Detrital Zircon Provenance of Mesoproterozoic to Cambrian Arenites in the Western United States and Northwestern Mexico

U-Pb isotopic dating of detrital zircon from supracrustal Proterozoic and Cambrian arenites from the western United States and northern Mexico reveal three main age groups, 1.90 to 1.62 Ga, 1.45 to 1.40 Ga, and 1.2 to 1.0 Ga. Small amounts of zircons with ages of 3.1 to 2.5 Ga, 1.57 Ga, 1.32 Ga, 1.26 Ga, 0.7 Ga, and 0.5 Ga are also present. Detrital zircons ranging in age from 1.90 to 1.62 Ga and from 1.45 to 1.40 Ga are considered to have been derived from Proterozoic crystalline basement rocks of these known ages, and probably in part from reworked Proterozoic supracrustal sedimentary rocks, of the western United States. The 1.2 to 1.0 Ga detrital zircon ages from California, Arizona, and Sonora are characterized by distinct spikes (1.11 Ga, in particular) in the age-probability plots. These spikes are interpreted to indicate the influx of zircon from major silicic volcanic fields. Igneous rocks such as the Pikes Peak Granite (1.093 Ga) of Colorado, and the Aibo Granite (1.110 Ga) of Sonora, Mexico, may represent the deeply eroded roots of such volcanic fields. Samples from farther north along the Cordilleran margin that contain abundant 1.2–1.0 Ga detrital zircons do not show spikes in the age distribution, but rather ages spread out across the entire 1.2–1.0 Ga range. These age spectra resemble those for detrital zircons from the Grenville province, which is considered their source. Less common detrital zircons had a variety of sources. Zircons ranging in age from 3.36 to 2.31 Ga were apparently derived from inland parts of the North American continent from Wyoming to Canada. Zircons of about 1.577 Ga are highly unusual and may have had an exotic source; they may have come from Australia and been deposited in North America when Australia and North America were juxtaposed as part of the hypothetical Rodinian supercontinent. Detrital zircon of ∼1.320 Ga apparently had the same source as that for tuff (1.320 Ga) in the Pioneer Shale of the Apache Group in Arizona. Detrital zircons of about 1.26 Ga in the Apache Group and Troy Quartzite appear to be related to local, approximately coeval volcanic fields. Zircons of about 0.7 Ga may have had a source in igneous rocks related to rifting of the Proterozoic supercontinent of Rodinia, and 0.5 Ga zircons a source in relatively small areas of granitic rocks of this known, or inferred, age in Oklahoma, Texas, New Mexico, and Colorado

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Reduced blood flow through intrapulmonary arteriovenous anastomoses at rest and during exercise in lowlanders during acclimatization to high altitude

Blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA ) is elevated during exercise at sea level (SL) and at rest in acute normobaric hypoxia. Following high altitude (HA) acclimatization, resting QIPAVA is similar to SL, but it is unknown if this is true during exercise at HA. We reasoned that exercise at HA (5,050 m) would exacerbate QIPAVA due to heightened pulmonary arterial pressure. Using a supine cycle ergometer, seven healthy adults free from intracardiac shunts underwent an incremental exercise test at SL (25, 50, 75% of SL VO2peak ) and at HA (25, 50% of SL VO2peak ). Echocardiography was used to determine cardiac output (Q) and pulmonary artery systolic pressure (PASP) and agitated saline contrast was used to determine QIPAVA (bubble score; 0-5). The principal findings were: (1) Q was similar at SL-rest (3.9 +/- 0.47 l min-1 ) compared with HA-rest (4.5 +/- 0.49 l min-1 ; P = 0.382), but increased from rest during both SL and HA exercise (P < 0.001); (2) PASP increased from SL-rest (19.2 +/- 0.7 mmHg) to HA-rest (33.7 +/- 2.8 mmHg; P = 0.001) and, compared with SL, PASP was further elevated during HA exercise (P = 0.003); (3) QIPAVA was increased from SL-rest (0) to HA-rest (median = 1; P = 0.04) and increased from resting values during SL exercise (P < 0.05), but were unchanged during HA exercise (P = 0.91), despite significant increases in Q and PASP. Theoretical modeling of microbubble dissolution suggests that the lack of QIPAVA in response to exercise at HA is unlikely caused by saline contrast instability

The RICORDO approach to semantic interoperability for biomedical data and models: strategy, standards and solutions.

BACKGROUND: The practice and research of medicine generates considerable quantities of data and model resources (DMRs). Although in principle biomedical resources are re-usable, in practice few can currently be shared. In particular, the clinical communities in physiology and pharmacology research, as well as medical education, (i.e. PPME communities) are facing considerable operational and technical obstacles in sharing data and models. FINDINGS: We outline the efforts of the PPME communities to achieve automated semantic interoperability for clinical resource documentation in collaboration with the RICORDO project. Current community practices in resource documentation and knowledge management are overviewed. Furthermore, requirements and improvements sought by the PPME communities to current documentation practices are discussed. The RICORDO plan and effort in creating a representational framework and associated open software toolkit for the automated management of PPME metadata resources is also described. CONCLUSIONS: RICORDO is providing the PPME community with tools to effect, share and reason over clinical resource annotations. This work is contributing to the semantic interoperability of DMRs through ontology-based annotation by (i) supporting more effective navigation and re-use of clinical DMRs, as well as (ii) sustaining interoperability operations based on the criterion of biological similarity. Operations facilitated by RICORDO will range from automated dataset matching to model merging and managing complex simulation workflows. In effect, RICORDO is contributing to community standards for resource sharing and interoperability.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Autocrine Activation of the MET Receptor Tyrosine Kinase in Acute Myeloid Leukemia

Although the treatment of acute myeloid leukemia (AML) has improved significantly, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating aberrant growth and survival of cancer cells. Thus, using a loss-of-function RNA interference genomic screen, we identified aberrant expression of the hepatocyte growth factor (HGF) as a critical factor in AML pathogenesis. We found HGF expression leading to autocrine activation of its receptor tyrosine kinase, MET, in nearly half of the AML cell lines and clinical samples studied. Genetic depletion of HGF or MET potently inhibited the growth and survival of HGF-expressing AML cells. However, leukemic cells treated with the specific MET kinase inhibitor crizotinib developed resistance due to compensatory upregulation of HGF expression, leading to restoration of MET signaling. In cases of AML where MET is coactivated with other tyrosine kinases, such as fibroblast growth factor receptor 1 (FGFR1), concomitant inhibition of FGFR1 and MET blocked compensatory HGF upregulation, resulting in sustained logarithmic cell kill both in vitro and in xenograft models in vivo. Our results demonstrate widespread dependence of AML cells on autocrine activation of MET, as well as the importance of compensatory upregulation of HGF expression in maintaining leukemogenic signaling by this receptor. We anticipate that these findings will lead to the design of additional strategies to block adaptive cellular responses that drive compensatory ligand expression as an essential component of the targeted inhibition of oncogenic receptors in human cancers

Genome Sequence of Fusobacterium nucleatum Subspecies Polymorphum — a Genetically Tractable Fusobacterium

Fusobacterium nucleatum is a prominent member of the oral microbiota and is a common cause of human infection. F. nucleatum includes five subspecies: polymorphum, nucleatum, vincentii, fusiforme, and animalis. F. nucleatum subsp. polymorphum ATCC 10953 has been well characterized phenotypically and, in contrast to previously sequenced strains, is amenable to gene transfer. We sequenced and annotated the 2,429,698 bp genome of F. nucleatum subsp. polymorphum ATCC 10953. Plasmid pFN3 from the strain was also sequenced and analyzed. When compared to the other two available fusobacterial genomes (F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii) 627 open reading frames unique to F. nucleatum subsp. polymorphum ATCC 10953 were identified. A large percentage of these mapped within one of 28 regions or islands containing five or more genes. Seventeen percent of the clustered proteins that demonstrated similarity were most similar to proteins from the clostridia, with others being most similar to proteins from other gram-positive organisms such as Bacillus and Streptococcus. A ten kilobase region homologous to the Salmonella typhimurium propanediol utilization locus was identified, as was a prophage and integrated conjugal plasmid. The genome contains five composite ribozyme/transposons, similar to the CdISt IStrons described in Clostridium difficile. IStrons are not present in the other fusobacterial genomes. These findings indicate that F. nucleatum subsp. polymorphum is proficient at horizontal gene transfer and that exchange with the Firmicutes, particularly the Clostridia, is common

Contextualizing students' alcohol use perceptions and practices within French culture: an analysis of gender and drinking among sport-science college students

Although research has examined alcohol consumption and sport in a variety of contexts, there is a paucity of research on gender and gender dynamics among French college students. The present study addresses this gap in the literature by examining alcohol use practices by men and women among a non-probability sample of French sport science students from five different universities in Northern France. We utilized both survey data (N = 534) and in-depth qualitative interviews (n = 16) to provide empirical and theoretical insight into a relatively ubiquitous health concern: the culture of intoxication. Qualitative data were based on students’ perceptions of their own alcohol use; analysis were framed by theoretical conceptions of gender. Survey results indicate gender differences in alcohol consumption wherein men reported a substantially higher frequency and quantity of alcohol use compared to their female peers. Qualitative findings confirm that male privilege and women’s concern for safety, masculine embodiment via alcohol use, gendering of alcohol type, and gender conformity pressures shape gender disparities in alcohol use behavior. Our findings also suggest that health education policy and educational programs focused on alcohol-related health risks need to be designed to take into account gender category and gender orientation