Gas-Phase Complexes of Americium and Lanthanides with a Bis-triazinyl Pyridine: Reactivity and Bonding of Archetypes for F-Element Separations.

Bis-triazinyl pyridines (BTPs) exhibit solution selectivity for trivalent americium over lanthanides (Ln), the origins of which remain uncertain. Here, electrospray ionization was used to generate gas-phase complexes [ML3]3+, where M = La, Lu, or Am and L is EtBTP 2,6-bis(5,6-diethyl-1,2,4-triazin-3-yl)-pyridine. Collision-induced dissociation (CID) of [ML3]3+ in the presence of H2O yielded a protonated ligand [L(H)]+ and hydroxide [ML2(OH)]2+ or hydrate [ML(L-H)(H2O)]2+, where (L-H)- is a deprotonated ligand. Although solution affinities indicate stronger binding of BTPs toward Am3+ versus Ln3+, the observed CID process is contrastingly more facile for M = Am versus Ln. To understand the disparity, density functional theory was employed to compute potential energy surfaces for two possible CID processes, for M = La and Am. In accordance with the CID results, both the rate determining transition state barrier and the net energy are lower for [AmL3]3+ versus [LaL3]3+ and for both product isomers, [ML2(OH)]2+ and [ML(L-H)(H2O)]2+. More facile removal of a ligand from [AmL3]3+ by CID does not necessarily contradict stronger Am3+-L binding, as inferred from solution behavior. In particular, the formation of new bonds in the products can distort kinetics and thermodynamics expected for simple bond cleavage reactions. In addition to correctly predicting the seemingly anomalous CID behavior, the computational results indicate greater participation of Am 5f versus La 4f orbitals in metal-ligand bonding

Concentrations of Metals in Aquatic Invertebrates from the Ozark National Scenic Riverways, Missouri

This report summarizes the findings of a study conducted as a pilot for part of a park-wide monitoring program being developed for the Ozark National Scenic Riverways (ONSR) of southeastern Missouri. The objective was to evaluate using crayfish (Orconectes spp.) and Asian clam (Corbicula fluminea) for monitoring concentrations of metals associated with lead-zinc mining. Lead-zinc mining presently (2007) occurs near the ONSR and additional mining has been proposed. Three composite samples of each type (crayfish and Asian clam), each comprising ten animals of approximately the same size, were collected during late summer and early fall of 2005 from five sites on the Current River and Jacks Fork within the ONSR and from one site on the Eleven Point River and the Big River, which are outside the ONSR. The Big River has been contaminated by mine tailings from historical leadzinc mining. Samples were analyzed by inductively coupled plasma mass spectrometry for lead, zinc, cadmium, cobalt, and nickel concentrations. All five metals were detected in all samples; concentrations were greatest in samples of both types from the Big River, and lowest in samples from sites within the ONSR. Concentrations of zinc and cadmium typically were greater in Asian clams than in crayfish, but differences were less evident for the other metals. In addition, differences among sites were small for cobalt in Asian clams and for zinc in crayfish, indicating that these metals are internally regulated to some extent. Consequently, both sample types are recommended for monitoring. Concentrations of metals in crayfish and Asian clams were consistent with those reported by other studies and programs that sampled streams in southeast Missouri

Concentrations of Metals in Aquatic Invertebrates from the Ozark National Scenic Riverways, Missouri

This report summarizes the findings of a study conducted as a pilot for part of a park-wide monitoring program being developed for the Ozark National Scenic Riverways (ONSR) of southeastern Missouri. The objective was to evaluate using crayfish (Orconectes spp.) and Asian clam (Corbicula fluminea) for monitoring concentrations of metals associated with lead-zinc mining. Lead-zinc mining presently (2007) occurs near the ONSR and additional mining has been proposed. Three composite samples of each type (crayfish and Asian clam), each comprising ten animals of approximately the same size, were collected during late summer and early fall of 2005 from five sites on the Current River and Jacks Fork within the ONSR and from one site on the Eleven Point River and the Big River, which are outside the ONSR. The Big River has been contaminated by mine tailings from historical leadzinc mining. Samples were analyzed by inductively coupled plasma mass spectrometry for lead, zinc, cadmium, cobalt, and nickel concentrations. All five metals were detected in all samples; concentrations were greatest in samples of both types from the Big River, and lowest in samples from sites within the ONSR. Concentrations of zinc and cadmium typically were greater in Asian clams than in crayfish, but differences were less evident for the other metals. In addition, differences among sites were small for cobalt in Asian clams and for zinc in crayfish, indicating that these metals are internally regulated to some extent. Consequently, both sample types are recommended for monitoring. Concentrations of metals in crayfish and Asian clams were consistent with those reported by other studies and programs that sampled streams in southeast Missouri

Biomonitoring of Lead, Zinc, and Cadmium in Streams Draining Lead-Mining and Non-Mining Areas, Southeast Missouri, USA

We evaluated exposure of aquatic biota to lead (Pb), zinc (Zn), and cadmium (Cd) in streams draining a Pb-mining district in southeast Missouri. Samples of plant biomass (detritus, periphyton, and filamentous algae), invertebrates (snails, crayfish, and riffle benthos), and two taxa of fish were collected from seven sites closest to mining areas (mining sites), four sites further downstream from mining (downstream sites), and eight reference sites in fall 2001. Samples of plant biomass from mining sites had highest metal concentrations, with means 10- to 60- times greater than those for reference sites. Mean metal concentrations in over 90% of samples of plant biomass from mining sites were significantly greater than those from reference sites. Mean concentrations of Pb, Zn, and Cd in most invertebrate samples from mining sites, and mean Pb concentrations in most fish samples from mining sites, were also significantly greater than those from reference sites. Concentrations of all three metals were lower in samples from downstream sites, but several samples of plant biomass from downstream sites had metal concentrations significantly greater than those from reference sites. Analysis of supplemental samples collected in the fall of 2002, a year of above-average stream discharge, had lower Pb concentrations and higher Cd concentrations than samples collected in 2001, near the end of a multi-year drought. Concentrations of Pb measured in fish and invertebrates collected from mining sites during 2001 and 2002 were similar to those measured at nearby sites in the 1970s, during the early years of mining in the Viburnum Trend. Results of this study demonstrate that long-term Pb mining activity in southeast Missouri has resulted in significantly elevated concentrations of Pb, Cd, and Zn in biota of receiving streams, compared to biota of similar streams without direct influence of mining. Our results also demonstrate that metal exposure in the study area differed significantly among sample types, habitats, and years, and that these factors should be carefully considered in the design of biomonitoring studies

Comparative transcription map of the wobbler critical region on mouse chromosome 11 and the homologous region on human chromosome 2p13-14

BACKGROUND: To support the positional cloning of the mouse mutation wobbler (wr) the corresponding regions on human Chr2p13-14 and mouse Chr11 were analyzed in detail and compared with respect to gene content, order, and orientation. RESULTS: The gene content of the investigated regions was highly conserved between the two species: 20 orthologous genes were identified on our BAC/YAC contig comprising 4.5 Mb between REL/Rel and RAB1A/Rab1a. Exceptions were pseudogenes ELP and PX19 whose mouse counterparts were not located within the analyzed region. Two independently isolated genomic clones indicate an inversion between man and mouse with the inverted segment being identical to the wobbler critical interval. We investigated the wobbler critical region by extensive STS/EST mapping and genomic sequencing. Additionally, the full-length cDNA sequences of four newly mapped genes as well as the previously mapped gene Otx1 were established and subjected to mutation analysis. Our data indicate that all genes in the wr critical region have been identified. CONCLUSION: Unexpectedly, neither mutation analysis of cDNAs nor levels of mRNAs indicated which of the candidate genes might be affected by the wr mutation. The possibility arises that there might be hitherto unknown effects of mutations, in addition to structural changes of the mRNA or regulatory abnormalities

Assessment of Elemental Concentrations in Streams of the New Lead Belt in Southeastern Missouri, 2002–05

Concerns about possible effects of lead-mining activities on the water quality of federally protected streams located in southeastern Missouri prompted a suite of multidisciplinary studies to be conducted by the U.S. Geological Survey. As part of this investigation, a series of biological studies were initiated in 2001 for streams in the current mining region and the prospecting area. In this report, results are examined for trace elements and other selected chemical measurements in sediment, surface water, and sediment interstitial (pore) water sampled between 2002 and 2005 in association with these biological studies. Compared to reference sites, fine sediments collected downstream from mining areas were enriched in metals by factors as large as 75 for cadmium, 62 for cobalt, 171 for nickel, 95 for lead, and 150 for zinc. Greatest metal concentrations in sediments collected in 2002 were from sites downstream from mines on Strother Creek, Courtois Creek, and the West Fork Black River. Sediments from sites on Bee Fork, Logan Creek, and Sweetwater Creek also were noticeably enriched in lead. Sediments in Clearwater Lake, at least 75 kilometers downstream from mining activity, had metal concentrations that were 1.5 to 2.1 times greater than sediments in an area of the lake with no upstream mining activity. Longitudinal sampling along three streams in 2004 indicated that sediment metal concentrations decreased considerably a few kilometers downstream from mining activities; however, in Strother Creek some metals were still enriched by a factor of five or more as far as 13 kilometers downstream from the Buick tailings impoundment. Compared with 2002 samples, metals concentrations were dramatically lower in sediments collected in 2004 at an upper West Fork Black River site, presumably because beneficiation operations at the West Fork mill ceased in 2000. Concentrations of metals and sulfate in sediment interstitial (pore) waters generally tracked closely with metal concentrations in sediments. Metals, including cobalt, nickel, lead, and zinc, were elevated substantially in laboratory-produced pore waters of fine sediments collected near mining operations in 2002 and 2004. Passive diffusion samplers (peepers) buried 4 to 6 centimeters deep in riffle-run stream sediments during 2003 and 2005 had much lower pore-water metal concentrations than the laboratory-produced pore waters of fine sediments collected in 2002 and 2004, but each sampling method produced similar patterns among sites. The combined mean concentration of lead in peeper samples from selected sites located downstream from mining activities for six streams was about 10-fold greater than the mean of the reference sites. In most instances, metals concentrations in surface water and peeper water were not greatly different, indicating considerable exchange between the surface water and pore water at the depths and locations where peepers were situated. Passive sampling probes used to assess metal lability in pore waters of selected samples during 2004 sediment toxicity tests indicated that most of the filterable lead in the laboratory-prepared pore water was relatively non-labile, presumably because lead was complexed by organic matter, or was present as colloidal species. In contrast, large percentages of cobalt and nickel in pore water appeared to be labile. Passive integrative samplers deployed in surface water for up to 3 weeks at three sites in July 2005 confirmed the presence of elevated concentrations of labile metals downstream from mining operations on Strother Creek and, to a lesser extent, Bee Fork. These samplers also indicated a considerable increase in metal loadings occurred for a few days at the Strother Creek site, which coincided with moderate increases in stream discharges in the area

Susceptibility Provision Enhances Effective De-escalation (SPEED): utilizing rapid phenotypic susceptibility testing in Gram-negative bloodstream infections and its potential clinical impact

Abstract Objectives We evaluated the performance and time to result for pathogen identification (ID) and antimicrobial susceptibility testing (AST) of the Accelerate Pheno™ system (AXDX) compared with standard of care (SOC) methods. We also assessed the hypothetical improvement in antibiotic utilization if AXDX had been implemented. Methods Clinical samples from patients with monomicrobial Gram-negative bacteraemia were tested and compared between AXDX and the SOC methods of the VERIGENE® and Bruker MALDI Biotyper® systems for ID and the VITEK® 2 system for AST. Additionally, charts were reviewed to calculate theoretical times to antibiotic de-escalation, escalation and active and optimal therapy Results ID mean time was 21 h for MALDI-TOF MS, 4.4 h for VERIGENE® and 3.7 h for AXDX. AST mean time was 35 h for VITEK® 2 and 9.0 h for AXDX. For ID, positive percentage agreement was 95.9% and negative percentage agreement was 99.9%. For AST, essential agreement was 94.5% and categorical agreement was 93.5%. If AXDX results had been available to inform patient care, 25% of patients could have been put on active therapy sooner, while 78% of patients who had therapy optimized during hospitalization could have had therapy optimized sooner. Additionally, AXDX could have reduced time to de-escalation (16 versus 31 h) and escalation (19 versus 31 h) compared with SOC. Conclusions By providing fast and reliable ID and AST results, AXDX has the potential to improve antimicrobial utilization and enhance antimicrobial stewardship

Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease

Palmisano R, Golfi P, Heimann P, et al. Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease. BMC Neuroscience. 2011;12(1): 24.Background: The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown but hypotheses about disease mechanisms include oxidative stress, defective axonal transport, mitochondrial dysfunction and disrupted RNA processing. Whereas familial ALS is well represented by transgenic mutant SOD1 mouse models, the mouse mutant wobbler (WR) develops progressive motor neuron degeneration due to a point mutation in the Vps54 gene, and provides an animal model for sporadic ALS. VPS54 protein as a component of a protein complex is involved in vesicular Golgi trafficking; impaired vesicle trafficking might also be mechanistic in the pathogenesis of human ALS. Results: In motor neurons of homozygous symptomatic WR mice, a massive number of endosomal vesicles significantly enlarged (up to 3 mu m in diameter) were subjected to ultrastructural analysis and immunohistochemistry for the endosome-specific small GTPase protein Rab7 and for amyloid precursor protein (APP). Enlarged vesicles were neither detected in heterozygous WR nor in transgenic SOD1(G93A) mice; in WR motor neurons, numerous APP/Rab7-positive vesicles were observed which were mostly LC3-negative, suggesting they are not autophagosomes. Conclusions: We conclude that endosomal APP/Rab7 staining reflects impaired vesicle trafficking in WR mouse motor neurons. Based on these findings human ALS tissues were analysed for APP in enlarged vesicles and were detected in spinal cord motor neurons in six out of fourteen sporadic ALS cases. These enlarged vesicles were not detected in any of the familial ALS cases. Thus our study provides the first evidence for wobbler-like aetiologies in human ALS and suggests that the genes encoding proteins involved in vesicle trafficking should be screened for pathogenic mutations