Extracellular Sodium Interacts with the HERG Channel at an Outer Pore Site

Most voltage-gated K+ currents are relatively insensitive to extracellular Na+ (Na+o), but Na+o potently inhibits outward human ether-a-go-go–related gene (HERG)–encoded K+ channel current (Numaguchi, H., J.P. Johnson, Jr., C.I. Petersen, and J.R. Balser. 2000. Nat. Neurosci. 3:429–30). We studied wild-type (WT) and mutant HERG currents and used two strategic probes, intracellular Na+ (Na+i) and extracellular Ba2+ (Ba2+o), to define a site where Na+o interacts with HERG. Currents were recorded from transfected Chinese hamster ovary (CHO-K1) cells using the whole-cell voltage clamp technique. Inhibition of WT HERG by Na+o was not strongly dependent on the voltage during activating pulses. Three point mutants in the P-loop region (S624A, S624T, S631A) with intact K+ selectivity and impaired inactivation each had reduced sensitivity to inhibition by Na+o. Quantitatively similar effects of Na+i to inhibit HERG current were seen in the WT and S624A channels. As S624A has impaired Na+o sensitivity, this result suggested that Na+o and Na+i act at different sites. Extracellular Ba2+ (Ba2+o) blocks K+ channel pores, and thereby serves as a useful probe of K+ channel structure. HERG channel inactivation promotes relief of Ba2+ block (Weerapura, M., S. Nattel, M. Courtemanche, D. Doern, N. Ethier, and T. Hebert. 2000. J. Physiol. 526:265–278). We used this feature of HERG inactivation to distinguish between simple allosteric and pore-occluding models of Na+o action. A remote allosteric model predicts that Na+o will speed relief of Ba2+o block by promoting inactivation. Instead, Na+o slowed Ba2+ egress and Ba2+ relieved Na+o inhibition, consistent with Na+o binding to an outer pore site. The apparent affinities of the outer pore for Na+o and K+o as measured by slowing of Ba2+ egress were compatible with competition between the two ions for the channel pore in their physiological concentration ranges. We also examined the role of the HERG closed state in Na+o inhibition. Na+o inhibition was inversely related to pulsing frequency in the WT channel, but not in the pore mutant S624A

Neutrino-Mixing-Generated Lepton Asymmetry and the Primordial 4^4He Abundance

It has been proposed that an asymmetry in the electron neutrino sector may be generated by resonant active-sterile neutrino transformations during Big Bang Nucleosynthesis (BBN). We calculate the change in the primordial $^4$He yield $Y$ resulting from this asymmetry, taking into account both the time evolution of the $\nu_e$ and $\bar\nu_e$ distribution function and the spectral distortions in these. We calculate this change in two schemes: (1) a lepton asymmetry directly generated by $\nu_e$ mixing with a lighter right-handed sterile neutrino $\nu_s$; and (2) a lepton asymmetry generated by a $\nu_\tau\leftrightarrow\nu_s$ or $\nu_\mu\leftrightarrow\nu_s$ transformation which is subsequently partially converted to an asymmetry in the $\nu_e\bar\nu_e$ sector by a matter-enhanced active-active neutrino transformation. In the first scheme, we find that the percentage change in $Y$ is between -1% and 9% (with the sign depending on the sign of the asymmetry), bounded by the Majorana mass limit m_{\nu_e}\la 1 eV. In the second scheme, the maximal percentage reduction in $Y$ is 2%, if the lepton number asymmetry in neutrinos is positive; Otherwise, the percentage increase in $Y$ is \la 5% for m^2_{\nu_\mu,\nu_\tau}-m^2_{\nu_s}\la 10^4 eV. We conclude that the change in the primordial $^4$He yield induced by a neutrino-mixing-generated lepton number asymmetry can be substantial in the upward direction, but limited in the downward direction.Comment: 15 pages, 7 figures, submitted to PR

Identification of α°-thalassaemia (–SEA) using an enzyme-linked immunosorbent assay (ELISA) for embryonic zeta-globin chain detection – a preliminary study

Objectives: This study aimed to evaluate the UBI MAGIWELTM ζ-GLOBIN ELISA Kit for the presumptive diagnosis of αo-thalassaemia. The ELISA results obtained were confirmed by molecular characterisation of αo-thalassaemia using a Duplex-PCR. Methods: Routine peripheral blood counts and red cell indices were determined in 94 blood samples sent for Hb analysis. Hb subtypes were quantified by high performance liquid chromatography (HPLC) and Hb electrophoresis conducted on agarose gel at pH 8.5. Zeta-globin chain levels were determined using the UBI MAGIWELTM ζ-GLOBIN ELISA Kit. Molecular analysis was performed using a duplex-PCR which simultaneously amplifies a normal 136 bp sequence between the ψα−α2-globin genes and a 730 bp Southeast Asian deletion-specific sequence (–SEA) between the ψα2−θ1-globin genes. Results: Using the ELISA assay kit, 20 blood samples were presumptively identified as α-thalassaemia carriers from elevated ζ-globin chains (OD>0.3) while the remaining 74 blood samples showed OD<0.3. Molecular characterisation confirmed amplification of the 136 bp normal fragment in all the blood samples. Seventeen of the 20 DNA samples from the α-thalassaemia carriers amplified the SEA-deletion specific fragment. The remaining three DNA samples did not amplify the SEA-deletion specific fragment but amplified the normal α-globin gene sequence, indicating the presence of amplifiable DNA in these samples. Further molecular characterisation of the α-3.7 and -α4.2 deletions and Hb Constant Spring (CS) mutation showed the absence of these defects in these 3 DNA samples. Conclusion: This preliminary investigation showed the sensitivity and specificity of the UBI MAGIWEL ζ-globin ELISA kit as 100 % and 96.1 % respectively in the detection of α-thalassaemia-1 carriers (–SEA)

Dynamical Mass Generation in a Finite-Temperature Abelian Gauge Theory

We write down the gap equation for the fermion self-energy in a finite-temperature abelian gauge theory in three dimensions. The instantaneous approximation is relaxed, momentum-dependent fermion and photon self-energies are considered, and the corresponding Schwinger-Dyson equation is solved numerically. The relation between the zero-momentum and zero-temperature fermion self-energy and the critical temperature T_c, above which there is no dynamical mass generation, is then studied. We also investigate the effect which the number of fermion flavours N_f has on the results, and we give the phase diagram of the theory with respect to T and N_f.Comment: 20 LaTeX pages, 4 postscript figures in a single file, version to appear in Physical Review

State Orthogonalization by Building a Hilbert Space: A New Approach to Electronic Quantum Transport in Molecular Wires

Quantum descriptions of many complex systems are formulated most naturally in bases of states that are not mutually orthogonal. We introduce a general and powerful yet simple approach that facilitates solving such models exactly by embedding the non-orthogonal states in a new Hilbert space in which they are by definition mutually orthogonal. This novel approach is applied to electronic transport in molecular quantum wires and is used to predict conductance antiresonances of a new type that arise solely out of the non-orthogonality of the local orbitals on different sites of the wire.Comment: 4 pages 1 figur

Multiple tumor suppressors regulate a HIF-dependent negative feedback loop via ISGF3 in human clear cell renal cancer.

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft model as its loss significantly enhances tumor growth. Conversely, reactivation of ISGF3 retards tumor growth by PBRM1-deficient ccRCC cells. Thus after VHL inactivation, HIF induces ISGF3, which is reversed by the loss of secondary tumor suppressors, suggesting that this is a key negative feedback loop in ccRCC. © 2018, Liao et al

A Survey of Local Group Galaxies Currently Forming Stars. I. UBVRI Photometry of Stars in M31 and M33

We present UBVRI photometry obtained from Mosaic images of M31 and M33 using the KPNO 4-m telescope. The survey covers 2.2 sq degrees of M31, and 0.8 sq degrees of M33, chosen so as to include all of the regions currently active in forming massive stars. The catalog contains 371,781 and 146,622 stars in M31 and M33, respectively, where every star has a counterpart (at least) in B, V, and R. We compare our photometry to previous studies. We provide cross references to the stars confirmed as members by spectroscopy, and compare the location of these to the complete set in color-magnitude diagrams. While follow-up spectroscopy is needed for many projects, we demonstrate the success of our photometry in being able to distinguish M31/M33 members from foreground Galactic stars. We also present the results of newly obtained spectroscopy, which identifies 34 newly confirmed members, including B-A supergiants, the earliest O star known in M31, and two new Luminous Blue Variable candidates whose spectra are similar to that of P Cygni.Comment: Accepted by the Astronomical Journal. A version with higher resolution figures can be found at: http://www.lowell.edu/users/massey/M3133.pdf.g

Suitability versus fidelity for rating single-photon guns

The creation of specified quantum states is important for most, if not all, applications in quantum computation and communication. The quality of the state preparation is therefore an essential ingredient in any assessment of a quantum-state gun. We show that the fidelity, under the standard definitions is not sufficient to assess quantum sources, and we propose a new measure of suitability that necessarily depends on the application for the source. We consider the performance of single-photon guns in the context of quantum key distribution (QKD) and linear optical quantum computation. Single-photon sources for QKD need radically different properties than sources for quantum computing. Furthermore, the suitability for single-photon guns is discussed explicitly in terms of experimentally accessible criteria.Comment: 4 pages, 2 figures Revised per referee suggestion

Planetary Nebulae as standard candles XI. Application to Spiral Galaxies

We report the results of an [O III] lambda 5007 survey for planetary nebulae (PN) in three spiral galaxies: M101 (NGC 5457), M51 (NGC 5194/5195) and M96 (NGC 3368). By comparing on-band/off-band [O III] lambda 5007 images with images taken in H-alpha and broadband R, we identify 65, 64 and 74 PN candidates in each galaxy, respectively. From these data, an adopted M31 distance of 770 kpc, and the empirical planetary nebula luminosity function (PNLF), we derive distances to M101, M51, and M96 of 7.7 +/- 0.5, 8.4 +/- 0.6, and 9.6 +/- 0.6 Mpc. These observations demonstrate that the PNLF technique can be successfully applied to late-type galaxies, and provide an important overlap between the Population I and Population II distance scales. We also discuss some special problems associated with using the PNLF in spiral galaxies, including the effects of dust and the possible presence of [O III] bright supernova remnants.Comment: 38 pages, TeX, with tables included but not figures. Uses epsf.tex and kpnobasic.tex. To be published in the Astophysical Journal. Full paper is available at http://www.astro.psu.edu/users/johnf/Text/research.htm