A strong glutathione S-transferase inhibitor overcomes the P-glycoprotein-mediated resistance in tumor cells - 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) triggers a caspase-dependent apoptosis in MDR1-expressing leukemia cells

The new glutathione S-transferase inhibitor 6-(7-nitro-2,1,3-benzoxadiazol- 4-ylthio)hexanol (NBDHEX) is cytotoxic toward P-glycoprotein-overexpressing tumor cell lines, i.e. CEM-VBL10, CEM-VBL100, and U-2 OS/DX580. The mechanism of cell death triggered by NBDHEX has been deeply investigated in leukemia cell lines. Kinetic data indicate a similar NBDHEX membrane permeability between multidrug resistance cells and their sensitive counterpart revealing that NBDHEX is not a substrate of the P-glycoprotein export pump. Unexpectedly, this molecule promotes a caspase-dependent apoptosis that is unusual in the P-glycoprotein-overexpressing cells. The primary event of the apoptotic pathway is the dissociation of glutathione S-transferase P1-1 from the complex with c-Jun N-terminal kinase. Interestingly, leukemia MDR1-expressing cells show lower LC50 values and a higher degree of apoptosis and caspase-3 activity than their drug-sensitive counterparts. The increased susceptibility of the multidrug resistance cells toward the NBDHEX action may be related to a lower content of glutathione S-transferase P1-1. Given the low toxicity of NBDHEX in vivo, this compound may represent an attractive basis for the selective treatment of MDR1 P-glycoproteinpositive tumors

X-Ray Polarimetry of the Dipping Accreting Neutron Star 4U1624–49

We present the first X-ray polarimetric study of the dipping accreting neutron star 4U 1624−49 with the Imaging X-ray Polarimetry Explorer. We report a detection of polarization in the nondip time intervals with a confidence level of 99.99%. We find an average polarization degree (PD) of 3.1% ± 0.7% and a polarization angle of 81° ± 6° east of north in the 2–8 keV band. We report an upper limit on the PD of 22% during the X-ray dips with 95% confidence. The PD increases with energy, reaching from 3.0% ± 0.9% in the 4–6 keV band to 6% ± 2% in the 6–8 keV band. This indicates the polarization likely arises from Comptonization. The high PD observed is unlikely to be produced by Comptonization in the boundary layer or spreading layer alone. It can be produced by the addition of an extended geometrically thin slab corona covering part of the accretion disk, as assumed in previous models of dippers, and/or a reflection component from the accretion disk

The Proceedings of the Fourth International Conference of the Association of Architecture Schools of Australasia

The Proceedings of the Fourth International Conference of the Association of Architecture Schools of Australasia. Each paper in the Proceedings has been double refereed by members of an independent panel of academic peers appointed by the Conference Committee. Papers were matched, where possible, to referees in the same field and with similar interests to the authors

A Two-week IXPE Monitoring Campaign on Mrk 421

X-ray polarization is a unique new probe of the particle acceleration in astrophysical jets made possible through the Imaging X-ray Polarimetry Explorer. Here we report on the first dense X-ray polarization monitoring campaign on the blazar Mrk 421. Our observations were accompanied by an even denser radio and optical polarization campaign. We find significant short-timescale variability in both X-ray polarization degree and angle, including an ∼90° angle rotation about the jet axis. We attribute this to random variations of the magnetic field, consistent with the presence of turbulence but also unlikely to be explained by turbulence alone. At the same time, the degree of lower-energy polarization is significantly lower and shows no more than mild variability. Our campaign provides further evidence for a scenario in which energy-stratified shock-acceleration of relativistic electrons, combined with a turbulent magnetic field, is responsible for optical to X-ray synchrotron emission in blazar jets

Transmission ratio distortion in the human body louse, Pediculus humanus (Insecta : Phthiraptera)

We studied inheritance at three microsatellite loci in eight F-1 and two F-2 families of the body (clothes) louse of humans, Pediculus humanus. The alleles of heterozygous female-parents were always inherited in a Mendelian fashion in these families. Alleles from heterozygous male-parents, however, were inherited in two different ways: (i) in a Mendelian fashion and (ii) in a non-Mendelian fashion, where males passed to their offspring only one of their two alleles, that is, 100% nonrandom transmission. In male body lice, where there was non-Mendelian inheritance, the paternally inherited set of alleles was eliminated. We interpret this pattern of inheritance as evidence for extreme transmission ratio distortion of paternal alleles in this species