The Dilemma of Direct Democracy

The dilemma of direct democracy is that voters may not always be able to make welfare- improving decisions. Lupia’s seminal work has led us to believe that voters can substitute voting cues for substantive policy knowledge. Lupia, however, emphasized that cues were valuable under certain conditions and not others. In what follows, we present three main findings regarding voters and what they know about California’s Proposition 7. First, much like Lupia reported, we show voters who are able to recall endorsements for or against a ballot measure vote similarly to people who recall certain basic facts about the initiative. We show, second, that voters whose stated policy preferences would otherwise suggest they would favor the “no” position cast their ballots with far less error than do people who favor the “yes” position. One thing this suggests is that many voters may employ a “defensive no” strategy when faced with complex policy choices on the ballot. Our third result is a bit surprising: we find that better- informed voters, whether this information is derived from factual knowledge of the initiative or from knowledge of well-publicized voting cues, are no more likely to make reasoned decisions than those who are, by our measure, uninformed. This suggests that existing theories of voter choice, especially in direct democracy, may be inadequate. We conclude with some preliminary policy recommendations that could help improve the information environment for initiatives and referenda by providing key information on the ballot

A Nutrient-Regulated Cyclic Diguanylate Phosphodiesterase Controls Clostridium difficile Biofilm and Toxin Production during Stationary Phase

ABSTRACT The signaling molecule cyclic diguanylate (c-di-GMP) mediates physiological adaptation to extracellular stimuli in a wide range of bacteria. The complex metabolic pathways governing c-di-GMP synthesis and degradation are highly regulated, but the specific cues that impact c-di-GMP signaling are largely unknown. In the intestinal pathogen Clostridium difficile , c-di-GMP inhibits flagellar motility and toxin production and promotes pilus-dependent biofilm formation, but no specific biological functions have been ascribed to any of the individual c-di-GMP synthases or phosphodiesterases (PDEs). Here, we report the functional and biochemical characterization of a c-di-GMP PDE, PdcA, 1 of 37 confirmed or putative c-di-GMP metabolism proteins in C. difficile 630. Our studies reveal that pdcA transcription is controlled by the nutrient-regulated transcriptional regulator CodY and accordingly increases during stationary phase. In addition, PdcA PDE activity is allosterically regulated by GTP, further linking c-di-GMP levels to nutrient availability. Mutation of pdcA increased biofilm formation and reduced toxin biosynthesis without affecting swimming motility or global intracellular c-di-GMP. Analysis of the transcriptional response to pdcA mutation indicates that PdcA-dependent phenotypes manifest during stationary phase, consistent with regulation by CodY. These results demonstrate that inactivation of this single PDE gene is sufficient to impact multiple c-di-GMP-dependent phenotypes, including the production of major virulence factors, and suggest a link between c-di-GMP signaling and nutrient availability

A Nutrient-Regulated Cyclic Diguanylate Phosphodiesterase Controls Clostridium difficile Biofilm and Toxin Production During Stationary Phase

The signaling molecule cyclic diguanylate (c-di-GMP) mediates physiological adaptation to extracellular stimuli in a wide range of bacteria. The complex metabolic pathways governing c-di-GMP synthesis and degradation are highly regulated, but the specific cues that impact c-di-GMP signaling are largely unknown. In the intestinal pathogen Clostridium difficile, c-di-GMP inhibits flagellar motility and toxin production and promotes pilus-dependent biofilm formation, but no specific biological functions have been ascribed to any of the individual c-di-GMP synthases or phosphodiesterases (PDEs). Here, we report the functional and biochemical characterization of a c-di-GMP PDE, PdcA, 1 of 37 confirmed or putative c-di-GMP metabolism proteins in C. difficile 630. Our studies reveal that pdcA transcription is controlled by the nutrient-regulated transcriptional regulator CodY and accordingly increases during stationary phase. In addition, PdcA PDE activity is allosterically regulated by GTP, further linking c-di-GMP levels to nutrient availability. Mutation of pdcA increased biofilm formation and reduced toxin biosynthesis without affecting swimming motility or global intracellular c-di-GMP. Analysis of the transcriptional response to pdcA mutation indicates that PdcA-dependent phenotypes manifest during stationary phase, consistent with regulation by CodY. These results demonstrate that inactivation of this single PDE gene is sufficient to impact multiple c-di-GMP-dependent phenotypes, including the production of major virulence factors, and suggest a link between c-di-GMP signaling and nutrient availability

Complementary Therapies for Significant Dysfunction from Tinnitus: Treatment Review and Potential for Integrative Medicine

Tinnitus is a prevalent and costly chronic condition; no universally effective treatment exists. Only 20% of patients who report tinnitus actually seek treatment, and when treated, most patients commonly receive sound-based and educational (SBE) therapy. Additional treatment options are necessary, however, for nonauditory aspects of tinnitus (e.g., anxiety, depression, and significant interference with daily life) and when SBE therapy is inefficacious or inappropriate. This paper provides a comprehensive review of (1) conventional tinnitus treatments and (2) promising complementary therapies that have demonstrated some benefit for severe dysfunction from tinnitus. While there has been no systematic study of the benefits of an Integrative Medicine approach for severe tinnitus, the current paper reviews emerging evidence suggesting that synergistic combinations of complementary therapies provided within a whole-person framework may augment SBE therapy and empower patients to exert control over their tinnitus symptoms without the use of medications, expensive devices, or extended programs

Review of the life history and conservation of federally endangered plant species of the Lower Rio Grande Valley, Texas, USA

This review aims to summarize information critical to the conservation of the federally listed endangered species of South Texas, which occur along the border of Texas and Mexico. This paper describes the characteristics, habitat, population status, distribution, life history, threats, and restoration of endangered plant species of the Lower Rio Grande Valley, Texas, which includes Cameron, Willacy, Hidalgo, and Starr County. Seven federally listed species are considered including Ambrosia cheiranthifolia, Asclepias prostrata, Astrophytum asterias, Ayenia limitaris, Manihot walkerae, Lesquerella thamnophila (syn. Physaria thamnophila), and Thymophylla tephroleuca. An eighth species, Physostegia correllii is under consideration for federal listing by the U.S. Fish and Wildlife Service. This paper assembles information on the background, biological status, major threats, and conservation to aid managers and the scientific community in restoring and managing these species. - El objetivo de esta revisión es resumir la información crítica para la conservación de las especies en peligro de extinción incluidas en la lista federal del sur de Texas, que se encuentran a lo largo de la frontera entre Texas y México. En este documento se describen las características, el hábitat, el estado de la población, la distribución, el ciclo biológico, las amenazas y la restauración de las especies vegetales en peligro de extinción del Valle Inferior del Río Grande, Texas, que incluye los condados de Cameron, Willacy, Hidalgo y Starr. Se consideran siete especies incluidas en la lista federal, entre ellas Ambrosia cheiranthifolia, Asclepias prostrata, Astrophytum asterias, Ayenia limitaris, Manihot walkerae, Lesquerella thamnophila (syn. Physaria thamnophila) y Thymophylla tephroleuca. Una octava especie, Physostegia correllii, está siendo considerada por el Servicio de Pesca y Vida Silvestre de EE.UU. para su inclusión en la lista federal. Este documento reúne información sobre los antecedentes, el estado biológico, las principales amenazas y la conservación para ayudar a los gestores y a la comunidad científica a restaurar y gestionar estas especies

Coordinated modulation of multiple processes through phase variation of a c-di-GMP phosphodiesterase in Clostridioides difficile

The opportunistic nosocomial pathogen Clostridioides difficile exhibits phenotypic heterogeneity through phase variation, a stochastic, reversible process that modulates expression. In C. difficile, multiple sequences in the genome undergo inversion through site-specific recombination. Two such loci lie upstream of pdcB and pdcC, which encode phosphodiesterases (PDEs) that degrade the signaling molecule c-di-GMP. Numerous phenotypes are influenced by c-di-GMP in C. difficile including cell and colony morphology, motility, colonization, and virulence. In this study, we aimed to assess whether PdcB phase varies, identify the mechanism of regulation, and determine the effects on intracellular c-di-GMP levels and regulated phenotypes. We found that expression of pdcB is heterogeneous and the orientation of the invertible sequence, or ‘pdcB switch’, determines expression. The pdcB switch contains a promoter that when properly oriented promotes pdcB expression. Expression is augmented by an additional promoter upstream of the pdcB switch. Mutation of nucleotides at the site of recombination resulted in phase-locked strains with significant differences in pdcB expression. Characterization of these mutants showed that the pdcB locked-ON mutant has reduced intracellular c-di-GMP compared to the locked-OFF mutant, consistent with increased and decreased PdcB activity, respectively. These alterations in c-di-GMP had concomitant effects on multiple known c-di-GMP regulated processes, indicating that phase variation of PdcB allows C. difficile to coordinately diversify multiple phenotypes in the population to enhance survival