Hexabromocyclododecane decreases the lytic function and ATP levels of human natural killer cells

This study investigates the effect of hexabromocyclododecane (HBCD) on the lytic function of human natural killer (NK) cells and on ATP levels in NK cells. NK cells are capable of lysing tumor cells, virally infected cells, and antibody-coated cells. HBCD is a brominated cyclic alkane used primarily as an additive flame retardant. If HBCD interferes with NK cell function, this could increase risk of tumor development and/or viral infection. NK cells were exposed to various concentrations of HBCD for 24 and 48 h and 6 days before determining lytic function and ATP levels. ATP levels and lytic function were also determined in NK cells that were exposed to HBCD for 1 h followed by 24 and 48 h, and 6 days in HBCD-free media. The results indicated that exposure of NK cells to 10 µm HBCD for 24 h causes a very significant decrease in both NK cell lytic function and ATP levels (93.5 and 90.5%, respectively). Exposure of NK cells to 10 µm HBCD for 1 h followed by 24 h in HBCD-free media showed a progressive and persistent loss of lytic function (89.3%) as well as a decrease in ATP levels (46.1%). The results indicate that HBCD exposures decreased lytic function as well as ATP levels. However, a decrease in lytic function was not necessarily accompanied by a similar decrease in ATP. Importantly, these results also indicate that a brief (1 h) exposure to HBCD causes a progressive loss of lytic function over a 6 day period

Hexabromocyclododecane decreases tumor-cell-binding capacity and cell-surface protein expression of human natural killer cells

Hexabromocyclododecane (HBCD) is a flame retardant that decreases the lytic function of human natural killer (NK) cells. NK cells defend against tumor cells and virally infected cells. Thus, HBCD has the potential to increase cancer incidence and viral infections. NK cells must bind to their targets for lysis to occur. Thus, concentrations of HBCD that decrease lytic function were examined for their ability to alter NK binding to tumor targets. Levels of HBCD that caused a loss of binding function were examined for effects on expression of cell surface proteins needed for binding. NK cells exposed to HBCD for 24 h, 48 h or 6 days or to HBCD for 1 h followed by 24 h, 48 h or 6 days in HBCD-free media were examined for binding function and cell surface protein expression. The results indicated that exposure of NK cells to 10 μM HBCD for 24 h (which caused a greater than 90% loss of lytic function) caused a very significant decrease in NK cell binding function (70.9%), and in CD16 and CD56 cell-surface protein expression (57.8 and 24.6% respectively). NK cells exposed to 10 μM HBCD for 1 h followed by 24 h in HBCD-free media (which caused a 89.3% loss of lytic function) showed decreased binding function (79.2%), and CD 16 expression (48.1%). Results indicate that HBCD exposures decreased binding function as well as cell-surface marker expression in NK cells and that these changes may explain the losses of lytic function induced by certain HBCD exposures

How the First Stars Regulated Star Formation. II. Enrichment by Nearby Supernovae

Metals from Population III (Pop III) supernovae led to the formation of less massive Pop II stars in the early universe, altering the course of evolution of primeval galaxies and cosmological reionization. There are a variety of scenarios in which heavy elements from the first supernovae were taken up into second-generation stars, but cosmological simulations only model them on the largest scales. We present small-scale, high-resolution simulations of the chemical enrichment of a primordial halo by a nearby supernova after partial evaporation by the progenitor star. We find that ejecta from the explosion crash into and mix violently with ablative flows driven off the halo by the star, creating dense, enriched clumps capable of collapsing into Pop II stars. Metals may mix less efficiently with the partially exposed core of the halo, so it might form either Pop III or Pop II stars. Both Pop II and III stars may thus form after the collision if the ejecta do not strip all the gas from the halo. The partial evaporation of the halo prior to the explosion is crucial to its later enrichment by the supernova.Comment: Accepted to Ap

Toward the assessment of the susceptibility of a digital system to lightning upset

Accomplishments and directions for further research aimed at developing methods for assessing a candidate design of an avionic computer with respect to susceptability to lightning upset are reported. Emphasis is on fault tolerant computers. Both lightning stress and shielding are covered in a review of the electromagnetic environment. Stress characterization, system characterization, upset detection, and positive and negative design features are considered. A first cut theory of comparing candidate designs is presented including tests of comparative susceptability as well as its analysis and simulation. An approach to lightning induced transient fault effects is included

Level of understanding of co-trimoxazole use among HIV infected, recurrent pulmonary tuberculosis suspects at a national referral tuberculosis clinic in Kampala, Uganda: a qualitative analysis.

Background: Co-trimoxazole use is the standard of care for preventing Pneumocystis jirovecii pneumonia in sub-Saharan Africa but implementation remains slow. Co-trimoxazole is self- administered with uncertain adherence. Knowledge of co-trimoxazole use among HIV infected persons is unknown.Objectives: To assess knowledge, attitudes and practices of co-trimoxazole use among HIV infected adults evaluated for recurrent PTB in Kampala, Uganda.Methods: A qualitative study utilizing 5 focus group discussions among 30 HIV infected PTB suspects at the national referral tuberculosis treatment centre in Kampala.Results: Males and females had similar median ages. 80% were currently on co-trimoxazole and 50% of participants were on HAART. Majority of participants defined co-trimoxazole as an analgesic. Few noted co-trimoxazole was a drug to treat cough and chest pain. However, few responses revealed that co-trimoxazole prevents opportunistic diseases among PLHIV. Most of participants believed HAART and anti-TB drugs work as co-trimoxazole thus it should not be taken together with them. This belief may lead to increased risk of opportunistic infections, morbidity and mortality.Conclusions: We revealed gaps in understanding of co-trimoxazole use among study participants. We therefore recommend that more facts about co-trimoxazle as prophylaxis against P. jirovecii, bacterial and diarrheal pathogens should be incorporated in VCT fact sheets.Key words: Recurrent tuberculosis; HIV; Co-trimoxazole use; Chemoprophylaxis; Adherenc

The Molecular Hydrogen Deficit in Gamma-Ray Burst Afterglows

Recent analysis of five gamma-ray burst (GRB) afterglow spectra reveal the absence of molecular hydrogen absorption lines, a surprising result in light of their large neutral hydrogen column densities and the detection of H$_2$ in similar, more local star-forming regions like 30 Doradus in the Large Magellanic Cloud (LMC). Observational evidence further indicates that the bulk of the neutral hydrogen column in these sight lines lies 100 pc beyond the progenitor and that H$_2$ was absent prior to the burst, suggesting that direct flux from the star, FUV background fields, or both suppressed its formation. We present one-dimensional radiation hydrodynamical models of GRB host galaxy environments, including self-consistent radiative transfer of both ionizing and Lyman-Werner photons, nine-species primordial chemistry with dust formation of H$_2$, and dust extinction of UV photons. We find that a single GRB progenitor is sufficient to ionize neutral hydrogen to distances of 50 - 100 pc but that a galactic Lyman-Werner background is required to dissociate the molecular hydrogen in the ambient ISM. Intensities of 0.1 - 100 times the Galactic mean are necessary to destroy H$_2$ in the cloud, depending on its density and metallicity. The minimum radii at which neutral hydrogen will be found in afterglow spectra is insensitive to the mass of the progenitor or the initial mass function (IMF) of its cluster, if present.Comment: 12 pages, 7 figures, accepted for Ap

Variable Hard X-ray Emission from the Candidate Accreting Black Hole in Dwarf Galaxy Henize 2-10

We present an analysis of the X-ray spectrum and long-term variability of the nearby dwarf starburst galaxy Henize 2-10. Recent observations suggest that this galaxy hosts an actively accreting black hole with mass ~10^6 M_sun. The presence of an AGN in a low-mass starburst galaxy marks a new environment for active galactic nuclei (AGNs), with implications for the processes by which "seed" black holes may form in the early Universe. In this paper, we analyze four epochs of X-ray observations of Henize 2-10, to characterize the long-term behavior of its hard nuclear emission. We analyze observations with Chandra from 2001 and XMM-Newton from 2004 and 2011, as well as an earlier, less sensitive observation with ASCA from 1997. Based on detailed analysis of the source and background, we find that the hard (2-10 keV) flux of the putative AGN has decreased by approximately an order of magnitude between the 2001 Chandra observation and exposures with XMM-Newton in 2004 and 2011. The observed variability confirms that the emission is due to a single source. It is unlikely that the variable flux is due to a supernova or ultraluminous X-ray source, based on the observed long-term behavior of the X-ray and radio emission, while the observed X-ray variability is consistent with the behavior of well-studied AGNs.Comment: 7 pages, 4 figures, 2 tables; accepted for publication in Ap

Comparative analysis of the complete sequence of the plastid genome of Parthenium argentatum and identification of DNA barcodes to differentiate Parthenium species and lines

<p>Abstract</p> <p>Background</p> <p><it>Parthenium argentatum </it>(guayule) is an industrial crop that produces latex, which was recently commercialized as a source of latex rubber safe for people with Type I latex allergy. The complete plastid genome of <it>P. argentatum </it>was sequenced. The sequence provides important information useful for genetic engineering strategies. Comparison to the sequences of plastid genomes from three other members of the Asteraceae, <it>Lactuca sativa, Guitozia abyssinica </it>and <it>Helianthus annuus </it>revealed details of the evolution of the four genomes. Chloroplast-specific DNA barcodes were developed for identification of <it>Parthenium </it>species and lines.</p> <p>Results</p> <p>The complete plastid genome of <it>P. argentatum </it>is 152,803 bp. Based on the overall comparison of individual protein coding genes with those in <it>L. sativa, G. abyssinica </it>and <it>H. annuus</it>, we demonstrate that the <it>P. argentatum </it>chloroplast genome sequence is most closely related to that of <it>H. annuus</it>. Similar to chloroplast genomes in <it>G. abyssinica, L. sativa </it>and <it>H. annuus</it>, the plastid genome of <it>P. argentatum </it>has a large 23 kb inversion with a smaller 3.4 kb inversion, within the large inversion. Using the <it>mat</it>K and <it>psb</it>A-<it>trn</it>H spacer chloroplast DNA barcodes, three of the four <it>Parthenium </it>species tested, <it>P. tomentosum</it>, <it>P. hysterophorus </it>and P. <it>schottii</it>, can be differentiated from <it>P. argentatum</it>. In addition, we identified lines within <it>P. argentatum</it>.</p> <p>Conclusion</p> <p>The genome sequence of the <it>P. argentatum </it>chloroplast will enrich the sequence resources of plastid genomes in commercial crops. The availability of the complete plastid genome sequence may facilitate transformation efficiency by using the precise sequence of endogenous flanking sequences and regulatory elements in chloroplast transformation vectors. The DNA barcoding study forms the foundation for genetic identification of commercially significant lines of <it>P</it>. <it>argentatum </it>that are important for producing latex.</p