Mechanistic Heterogeneity in Site Recognition by the Structurally Homologous DNA-Binding Domains of the ETS-Family Transcription Factors Ets-1 and PU.1

ETS-family transcription factors regulate diverse genes through binding at cognate DNA sites that overlap substantially in sequence. The DNA-binding domains of ETS proteins (ETS domains) are highly conserved structurally, yet share limited amino acid homology. To define the mechanistic implications of sequence diversity within the ETS family, we characterized the thermodynamics and kinetics of DNA site recognition by the ETS domains of Ets-1 and PU.1, which represent the extremes in amino acid divergence among ETS proteins. Even though the two ETS domains bind their optimal sites with similar affinities under physiologic conditions, their nature of site recognition differs strikingly in terms of the role of hydration and counter-ion release. The data suggest two distinct mechanisms wherein Ets-1 follows a “dry” mechanism that rapidly parses sites through electrostatic interactions and direct protein-DNA contacts, while PU.1 utilizes hydration to interrogate sequence-specific sites and form a long-lived complex relative to the Ets-1 counterpart. The kinetic persistence of the high-affinity PU.1/DNA complex may be relevant to an emerging role of PU.1, but not Ets-1, as a pioneer transcription factor in vivo. In addition, PU.1 activity is critical to the development and function of macrophages and lymphocytes, which present osmotically variable environments, and hydrationdependent specificity may represent an important regulatory mechanism in vivo, a hypothesis that finds support in gene expression profiles of primary murine macrophages

Mechanistic Heterogeneity in Site Recognition by the Structurally Homologous DNA-Binding Domains of the ETS-Family Transcription Factors Ets-1 and PU.1

ETS-family transcription factors regulate diverse genes through binding at cognate DNA sites that overlap substantially in sequence. The DNA-binding domains of ETS proteins (ETS domains) are highly conserved structurally, yet share limited amino acid homology. To define the mechanistic implications of sequence diversity within the ETS family, we characterized the thermodynamics and kinetics of DNA site recognition by the ETS domains of Ets-1 and PU.1, which represent the extremes in amino acid divergence among ETS proteins. Even though the two ETS domains bind their optimal sites with similar affinities under physiologic conditions, their nature of site recognition differs strikingly in terms of the role of hydration and counter-ion release. The data suggest two distinct mechanisms wherein Ets-1 follows a “dry” mechanism that rapidly parses sites through electrostatic interactions and direct protein-DNA contacts, while PU.1 utilizes hydration to interrogate sequence-specific sites and form a long-lived complex relative to the Ets-1 counterpart. The kinetic persistence of the high-affinity PU.1/DNA complex may be relevant to an emerging role of PU.1, but not Ets-1, as a pioneer transcription factor in vivo. In addition, PU.1 activity is critical to the development and function of macrophages and lymphocytes, which present osmotically variable environments, and hydrationdependent specificity may represent an important regulatory mechanism in vivo, a hypothesis that finds support in gene expression profiles of primary murine macrophages

A scoping review of research on complementary and alternative medicine (CAM) and the mass media: Looking back, moving forward

<p>Abstract</p> <p>Background</p> <p>The use of complementary and alternative medicine (CAM) has become more common in Western developed countries in recent years, as has media reporting on CAM and related issues. Correspondingly, media reports are a primary information source regarding decisions to use CAM. Research on CAM related media reports is becoming increasingly relevant and important; however, identifying key concepts to guide future research is problematic due to the dispersed nature of completed research in this field. A scoping review was conducted to: 1) determine the amount, focus and nature of research on CAM and the mass media; and 2) summarize and disseminate related research results.</p> <p>Methods</p> <p>The main phases were: 1) searching for relevant studies; 2) selecting studies based on pre-defined inclusion criteria; 3) extracting data; and 4) collating, summarizing and reporting the results.</p> <p>Results</p> <p>Of 4,454 studies identified through various search strategies, 16 were relevant to our objectives and included in a final sample. CAM and media research has focused primarily on print media coverage of a range of CAM therapies, although only a few studies articulated differences within the range of therapies surveyed. Research has been developed through a variety of disciplinary perspectives, with a focus on representation research. The research reviewed suggests that journalists draw on a range of sources to prepare media reports, although most commonly they cite conventional (versus CAM) sources and personal anecdotes. The tone of media reports appears generally positive, which may be related to a lack of reporting on issues related to risk and safety. Finally, a variety of discourses within media representations of CAM are apparent that each appeal to a specific audience through resonance with their specific concerns.</p> <p>Conclusion</p> <p>Research on CAM and the mass media spans multiple disciplines and strategies of inquiry; however, despite the diversity in approach, it is clear that issues related to production and reception of media content are in need of research attention. To address the varied issues in a comprehensive manner, future research needs to be collaborative, involving researchers across disciplines, journalists and CAM users.</p

A media framing analysis of urban flooding in Nigeria: current narratives and implications for policy

© 2017, The Author(s). A critical element of current flood management is the importance of engaging key policy actors when policy decisions are to be made. However, there is still only limited understanding of how narratives of flood management actors may influence flood management policies, even though there is a suggestion that actors can strategically use their narratives to influence policy directions. In a developing country like Nigeria, there are still questions around lessons that can be learnt from understanding the narratives of policy actors, to unravel the complex nature of strategies and policy directions in managing urban floods. To help fill these gaps, this paper uses quantitative content analysis to explore the frame of five policy actor groups (government, local communities, business, multilateral organisations and non-governmental organisations (NGOs)) as expressed in local and national newspapers between 2012 and 2016 to understand their narratives of causes and strategies to solve the problem of urban flooding in Nigeria. The narratives of government, local communities and businesses align with the premise that flooding can and should be prevented whilst that of multilateral and business actors champion adaptation strategies on the basis that flooding is inevitable and hence more energy should be directed at ‘living with water’—emergency response, damage reduction and the aftermath. The study also identified areas of potential consensus and conflict between direct actors such as government and local communities on the one hand and funders on the other. Better discussion among actors aiding understanding of contemporary thinking and local realities will aid policy-making and policy implementation in the Nigerian context. An important step will be in the collaborative design of an urgently needed ‘Nigerian policy on flooding’ which currently does not exist

A historical overview of the classification, evolution, and dispersion of Leishmania parasites and sandflies

Background The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale. Methodology and Principal Findings Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate? Conclusions and Significance We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

A Global Perspective on the Population Structure and Reproductive System of Phyllosticta citricarpa

The citrus pathogen Phyllosticta citricarpa was first described 117 years ago in Australia, and subsequently from the summer rainfall citrus-growing regions in China, Africa, South America and recently the United States of America (USA). Limited information is available on the pathogen's population structure, mode of reproduction and introduction pathways, which were investigated by genotyping 383 isolates representing 12 populations from South Africa, USA, Australia, China and Brazil. Populations were genotyped using seven published and eight newly developed polymorphic simple sequence repeat (SSR) markers. The Chinese and Australian populations had the highest genetic diversities, whereas populations from Brazil, USA and South Africa exhibited characteristics of founder populations. The USA population was clonal. Based on principal coordinate and minimum spanning network analyses the Chinese populations were distinct from the other populations. Population differentiation and clustering analyses revealed high connectivity and possibly linked introduction pathways between South Africa, Australia and Brazil. With the exception of the clonal USA populations that only contained one mating type, all the other populations contained both mating types in a ratio that did not deviate significantly from 1:1. Whilst most populations exhibited sexual reproduction, linkage disequilibrium analyses indicated that asexual reproduction is important in the pathogen's life cycle.This work was financially supported by Citrus Research International and The Technology and Human Resources for Industry Programme. We thank CenGen (Pty.) Ltd., and S. Langenhoven and A. Pretorius (Department of Plant Pathology, Stellenbosch University), for assistance in the laboratory and technical support; and S. Maduna and A. van der Merwe (Department of Genetics, Stellenbosch University) for assistance with analyses in R