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Tetrabromobisphenol A (TBBPA), a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA) for these tumors involves an increase in the bioavailability of estradiol as a result of TBBPA inhibiting estrogen sulfotransferases (ES), the enzymes responsible for inactivating and enhancing the elimination of estradiol. The objective of this study was to evaluate the effect of dose and repeated administration of TBBPA on the level of TBBPA, TBBPA-glucuronide (GA) and TBBPA-sulfate (S) conjugates in plasma, liver and uterus of female Wistar Han rats administered TBBPA (50, 100, 250, 500 or 1000 mg/kg) for 28 consecutive days. In accordance with this objective, TBBPA sulfation was used as a surrogate for evaluating the potential for estradiol sulfation to be limited at high dose levels of TBBPA. Blood samples were collected at 4 and 8 h post-dosing on study day 7, 14, and 28, while liver and uterus were collected at the same time points following 28 days of dosing. Tissue samples were analyzed for TBBPA, TBBPA-GA and TBBPA-S by LC–MS/MS. A dose-related increase in the concentration of all three analytes occurred in plasma (day 7, 14, and 28) as well as liver and uterus tissue (day 28) at both 4 and 8 h post dose. The plasma concentration of TBBPA-GA and TBBPA-S was higher in animals dosed for 28 days compared to those dosed for 7 or 14 days showing an increase in systemic circulation of these conjugates with repeated administration. The balance of these conjugates was also different in tissues with TBBPA-S > TBBPA-GA at high doses in the liver and TBBPA-GA > TBBPA-S in both plasma and uterus. In all three tissues the ratio of TBBPA-S/TBBPA-GA showed a decreasing trend with dose, suggesting that at high TBBPA dose levels sulfation of TBBPA becomes limited. This effect was most apparent in the liver and plasma at 28 days of administration. Together these data show that administration of high doses of TBBPA associated with the induction of uterine tumors, results in a disruption in the balance of conjugates reflected by a decrease in the TBBPA-S/TBBPA-GA ratio. A limitation in the sulfation of TBBPA in vivo supports in vitro data defining TBBPA as an inhibitor of ES activity, thus providing further support that the proposed MoA occurs under conditions of high dose, chronic TBBPA administration to Wistar Han rats. Given that the uterine tumors observed in rats (250–1000 mg/kg-day) only occur at very high doses that perturb homeostatic control, it is unlikely such effects would occur in humans given that current TBBPA exposure levels are approximately eight orders of magnitude lower than these doses that are associated with exceeding the capacity of conjugation pathways in animal studies. Keywords: TBBPA, Estrogen sulfotransferases, Glucuronidation, Uterus, Liver

We present a source catalog from the first deep hard X-ray (E > 10 keV) survey of the Small Magellanic Cloud (SMC), the Nuclear Spectroscopic Telescope Array (NuSTAR) Legacy Survey of the SMC. We observed three fields, for a total exposure time of 1 Ms, along the bar of this nearby star-forming galaxy. Fields were chosen for their young stellar and accreting binary populations. We detected 10 sources above a 3σ significance level (4–25 keV) and obtained upper limits on an additional 40 sources. We reached a 3σ limiting luminosity in the 4–25 keV band of ∼1035 erg s−1, allowing us to probe fainter X-ray binary (XRB) populations than has been possible with other extragalactic NuSTAR surveys. We used hard X-ray colors and luminosities to constrain the compact-object type, exploiting the spectral differences between accreting black holes and neutron stars at E > 10 keV. Several of our sources demonstrate variability consistent with previously observed behavior. We confirmed pulsations for seven pulsars in our 3σ sample. We present the first detection of pulsations from a Be-XRB, SXP 305 (CXO J005215.4–73191), with an X-ray pulse period of 305.69 ± 0.16 s and a likely orbital period of ∼1160–1180 days. Bright sources (≳5 × 1036 erg s−1) in our sample have compact-object classifications consistent with their previously reported types in the literature. Lower-luminosity sources (≲5 × 1036 erg s−1) have X-ray colors and luminosities consistent with multiple classifications. We raise questions about possible spectral differences at low luminosity between SMC pulsars and the Galactic pulsars used to create the diagnostic diagrams. [ABSTRACT FROM AUTHOR]

We present 15 high-mass X-ray binary (HMXB) candidates in the disk of M31 for which we are able to infer compact object type, spectral type of the donor star, and age using multiwavelength observations from NuSTAR, Chandra, and the Hubble Space Telescope. The hard X-ray colors and luminosities from NuSTAR permit the tentative classification of accreting X-ray binary systems by compact object type, distinguishing black hole from neutron star systems. We find hard-state black holes, pulsars, and non-magnetized neutron stars associated with optical point-source counterparts with similar frequency. We also find nine non-magnetized neutron stars coincident with globular clusters and an equal number of pulsars with and without point-source optical counterparts. We perform spectral energy distribution (SED) fitting for the most likely optical counterparts to the HMXB candidates, finding seven likely high-mass stars and one possible red helium-burning star. The remaining seven HMXB optical counterparts have poor SED fits, so their companion stars remain unclassified. Using published star formation histories, we find that the majority of HMXB candidates—X-ray sources with UV-bright point-source optical counterpart candidates—are found in regions with star formation bursts less than 50 Myr ago, and three are associated with young stellar ages (<10 Myr). This is consistent with similar studies of HMXB populations in the Magellanic Clouds, M33, NGC 300, and NGC 2403. [ABSTRACT FROM AUTHOR]

We report the identification of a bright hard X-ray source dominating the M31 bulge above 25 keV from a simultaneous NuSTAR–Swift observation. We find that this source is the counterpart to Swift J0042.6+4112, which was previously detected in the Swift BAT All-sky Hard X-ray Survey. This Swift BAT source had been suggested to be the combined emission from a number of point sources; our new observations have identified a single X-ray source from 0.5 to 50 keV as the counterpart for the first time. In the 0.5–10 keV band, the source had been classified as an X-ray Binary candidate in various Chandra and XMM-Newton studies; however, since it was not clearly associated with Swift J0042.6+4112, the previous E < 10 keV observations did not generate much attention. This source has a spectrum with a soft X-ray excess (kT ∼ 0.2 keV) plus a hard spectrum with a power law of and a cutoff around 15–20 keV, typical of the spectral characteristics of accreting pulsars. Unfortunately, any potential pulsation was undetected in the NuSTAR data, possibly due to insufficient photon statistics. The existing deep HST images exclude high-mass (>3 ) donors at the location of this source. The best interpretation for the nature of this source is an X-ray pulsar with an intermediate-mass (<3 ) companion or a symbiotic X-ray binary. We discuss other possibilities in more detail. [ABSTRACT FROM AUTHOR]

Some dark matter candidates, e.g., sterile neutrinos, provide observable signatures in the form of mono-energetic line emission. We present the first search for dark matter line emission in the range in a pointed observation of the Bullet Cluster with NuSTAR. We do not detect any significant line emission and instead we derive upper limits (95% CL) on the flux, and interpret these constraints in the context of sterile neutrinos and more generic dark matter candidates. NuSTAR does not have the sensitivity to constrain the recently claimed line detection at , but improves on the constraints for energies of . [ABSTRACT FROM AUTHOR]

We present 15 high-mass X-ray binary (HMXB) candidates in the disk of M31 for which we are able to infer compact object type, spectral type of the donor star, and age using multiwavelength observations from NuSTAR , Chandra , and the Hubble Space Telescope . The hard X-ray colors and luminosities from NuSTAR permit the tentative classification of accreting X-ray binary systems by compact object type, distinguishing black hole from neutron star systems. We find hard-state black holes, pulsars, and non-magnetized neutron stars associated with optical point-source counterparts with similar frequency. We also find nine non-magnetized neutron stars coincident with globular clusters and an equal number of pulsars with and without point-source optical counterparts. We perform spectral energy distribution (SED) fitting for the most likely optical counterparts to the HMXB candidates, finding seven likely high-mass stars and one possible red helium-burning star. The remaining seven HMXB optical counterparts have poor SED fits, so their companion stars remain unclassified. Using published star formation histories, we find that the majority of HMXB candidates-X-ray sources with UV-bright point-source optical counterpart candidates-are found in regions with star formation bursts less than 50 Myr ago, and three are associated with young stellar ages (<10Myr). This is consistent with similar studies of HMXB populations in the Magellanic Clouds, M33, NGC 300, and NGC 2403.

Introduction: Fabry's disease is associated with an increased incidence of thrombotic events and rejection. Spontaneous thrombosis of a functioning cadaveric renal allograft in a recipient with Fabry's disease prompted prospective evaluation of all transplant candidates with Fabry's disease for hypercoagulability., Materials and Methods: Transplant candidates with Fabry's disease were tested for hypercoagulability, analyzed for HLA-type and ABO group, and comorbid conditions suggestive of hypercoagulability., Results: A unique association of Fabry's disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabry's disease. Four of five patients were blood group A and had no significant comorbid conditions suggestive of hypercoagulability. The resistance to activation of protein C (APCR)(+) patients shared HLA loci-B8 and Dr3, although the APCR(-) patients shared HLA loci-B27 and -B38., Conclusions: Due to the observed increase in the incidence of APCR in our Fabry's cohort, we suggest screening all patients with Fabry's disease for APCR. Because factor V and factor Va receptors are found on vascular endothelium and peripheral blood monocytes, APCR in the presence of Fabry's disease may be a nonimmunological stimulus for rejection. Analysis of HLA typing in patients with Fabry's disease may further elucidate HLA-based association of Fabry's disease and resistance to activated protein C with the risk of thrombosis and rejection.