Climatic control of riverine and seawater uranium-isotope ratios

The large variation in the ratio of uranium-234 to uranium-238 (234U/238U) in rivers is not well understood, but may provide information about past weathering and rainfall and is important because it controls seawater (234U/238U). Here, we demonstrate the importance of physical weathering and rainfall for (234U/238U), using rivers from South Island, New Zealand. These data allow interpretation of an existing speleothem (234U/238U) record and suggest that New Zealand glacier advance 13,000 years ago was influenced by increased rainfall rather than by Younger Dryas-like cooling. A model of seawater (234U/238U) during glacial cycles indicates that rejection of corals based on modern (234U/238U) +/- <0.01 is not merited and may reject the highest quality ages.     

Mutational inactivation of STAG2 causes aneuploidy in human cancer

Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins of aneuploidy through integrative genomic analyses of human tumors. A diverse range of tumor types were found to harbor deletions or inactivating mutations of STAG2, a gene encoding a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Because STAG2 is on the X chromosome, its inactivation requires only a single mutational event. Studying a near-diploid human cell line with a stable karyotype, we found that targeted inactivation of STAG2 led to chromatid cohesion defects and aneuploidy, whereas in two aneuploid human glioblastoma cell lines, targeted correction of the endogenous mutant alleles of STAG2 led to enhanced chromosomal stability. Thus, genetic disruption of cohesin is a cause of aneuploidy in human cancer.     

Cross-linking cellular prion protein triggers neuronal apoptosis in vivo

Neuronal death is a prominent, but poorly understood, pathological hallmark of prion disease. Notably, in the absence of the cellular prion protein (PrPC), the disease-associated isoform, PrPSc, appears not to be intrinsically neurotoxic, suggesting that PrPC itself may participate directly in the prion neurodegenerative cascade. Here, cross-linking PrPC in vivo with specific monoclonal antibodies was found to trigger rapid and extensive apoptosis in hippocampal and cerebellar neurons. These findings suggest that PrPC functions in the control of neuronal survival and provides a model to explore whether cross-linking of PrPC by oligomeric PrPSc can promote neuronal loss during prion infection.     

A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A

The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1.     

Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation

The canonical Wnt-beta-catenin signaling pathway is initiated by inducing phosphorylation of one of the Wnt receptors, low-density lipoprotein receptor-related protein 6 (LRP6), at threonine residue 1479 (Thr1479) and serine residue 1490 (Ser1490). By screening a human kinase small interfering RNA library, we identified phosphatidylinositol 4-kinase type II alpha and phosphatidylinositol-4-phosphate 5-kinase type I (PIP5KI) as required for Wnt3a-induced LRP6 phosphorylation at Ser1490 in mammalian cells and confirmed that these kinases are important for Wnt signaling in Xenopus embryos. Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates [PtdIns (4,5)P2] through frizzled and dishevelled, the latter of which directly interacted with and activated PIP5KI. In turn, PtdIns (4,5)P2 regulated phosphorylation of LRP6 at Thr1479 and Ser1490. Therefore, our study reveals a signaling mechanism for Wnt to regulate LRP6 phosphorylation.     

Carotenogenesis up-regulation in Scenedesmus sp. using a targeted metabolomics approach by liquid chromatography-high-resolution mass spectrometry

Carotenoids have potent antioxidant activity as well as therapeutic value, and their formation has been seen to be induced in algae by stress, including high-salt culture conditions. A differential profiling of carotenoids was conducted using a targeted metabolomics approach with accurate mass data generated by liquid chromatography-electrospray-time-of-flight (LC-ESI-TOF) mass spectrometry followed by postacquisition filtering based on isotope patterns and mass defects to detect carotenoids up-regulated in Scenedesmus sp. exposed to high-salt conditions. Algal cultures treated with high concentrations of sodium acetate or sodium chloride were found to cause an increase in various carotenoids. On the basis of differential analysis, astaxanthin and canthaxanthin increased upon salt treatment. Astaxanthin, in its free form and as fatty acid esters, was seen to increase in Scenedesmus sp. using accurate mass MS. A few other carotenoid compounds increased upon salt treatment, including echinenone and adonirubin, involved in the pathway of astaxanthin biosynthesis from β-carotene, as well as isomers of astaxanthin and canthaxanthin. A time course study of acetate treatment was done to observe the time-dependent up-regulation of carotenogenesis.     

Optimized denitrification bioreactor treatment through simulated drainage containment

In the design of wood-based, enhanced-denitrification bioreactors to treat nitrate in agricultural drainage, the consideration of the highly variable flow rates and nitrate concentrations inherent to many drainage systems is important. For optimized mitigation of these nitrate loads, it may be best to contain drainage water prior to treatment in order to facilitate longer, more constant retention times rather than to allow cycles of flushing and dry periods in the denitrification bioreactor. Simulated containment prior to bioreactor treatment compared to passing drainage directly through a bioreactor was investigated with the use of six pilot-scale denitrification bioreactors constructed with plywood and filled with Pinus radiata woodchips at Massey University No. 4 Dairy Farm (Palmerston North, New Zealand). Initial bromide tracer tests were followed with a series of five simulated drainage events each at successively declining inflow nitrate concentrations. During each drainage event, three pilot bioreactors received a simulated hydrograph lasting 1.5 days (Non-Containment treatment) and three pilot bioreactors received the same total drainage volume treated over 4 days at a constant flow rate (i.e. constant retention time; Containment treatment). Results showed significantly different total mass removal efficiencies of 14.0% vs. 36.9% and significantly different removal rates of 2.1 g N m⁻³ day⁻¹ vs. 6.7 g N m⁻³ day⁻¹ for the Non-Containment and Containment treatments, respectively, which indicated that treating drainage at constant retention times provided more optimized nitrate removal. While this work was done to evaluate treatment under New Zealand drainage conditions, it also provides valuable information for optimizing agricultural drainage denitrification bioreactor performance in general.     

A comparison of the relative toxicity of bone meal and other P sources used as remedial treatments to the earthworm Eisenia fetida

It has been suggested that sources of P could be used to remediate metal-contaminated soil. The toxicity of four potential P sources, potassium hydrogen phosphate (PHP), triple superphosphate (TSP), rock phosphate (RP) and raw bone meal (RBM) to Eisenia fetida was determined. The concentration of P that is statistically likely to kill 50% of the population (LC50) for PHP, TSP and RBM was determined in OECD acute toxicity tests. 14 day LC50s expressed as bulk P concentration lay in the range 3319–4272 mg kg^?1 for PHP, 3107–3590 mg kg^?1 for TSP and 1782–2196 mg kg^?1 for RBM (ranges present the 95% confidence intervals). For PHP and TSP mortality was significantly impacted by the electrical conductivity of the treated soils. No consistent relationship existed between mortality and electrical conductivity, soil pH and available (Olsen) P across the PHP, TSP and RBM amendment types. In RP toxicity tests mortality was low and it was not possible to determine a LC50 value. Incineration of bone meal at temperatures between 200 and 300 °C, pre-washing the bone meal, co-amendment with 5% green waste compost and delaying introduction of earthworms after bone meal amendments by 21 days or more led to significant reductions in the bone meal toxicity. These results are consistent with the toxicity being associated with the release and/or degradation of a soluble organic component present in raw bone meal. Bone meal can be used as an earthworm-friendly remedial amendment in metal-contaminated soils but initial additions may have a negative effect on any earthworms surviving in the contaminated soil before the organic component in the bone meal degrades in the soil.     

Development of a novel diagnostic test for detection of bovine viral diarrhea persistently infected animals using hair

The purpose of this study was to determine whether manually plucked hairs might serve as an alternative sample for a quantitative real time polymerase chain reaction (qRT-PCR) testing. Twenty three, 1~3 week old, non-bovine viral diarrhea virus (BVDV) vaccinated calves, found to be positive for BVDV by immunohistochemical staining, were selected and hairs were manually plucked from the ear. qRT-PCR was performed on samples consisting of more than 30 hairs (30~100) and whole blood. All 23 animals were positive for the virus by qRT-PCR performed on the whole blood and when samples of more than 30 hairs were assayed. Additionally, qRT-PCR was performed on groups of 10 and 20 hairs harvested from 7 out of 23 immunohistochemical staining-positive calves. When groups of 20 and 10 hairs were tested, 6 and 4 animals, respectively, were positive for the virus.