Using ⁸⁷Sr/⁸⁶Sr Ratios to Date Fossil Methane Seep Deposits: Methodological Requirements and an Example from the Great Valley Group, California

Methane seep carbonates preserve information about the history of methane seepage and of the fauna inhabiting these ecosystems. For this information to be useful, a reliable determination of the carbonates’ stratigraphic ages is required, but this is not always available. Here we investigate the using strontium isotope stratigraphy to date fossil methane seep carbonates via detailed petrographic and geochemical investigation of the different carbonate phases in biostratigraphically well-dated seep carbonates of Paleozoic, Mesozoic, and Cenozoic age. The best results are obtained from banded, botryoidal rim cements from carbonate phases showing a weak or no cathodoluminescence signal, an oxygen isotope signature close to that of seawater, and the lowest Mn concentrations. We then applied the method to a presumably late Jurassic seep carbonate from the Great Valley Group in California. Strontium isotope ratios of the least diagenetically altered carbonate phases indicate a Tithonian (late Jurassic) age for this seep site, which is in conflict with a recent study that suggested the absence of Jurassic strata from the Great Valley Group

Geochemische Klassifikation und Sm-Nd Isotopensystematik proterozoischer Metasedimente des Baltischen Schildes (Västervik Region, SESchweden)

Die Västervik Region liegt an einer Haupt-Terran-Grenze im Baltischen Schild. Im NE schließen sich die Einheiten des Südsvecofennischen Vulkanitgürtels mit Altern >1,85Ga an, im SW folgen die Granitoide des Transskandinavischen Magmatitgürtles (TMZ) mit Altern <1,85Ga. Die Metasedimente der Västervik Formation bilden die stratigraphisch älteste Einheit der Västervik Region. Ihre Stellung in Bezug auf die svecofennischen Metasedimente des Bothnischen Beckens ist noch unklar. Sie können nach ihren mineralogischen Paragenesen in vier Gruppen klassifiziert werden: reine Quarzite, glimmerführende Quarzite, Glimmerquarzite und quarzitische Gneise. Vermutlich zeitgleich mit der Intrusion der großvolumigen Granitoidmagmen ab 1.85 Ga wurde die Västervik Formation amphibolitfaziell überprägt. Dies führte innerhalb der Metasedimente zur Bildung von Cordierit, Sillimanit und Andalusit sowie akzessorischem Granat. Der Beginn der Sedimentation ist begrenzt durch das Vorkommen detritischer Zirkone mit Altern ab 1.87Ga. Etwa 75% der gemessenen detritische Zirkone zeigt eine Altersgruppierung von 1,8 bis 2,1 Ga, die restlichen 25% zeigen archaische U/Pb-Alter von 2,8 bis 3,0 Ga (Claesson et al. 1993, Sultan et al. 2005). Die Nd-Isotopensignaturen der Proben zeigen eine sehr homogene Mischung und Schüttung der Sedimente mit subparallelem Verlauf der Nd- Entwicklungslinien und einem sehr engen TDM (Nd) Altersspektrum von 2,2 bis 2,4Ga. Diese Ergebnisse deuten auf ein konstantes Mischungsverhältnis von proterozoischen und archaischen Anteilen hin...conferenc

Identification of a Danish breast/ovarian cancer family double heterozygote for BRCA1 and BRCA2 mutations

Mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2 are associated with increased risk of breast and ovarian cancer. Patients with mutations in both genes are rarely reported and often involve Ashkenazi founder mutations. Here we report the first identification of a Danish breast and ovarian cancer family heterozygote for mutations in the BRCA1 and BRCA2 genes. The BRCA1 nucleotide 5215G > A/c.5096G > A mutation results in the missense mutation Arg1699Gln, while the BRCA2 nucleotide 859 + 4A > G/c.631 + 4A > G is novel. Exon trapping experiments and reverse transcriptase (RT)–PCR analysis revealed that the BRCA2 mutation results in skipping of exon 7, thereby introducing a frameshift and a premature stop codon. We therefore classify the mutation as disease causing. Since the BRCA1 Arg1699Gln mutation is also suggested to be disease-causing, we consider this family double heterozygote for BRCA1 and BRCA2 mutations

A pig model of acute Staphylococcus aureus induced pyemia

<p>Abstract</p> <p>Background</p> <p>Sepsis caused by <it>Staphylococcus aureus </it>constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with <it>S. aureus</it>, with the aim of mimicking human sepsis and pyemia.</p> <p>Methods</p> <p>The study was conducted in anaesthetized and intravenously inoculated pigs, and was based on bacteriological examination of blood and testing of blood for IL-6 and C-reactive protein. Following killing of the animals and necropsy bacteriological and histological examinations of different organs were performed 4, 5 or 6 h after inoculation.</p> <p>Results</p> <p>Clearance of bacteria from the blood was completed within the first 2 h in some of the pigs and the highest bacterial load was recorded in the lungs as compared to the spleen, liver and bones. This probably was a consequence of both the intravenous route of inoculation and the presence of pulmonary intravascular macrophages. Inoculation of bacteria induced formation of acute microabscesses in the lungs, spleen and liver, but not in the kidneys or bones. No generalized inflammatory response was recorded, i.e. IL-6 was not detected in the blood and C-reactive protein did not increase, probably because of the short time course of the study.</p> <p>Conclusion</p> <p>This study demonstrates the successful induction of acute pyemia (microabscesses), and forms a basis for future experiments that should include inoculation with strains of <it>S. aureus </it>isolated from man and an extension of the timeframe aiming at inducing sepsis, severe sepsis and septic shock.</p

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

The population genomic legacy of the second plague pandemic

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.publishedVersio

Differential gene expression in nearly isogenic lines with QTL for partial resistance to Puccinia hordei in barley

<p>Abstract</p> <p>Background</p> <p>The barley-<it>Puccinia hordei </it>(barley leaf rust) pathosystem is a model for investigating partial disease resistance in crop plants and genetic mapping of phenotypic resistance has identified several quantitative trait loci (QTL) for partial resistance. Reciprocal QTL-specific near-isogenic lines (QTL-NILs) have been developed that combine two QTL, <it>Rphq</it>2 and <it>Rphq</it>3, the largest effects detected in a recombinant-inbred-line (RIL) population derived from a cross between the super-susceptible line L94 and partially-resistant line Vada. The molecular mechanism underpinning partial resistance in these QTL-NILs is unknown.</p> <p>Results</p> <p>An Agilent custom microarray consisting of 15,000 probes derived from barley consensus EST sequences was used to investigate genome-wide and QTL-specific differential expression of genes 18 hours post-inoculation (hpi) with <it>Puccinia hordei</it>. A total of 1,410 genes were identified as being significantly differentially expressed across the genome, of which 55 were accounted for by the genetic differences defined by QTL-NILs at <it>Rphq</it>2 and <it>Rphq</it>3. These genes were predominantly located at the QTL regions and are, therefore, positional candidates. One gene, encoding the transcriptional repressor Ethylene-Responsive Element Binding Factor 4 (<it>HvERF4</it>) was located outside the QTL at 71 cM on chromosome 1H, within a previously detected eQTL hotspot for defence response. The results indicate that <it>Rphq</it>2 or <it>Rphq</it>3 contains a <it>trans</it>-eQTL that modulates expression of <it>HvERF4</it>. We speculate that HvERF4 functions as an intermediate that conveys the response signal from a gene(s) contained within <it>Rphq</it>2 or <it>Rphq</it>3 to a host of down-stream defense responsive genes. Our results also reveal that barley lines with extreme or intermediate partial resistance phenotypes exhibit a profound similarity in their spectrum of <it>Ph</it>-responsive genes and that hormone-related signalling pathways are actively involved in response to <it>Puccinia hordei</it>.</p> <p>Conclusions</p> <p>Differential gene expression between QTL-NILs identifies genes predominantly located within the target region(s) providing both transcriptional and positional candidate genes for the QTL. Genetically mapping the differentially expressed genes relative to the QTL has the potential to discover <it>trans</it>-eQTL mediated regulatory relays initiated from genes within the QTL regions.</p

The Glycosyltransferase Repertoire of the Spikemoss Selaginella moellendorffii and a Comparative Study of Its Cell Wall

Spike mosses are among the most basal vascular plants, and one species, Selaginella moellendorffii, was recently selected for full genome sequencing by the Joint Genome Institute (JGI). Glycosyltransferases (GTs) are involved in many aspects of a plant life, including cell wall biosynthesis, protein glycosylation, primary and secondary metabolism. Here, we present a comparative study of the S. moellendorffii genome across 92 GT families and an additional family (DUF266) likely to include GTs. The study encompasses the moss Physcomitrella patens, a non-vascular land plant, while rice and Arabidopsis represent commelinid and non-commelinid seed plants. Analysis of the subset of GT-families particularly relevant to cell wall polysaccharide biosynthesis was complemented by a detailed analysis of S. moellendorffii cell walls. The S. moellendorffii cell wall contains many of the same components as seed plant cell walls, but appears to differ somewhat in its detailed architecture. The S. moellendorffii genome encodes fewer GTs (287 GTs including DUF266s) than the reference genomes. In a few families, notably GT51 and GT78, S. moellendorffii GTs have no higher plant orthologs, but in most families S. moellendorffii GTs have clear orthologies with Arabidopsis and rice. A gene naming convention of GTs is proposed which takes orthologies and GT-family membership into account. The evolutionary significance of apparently modern and ancient traits in S. moellendorffii is discussed, as is its use as a reference organism for functional annotation of GTs