RidA proteins prevent metabolic damage inflicted by PLP-dependent dehydratases in all domains of life

ABSTRACT Pyridoxal 5′-phosphate (PLP) is a coenzyme synthesized by all forms of life. Relevant to the work reported here is the mechanism of the PLP-dependent threonine/serine dehydratases, which generate reactive enamine/imine intermediates that are converted to keto acids by members of the RidA family of enzymes. The RidA protein of Salmonella enterica serovar Typhimurium LT2 is the founding member of this broadly conserved family of proteins (formerly known as YjgF/YER057c/UK114). RidA proteins were recently shown to be enamine deaminases. Here we demonstrate the damaging potential of enamines in the absence of RidA proteins. Notably, S. enterica strains lacking RidA have decreased activity of the PLP-dependent transaminase B enzyme IlvE, an enzyme involved in branched-chain amino acid biosynthesis. We reconstituted the threonine/serine dehydratase (IlvA)-dependent inhibition of IlvE in vitro, show that the in vitro system reflects the mechanism of RidA function in vivo, and show that IlvE inhibition is prevented by RidA proteins from all domains of life. We conclude that 2-aminoacrylate (2AA) inhibition represents a new type of metabolic damage, and this finding provides an important physiological context for the role of the ubiquitous RidA family of enamine deaminases in preventing damage by 2AA. IMPORTANCE External stresses that disrupt metabolic components can perturb cellular functions and affect growth. A similar consequence is expected if endogenously generated metabolites are reactive and persist in the cellular environment. Here we show that the metabolic intermediate 2-aminoacrylate (2AA) causes significant cellular damage if allowed to accumulate aberrantly. Furthermore, we show that the widely conserved protein RidA prevents this accumulation by facilitating conversion of 2AA to a stable metabolite. This work demonstrates that the reactive metabolite 2AA, previously considered innocuous in the cell due to a short half-life in aqueous solution, can survive in the cellular environment long enough to cause damage. This work provides insights into the roles and persistence of reactive metabolites in vivo and shows that the RidA family of proteins is able to prevent damage caused by a reactive intermediate that is created as a consequence of PLP-dependent chemistry

A Tool for Assessing, Implementing, and Evaluating Science Curriculum (K-12) for Iowa Schools

In the fall of 1977 the Iowa Department of Public Instruction (DPI) began to receive many requests for assistance in developing coordinated science programs. Local schools faced with aging science materials, economic constraints, increasing pressure from publishing companies, and decreasing student reading and computing skills needed guidelines for assessing, implementing and evaluating their science curriculum. The purpose of this tool is to provide such assistance

A systematic review of Hepatitis B virus (HBV) prevalence and genotypes in Kenya: Data to inform clinical care and health policy

The aim of this systematic review and meta-analysis is to evaluate available prevalence and viral sequencing data representing chronic hepatitis B (CHB) infection in Kenya. More than 20% of the global disease burden from CHB is in Africa, however there is minimal high quality seroprevalence data from individual countries and little viral sequencing data available to represent the continent. We undertook a systematic review of the prevalence and genetic data available for hepatitis B virus (HBV) in Kenya using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 checklist. We identified 23 studies reporting HBV prevalence and 8 studies that included HBV genetic data published in English between January 2000 and December 2021. We assessed study quality using the Joanna Briggs Institute critical appraisal checklist. Due to study heterogeneity, we divided the studies to represent low, moderate, high and very high-risk for HBV infection, identifying 8, 7, 5 and 3 studies in these groups, respectively. We calculated pooled HBV prevalence within each group and evaluated available sequencing data. Pooled HBV prevalence was 3.4% (95% CI 2.7–4.2%), 6.1% (95% CI 5.1–7.4%), 6.2% (95% CI 4.64–8.2) and 29.2% (95% CI 12.2–55.1), respectively. Study quality was overall low; only three studies detailed sample size calculation and 17/23 studies were cross sectional. Eight studies included genetic information on HBV, with two undertaking whole genome sequencing. Genotype A accounted for 92% of infections. Other genotypes included genotype D (6%), D/E recombinants (1%) or mixed populations (1%). Drug resistance mutations were reported by two studies. There is an urgent need for more high quality seroprevalence and genetic data to represent HBV in Kenya to underpin improved HBV screening, treatment and prevention in order to support progress towards elimination targets

Toward a Theory of Innovation

The purpose of this article is to eliminate further conceptual obstacles to the develop ment of a workable theory of innovation and to move toward a better theoretic statement. The approach to overcoming the conceptual problems centers primarily around four ideas: (1) building a theory around the "innovation decision" as the unit of analysis, rather than either innovations or adopters: (2) lifting the level of general ity of independent variables so that a great deal of statistical interaction is avoided; (3) splitting the act of innovation into two stages, diffusion and adoption, to eliminate the confounding effects of time of awareness in studies of innovation; (4) introducing the idea of a "fair-trial point" into the conceptualization of innovation, solving sev eral additional problems at once.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68286/2/10.1177_009539977901000401.pd

Self-interest And Public Interest: The Motivations Of Political Actors

Self-Interest and Public Interest in Western Politics showed that the public, politicians, and bureaucrats are often public spirited. But this does not invalidate public-choice theory. Public-choice theory is an ideal type, not a claim that self-interest explains all political behavior. Instead, public-choice theory is useful in creating rules and institutions that guard against the worst case, which would be universal self-interestedness in politics. In contrast, the public-interest hypothesis is neither a comprehensive explanation of political behavior nor a sound basis for institutional design

Chatham County, North Carolina : a community diagnosis including secondary and qualitative data collection and analysis

The Chatham County Health Department, the United Way of Chatham County, Chatham Hospital, and six graduate students from the Department of Health Behavior and Health Education at the UNC School of Public Health collaborated to conduct this community diagnosis of Chatham County. The purpose of this community diagnosis was to learn about the health and quality of life concerns of people across the county, and the resources and strengths that exist in the county for dealing with those concerns. The community diagnosis process used primary and secondary data to discover and analyze both the concerns and strengths of the county. Methodology Secondary data was gathered from a variety of published sources. Main sources of secondary data included area newspapers, the Chatham County Economic Development Commission Report, the North Carolina Statistical Abstract, the U.S. Census, and the North Carolina Center for Health Statistics. Primary data was gathered from focus groups and interviews with community members and service providers. The development of the interview and focus group guides, as well as the identification and recruitment of interview and focus group participants, was completed using a process of close collaboration between all members of the community assessment team. Interview and focus group guides comprised of open-ended questions were designed to facilitate discussion about thoughts and experiences of Chatham County residents and service providers. During a four-month period, the team conducted 18 focus groups and eight interviews with a total of 157 residents and/or service providers. One hundred of those participants were female and 57 were males. Eighty-nine participants were White (57%), 40 were African American (25%), and 28 were Latino (18%). Coding and data analysis began after completion of the focus groups and interviews. After reading the interview and focus group notes, the team categorized comments from the interviews and focus groups into themes. All of the comments within each specific theme then were examined together to provide a complete picture of each issue. Limitations of the Methodology Because the 1990 U.S. Census provided much of the demographic information for the secondary data section, limitations exist in describing the recent population growth in northern Chatham and in the Latino community. Since focus group and interview participants were not recruited randomly, a limitation also exists in our primary data collection. While attempts were made to maximize representativeness of the Chatham County population by seeking residents from different parts of the county, and of various ethnicities, occupations, and socioeconomic statuses, it is unclear whether the participants were representative of the Chatham County population as a whole. Findings Please see the complete document for a substantive discussion of the issues of community assets, racial and ethnic diversity, growth of the Latino population, growth in North Chatham, economic development, housing, water and sewer, transportation, day care, recreation, education, health, substance abuse, and communication, as well as for a discussion of future recommendations. Findings regarding some of the most salient issues are highlighted below. Community Assets Chatham County is a community rich with both potential and currently used resources. Residents spoke with pride about their community, mentioning many of its strengths, such as the natural beauty of the county, the diversity among county residents, a neighborly attitude, collaboration between businesses and county agencies, and the numerous leaders of the county, both formal and informal. Residents frequently cited the community’s churches as sources of support. Finally, many residents felt that Chatham is strengthened by its active volunteerism, though some also often mentioned the need to sustain and further increase the volunteer efforts within the county. Racial and Ethnic Diversity Chatham County residents discussed both the benefits of and the challenges from the increasing racial diversity resulting from the growth of the Latino population. Community members spoke of the opportunities for learning and personal growth as a result of the increasing diversity. Also noted was the increase in interracial church and civic groups within the county. However, some in the county hold concerns about the growing Latino community, as evidenced by a recent anti-immigration demonstration in Siler City. A service provider suggested that the negative perceptions about the Latino community could be changed by community leaders demonstrating accepting attitudes. Moreover, another resident felt that the acknowledgement of Latino residents’ contribution to the local economy would change negative perceptions. Housing Many county residents were concerned about the lack of quality, affordable housing within the county. While the number of housing units in Chatham County has increased, much of the new housing is beyond the financial means of many current residents. More than half (1549) of the 3067 very low-income households in the county paid more than 30% of their income for housing in 1990 (Chatham Habitat, 1999). Residents mentioned problems such as the “run-down” nature of houses, lack of heating or air conditioning, and broken plumbing. County residents of various ethnicities felt that a lack of quality housing was especially a concern for rural residents and for Latinos living in the Siler City area. Recreation The lack of adequate recreational opportunities within the county was raised in nearly every focus group and interview conducted for this community assessment. These concerns mirrored the findings of a recent survey, in which 65% of the 590 respondents characterized the recreational facilities and activities in the county as “inadequate” (Chatham County Department of Parks and Recreation, 1999). County residents perceive the lack of recreational opportunities as affecting all age groups in the county. Many residents feel that the problem especially affects county youth. Solutions proposed by community members to address the lack of recreational opportunities included increasing the amount of county funding for recreational activities, utilizing school buildings for recreational activities on the evenings and weekends, as well as applying for grants. In September of 1999, the County Board of Commissioners approved a parks and recreation master plan that addresses many of these concerns of county residents. Education The quality of education was an area of concern for many county residents. Secondary data from the Department of Public Instruction (1998) affirms these concerns, showing that the average Chatham County SAT score (973) is lower than the state average (982). Moreover, residents noted that disparities in quality exist among the schools within the county, stating that schools in Moncure and Siler City have many needs. Some residents feel that the school system should improve its ability to recruit and retain good teachers. Community members, especially Latino community members, were also concerned about the lack of English as a Second Language (ESL) teachers within the district. According to community residents, a result of the growing student population is that the schools are unable to maintain the quality of education they offer, and this, in turn, impedes future growth in the county. Health The health problems most often cited as concerns by the community were not the leading causes of mortality in Chatham County, which are heart disease, cancer, and cerebrovascular disease. Rather, residents were most often concerned about dental care, diabetes, and sexually transmitted diseases. A common sentiment expressed by a wide range of county residents was the need for additional health education and preventative health care. The barriers to accessing health care commonly mentioned by residents were a lack of transportation and inadequate financial resources. Residents suggested sliding scale clinics and the ability to pay for medical care incrementally as ways to overcome the financial barriers. Economic Development Many Chatham County residents expressed a wide variety of often-conflicting ideas for methods to increase economic development in the county. However, most Chatham County residents agreed that increasing the number of businesses and employment opportunities within the county was critical to the future of Chatham. Some residents felt that increased employment opportunities within the county were necessary for current residents to have the ability to work without commuting out of the county. Increased employment opportunities were also considered necessary for Chatham’s youth to have the capability in the future to stay, work, and live in the county. Moreover, residents stated that strengthening Chatham’s economy was necessary to increase the tax base within the county. Recommendations Chatham County residents have many recommendations for the future of the county. One of the most critical recommendations mentioned by many residents is the need for increased communication within the county. Many residents feel that the current lack of communication within the county contributes to many of the concerns discussed above. Currently, residents do not all rely on a single news medium, causing difficulties in communication between different parts of the county. Moreover, many residents felt that the county lacked spaces such as community centers where different groups could interact, further inhibiting communication between different groups within the county. The lack of communication can be addressed on many levels. At the policy level, county government could work to develop a method to increase communication across the county, as well as to provide funding for spaces in the community that would encourage communication between different groups. At the community level, residents could collaborate with county officials to create these spaces and to encourage the various communities within Chatham to continue current discussions as well as engage in future discussions.Master of Public Healt

Party control, party competition and public service performance

publication-status: Acceptedtypes: ArticleThis article assesses party effects on the performance of public services. A policy-seeking model, hypothesizing that left and right party control affects performance, and an instrumental model, where all parties strive to raise performance, are presented. The framework also suggests a mixed model in which party effects are contingent on party competition, with parties raising performance as increasing party competition places their control of government at increasing risk. These models are tested against panel data on English local governments’ party control and public service performance. The results question the traditional account of left and right parties, showing a positive relationship between rightwing party control and performance that is contingent on a sufficiently high level of party competition. The findings suggest left–right models should be reframed for the contemporary context

The role of "costs" in political choice: a review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67848/2/10.1177_002200276300700209.pd

Why and how do political actors pursue risky welfare state reforms?

Why and how do political actors pursue risky welfare state reforms, in spite of the institutional mechanisms and political resistance that counteract change? This is one of the key puzzles of contemporary welfare state research, which is brought about by the absence of a complete account that identifies both the cause and causal mechanisms of risky reforms. In this article we offer a remedy for this lacuna. Prospect theory teaches us that political actors will only undertake risky reforms if they consider themselves to be in a losses domain, that is when their current situation is unacceptable. Next, we discuss the strategies that political actors use to avoid the blame associated with risky reforms. These provide the causal mechanisms linking cause and effect. The sudden outburst of risky reforms in formerly 'immovable' Italy provides an empirical illustration of our account. Copyright © 2007 Sage Publications