Beschreibung: We analyzed paleomagnetic samples and documented the stratigraphy from two sections near Miles City, Montana to determine the geomagnetic polarity stratigraphy and to constrain the age and duration of the Lebo and Tongue River Members of the Fort Union Formation in the northeastern Powder River Basin. The resulting polarity sequence can be correlated to subchrons C29n–C26r of the geomagnetic polarity time scale. By interpolating measured sediment accumulation rates from the base of C28r to the top of C27n, and then extrapolating to the top of the Tongue River Member and the bottom of the Lebo Member, we developed two age models to estimate the durations of the Lebo and Tongue River Members. Based on the first model, which uses different sedimentation rates for the Lebo and Tongue River Members, we estimate the duration of deposition of the Lebo to be between 1.30 and 1.74 million years and of the Tongue River to be between 1.42 and 1.61 million years. Using the second model, which uses the same sedimentation rate for the Lebo and Tongue River Members, we estimate the duration of deposition of the Lebo to be between 1.33 and 1.76 million years and of the Tongue River to be between 1.00 and 1.25 million years. Our results indicate a decrease in sediment accumulation rates in C27r, which is likely the result of a 0.26 to 0.62 million-year long depositional hiatus in the middle of C27r, represented by the Lebo–Tongue River contact. This unconformity occurs ~2 million years earlier than previously suggested and is likely contemporaneous with unconformities in the Williston Basin and in southwestern Alberta, suggesting that it may be regionally significant.

Beschreibung: Background: Dihydroorotase (DHO) is a zinc metalloenzyme, although the number of active site zinc ions has been controversial. E. coli DHO was initially thought to have a mononuclear metal center, but the subsequent X-ray structure clearly showed two zinc ions, alpha and beta, at the catalytic site. Aquifex aeolicus DHO, is a dodecamer comprised of six DHO and six aspartate transcarbamoylase (ATC) subunits. The isolated DHO monomer, which lacks catalytic activity, has an intact alpha-site and conserved beta-site ligands, but the geometry of the second metal binding site is completely disrupted. However, the putative beta-site is restored when the complex with ATC is formed and DHO activity is regained. Nevertheless, the X-ray structure of the complex revealed a single zinc ion at the active site. The structure of DHO from the pathogenic organism, S. aureus showed that it also has a single active site metal ion. Results: Zinc analysis showed that the enzyme has one zinc/DHO subunit and the addition of excess metal ion did not stimulate catalytic activity, nor alter the kinetic parameters. The metal free apoenzyme was inactive, but the full activity was restored upon the addition of one equivalent of Zn2+ or Co2+. Moreover, deletion of the beta-site by replacing the His180 and His232 with alanine had no effect on catalysis in the presence or absence of excess zinc. The 2.2 A structure of the double mutant confirmed that the beta-site was eliminated but that the active site remained otherwise intact. Conclusions: Thus, kinetically competent A. aeolicus DHO has a mononuclear metal center. In contrast, elimination of the putative second metal binding site in amidohydrolyases with a binuclear metal center, resulted in the abolition of catalytic activity. The number of active site metal ions may be a consideration in the design of inhibitors that selectively target either the mononuclear or binuclear enzymes.

Beschreibung: Hotspot tracks represent plate motions relative to mantle sources, and paleomagnetic data from magmatic units along those tracks can quantify motions of those mantle anomalies relative to the Earth's magnetic field and rotational axis. The Ediacaran Period is notable for rapid and large paleomagnetic apparent polar wander (APW) for many continents. Whereas magmatic units attributed to the “Sutton” mantle plume suggest a practically stationary hotspot track, paleolatitudes of Laurentia for that interval vary dramatically; geologic and paleomagnetic data are at odds unless true polar wander (TPW) is invoked to explain a majority of APW. Here we test the plume-TPW hypothesis by generating the predicted Sutton hotspot track for a stationary plume under a moving plate along the Laurentian margin during the interval from 615 to 530 Ma. Our model is the first to provide a kinematic framework for the extensive large igneous province associated with opening the Iapetus Ocean.

Beschreibung: The supercontinent Rodinia is hypothesized to have been assembled and positioned in tropical latitudes by the early Neoproterozoic Era. Paleomagnetic data from limestones of Svalbard and basaltic dikes of South China have been interpreted to record rapid changes in paleogeography driven by true polar wander that may have rotated the supercontinent in association with the ∼800 Ma Bitter Springs carbon isotope event. To further constrain early Neoproterozoic paleogeography and to test proposed rapid rotations, we have developed sequence- and chemo-stratigraphically constrained paleomagnetic data from the Bitter Springs Formation of the Amadeus Basin of central Australia. A new paleomagnetic pole for the post–Bitter Springs stage ∼770 Ma Johnny's Creek Member (Bitter Springs Formation) provides a positive test for a long-lived history of Australia and Laurentia in a single supercontinent as its similar position to late Mesoproterozoic north Australia poles reproduces the closure of the Laurentian “Grenville Loop.” This new pole also provides support for the hypothesis that there was significant rotation between north and south+west Australia at the end of the Neoproterozoic as this rotation brings the south+west Australia ∼755 Ma Mundine Well pole into much closer proximity to the north Australia Johnny's Creek pole. Syn–Bitter Springs stage carbonates of the Love's Creek Member of the formation contain a well-behaved remanence held by magnetite. The direction of this remanent magnetization falls on the Cambrian portion of Australia's apparent polar wander path suggesting that the magnetite may have formed authigenically at that time. If primary, the Love's Creek direction is consistent with the true polar wander hypothesis for the Bitter Springs stage, is internally consistent with the relative sea level changes inferred from the formation, and can constrain Australia to a SouthWest North America East AnTarctica (SWEAT) fit. A remanence held by pyrrhotite in carbonates of the Bitter Springs Formation corresponds to the apparent polar wander path of Australia at ∼350 Ma. This component can be used to constrain the history of the Devonian-Carboniferous Alice Springs Orogeny as it demonstrates that regional folding of basinal sediments occurred prior to ∼350 Ma, but that the latest stages of tectonism in the hinterland drove fluids through the sediments that altered redox conditions to favor pyrrhotite precipitation.

Beschreibung: Background: Substantial numbers of adolescents self-harm, but the majority of cases do not reach the attention of medical services, making community studies essential. The prevalence of suicidal thoughts and plans at this age, and the inter-relationships between suicidal thoughts, plans and self-harm remain largely unexplored.MethodCross-sectional analysis of a postal survey of the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, England. Respondents (n=4810) were aged 16-17 years old. Results: Of all respondents, 905 (18.8%) had ever self-harmed - one quarter of whom wanted to die in their most recent episode - 15.8% had ever thought of killing themselves, and 4.3% had ever made plans to do so. Among those who had self-harmed and wanted to die, 90.4% had ever had suicidal thoughts, compared to 37.6% of those who had self-harmed but not wanted to die, and 7.8% of those who had never self-harmed (chi-square statistic =102.3, p

Beschreibung: Background: Severe hypoglycaemia (SH) is one of the most feared complications of type 1 diabetes (T1DM) with a reported prevalence of nearly 40%. In randomized trials of Multiple Daily Injections (MDI) and Continuous Subcutaneous Insulin Infusion (CSII) therapy there is a possible benefit of CSII in reducing SH. However few trials have used basal insulin analogues as the basal insulin in the MDI group and individuals with established SH have often been excluded from prospective studies. In published studies investigating the effect of Real Time Continuous Glucose Monitoring (RT-CGM) benefit in terms of reduced SH has not yet been demonstrated. The primary objective of this study is to elucidate whether in people with T1DM complicated by impaired awareness of hypoglycaemia (IAH), rigorous prevention of biochemical hypoglycaemia using optimized existing self-management technology and educational support will restore awareness and reduce risk of recurrent SH. Methods: This is a multicentre prospective RCT comparing hypoglycaemia avoidance with optimized MDI and CSII with or without RT-CGM in a 2x2 factorial design in people with type 1 diabetes who have IAH. The primary outcome measure for this study is the difference in IAH (Gold score) at 24 weeks. Secondary outcomes include biomedical measures such as HbA1c, SH incidence, blinded CGM analysis, self monitored blood glucose (SMBG) and response to hypoglycaemia in gold standard clamp studies. Psychosocial measures including well-being and quality of life will also be assessed using several validated and novel measures. Analysis will be on an intention-to-treat basis.DiscussionMost existing RCTs using this study's interventions have been powered for change in HbA1c rather than IAH or SH. This trial will demonstrate whether IAH can be reversed and SH prevented in people with T1DM in even those at highest risk by using optimized conventional management and existing technology.Trial Registration: ISRCTN52164803 Eudract No: 2009-015396-27