mixed or transitional mantle sources. From these shipboard identifications of mantle domain, three fundamental observations can be made: No Indian-type mantle occurs east of the regional residual depth anomaly. Pacific- and especially Transitional-Pacific-type mantle occurs throughout the depth anomaly in the study area. Between ~28 and 14 Ma, Indian and Pacific mantle types alternated in western Zone A on a time scale of a few million years. These observations lead to the following tentative conclusions which require careful testing as isotopic data become available. A discrete mantle boundary comparable to the present-day boundary in the AAD cannot be mapped through the entire 14- to 28-Ma time interval encompassed by Leg 187 sites, although comparable boundaries have existed for relatively short, discrete time intervals. We conclude that, in the long term, the eastern limit of the Indian mantle province corresponds closely to the eastern edge of the residual depth anomaly. Its locus must lie close to the -500-m residual depth contour that tracks south to connect with the known location of the Indian/Pacific boundary on younger seafloor of the AAD. West of this boundary, sporadic occurrences of Transitional-Pacific-type and even Pacific-type mantle are interspersed with the predominant Indian-type mantle. The western limit of Pacific or Transitional-Pacific mantle is not closely defined by our data, but it is most likely associated with the western boundary of the depth anomaly. The alternation of Indian-type sites with Pacific- and Transitional-Pacific-type sites in western Zone A on time scales of a few million years can be interpreted in terms of discrete incursions, either of Indian mantle beneath Zone A or, perhaps more likely, of Pacific mantle into the dominantly Indian region of the depth anomaly. Samples from Leg 187 will undergo extensive elemental and isotopic analysis to refine the definition of the isotopic boundary and to improve our understanding of the nature and origin of the AAD, the mantle boundary, and the distinctive Indian Ocean mantle province. In addition, a battery of samples collected as quickly as possible under conditions that were as sterile as possible were placed in a variety of media in order to characterize the microbial population of the deep seafloor. Complementary electron microscope studies will seek to characterize fossil and living microbes involved with biodegradation of basaltic glass and their habitats