Copper Complexation by Dissolved Organic Matter in arid Soils: A Voltametric Study

A voltammetric method was used to estimate the complexing capacity of water extracts from both desert soils sampled at the root zone of creosote and salt cedar plants, and in soils from interspace or background regions where no vegetative influence was apparent. The copper complexing capacity of water extracts of these desert soils was influenced by contact time and pH. In soils from the root zones of creosote and salt cedar plant, copper complexation capacities at pH 8 were from 5 µM to 60 µM after five min contact periods, while 18 h contact periods yielded copper complexation capacities of 40 µM–80 µM. Soils with no vegetative influence had copper complexing capacities of less the 2 µM. The copper complexing capacities of these soils are well correlated with the concentration of organic carbon in the water extract (r2 = 0.86). The abundance of soluble organic matter in the root zone of desert shrubs has the potential to control the solution speciation of Cu2+. The formation of soluble complexes should also have an important influence on the plant uptake and transport of copper, as well as other heavy metals in the root zones of desert shrubs and beyond

241Pu and 241Am in sediments from coastal basins off California and Mexico

In sediments deposited in the coastal basins off the western North American continent since the early 1960's, there is more 241Am activity than one would predict if its presence was solely due to the decay of 241Pu that was produced during the testing of weapons in 1961-1962 (taken as July 1, 1962 for calculations). This excess can be accounted for by the decay of 241Pu, if pre-1962 fallout (fallout from the pre-moratorium testing) has been continuously introduced into the recent sediments along with fallout from post-moratorium testing. This hypothesis is supported by the plutonium depth profiles which do not reflect direct fallout from the atmosphere, as characterized by two peaks corresponding to the two major weapons testing periods, but continuously increasing plutonium and americium concentrations from 1954 to 1974. Thus, the nuclides may be coming from a large reservoir that has accumulated and mixed fallout since 1952. Such a concentration gradient for all of the nuclides requires their immobilization in the sediment after deposition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23208/1/0000137.pd

Tumor Associated Stromal Cells Play a Critical Role on the Outcome of the Oncolytic Efficacy of Conditionally Replicative Adenoviruses

The clinical efficacy of conditionally replicative oncolytic adenoviruses (CRAd) is still limited by the inefficient infection of the tumor mass. Since tumor growth is essentially the result of a continuous cross-talk between malignant and tumor-associated stromal cells, targeting both cell compartments may profoundly influence viral efficacy. Therefore, we developed SPARC promoter-based CRAds since the SPARC gene is expressed both in malignant cells and in tumor-associated stromal cells. These CRAds, expressing or not the Herpes Simplex thymidine kinase gene (Ad-F512 and Ad(I)-F512-TK, respectively) exerted a lytic effect on a panel of human melanoma cells expressing SPARC; but they were completely attenuated in normal cells of different origins, including fresh melanocytes, regardless of whether cells expressed or not SPARC. Interestingly, both CRAds displayed cytotoxic activity on SPARC positive-transformed human microendothelial HMEC-1 cells and WI-38 fetal fibroblasts. Both CRAds were therapeutically effective on SPARC positive-human melanoma tumors growing in nude mice but exhibited restricted efficacy in the presence of co-administered HMEC-1 or WI-38 cells. Conversely, co-administration of HMEC-1 cells enhanced the oncolytic efficacy of Ad(I)-F512-TK on SPARC-negative MIA PaCa-2 pancreatic cancer cells in vivo. Moreover, conditioned media produced by stromal cells pre-infected with the CRAds enhanced the in vitro viral oncolytic activity on pancreatic cancer cells, but not on melanoma cells. The whole data indicate that stromal cells might play an important role on the outcome of the oncolytic efficacy of conditionally replicative adenoviruses

RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data

Objectives To identify predictors of remission and disease activity patterns in patients with rheumatoid arthritis (RA) using individual participant data (IPD) from clinical trials. Methods Phases II and III clinical trials completed between 2002 and 2012 were identified by systematic literature review and contact with UK market authorisation holders. Anonymised baseline and follow-up IPD from non-biological arms were amalgamated. Multiple imputation was used to handle missing outcome and covariate information. Random effects logistic regression was used to identify predictors of remission, measured by the DAS28 score at 6 months. Novel latent class mixed models characterised DAS28 over time.Results IPD of 3290 participants from 18 trials were included. Of these participants, 92% received methotrexate (MTX). Remission rates were estimated at 8.4% (95%CI: 7.4%-9.5%) overall, 17% (95%CI: 14.8%-19.4%) for MTX-naïve early RA patients, and 3.2% (95%CI: 2.4%-4.3%) for those with prior MTX exposure at entry. In prior MTX-exposed patients, lower baseline DAS28 and MTX-re-initiation were associated with remission. In MTX-naïve patients, being young, white, male, with better functional and mental health, lower baseline DAS28 and receiving concomitant glucocorticoids were associated with remission. Three DAS28 trajectory sub-populations were identified in MTX-naïve and MTX-exposed patients. A number of variables were associated with sub-population membership and DAS28 levels within sub-populations. Conclusions Predictors of remission differed between MTX-naïve and prior MTX-exposed patients at entry. Latent class mixed models supported differential non-biologic therapy response, with three distinct trajectories observed in both MTX-naïve and MTX-exposed patients. Findings should be useful when designing future RA trials and interpreting results of biomarker studies. <br/

Application of field portable-XRF to the analysis of desert varnish samples in areas impacted by coal-fired power plants

Desert varnish samples were collected near two coal-fired power plants to determine if the varnish contained a record of recent air pollution. Samples were collected: (1) in the fallout patterns of the shuttered Mohave Power Plant (MPP), located in Laughlin, NV; and (2) near the operating Reid-Gardner Power Plant (RGPP), just east of Las Vegas, NV. Small pieces of varnished rocks were analysed by field portable X-ray fluorescence spectroscopy (FPXRF). Results were obtained for 15 elements: Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Zr, Mo, Hg and Pb. The FPXRF data indicate that the elements commonly found in fly ash from coal-fired power plants (e.g. Cr, Zn, As and Pb) had significantly higher concentrations in the rock coatings in relation to the unvarnished substrate rock. For one of the power plants, where tracer plume studies had been carried out, the highest concentrations in the desert varnish coincided with the peak tracer concentration locations. Thus, these elements in desert varnish hold promise for identifying those geographical regions affected by nearby power plants. However, additional samples are required to demonstrate unequivocally that the power plants are indeed the sources of these elements. Overall, it is apparent that desert varnish can be utilised as a passive environmental monitor to investigate recent air pollution (past 20–30 years) and that FPXRF can be used as a surveying tool to obtain multi-element data from a large number of samples

Analysis of Mercury in Desert Varnish Samples in Areas Impacted by Coal-fired Power Plants

Rock varnish is a manganese–iron rich coating that forms on rocks, most often in arid climates. To assess its utility as an environmental monitor of mercury contamination, cold vapor atomic absorption spectrometry (CVAAS) was used for analysis. Samples were collected in the fallout patterns of two coal-fired power plants in southern Nevada: the defunct Mohave Power Plant (MPP) and the operating Reid Gardner Power Plant (RGPP). The resultant Hg concentrations in rock varnishes were plotted as a function of the distance from each power plant. The highest concentrations of Hg occurred at locations that suggest the power plants are the main source of pollutants. In addition, past tracer plume studies carried out at MPP show that the highest tracer concentrations coincide with the highest rock varnish Hg concentrations. However, additional samples are required to further demonstrate that power plants are indeed the sources of mercury in varnishes