Nucleon and Nucleon to Delta Axial form factors from Lattice QCD

We present results on the nucleon axial vector form factors $G_A(q^2)$ and $G_p(q^2)$ in the quenched theory and using two degenerate flavors of dynamical Wilson fermions for momentum transfer squared from about 0.1 to about 2 GeV^2 and for pion masses in the range of 380 to 600 MeV. We also present results on the corresponding N to Delta axial vector transition form factors $C_5^A(q^2)$ and $C_6^A(q^2)$ using, in addition to Wilson fermions, domain wall valence quarks and dynamical staggered sea quarks provided by the MILC collaboration.Comment: 7 pages, 4 figures, talk presented at the XXV International Symposium on Lattice Field Theory, July 30 - August 4 2007, Regensburg, German

Axial Nucleon to Delta transition form factors on 2+1 flavor hybrid lattices

We correct the values of the dominant nucleon to Delta axial transition form factors CA_5 and CA_6 published in C. Alexandrou et.al., Phys. Rev. D 76,094511 (2007). The analysis error affects only the values obtained when using the hybrid action in the low Q^2 regime bringing them into agreement with those obtained with Wilson fermions.Comment: 1+2 pages, 2 figures, 1 Table, Erratum to C. Alexandrou et.al., Phys. Rev. D 76, 094511 (2007

The axial N to Delta transition form factors from Lattice QCD

We evaluate the N to Delta axial transition form factors in lattice QCD in the quenched theory, with two degenerate flavors of dynamical Wilson fermions and using domain wall valence fermions with staggered sea quark configurations. We predict the ratio $C_5^A(q^2)/C_3^V(q^2)$ relevant to the parity violating asymmetry and check the validity of the off-diagonal Goldberger-Treiman relation.Comment: Version as accepted for publication, Fig.2 replaced, Normalization factor corrected in Fig.4; 4 pages, 5 figure

mAMSA resistant human topoisomerase IIβ mutation G465D has reduced ATP hydrolysis activity

Type II Human DNA Topoisomerases (topos II) play an essential role in DNA replication and transcription and are important targets for cancer chemotherapeutic drugs. Topoisomerase II causes transient double-strand breaks in DNA, forming a gate through which another double helix is passed, and acts as a DNA dependent ATPase. Mutations in topoII have been linked to atypical multi-drug resistance. Both human Topoisomerase II isoforms, α and β, are targeted by amsacrine. We have used a forced molecular evolution approach to identify mutations conferring resistance to acridines. Here we report mutation βG465D, which was selected with mAMSA and DACA and is cross-resistant to etoposide, ellipticine and doxorubicin. Resistance to mAMSA appears to decrease over time indicating a previously unreported resistance mechanism. G465D lies within the B′ domain in the region that contacts the cleaved gate helix. There is a 3-fold decrease in ATP affinity and ATP hydrolysis and an altered requirement for magnesium in decatenation assays. The decatenation rate is decreased for the mutated G465D protein. And we report for the first time the use of fluorescence anisotropy with intact human topoisomerase II

Delta-baryon electromagnetic form factors in lattice QCD

We develop techniques to calculate the four Delta electromagnetic form factors using lattice QCD, with particular emphasis on the sub-dominant electric quadrupole form factor that probes deformation of the Delta. Results are presented for pion masses down to approximately 350 MeV for three cases: quenched QCD, two flavors of dynamical Wilson quarks, and three flavors of quarks described by a mixed action combining domain wall valence quarks and dynamical staggered sea quarks. The magnetic moment of the Delta is chirally extrapolated to the physical point and the Delta charge density distributions are discussed.Comment: 4 pages, 5 figure

The Impact of the C-Terminal Domain on the Interaction of Human DNA Topoisomerase II α and β with DNA

<b>Background</b> Type II DNA topoisomerases are essential, ubiquitous enzymes that act to relieve topological problems arising in DNA from normal cellular activity. Their mechanism of action involves the ATP-dependent transport of one DNA duplex through a transient break in a second DNA duplex; metal ions are essential for strand passage. Humans have two isoforms, topoisomerase IIα and topoisomerase IIβ, that have distinct roles in the cell. The C-terminal domain has been linked to isoform specific differences in activity and DNA interaction. <b>Methodology/Principal Findings</b> We have investigated the role of the C-terminal domain in the binding of human topoisomerase IIα and topoisomerase IIβ to DNA in fluorescence anisotropy assays using full length and C-terminally truncated enzymes. We find that the C-terminal domain of topoisomerase IIβ but not topoisomerase IIα affects the binding of the enzyme to the DNA. The presence of metal ions has no effect on DNA binding. Additionally, we have examined strand passage of the full length and truncated enzymes in the presence of a number of supporting metal ions and find that there is no difference in relative decatenation between isoforms. We find that calcium and manganese, in addition to magnesium, can support strand passage by the human topoisomerase II enzymes. <b>Conclusions/Significance</b> The C-terminal domain of topoisomerase IIβ, but not that of topoisomerase IIα, alters the enzyme's KD for DNA binding. This is consistent with previous data and may be related to the differential modes of action of the two isoforms in vivo. We also show strand passage with different supporting metal ions for human topoisomerase IIα or topoisomerase IIβ, either full length or C-terminally truncated. They all show the same preferences, whereby Mg > Ca > Mn

Nucleon Structure using lattice QCD

Additional references included. Invited talk at the 3rd Workshop on the QCD Structure of the Nucleon (QCD-N'12), 22-26 October 2012, Bilbao, Spain. 8 pages & 14 figuresA review of recent nucleon structure calculations within lattice QCD is presented. The nucleon excited states, the axial charge, the isovector momentum fraction and helicity distribution are discussed, assessing the methods applied for their study, including approaches to evaluate the disconnected contributions. Results on the spin carried by the quarks in the nucleon are also presented

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The Immunophilin-Like Protein XAP2 Is a Negative Regulator of Estrogen Signaling through Interaction with Estrogen Receptor α

XAP2 (also known as aryl hydrocarbon receptor interacting protein, AIP) is originally identified as a negative regulator of the hepatitis B virus X-associated protein. Recent studies have expanded the range of XAP2 client proteins to include the nuclear receptor family of transcription factors. In this study, we show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells. Interestingly, we show that XAP2 downregulates the E2-dependent transcriptional activation in an estrogen receptor (ER) isoform-specific manner: XAP2 inhibits ERα but not ERβ-mediated transcription. Thus, knockdown of intracellular XAP2 levels leads to increased ERα activity. XAP2 proteins, carrying mutations in their primary structures, loose the ability of interacting with ERα and can no longer regulate ER target gene transcription. Taken together, this study shows that XAP2 exerts a negative effect on ERα transcriptional activity and may thus prevent ERα-dependent events