THE INFLUENCE OF TRP53 IN THE DOSE RESPONSE OF RADIATIONINDUCED APOPTOSIS, DNA REPAIR AND GENOMIC STABILITY IN MURINE HAEMATOPOIETIC CELLS

Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01- 2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiationinduced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type (Trp53+/+) and heterozygous (Trp53+/-) mice. The dose response for Trp53+/+ mice showed higher initial levels of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation

Influence of Sediment Characteristics on the Composition of Soft-Sediment Intertidal Communities in the Northern Gulf of Mexico

Benthic infaunal communities are important components of coastal ecosystems. Understanding the relationships between the structure of these communities and characteristics of the habitat in which they live is becoming progressively more important as coastal systems face increasing stress from anthropogenic impacts and changes in climate. To examine how sediment characteristics and infaunal community composition were related along the northern Gulf of Mexico coast, we sampled intertidal infaunal communities at seven sites covering common habitat types at a regional scale. Across 69 samples, the communities clustered into four distinct groups on the basis of faunal composition. Nearly 70% of the variation in the composition of the communities was explained by salinity, median grain size, and total organic content. Our results suggest that at a regional level coarse habitat characteristics are able to explain a large amount of the variation among sites in infaunal community structure. By examining the relationships between infaunal communities and their sedimentary habitats, we take a necessary first step that will allow the exploration of how changes in habitat and community composition influence higher trophic levels and ecosystem scale processes

Influence of Sediment Characteristics on the Composition of Soft-Sediment Intertidal Communities in the Northern Gulf of Mexico

Benthic infaunal communities are important components of coastal ecosystems. Understanding the relationships between the structure of these communities and characteristics of the habitat in which they live is becoming progressively more important as coastal systems face increasing stress from anthropogenic impacts and changes in climate. To examine how sediment characteristics and infaunal community composition were related along the northern Gulf of Mexico coast, we sampled intertidal infaunal communities at seven sites covering common habitat types at a regional scale. Across 69 samples, the communities clustered into four distinct groups on the basis of faunal composition. Nearly 70% of the variation in the composition of the communities was explained by salinity, median grain size, and total organic content. Our results suggest that at a regional level coarse habitat characteristics are able to explain a large amount of the variation among sites in infaunal community structure. By examining the relationships between infaunal communities and their sedimentary habitats, we take a necessary first step that will allow the exploration of how changes in habitat and community composition influence higher trophic levels and ecosystem scale processes

Influence of Sediment Characteristics on the Composition of Soft-Sediment Intertidal Communities in the Northern Gulf of Mexico

Benthic infaunal communities are important components of coastal ecosystems. Understanding the relationships between the structure of these communities and characteristics of the habitat in which they live is becoming progressively more important as coastal systems face increasing stress from anthropogenic impacts and changes in climate. To examine how sediment characteristics and infaunal community composition were related along the northern Gulf of Mexico coast, we sampled intertidal infaunal communities at seven sites covering common habitat types at a regional scale. Across 69 samples, the communities clustered into four distinct groups on the basis of faunal composition. Nearly 70% of the variation in the composition of the communities was explained by salinity, median grain size, and total organic content. Our results suggest that at a regional level coarse habitat characteristics are able to explain a large amount of the variation among sites in infaunal community structure. By examining the relationships between infaunal communities and their sedimentary habitats, we take a necessary first step that will allow the exploration of how changes in habitat and community composition influence higher trophic levels and ecosystem scale processes

Expanding the phenotype of de novo SLC25A4-linked mitochondrial disease to include mild myopathy.

OBJECTIVE: To determine the disease relevance of a novel de novo dominant variant in the SLC25A4 gene, encoding the muscle mitochondrial adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier, identified in a child presenting with a previously unreported phenotype of mild childhood-onset myopathy. METHODS: Immunohistochemical and western blot analysis of the patient's muscle tissue were used to assay for the evidence of mitochondrial myopathy and for complex I-V protein levels. To determine the effect of a putative pathogenic p.Lys33Gln variant on ADP/ATP transport, the mutant protein was expressed in Lactococcus lactis and its transport activity was assessed with fused membrane vesicles. RESULTS: Our data demonstrate that the heterozygous c.97A>T (p.Lys33Gln) SLC25A4 variant is associated with classic muscle biopsy findings of mitochondrial myopathy (cytochrome c oxidase [COX]-deficient and ragged blue fibers), significantly impaired ADP/ATP transport in Lactococcus lactis and decreased complex I, III, and IV protein levels in patient's skeletal muscle. Nonetheless, the expression levels of the total ADP/ATP carrier (AAC) content in the muscle biopsy was largely unaffected. CONCLUSIONS: This report further expands the clinical phenotype of de novo dominant SLC25A4 mutations to a childhood-onset, mild skeletal myopathy, without evidence of previously reported clinical features associated with SLC25A4-associated disease, such as cardiomyopathy, encephalopathy or ophthalmoplegia. The most likely reason for the milder disease phenotype is that the overall AAC expression levels were not affected, meaning that expression of the wild-type allele and other isoforms may in part have compensated for the impaired mutant variant

Introduction to COFFE: The Next-Generation HPCMP CREATE-AV CFD Solver

HPCMP CREATE-AV Conservative Field Finite Element (COFFE) is a modular, extensible, robust numerical solver for the Navier-Stokes equations that invokes modularity and extensibility from its first principles. COFFE implores a flexible, class-based hierarchy that provides a modular approach consisting of discretization, physics, parallelization, and linear algebra components. These components are developed with modern software engineering principles to ensure ease of uptake from a user's or developer's perspective. The Streamwise Upwind/Petrov-Galerkin (SU/PG) method is utilized to discretize the compressible Reynolds-Averaged Navier-Stokes (RANS) equations tightly coupled with a variety of turbulence models. The mathematics and the philosophy of the methodology that makes up COFFE are presented

NADPH and glutathione redox link TCA cycle activity to endoplasmic reticulum homeostasis

Many metabolic diseases disrupt endoplasmic reticulum (ER) homeostasis, but little is known about how metabolic activity is communicated to the ER. Here, we show in hepatocytes and other metabolically active cells that decreasing the availability of substrate for the tricarboxylic acid (TCA) cycle diminished NADPH production, elevated glutathione oxidation, led to altered oxidative maturation of ER client proteins, and attenuated ER stress. This attenuation was prevented when glutathione oxidation was disfavored. ER stress was also alleviated by inhibiting either TCA-dependent NADPH production or Glutathione Reductase. Conversely, stimulating TCA activity increased NADPH production, glutathione reduction, and ER stress. Validating these findings, deletion of the Mitochondrial Pyruvate Carrier-which is known to decrease TCA cycle activity and protect the liver from steatohepatitis-also diminished NADPH, elevated glutathione oxidation, and alleviated ER stress. Together, our results demonstrate a novel pathway by which mitochondrial metabolic activity is communicated to the ER through the relay of redox metabolites

Obscured star formation in intermediate-density environments:A Spitzer study of the Abell 901/902 supercluster

We explore the amount of obscured star formation as a function of environment in the Abell 901/902 (A901/902) supercluster at z = 0.165 in conjunction with a field sample drawn from the A901 and CDFS fields, imaged with the Hubble Space Telescope as part of the Space Telescope A901/902 Galaxy Evolution Survey and Galaxy Evolution from Morphology and Spectral Energy Distributions (SEDs) Survey. We combine the combo-17 near-UV/optical SED with Spitzer 24 mu m photometry to estimate both the unobscured and obscured star formation in galaxies with M-* > 10(10) M-circle dot. We find that the star formation activity in massive galaxies is suppressed in dense environments, in agreement with previous studies. Yet, nearly 40% of the star-forming (SF) galaxies have red optical colors at intermediate and high densities. These red systems are not starbursting; they have star formation rates (SFRs) per unit stellar mass similar to or lower than blue SF galaxies. More than half of the red SF galaxies have low infrared-to-ultraviolet (IR-to-UV) luminosity ratios, relatively high Sersicindices, and they are equally abundant at all densities. They might be gradually quenching their star formation, possibly but not necessarily under the influence of gas-removing environmental processes. The other greater than or similar to 40% of the red SF galaxies have high IR-to-UV luminosity ratios, indicative of high dust obscuration. They have relatively high specific SFRs and are more abundant at intermediate densities. Our results indicate that while there is an overall suppression in the SF galaxy fraction with density, the small amount of star formation surviving the cluster environment is to a large extent obscured, suggesting that environmental interactions trigger a phase of obscured star formation, before complete quenching