521 research outputs found
Controls on the fate and speciation of Np(V) during iron (oxyhydr)oxide crystallization
The speciation and fate of neptunium as Np(V)O2+ during the crystallization of ferrihydrite to hematite and goethite was explored in a range of systems. Adsorption of NpO2+ to iron(III) (oxyhydr)oxide phases was reversible and, for ferrihydrite, occurred through the formation of mononuclear bidentate surface complexes. By contrast, chemical extractions and X-ray absorption spectroscopy (XAS) analyses showed the incorporation of Np(V) into the structure of hematite during its crystallization from ferrihydrite (pH 10.5). This occurred through direct replacement of octahedrally coordinated Fe(III) by Np(V) in neptunate-like coordination. Subsequent analyses on mixed goethite and hematite crystallization products (pH 9.5 and 11) showed that Np(V) was incorporated during crystallization. Conversely, there was limited evidence for Np(V) incorporation during goethite crystallization at the extreme pH of 13.3. This is likely due to the formation of a Np(V) hydroxide precipitate preventing incorporation into the goethite particles. Overall these data highlight the complex behavior of Np(V) during the crystallization of iron(III) (oxyhydr)oxides, and demonstrate clear evidence for neptunium incorporation into environmentally important mineral phases. This extends our knowledge of the range of geochemical conditions under which there is potential for long-term immobilization of radiotoxic Np in natural and engineered environments
Incorporation and retention of 99-Tc(IV) in magnetite under high pH conditions
Technetium incorporation into magnetite and its behavior during subsequent oxidation has been investigated at high pH to determine the technetium retention mechanism(s) on formation and oxidative perturbation of magnetite in systems relevant to radioactive waste disposal. Ferrihydrite was exposed to Tc(VII)(aq) containing cement leachates (pH 10.5-13.1), and crystallization of magnetite was induced via addition of Fe(II)aq. A combination of X-ray diffraction (XRD), chemical extraction, and X-ray absorption spectroscopy (XAS) techniques provided direct evidence that Tc(VII) was reduced and incorporated into the magnetite structure. Subsequent air oxidation of the magnetite particles for up to 152 days resulted in only limited remobilization of the incorporated Tc(IV). Analysis of both X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) data indicated that the Tc(IV) was predominantly incorporated into the magnetite octahedral site in all systems studied. On reoxidation in air, the incorporated Tc(IV) was recalcitrant to oxidative dissolution with less than 40% remobilization to solution despite significant oxidation of the magnetite to maghemite/goethite: All solid associated Tc remained as Tc(IV). The results of this study provide the first direct evidence for significant Tc(IV) incorporation into the magnetite structure and confirm that magnetite incorporated Tc(IV) is recalcitrant to oxidative dissolution. Immobilization of Tc(VII) by reduction and incorporation into magnetite at high pH and with significant stability upon reoxidation has clear and important implications for limiting technetium migration under conditions where magnetite is formed including in geological disposal of radioactive wastes
RB1 deletion in retinoblastoma protein pathway-disrupted cells results in DNA damage and cancer progression
Proliferative control in cancer cells is frequently disrupted by mutations in the retinoblastoma protein (RB) pathway. Intriguingly, RB1 mutations can arise late in tumorigenesis in cancer cells whose RB pathway is already compromised by another mutation. In this study, we present evidence for increased DNA damage and instability in cancer cells with RB pathway defects when RB1 mutations are induced. We generated isogenic RB1 mutant genotypes with CRISPR/Cas9 in a number of cell lines. Cells with even one mutant copy of RB1 have increased basal levels of DNA damage and increased mitotic errors. Elevated levels of reactive oxygen species as well as impaired homologous recombination repair underlie this DNA damage. When xenografted into immunocompromised mice, RB1 mutant cells exhibit an elevated propensity to seed new tumors in recipient lungs. This study offers evidence that late-arising RB1 mutations can facilitate genome instability and cancer progression that are beyond the preexisting proliferative control deficit
The Disappearing Act of KH 15D: Photometric Results from 1995 to 2004
We present results from the most recent (2002-2004) observing campaigns of
the eclipsing system KH 15D, in addition to re-reduced data obtained at Van
Vleck Observatory (VVO) between 1995 and 2000. Phasing nine years of
photometric data shows substantial evolution in the width and depth of the
eclipses. The most recent data indicate that the eclipses are now approximately
24 days in length, or half the orbital period. These results are interpreted
and discussed in the context of the recent models for this system put forward
by Winn et al. and Chiang & Murray-Clay. A periodogram of the entire data set
yields a highly significant peak at 48.37 +/- 0.01 days, which is in accord
with the spectroscopic period of 48.38 +/- 0.01 days determined by Johnson et
al. Another significant peak, at 9.6 days, was found in the periodogram of the
out-of-eclipse data at two different epochs. We interpret this as the rotation
period of the visible star and argue that it may be tidally locked in
pseudosynchronism with its orbital motion. If so, application of Hut's theory
implies that the eccentricity of the orbit is e = 0.65 +/- 0.01. Analysis of
the UVES/VLT spectra obtained by Hamilton et al. shows that the v sin(i) of the
visible star in this system is 6.9 +/- 0.3 km/sec. Using this value of v sin(i)
and the measured rotation period of the star, we calculate the lower limit on
the radius to be R = (1.3 +/- 0.1), R_Sun, which concurs with the value
obtained by Hamilton et al. from its luminosity and effective temperature. Here
we assume that i = 90 degrees since it is likely that the spin and orbital
angular momenta vectors are nearly aligned.Comment: 55 pages, 18 figures, 1 color figure, to appear the September issue
of the Astronomical Journa
Localization by immunofluorescence and by light- and electron-microscopic immunoperoxidase techniques of Tamm–Horsfall glycoprotein in adult hamster kidney
Clinical care of incarcerated people with HIV, viral hepatitis, or tuberculosis
The burden of HIV/AIDS and other transmissible diseases is higher in prison and jail settings than in the non-incarcerated communities that surround them. In this comprehensive review, we discuss available literature on the topic of clinical management of people infected with HIV, hepatitis B and C viruses, and tuberculosis in incarcerated settings in addition to co-occurrence of one or more of these infections. Methods such as screening practices and provision of treatment during detainment periods are reviewed to identify the effect of community-based treatment when returning inmates into the general population. Where data are available, we describe differences in the provision of medical care in the prison and jail settings of low-income and middle-income countries compared with high-income countries. Structural barriers impede the optimal delivery of clinical care for prisoners, and substance use, mental illness, and infectious disease further complicate the delivery of care. For prison health care to reach the standards of community-based health care, political will and financial investment are required from governmental, medical, and humanitarian organisations worldwide. In this review, we highlight challenges, gaps in knowledge, and priorities for future research to improve health-care in institutions for prisoners
G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy
Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in ∼1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to be associated with MSA. © 2007 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56014/1/21343_ftp.pd
An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences
Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments. We generated a mutant mouse strain carrying an F832A mutation in Rb1 that is defective for recruitment to repetitive sequences. Loss of pRB-EZH2 complexes from repeats disperses H3K27me3 from these genomic locations and permits repeat expression. Consistent with maintenance of H3K27me3 at the Hox clusters, these mice are developmentally normal. However, susceptibility to lymphoma suggests that pRB-EZH2 recruitment to repetitive elements may be cancer relevant
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Gene-silencing antisense oligomers inhibit Acinetobacter growth in vitro and in vivo
Background: Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA/RNA analogs that silence expression of specific genes. We studied whether PPMOs targeted to essential genes in Acinetobacter lwoffii and A. baumannii are active in vitro and in vivo. Methods: PPMOs were evaluated in vitro using MIC and viability assays, and in vivo using murine pulmonary infection models with intranasal PPMO treatment. Results: MICs of PPMOs ranged from 0.1 and 64 μM (~0.6 to 38 μg/ml). The most effective PPMO tested was (RXR)₄-AcpP, which is targeted to acpP. (RXR)₄-AcpP reduced viability of A. lwoffii and A. baumannii by > 10³ cfu/ml at 5 to 8 x MIC. Mice treated with 0.25 mg/kg or more of (RXR)₄-AcpP survived longer and had less inflammation and bacterial lung burden than mice treated with a scrambled-sequence PPMO or PBS. Treatment could be delayed after infection and still increase survival. Conclusions: PPMOs targeted to essential genes of A. lwoffii and A. baumannii were bactericidal and had MICs in a clinically relevant range. (RXR)₄-AcpP increased survival of mice infected with A. lwoffii or A. baumannii, even when initial treatment was delayed after infection. PPMOs could be a viable therapeutic approach in dealing with multidrug resistant Acinetobacter species.This article is published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in the Journal of Infectious Diseases following peer review. The definitive publisher-authenticated version, Geller, B. L., Marshall-Batty, K., Schnell, F. J., McKnight, M. M., Iversen, P. L., & Greenberg, D. E. (2013). Gene-Silencing Antisense Oligomers Inhibit Acinetobacter Growth In Vitro and In Vivo. Journal of Infectious Diseases, 208(10), 1553-1560. doi:10.1093/infdis/jit460, is available online at: http://jid.oxfordjournals.org/content/208/10/1553.full.pdf?keytype=ref&ijkey=qepbqtxt5pt.Keywords: antisense, infection, respiratory infection, phosphorodiamidate morpholino oligomer, lwoffii, baumannii, oligomer, MIC, Acinetobacter, PMO, morpholino, mous
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