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

Population genomics of a predatory mammal reveals patterns of decline and impacts of exposure to toxic toads

Mammal declines across northern Australia are one of the major biodiversity loss events occurring globally. There has been no regional assessment of the implications of these species declines for genomic diversity. To address this, we conducted a species-wide assessment of genomic diversity in the northern quoll (Dasyurus hallucatus), an Endangered marsupial carnivore. We used next generation sequencing methods to genotype 10,191 single nucleotide polymorphisms (SNPs) in 352 individuals from across a 3220-km length of the continent, investigating patterns of population genomic structure and diversity, and identifying loci showing signals of putative selection. We found strong heterogeneity in the distribution of genomic diversity across the continent, characterized by (i) biogeographical barriers driving hierarchical population structure through long-term isolation, and (ii) severe reductions in diversity resulting from population declines, exacerbated by the spread of introduced toxic cane toads (Rhinella marina). These results warn of a large ongoing loss of genomic diversity and associated adaptive capacity as mammals decline across northern Australia. Encouragingly, populations of the northern quoll established on toad-free islands by translocations appear to have maintained most of the initial genomic diversity after 16 years. By mapping patterns of genomic diversity within and among populations, and investigating these patterns in the context of population declines, we can provide conservation managers with data critical to informed decision-making. This includes the identification of populations that are candidates for genetic management, the importance of remnant island and insurance/translocated populations for the conservation of genetic diversity, and the characterization of putative evolutionarily significant units

Diffusion of School-Based Prevention Programs in Two Urban Districts: Adaptations, Rationales, and Suggestions for Change

The diffusion of school-based preventive interventions involves the balancing of high-fidelity implementation of empirically-supported programs with flexibility to permit local stakeholders to target the specific needs of their youth. There has been little systematic research that directly seeks to integrate research- and community-driven approaches to diffusion. The present study provides a primarily qualitative investigation of the initial roll-out of two empirically-supported substance and violence prevention programs in two urban school districts that serve a high proportion of low-income, ethnic minority youth. The predominant ethnic group in most of our study schools was Asian American, followed by smaller numbers of Latinos, African Americans, and European Americans. We examined the adaptations made by experienced health teachers as they implemented the programs, the elicitation of suggested adaptations to the curricula from student and teacher stakeholders, and the evaluation of the consistency of these suggested adaptations with the core components of the programs. Data sources include extensive classroom observations of curricula delivery and interviews with students, teachers, and program developers. All health teachers made adaptations, primarily with respect to instructional format, integration of real-life experiences into the curriculum, and supplementation with additional resources; pedagogical and class management issues were cited as the rationale for these changes. Students and teachers were equally likely to propose adaptations that met with the program developers’ approval with respect to program theory and implementation logistics. Tensions between teaching practice and prevention science—as well as implications for future research and practice in school-based prevention—are considered

Measurement of W Polarisation at LEP

The three different helicity states of W bosons produced in the reaction e+ e- -> W+ W- -> l nu q q~ at LEP are studied using leptonic and hadronic W decays. Data at centre-of-mass energies \sqrt s = 183-209 GeV are used to measure the polarisation of W bosons, and its dependence on the W boson production angle. The fraction of longitudinally polarised W bosons is measured to be 0.218 \pm 0.027 \pm 0.016 where the first uncertainty is statistical and the second systematic, in agreement with the Standard Model expectation

Measurement of W Polarisation at LEP

The three different helicity states of W bosons produced in the reaction e+ e- -> W+ W- -> l nu q q~ at LEP are studied using leptonic and hadronic W decays. Data at centre-of-mass energies \sqrt s = 183-209 GeV are used to measure the polarisation of W bosons, and its dependence on the W boson production angle. The fraction of longitudinally polarised W bosons is measured to be 0.218 \pm 0.027 \pm 0.016 where the first uncertainty is statistical and the second systematic, in agreement with the Standard Model expectation

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

Study of the e+e- -> Ze+e- process at LEP

The cross section of the process e+e- -> Ze+e is measured with 0.7fb^-1 of data collected with the L3 detector at LEP. Decays of the Z boson into quarks and muons are considered at centre-of-mass energies ranging from 183GeV up to 209GeV. The measurements are found to agree with Standard Model predictions, achieving a precision of about 10% for the hadronic channel

Lambda and Sigma0 Pair Production in Two-Photon Collisions at LEP

Strange baryon pair production in two-photon collisions is studied with the L3 detector at LEP. The analysis is based on data collected at e+e- centre-of-mass energies from 91 GeV to 208 GeV, corresponding to an integrated luminosity of 844 pb-1. The processes gamma gamma -> Lambda Anti-lambda and gamma gamma -> Sigma0 Anti-sigma0 are identified. Their cross sections as a function of the gamma gamma centre-of-mass energy are measured and results are compared to predictions of the quark-diquark model

Search for a Higgs Boson Decaying to Weak Boson Pairs at LEP

A Higgs particle produced in association with a Z boson and decaying into weak boson pairs is searched for in 336.4 1/pb of data collected by the L3 experiment at LEP at centre-of-mass energies from 200 to 209 GeV. Limits on the branching fraction of the Higgs boson decay into two weak bosons as a function of the Higgs mass are derived. These results are combined with the L3 search for a Higgs boson decaying to photon pairs. A Higgs produced with a Standard Model e+e- --> Zh cross section and decaying only into electroweak boson pairs is excluded at 95% CL for a mass below 107 GeV