69 research outputs found
NMR Spectroscopic Investigation of Lanthanide, Actinide, and Selenium Containing Complexes Related to the Environment or Nuclear Waste Disposals
The ultimate goal of this work is providing insights into fundamental (physico-) chemical (redox) behavior of hexavalent uranium (U(VI)), trivalent europium (Eu(III)) and selenium (Se), and upon their interaction with ubiquitous small biomolecules (in case of U(VI) and Eu(III)) or alkaline earth metal ions (in case of Se(IV) and Se(VI)) by application of Nuclear Magnetic Resonance (NMR) spectroscopy. NMR spectroscopy is a powerful method proving its usefulness also to environmental and nuclear waste related studies in aqueous solutions by determination of (potential) binding sites, molecular structures (even conformation and configuration) as well as intra- and intermolecular dynamics, (redox) reaction pathways and mechanisms.
The present work comprises extensive NMR spectroscopic investigations in aqueous (D2O) solutions on (i) glutathione (GSH) and glutathione disulfide (GSSG) interactions with trivalent lanthanides (Ln(III), particularly Eu(III)) and U(VI), (ii) molecular structures of citrate (Cit) complexes of U(VI), and their reactions upon light-irradiation, as well as (iii) pH- and temperature-dependent speciation of selenium oxyanions, i.e., Se(VI) (selenate) and Se(IV) (selenite and, notably, hydrogen selenite) as well as Se(VI) and Se(IV) interaction with alkaline earth metal ions. These investigations are supported by time-resolved laser-induced fluorescence spectroscopy (TRLFS), ultraviolet-visible-near infrared (UV-Vis-NIR), IR/Raman, and extended X-ray absorption fine structure (EXAFS) spectroscopy, transmission electron microscopy (TEM), as well as quantum chemical calculations on density functional theory (DFT) level.
For NMR spectroscopic data on GSH/GSSG complexation towards both Eu(III) and U(VI) are lacking, the herein presented results are new, and nicely complement other spectroscopic studies. Ln(III) complexes of GSH are characterized by their high solubility at least up to 300 mM and pD 5. However, the formation constant of the Eu(III)–GSH 1:1 complex is quite low with log K = 1.71 ± 0.01 as determined by Eu(III)-TRLFS. The diamagnetic La(III) and Lu(III) showed only little effect on the NMR spectra (< 2 ppm) while analogous Eu(III) solutions revealed hyperfine shifts up to 40 ppm. Eu(III)-induced 1H chemical shift changes are solely upfield and attributed to be predominantly due to pseudocontact contribution caused by dipolar interaction. In contrast, Eu(III)-induced 13C chemical shift changes of adjacent atoms – at least for the carboxyl and α-carbons – show alternating signs, indicating spin polarization effects owing to contact contribution. As expected for hard LEWIS acids and shown by other spectroscopies, complexation facilitates by the carboxyl groups. Qualitative differences between the glutamyl and glycyl carboxylate in metal ion complexation are ascribed to COULOMB repulsion due to the positively charged NH3+ in direct vicinity.
Investigations of the U(VI)–GSH system covered experiments under both oxidizing and reducing conditions, performed with GSH’s oxidized form, GSSG, at ambient conditions, while samples with reduced GSH were handled under N2 atmosphere. For either condition, U(VI) showed interaction in aqueous (D2O) solution with both GSH and GSSG as determined by U(VI)-induced 1H and 13C chemical shift changes and U(VI) TRLFS, the latter comprising measurements at 25 °C and –120 °C. In principle, the interactions are stronger as compared to the Ln(III) system, and the speciation in both solution and solid is more complex owing to the aqueous chemistry of uranium. Observed binary GSH complexes are [UO2(H2GSH)]2+ for pD values up to ≈ 2.3, and [UO2(HGSH)]+ predominating for pD > 2.3. Complementary to the Eu(III) results, whenever net neutral binary GSH/GSSG or ternary hydroxo GSH/GSSG U(VI) complexes form in solution, both these U(VI) systems revealed extensive precipitation because of the low solubility of these complexes. Binary U(VI) GSSG and ternary U(VI) hydroxo GSSG complexes yield solid phases from pD 2 through 8, even in carbonatic media. The largest quantities of aqueous GSSG–U(VI) complexes are observed for pD ≈ 3.5, with the association constant for pH 3 determined by TRLFS as log K = 4.81 ± 0.08 for a 1:1 complex. GSH cannot compete with hydroxo ligands for complexation as of pD 6, whereas GSSG can at least partially compete with hydroxo and carbonate ligands upon formation of both quaternary U(VI) hydroxo carbonate GSSG, and ternary U(VI) carbonate GSSG (poly-)anionic species of high solubility.
Under reducing and near-neutral conditions (pD 6 – 9) GSH immediately reduced U(VI) with subsequent formation of nanocrystalline UO2+x. After centrifugation of the starting material and allowing the decanted supernatant to age, the dissolved nanocrystals assemble network-like as disclosed by TEM, and further analysed by selected-area electron diffraction (SAED), energy-dispersive X-ray (EDX) and UV-Vis spectroscopy, revealing hyper-stoichiometric UO2+x phases. Such network-like assembled actinide containing nanocrystals, with the arrangement most likely provoked by the presence of GSSG, have never been shown before. Complementary, the precipitate that has also been allowed to age as a wet paste, showed color changes from yellow via olive to black, indicating a reaction to proceed. The repeatedly probed and dissolved material exhibited GSSG in NMR spectra, and UV-Vis-NIR absorption bands attributed to U(IV) and, notably, U(V), the latter implying a one-electron transfer with subsequent disproportionation of U(V) to U(IV) and U(VI). Therefore, obtained results advance the understanding of both fundamental redox behavior of uranium and the role of GSH (and related molecules) in U(VI) detoxification processes in vivo.
Although investigated for over 70 years, there are still controversial discussions on both speciation and structures of U(VI)–Cit complexes. By means of NMR’s strength in both structure determination and sensitivity to dynamic processes, studies regarding the U(VI)–Cit system allowed further fundamental insights into the structures of the formed complexes on a molecular level. Upon complexation a chiral center is induced in Cit’s central carbon, resulting in the formation of two diastereomeric pairs of enantiomers, whereupon the dimeric complexes exhibit syn and anti configured isomers. In fact, the combination of 17O NMR (note: at natural abundance) and quantum chemical calculations allowed an unambiguous decision on complex geometry and overall configurations. It is evidenced for the first time that the syn isomer is favored in aqueous solution in contrast to the preferably crystallizing anti isomer. Both isomers coexist and interconvert among one another, with a rate estimated to be in the order of 102 s–1 at 25 °C in acidic media, and a corresponding activation energy of approximately 60 kJ mol–1. Moreover, clear indications for uranium chirality is observed for U4+, with the 1:1 U(IV)–Cit complexes also forming two diastereomeric pairs of enantiomers. Comprehensive spectroscopic experiments combined with quantum chemical calculations improved basic understanding of the photo-reaction mechanism in the U(VI)–Cit system. Regardless of sample conditions, Cit is degraded to β-ketoglutarate, acetoacetate, and acetone, while U(VI) was reduced to U(IV) at pD 2 and U(V) at pD 5, suggesting a two- and a one-electron transfer, respectively. NMR signals observed for pD 5 samples at remarkable 1H chemical shift values between 25 and 53 ppm, in combination with UV-Vis-NIR absorptions at about 750 and 930 nm, are assigned to U(V) complexes of citrate. With regard to reported pH dependence on reaction rate and yield in the literature combined with observations in this work, H+/D+ are considered mechanistically crucial constituents. Furthermore, the photoreaction proceeds intermolecularly, requiring for free Cit to be present in solution.
In consideration of both the U(VI)–Cit photoreaction and the U(VI)–GSH chemical redox reaction, regardless of the particular mechanism, in both cases the process is intermolecular. This is not only a highly interesting, but the more a very important result, rendering the reductants not required to be bound to U(VI) in order to reduce it.
Owing to the suitability of 77Se as NMR-active but non-radioactive Se isotope, this spectroscopy was also applied to study chemical behavior of the nuclear waste related long-lived 79Se. For the first time spectroscopic evidence is given for hydrogen selenite dimerization in aqueous solution upon formation of homo-dimers by hydrogen bonding that are stable up to 60 °C and so are other selenium oxyanionic species. Additionally, a remarkably higher 77Se chemical shift temperature coefficient of the dimer – as compared to corresponding selenite and selenous acid – was found. These findings are attributed to a significant deshielding upon heating due to remarkably different rovibrational modes upon stretching the dimer as a whole instead of its dissociation into monomers owing to the rather strong hydrogen bonds. Interaction of selenium oxyanions with ubiquitous alkaline earth metals, i.e., Ca2+ and Mg2+, showed formation of weak aqueous complexes of both selenite and hydrogen selenite dimer for excessive selenium, however, at high ionic strength (5.6 M) for equimolar Ca2+ and Se(IV) even at pHc 5 crystalline calcium selenite is formed
Using the Discrete Dipole Approximation and Holographic Microscopy to Measure Rotational Dynamics of Non-spherical Colloidal Particles
We present a new, high-speed technique to track the three-dimensional
translation and rotation of non-spherical colloidal particles. We capture
digital holograms of micrometer-scale silica rods and sub-micrometer-scale
Janus particles freely diffusing in water, and then fit numerical scattering
models based on the discrete dipole approximation to the measured holograms.
This inverse-scattering approach allows us to extract the the position and
orientation of the particles as a function of time, along with static
parameters including the size, shape, and refractive index. The best-fit sizes
and refractive indices of both particles agree well with expected values. The
technique is able to track the center of mass of the rod to a precision of 35
nm and its orientation to a precision of 1.5, comparable to or better
than the precision of other 3D diffusion measurements on non-spherical
particles. Furthermore, the measured translational and rotational diffusion
coefficients for the silica rods agree with hydrodynamic predictions for a
spherocylinder to within 0.3%. We also show that although the Janus particles
have only weak optical asymmetry, the technique can track their 2D translation
and azimuthal rotation over a depth of field of several micrometers, yielding
independent measurements of the effective hydrodynamic radius that agree to
within 0.2%. The internal and external consistency of these measurements
validate the technique. Because the discrete dipole approximation can model
scattering from arbitrarily shaped particles, our technique could be used in a
range of applications, including particle tracking, microrheology, and
fundamental studies of colloidal self-assembly or microbial motion.Comment: 11 pages, 9 figures, 2 table
Efficient ancestry and mutation simulation with msprime 1.0
Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this, a large number of specialized simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and the tskit library. We summarize msprime’s many features, and show that its performance is excellent, often many times faster and more memory efficient than specialized alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement
Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe
Evidence for Increased Genetic Risk Load for Major Depression in Patients Assigned to Electroconvulsive Therapy
Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant
depression; disorder severity and unfavorable treatment outcomes are shown to be influenced
by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment
and response/nonresponse are associated with an increased genetic burden for major
depression (MD) using polygenic risk score (PRS), which summarize the contribution of diseaserelated
common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive
episode underwent ECT. MD-PRS were calculated for these inpatients and a separate
population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary
statistics from the Psychiatric Genomics Consortium MDD-working group (Cases:
n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status
between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher
MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between
ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response
(50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate
that ECT cohorts show an increased genetic burden for MD and are consistent with the
hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic
risk for MD. Larger samples are needed to better substantiate these findings
A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank.
Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, pFDR: 0.049 to 1.28 × 10-14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression
Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression
Background The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. Methods We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4). Results No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95 confidence interval = 0.97–0.99). Conclusions We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes
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