Metabolomic Analysis Reveals Contributions of Citric and Citramalic Acids to Rare Earth Bioleaching by a Paecilomyces Fungus.

Conventional methods for extracting rare earth elements from monazite ore require high energy inputs and produce environmentally damaging waste streams. Bioleaching offers a potentially more environmentally friendly alternative extraction process. In order to better understand bioleaching mechanisms, we conducted an exo-metabolomic analysis of a previously isolated rare earth bioleaching fungus from the genus Paecilomyces (GenBank accession numbers KM874779 and KM 874781) to identify contributions of compounds exuded by this fungus to bioleaching activity. Exuded compounds were compared under two growth conditions: growth with monazite ore as the only phosphate source, and growth with a soluble phosphate source (K2HPO4) added. Overall metabolite profiling, in combination with glucose consumption and biomass accumulation data, reflected a lag in growth when this organism was grown with only monazite. We analyzed the relationships between metabolite concentrations, rare earth solubilization, and growth conditions, and identified several metabolites potentially associated with bioleaching. Further investigation using laboratory prepared solutions of 17 of these metabolites indicated statistically significant leaching contributions from both citric and citramalic acids. These contributions (16.4 and 15.0 mg/L total rare earths solubilized) accounted for a portion, but not all, of the leaching achieved with direct bioleaching (42 ± 15 mg/L final rare earth concentration). Additionally, citramalic acid released significantly less of the radioactive element thorium than did citric acid (0.25 ± 0.01 mg/L compared to 1.18 ± 0.01 mg/L), suggesting that citramalic acid may have preferable leaching properties for a monazite bioleaching process

Super-ASTROD: Probing primordial gravitational waves and mapping the outer solar system

Super-ASTROD (Super Astrodynamical Space Test of Relativity using Optical Devices or ASTROD III) is a mission concept with 3-5 spacecraft in 5 AU orbits together with an Earth-Sun L1/L2 spacecraft ranging optically with one another to probe primordial gravitational-waves with frequencies 0.1 microHz - 1 mHz, to test fundamental laws of spacetime and to map the outer solar system. In this paper we address to its scientific goals, orbit and payload selection, and sensitivity to gravitational waves.Comment: 7 pages, 1 figure, presented to 7th International LISA Symposium, 16-20 June 2008, Barcelona; submitted to Classical and Quantum Gravity; presentation improve

An empty E1−, E3−, E4− adenovirus vector protects photoreceptors from light-induced degeneration

We have previously identified a neuroprotective effect associated with empty (E1−, E3−, E4−) adenovirus vector delivery in a model of light-induced, photoreceptor cell death. In this study, we further characterize this protective effect in light-injured retina and investigate its molecular basis. Dark-adapted BALB/c mice, aged 6–8 weeks, were exposed to standardized, intense fluorescent light for 96 or 144 h. Prior to dark adaptation, all mice received intravitreous injection of 1 × 109 particles of an empty (E1−, E3−, E4−) adenovirus vector in one eye and vehicle in the other. Following light challenge of 96 or 144 h, histopathological analysis and quantitative photoreceptor cell counts were conducted. Semiquantitative assessment of messenger ribonucleic acid (mRNA) for the apoptosis related genes: p50, p65, IkBa, caspase-1, caspase-3, Bad, c-Jun, Bax, Bak, Bcl-2, c-Fos, and p53 using quantitative reverse transcriptase polymerase chain reaction was performed on eyes following 12 h of light exposure. Following 96 h of light exposure, the photoreceptor cell density for E1−, E3−, E4− adenovirus vector and vehicle-injected eyes were 87.5 ± 9.5 and 79.3 ± 10.1, respectively, (p = 0.79). After 144 h of light exposure, the photoreceptor cell density was preserved in vector-injected eyes as compared to vehicle treated eyes, 68.9 ± 10.0 and 49.2 ± 4.6, respectively (p = 0.016). Relative mRNA levels of c-Fos and c-Jun at 12-h light exposure after injection differed significantly between vector- and vehicle-injected eyes (p = 0.036, 0.016, respectively). The expression of the other apoptosis-related genes evaluated was not significantly affected. This study investigates the molecular basis of photoreceptor neuroprotective pathway induction associated with E1−, E3−, E4− adenovirus vectors. The results indicate that empty adenovirus vectors protect photoreceptors from light-induced degeneration by the modulation of apoptotic pathways. Gene expression changes suggest that the suppression of c-Fos and c-Jun upregulation contributes significantly to the neuroprotective effect. Understanding the molecular basis of the neuroprotective pathway induction in photoreceptors is critical to the development of novel therapies for retinal degenerations

Incomplete Wood-Ljungdahl pathway facilitates one-carbon metabolism in organohalide-respiring Dehalococcoides mccartyi.

The acetyl-CoA "Wood-Ljungdahl" pathway couples the folate-mediated one-carbon (C1) metabolism to either CO2 reduction or acetate oxidation via acetyl-CoA. This pathway is distributed in diverse anaerobes and is used for both energy conservation and assimilation of C1 compounds. Genome annotations for all sequenced strains of Dehalococcoides mccartyi, an important bacterium involved in the bioremediation of chlorinated solvents, reveal homologous genes encoding an incomplete Wood-Ljungdahl pathway. Because this pathway lacks key enzymes for both C1 metabolism and CO2 reduction, its cellular functions remain elusive. Here we used D. mccartyi strain 195 as a model organism to investigate the metabolic function of this pathway and its impacts on the growth of strain 195. Surprisingly, this pathway cleaves acetyl-CoA to donate a methyl group for production of methyl-tetrahydrofolate (CH3-THF) for methionine biosynthesis, representing an unconventional strategy for generating CH3-THF in organisms without methylene-tetrahydrofolate reductase. Carbon monoxide (CO) was found to accumulate as an obligate by-product from the acetyl-CoA cleavage because of the lack of a CO dehydrogenase in strain 195. CO accumulation inhibits the sustainable growth and dechlorination of strain 195 maintained in pure cultures, but can be prevented by CO-metabolizing anaerobes that coexist with D. mccartyi, resulting in an unusual syntrophic association. We also found that this pathway incorporates exogenous formate to support serine biosynthesis. This study of the incomplete Wood-Ljungdahl pathway in D. mccartyi indicates a unique bacterial C1 metabolism that is critical for D. mccartyi growth and interactions in dechlorinating communities and may play a role in other anaerobic communities

ASTROD, ASTROD I and their gravitational-wave sensitivities

ASTROD (Astrodynamical Space Test of Relativity using Optical Devices) is a mission concept with three spacecraft -- one near L1/L2 point, one with an inner solar orbit and one with an outer solar orbit, ranging coherently with one another using lasers to test relativistic gravity, to measure the solar system and to detect gravitational waves. ASTROD I with one spacecraft ranging optically with ground stations is the first step toward the ASTROD mission. In this paper, we present the ASTROD I payload and accelerometer requirements, discuss the gravitational-wave sensitivities for ASTROD and ASTROD I, and compare them with LISA and radio-wave PDoppler-tracking of spacecraft.Comment: presented to the 5th Edoardo Amaldi Conference (July 6-11, 2003) and submitted to Classical and Quantum Gravit

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

ObjectiveTo determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.MethodsFor this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.ResultsOf 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score.ConclusionFLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status

Language attitudes and use in a transplanted setting: Greek Cypriots in London

In this paper we explore language attitudes and use in the Greek Cypriot community in London, England. Our study is based on an earlier survey carried out in Nicosia, Cyprus and we compare attitudes to language and reported language use in the two communities. We thereby highlight the significance of sociolinguistic variables on similar groups of speakers. We further extend our investigation to include codeswitching practices in the London community. \ud Analysis of language attitudes and use within the Greek-Cypriot population of London, and comparisons with findings in Nicosia, reflect symbolic forces operating in the two contexts. Despite obvious differences between the two communities, (most obviously the official languages and distinct cultural backgrounds of the two nations), the Greek Cypriot Dialect continues to play an active role in both. English is however the ‘default choice‘ for young Cypriots in the UK and Standard Modern Greek occupies a much more limited role than in Cyprus. It is argued that differences in language attitudes and use can be interpreted in light of different market forces operating in the nation (i.e. Cyprus) and the Diaspora (i.e. UK)

Identification of actionable targets for breast cancer intervention using a diversity outbred mouse model

HER2-targeted therapy has improved breast cancer survival, but treatment resistance and disease prevention remain major challenges. Genes that enable HER2/Neu oncogenesis are the next intervention targets. A bioinformatics discovery platform of HER2/Neu-expressing Diversity Outbred (DO) F1 Mice was established to identify cancer-enabling genes. Quantitative Trait Loci (QTL) associated with onset ages and growth rates of spontaneous mammary tumors were sought. Twenty-six genes in 3 QTL contain sequence variations unique to the genetic backgrounds that are linked to aggressive tumors and 21 genes are associated with human breast cancer survival. Concurrent identification of TSC22D3, a transcription factor, and its target gene LILRB4, a myeloid cell checkpoint receptor, suggests an immune axis for regulation, or intervention, of disease. We also investigated TIEG1 gene that impedes tumor immunity but suppresses tumor growth. Although not an actionable target, TIEG1 study revealed genetic regulation of tumor progression, forming the basis of the genetics-based discovery platform

Imprints of Nuclear Symmetry Energy on Properties of Neutron Stars

Significant progress has been made in recent years in constraining the density dependence of nuclear symmetry energy using terrestrial nuclear laboratory data. Around and below the nuclear matter saturation density, the experimental constraints start to merge in a relatively narrow region. At supra-saturation densities, there are, however, still large uncertainties. After summarizing the latest experimental constraints on the density dependence of nuclear symmetry energy, we highlight a few recent studies examining imprints of nuclear symmetry energy on the binding energy, energy release during hadron-quark phase transitions as well as the $w$-mode frequency and damping time of gravitational wave emission of neutron stars.Comment: 10 pages. Invited talk given in the Nuclear Astrophysics session of INPC2010, July 4-9, 2010, Vancouver, Canada; Journal of Physics: Conference Series (2011