A novel oral formulation of BIO 300 confers prophylactic radioprotection from acute radiation syndrome in mice.

PURPOSE: Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome (H-ARS) and delayed effects of acute radiation exposure (DEARE). There is no radiation medical countermeasure (MCM) approved by the U.S. Food and Drug Administration which can be used prior to radiation exposure to protect exposed individuals. Different formulations containing synthetic genistein (BIO 300) are being developed to counter the harmful effects of radiation exposure. MATERIALS AND METHODS: We investigated the efficacy of a BIO 300 oral powder (OP) formulation as a prophylactic radiation MCM against a lethal dose of cobalt-60 gamma-radiation in CD2F1 male mice while comparing to other formulations of BIO 300 and Neulasta (PEGylated filgrastim), a standard of care drug for H-ARS. RESULTS: BIO 300 OP provided significant radioprotection against ionizing radiation in mice when administered twice per day for six days prior to total-body radiation exposure. Its radioprotective efficacy in the murine model was comparable to the efficacy of a single subcutaneous (sc) injection of Neulasta administered after total-body radiation exposure. CONCLUSIONS: Our results demonstrate that BIO 300 OP, which can be administered orally, is a promising prophylactic radiation countermeasure for H-ARS.

Stable isotopes provide insight into sources and cycling of N compounds in the Sacramento-San Joaquin Delta, California, USA.

River deltas and their diverse array of aquatic environments are increasingly impacted by anthropogenic inputs of nitrogen (N). These inputs can alter the N biogeochemistry of these systems and promote undesirable phenomena including harmful algae blooms and invasive aquatic macrophytes. To examine N sources and biogeochemical processes in the Sacramento-San Joaquin Delta, a river delta located in central California, USA, that is fed primarily by the Sacramento River, we utilized a multi-tracer approach that measured N species concentrations and stable isotope values monthly from April 2011 to November 2012 in samples collected from the channelized mainstem of the Sacramento River, two channelized distributaries of the Sacramento River, and the Cache Slough Complex, a network of Sacramento River tributaries and shallow water wetland habitat. We found that the Sacramento River and its channelized distributaries received N primarily in the form of NH4+ from treated wastewater effluent and that NH4+ was lost rapidly while NO3- was gained more slowly during subsequent downstream transit, driven by an array of biogeochemical processes whose identities could be constrained via examination of stable isotope values. The Cache Slough Complex, which was characterized by lower net flows and higher water residence times than the Sacramento River and its distributaries, received variable inputs of low conductivity water elevated in NH4+ from the Sacramento River and higher conductivity water elevated in NO3- from landward tributaries. Deviations from expected conservative mixing of these sources were spatially variable but broadly indicative of local inputs of treated wastewater effluent NO3-, conversion of Sacramento River NH4+ to NO3- via nitrification, uptake of NH4+ and NO3- by phytoplankton, and remineralization of organic N. These findings highlight both the diversity in N dynamics in anthropogenically impacted river delta environments and the utility of a multi-tracer approach in constraining these processes in such complex systems.

Sedimentology and chemostratigraphy of the terminal Ediacaran Dengying Formation at the Gaojiashan section, South China.

The late Ediacaran Dengying Formation (ca. 551.1-538.8 Ma) in South China is one of two successions where Ediacara-type macrofossils are preserved in carbonate facies along with skeletal fossils and bilaterian animal traces. Given the remarkable thickness of carbonate-bearing strata deposited in less than 12.3 million years, the Dengying Formation holds the potential for a relatively continuous chemostratigraphic profile for the terminal Ediacaran stage. In this study, a detailed sedimentological and chemostratigraphic (δ13Ccarb, δ18Ocarb, δ13Corg, δ34Spyrite, and 87Sr/86Sr) investigation was conducted on the Dengying Formation at the Gaojiashan section, Ningqiang County of the southern Shaanxi Province, South China. Sedimentological results reveal an overall shallow marine depositional environment. Carbonate breccia, void-filling botryoidal precipitates, and aragonite crystal fans are common in the Algal Dolomite Member of the Dengying Formation, suggesting that peritidal facies were repeatedly karstified. The timing of karstification was likely early, probably soon after the deposition of the dolomite sediments. The presence of authigenic aragonite cements suggests high alkalinity in the terminal Ediacaran ocean. Geochemical analysis of micro-drilled samples shows that distinct compositions are registered in different carbonate phases, which should be considered when constructing chemostratigraphic profiles representative of true temporal variations in seawater chemistry. Integrated chemostratigraphic data suggest enhanced burial of organic carbon and pyrite, and the occurrence of extensive marine anoxia (at least in the Gaojiashan Member). Rapid basinal subsidence and carbonate accumulation during a time of elevated seawater alkalinity and increased rates of pyrite burial may have facilitated the evolutionary innovation of early biomineralizing metazoans.

Coral Skeleton δ15N as a Tracer of Historic Nutrient Loading to a Coral Reef in Maui, Hawaii.

Excess nutrient loading to nearshore environments has been linked to declining water quality and ecosystem health. Macro-algal blooms, eutrophication, and reduction in coral cover have been observed in West Maui, Hawaii, and linked to nutrient inputs from coastal submarine groundwater seeps. Here, we present a forty-year record of nitrogen isotopes (δ15N) of intra-crystalline coral skeletal organic matter in three coral cores collected at this site and evaluate the record in terms of changes in nitrogen sources. Our results show a dramatic increase in coral δ15N values after 1995, corresponding with the implementation of biological nutrient removal at the nearby Lahaina Wastewater Reclamation Facility (LWRF). High δ15N values are known to be strongly indicative of denitrification and sewage effluent, corroborating a previously suggested link between local wastewater injection and degradation of the reef environment. This record demonstrates the power of coral skeletal δ15N as a tool for evaluating nutrient dynamics within coral reef environments.

Internal loading of phosphate in Lake Erie Central Basin.

After significant reductions in external phosphorus (P) loads, and subsequent water quality improvements in the early 1980s, the water quality of Lake Erie has declined considerably over the past decade. The frequency and magnitude of harmful algal blooms (primarily in the western basin) and the extent of hypoxic bottom waters in the central basin have increased. The decline in ecosystem health, despite meeting goals for external P loads, has sparked a renewed effort to understand P cycling in the lake. We use pore-water P concentration profiles and sediment cores incubation experiments to quantify the P flux from Lake Erie central basin sediments. In addition, the oxygen isotopes of phosphate were investigated to assess the isotopic signature of sedimentary phosphate inputs relative to the isotopic signature of phosphate in lake water. Extrapolating the total P sediment flux based on the pore-water profiles to the whole area of the central basin ranged from 300 to 1250metric tons per year and using the flux based on core incubation experiments an annual flux of roughly 2400metric tons of P is calculated. These estimates amount to 8-20% of the total external input of P to Lake Erie. The isotopic signature of phosphate in the extractable fraction of the sediments (~18‰) can explain the non-equilibrium isotope values of dissolved phosphate in the deep water of the central basin of Lake Erie, and this is consistent with sediments as an important internal source of P in the Lake.