Accumulation of non-traditional risk factors for coronary heart disease is associated with incident coronary heart disease hospitalization and death

Assessing multiple traditional risk factors improves prediction for late-life diseases, including coronary heart disease (CHD). It appears that non-traditional risk factors can also predict risk. The objective was to investigate contributions of non-traditional risk factors to coronary heart disease risk using a deficit accumulation approach.Community-dwelling adults with no known history of CHD (n = 2195, mean age 46.9±18.7 years, 51.8% women) participated in the 1995 Nova Scotia Health Survey. Three risk factor indices were constructed to quantify the proportion of deficits present in individuals: 1) a 17-item Non-Traditional Risk Factor Index (e.g. sinusitis, arthritis); 2) a 9-item Traditional Risk Factor Index (e.g. hypertension, diabetes); and 3) a frailty index (25 items combined from the other two index measures). Ten-year risks of CHD events (defined as CHD-related hospitalization and CHD-related mortality) were evaluated.The Non-Traditional Risk Factor Index, made up of health deficits unrelated to CHD, was independently associated with incident CHD events over 10 years after controlling for age, sex, and the Traditional Risk Factor Index [adjusted {adj.} Hazard Ratio {HR} = 1.31; Confidence Interval {CI} 1.14-1.51]. When all health deficits, both those related and unrelated to CHD, were included in a frailty index the corresponding adjusted hazard ratio was 1.61; CI 1.40-1.85.Both traditional and non-traditional risk factor indices are independently associated with incident CHD events. CHD risk assessment may benefit from consideration of general health information as well as from traditional risk factors.Lindsay M. K. Wallace, Olga Theou, Susan A. Kirkland, Michael R. H. Rockwood, Karina W. Davidson, Daichi Shimbo, Kenneth Rockwoo

Polymorphism in TGFB1 is associated with worse non-relapse mortality and overall survival after stem cell transplantation with unrelated donors.

Transforming growth factor beta-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiological and pathogenic processes. We have sequenced TGFB1 regulatory region and assigned allelic genotypes in a large cohort of hematopoietic stem cell transplantation patients and donors. In this study, we analyzed 522 unrelated donor-patient pairs and examined the combined effect of all the common polymorphisms in this genomic region. In univariate analysis, we found that patients carrying a specific allele, 'p001', showed significantly reduced overall survival (5-year overall survival 30.7% for p001/ p001 patients vs. 41.6% others; P=0.032) and increased non-relapse mortality (1-year nonrelapse mortality: 39.0% vs. 25.4%; P=0.039) after transplantation. In multivariate analysis, the presence of a p001/ p001 genotype in patients was confirmed as an independent factor for reduced overall survival [hazard ratio=1.53 (1.04-2.24); P=0.031], and increased non-relapse mortality [hazard ratio=1.73 (1.06-2.83); P=0.030]. In functional experiments we found a trend towards a higher percentage of surface transforming growth factor beta-1-positive regulatory T cells after activation when the cells had a p001 allele (P=0.07). Higher or lower production of transforming growth factor beta-1 in the inflammatory context of hematopoietic stem cell transplantation may influence the development of complications in these patients. Findings indicate that TGFB1 genotype could potentially be of use as a prognostic factor in hematopoietic stem cell transplantation risk assessment algorithms

Spatial Distribution of Competing Ions around DNA in Solution

The competition of monovalent and divalent cations for proximity to negatively charged DNA is of biological importance and can provide strong constraints for theoretical treatments of polyelectrolytes. Resonant x-ray scattering experiments have allowed us to monitor the number and distribution of each cation in a mixed ion cloud around DNA. These measurements provide experimental evidence to support a general theoretical prediction: the normalized distribution of each ion around polyelectrolytes remains constant when ions are mixed at different ratios. In addition, the amplitudes of the scattering signals throughout the competition provide a measurement of the surface concentration parameter that predicts the competition behavior of these cations. The data suggest that ion size needs to be taken into account in applying Poisson-Boltzmann treatments to polyelectrolytes such as DNA

Apatite: a U-Pb thermochronometer or geochronometer?

Apatite is an accessory mineral that is frequently found in both igneous and clastic sedimentary rocks. It is conventionally considered to be characterized by a closure temperature range between 375 and 600 °C and hence has been employed to address mid-temperature thermochronology questions relevant to the reconstruction of thermal events in the middle to lower crust. However, questions remain as to whether apatite faithfully records thermally-activated volume diffusion profiles, or rather is influenced by recrystallization and new growth processes. We present a case study of two apatite samples from the Akia Terrane in Greenland that help chart some of the post magmatic history of this region. Apatite in a tonalitic gneiss has distinct U-enriched rims and its U-Pb apparent ages correlate with Mn chemistry, with a high Mn group yielding an age of c. 2813 Ma. The U-Pb and trace element chemistry and morphology support an interpretation in which these apatite crystals are originally igneous and record cooling after metamorphism, with subsequent generation of discrete new rims. Epidote observed in the sample implies a <600 °C fluid infiltration event associated with apatite rims. The second sample, from a granitic leucosome, contains apparently homogeneous apatite, however U-Pb analyses define two distinct discordia arrays with different common Pb components. An older, c. 2490 Ma, component is associated with elevated Sr, whereas a younger, c. 1800 Ma, component has lower Sr concentration. A depth profile reveals an older core with progressively younger ages towards a compositionally discrete late Paleoproterozoic rim. The chemical and age profiles do not directly correspond, implying different diffusion rates between trace elements and U and Pb. The variation in core ages is interpreted to reflect radiogenic-Pb loss from a metamorphic population during new rim growth. The younger, c. 1800 Ma U-Pb age is interpreted to date new apatite growth from a compositionally distinct reservoir driven by tectonothermal and fluid activity, consistent with regional mica Ar-Ar ages. Results from these two samples show that recrystallization, dissolution and regrowth processes likely formed the younger rim overgrowths, and at temperatures below those often considered to be closure temperatures for Pb diffusion in apatite. The results from these samples imply many apatite grains may not record simple thermally activated Pb diffusion profiles and cautions against inversion of apatite U-Pb data to thermal histories without detailed knowledge of the grain growth/alteration processes

Tissue Mechanics Regulate Mitotic Nuclear Dynamics during Epithelial Development.

Cell divisions are essential for tissue growth. In pseudostratified epithelia, where nuclei are staggered across the tissue, each nucleus migrates apically before undergoing mitosis. Successful apical nuclear migration is critical for planar-orientated cell divisions in densely packed epithelia. Most previous investigations have focused on the local cellular mechanisms controlling nuclear migration. Inter-species and inter-organ comparisons of different pseudostratified epithelia suggest global tissue architecture may influence nuclear dynamics, but the underlying mechanisms remain elusive. Here, we use the developing Drosophila wing disc to systematically investigate, in a single epithelial type, how changes in tissue architecture during growth influence mitotic nuclear migration. We observe distinct nuclear dynamics at discrete developmental stages, as epithelial morphology changes. We use genetic and physical perturbations to show a direct effect of cell density on mitotic nuclear positioning. We find Rho kinase and Diaphanous, which facilitate mitotic cell rounding in confined cell conditions, are essential for efficient apical nuclear movement. Perturbation of Diaphanous causes increasing defects in apical nuclear migration as the tissue grows and cell density increases, and these defects can be reversed by acute physical reduction of cell density. Our findings reveal how the mechanical environment imposed on cells within a tissue alters the molecular and cellular mechanisms adopted by single cells for mitosis

Titanite petrochronology linked to phase equilibrium modelling constrains tectono-thermal events in the Akia Terrane, West Greenland

GeoHistory Facility instruments (part of the John de Laeter Centre) were funded via an Australian Geophysical Observing System (AGOS) grant provided to AuScope by the AQ44 Australian Education Investment Fund.The Mesoarchean Akia Terrane in West Greenland contains a detailed magmatic and metamorphic mineral growth record from 3.2 Ga to at least c. 2.5 Ga. This time span makes this region an important case study in the quest to track secular changes in geodynamic style which may ultimately inform on the development of plate tectonics as a globally linked system of lateral rigid plate motions. The common accessory mineral titanite has recently become recognised as a powerful high temperature geochronometer whose chemistry may chart the thermal conditions of its growth. Furthermore, titanite offers the potential to record the time-temperature history of mafic lithologies, which may lack zircon. Although titanite suffers from higher levels of common Pb than many other UPb chronometers, we show how measurement of 207Pb/206Pb in texturally coeval biotite may assist in the characterization of the appropriate common Pb composition in titanite. Titanite extracted from two samples of mafic gneisses from the Akia Terrane both yield UPb ages of c. 2.54 Ga. Although coeval, their chemistry implies growth under two distinctly different processes. In one case, the titanite has elevated total REE, high Th/U and grew from an in-situ partial melt, consistent with an identical date to granite dyke zircon. In contrast, the second titanite sample contains greater common Pb, lower total REE, lower Th/U, and grew from dominantly hydrothermal fluids. Zr-in-titanite thermometry for partial melt-derived titanite, with activities constrained by phase equilibrium modelling, indicates maxima of c. 690 °C. Elsewhere in the Akia Terrane, coeval metamorphism linked to growth of hydrothermal titanite is estimated at temperatures of c. 670 °C. These new results when coupled with existing findings indicate punctuated, repeated metamorphic events in the Akia Terrane, in which high temperature conditions (re)occurred at least three times between 3.0 and 2.5 Ga, but crucially changed in style across a c. 3.0 Ga change point. We interpret this change in metamorphism as reflecting a fundamental shift in geodynamic style in West Greenland at 3.0 Ga, consistent with other estimates for the onset of widespread plate tectonic-type processes.Publisher PDFPeer reviewe

Mesoarchean partial melting of mafic crust and tonalite production during high-T–low-P stagnant tectonism, Akia Terrane, West Greenland

The Ministry of Mineral Resources and Labour, Greenland Government supported field and analytical work. NJG acknowledges support from Australian Research Council grant FL160100168.Different geodynamic models exist for the growth and differentiation of Archean continental crust, ranging from horizontal tectonics with subduction zones to vertical tectonics with foundering of greenstone sequences. U–Pb zircon geochronology, field relationships, and pressure–temperature constraints from granulite-facies metabasite of the Akia Terrane of the North Atlantic Craton in West Greenland show that this terrane grew through two major magmatic growth episodes: an earlier one at c. 3.2 Ga, and a later one at c. 3.05–2.97 Ga. Phase equilibrium modelling for assemblages related to the latter indicates temperatures of >800 °C at 0.8 GPa in the stability field of garnet. U–Pb zircon geochronology and existing Hf isotope data are also consistent with a model involving protracted Mesoarchean magmatic growth with limited mantle addition during a prolonged period of high temperatures in a relatively stagnant tectonic regime prior to Neoarchean compressional tectonism in the Akia Terrane.Publisher PDFPeer reviewe