Structural insights into the autoregulation and cooperativity of the human transcription factor Ets-2

Ets-2, like its closely related homologue Ets-1, is a member of the Ets family of DNA binding transcription factors. Both proteins are subject to multiple levels of regulation of their DNA binding and transactivation properties. One such regulatory mechanism is the presence of an autoinhibitory module, which in Ets-1 allosterically inhibits the DNA binding activity. This inhibition can be relieved by interaction with protein partners or cooperative binding to closely separated Ets binding sites in a palindromic arrangement. In this study we describe the 2.5 Å resolution crystal structure of a DNA complex of the Ets-2 Ets domain. The Ets domain crystallized with two distinct species in the asymmetric unit, which closely resemble the autoinhibited and DNA bound forms of Ets-1. This discovery prompted us to re-evaluate the current model for the autoinhibitory mechanism and the structural basis for cooperative DNA binding. In contrast to Ets-1, in which the autoinhibition is caused by a combination of allosteric and steric mechanisms, we were unable to find clear evidence for the allosteric mechanism in Ets-2. We also demonstrated two possibly distinct types of cooperative binding to substrates with Ets binding motifs separated by four and six base pairs and suggest possible molecular mechanisms for this behavior

Interactions of Oxygen and Hydrogen on Pd(111) surface

The coadsorption and interactions of oxygen and hydrogen on Pd(1 1 1) was studied by scanning tunneling microscopy and density functional theory calculations. In the absence of hydrogen oxygen forms a (2 x 2) ordered structure. Coadsorption of hydrogen leads to a structural transformation from (2 x 2) to a ({radical}3 x {radical}3)R30 degree structure. In addition to this transformation, hydrogen enhances the mobility of oxygen. To explain these observations, the interaction of oxygen and hydrogen on Pd(1 1 1) was studied within the density functional theory. In agreement with the experiment the calculations find a total energy minimum for the oxygen (2 x 2) structure. The interaction between H and O atoms was found to be repulsive and short ranged, leading to a compression of the O islands from (2 x 2) to ({radical}3 x {radical}3)R30 degree ordered structure at high H coverage. The computed energy barriers for the oxygen diffusion were found to be reduced due to the coadsorption of hydrogen, in agreement with the experimentally observed enhancement of oxygen mobility. The calculations also support the finding that at low temperatures the water formation reaction does not occur on Pd(1 1 1)

Long-Term Variations in the Growth and Decay Rates of Sunspot Groups

Using the combined Greenwich (1874-1976) and Solar Optical Observatories Network (1977-2009) data on sunspot groups, we study the long-term variations in the mean daily rates of growth and decay of sunspot groups. We find that the minimum and the maximum values of the annually averaged daily mean growth rates are ~52% per day and ~183% per day, respectively, whereas the corresponding values of the annually averaged daily mean decay rates are ~21% per day and ~44% per day, respectively. The average value (over the period 1874-2009) of the growth rate is about 70% more than that of the decay rate. The growth and the decay rates vary by about 35% and 13%, respectively, on a 60-year time-scale. From the beginning of Cycle 23 the growth rate is substantially decreased and near the end (2007-2008) the growth rate is lowest in the past about 100 years.Comment: 1 table, 13 figures, accepted by Solar Physic

Threshold Electrodisintegration of ^3He

Cross sections were measured for the near-threshold electrodisintegration of ^3He at momentum transfer values of q=2.4, 4.4, and 4.7 fm^{-1}. From these and prior measurements the transverse and longitudinal response functions R_T and R_L were deduced. Comparisons are made against previously published and new non-relativistic A=3 calculations using the best available NN potentials. In general, for q<2 fm^{-1} these calculations accurately predict the threshold electrodisintegration of ^3He. Agreement at increasing q demands consideration of two-body terms, but discrepancies still appear at the highest momentum transfers probed, perhaps due to the neglect of relativistic dynamics, or to the underestimation of high-momentum wave-function components.Comment: 9 pages, 7 figures, 1 table, REVTEX4, submitted to Physical Review

Structures of the Ets Protein DNA-binding Domains of Transcription Factors Etv1, Etv4, Etv5, and Fev: Determinants of DNA Binding and Redox Regulation by Disulfide Bond Formation.

Ets transcription factors, which share the conserved Ets DNA-binding domain, number nearly 30 members in humans and are particularly involved in developmental processes. Their deregulation following changes in expression, transcriptional activity, or by chromosomal translocation plays a critical role in carcinogenesis. Ets DNA binding, selectivity, and regulation have been extensively studied; however, questions still arise regarding binding specificity outside the core GGA recognition sequence and the mode of action of Ets post-translational modifications. Here, we report the crystal structures of Etv1, Etv4, Etv5, and Fev, alone and in complex with DNA. We identify previously unrecognized features of the protein-DNA interface. Interactions with the DNA backbone account for most of the binding affinity. We describe a highly coordinated network of water molecules acting in base selection upstream of the GGAA core and the structural features that may account for discrimination against methylated cytidine residues. Unexpectedly, all proteins crystallized as disulfide-linked dimers, exhibiting a novel interface (distant to the DNA recognition helix). Homodimers of Etv1, Etv4, and Etv5 could be reduced to monomers, leading to a 40-200-fold increase in DNA binding affinity. Hence, we present the first indication of a redox-dependent regulatory mechanism that may control the activity of this subset of oncogenic Ets transcription factors

CDMS, Supersymmetry and Extra Dimensions

The CDMS experiment aims to directly detect massive, cold dark matter particles originating from the Milky Way halo. Charge and lattice excitations are detected after a particle scatters in a Ge or Si crystal kept at ~30 mK, allowing to separate nuclear recoils from the dominating electromagnetic background. The operation of 12 detectors in the Soudan mine for 75 live days in 2004 delivered no evidence for a signal, yielding stringent limits on dark matter candidates from supersymmetry and universal extra dimensions. Thirty Ge and Si detectors are presently installed in the Soudan cryostat, and operating at base temperature. The run scheduled to start in 2006 is expected to yield a one order of magnitude increase in dark matter sensitivity.Comment: To be published in the proceedings of the 7th UCLA symposium on sources and detection of dark matter and dark energy in the universe, Marina del Rey, Feb 22-24, 200

Relation Between Chiral Susceptibility and Solutions of Gap Equation in Nambu--Jona-Lasinio Model

We study the solutions of the gap equation, the thermodynamic potential and the chiral susceptibility in and beyond the chiral limit at finite chemical potential in the Nambu--Jona-Lasinio (NJL) model. We give an explicit relation between the chiral susceptibility and the thermodynamic potential in the NJL model. We find that the chiral susceptibility is a quantity being able to represent the furcation of the solutions of the gap equation and the concavo-convexity of the thermodynamic potential in NJL model. It indicates that the chiral susceptibility can identify the stable state and the possibility of the chiral phase transition in NJL model.Comment: 21 pages, 6 figures, misprints are correcte

Confusing non-standard neutrino interactions with oscillations at a neutrino factory

Most neutrino mass theories contain non-standard interactions (NSI) of neutrinos which can be either non-universal (NU) or flavor-changing (FC). We study the impact of such interactions on the determination of neutrino mixing parameters at a neutrino factory using the so-called ``golden channels'' \pnu{e}\to\pnu{\mu} for the measurement of \theta_{13}. We show that a certain combination of FC interactions in neutrino source and earth matter can give exactly the same signal as oscillations arising due to \theta_{13}. This implies that information about \theta_{13} can only be obtained if bounds on NSI are available. Taking into account the existing bounds on FC interactions, this leads to a drastic loss in sensitivity in \theta_{13}, at least two orders of magnitude. A near detector at a neutrino factory offers the possibility to obtain stringent bounds on some NSI parameters. Such near site detector constitutes an essential ingredient of a neutrino factory and a necessary step towards the determination of \theta_{13} and subsequent study of leptonic CP violation.Comment: 23 pages, 5 figures, improved version, accepted for publication in Phs. Rev. D, references adde

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Bose-Einstein Correlations of Neutral and Charged Pions in Hadronic Z Decays

Bose-Einstein correlations of both neutral and like-sign charged pion pairs are measured in a sample of 2 million hadronic Z decays collected with the L3 detector at LEP. The analysis is performed in the four-momentum difference range 300 MeV < Q < 2 GeV. The radius of the neutral pion source is found to be smaller than that of charged pions. This result is in qualitative agreement with the string fragmentation model