The unstructured C-terminus of the τ subunit of Escherichia coli DNA polymerase III holoenzyme is the site of interaction with the α subunit

The τ subunit of Escherichia coli DNA polymerase III holoenzyme interacts with the α subunit through its C-terminal Domain V, τC16. We show that the extreme C-terminal region of τC16 constitutes the site of interaction with α. The τC16 domain, but not a derivative of it with a C-terminal deletion of seven residues (τC16Δ7), forms an isolable complex with α. Surface plasmon resonance measurements were used to determine the dissociation constant (KD) of the α−τC16 complex to be ∼260 pM. Competition with immobilized τC16 by τC16 derivatives for binding to α gave values of KD of 7 μM for the α−τC16Δ7 complex. Low-level expression of the genes encoding τC16 and τC16▵7, but not τC16Δ11, is lethal to E. coli. Suppression of this lethal phenotype enabled selection of mutations in the 3′ end of the τC16 gene, that led to defects in α binding. The data suggest that the unstructured C-terminus of τ becomes folded into a helix–loop–helix in its complex with α. An N-terminally extended construct, τC24, was found to bind DNA in a salt-sensitive manner while no binding was observed for τC16, suggesting that the processivity switch of the replisome functionally involves Domain IV of τ

Partners No More: Relational Transformation and the Turn to Litigation in Two Conservationist Organizations

The rise in litigation against administrative bodies by environmental and other political interest groups worldwide has been explained predominantly through the liberalization of standing doctrines. Under this explanation, termed here the floodgate model, restrictive standing rules have dammed the flow of suits that groups were otherwise ready and eager to pursue. I examine this hypothesis by analyzing processes of institutional transformation in two conservationist organizations: the Sierra Club in the United States and the Society for the Protection of Nature in Israel (SPNI). Rather than an eagerness to embrace newly available litigation opportunities, as the floodgate model would predict, the groups\u27 history reveals a gradual process of transformation marked by internal, largely intergenerational divisions between those who abhorred conflict with state institutions and those who saw such conflict as not only appropriate but necessary to the mission of the group. Furthermore, in contrast to the pluralist interactions that the floodgate model imagines, both groups\u27 relations with pertinent agencies in earlier eras better accorded with the partnership-based corporatist paradigm. Sociolegal research has long indicated the importance of relational distance to the transformation of interpersonal disputes. I argue that, at the group level as well, the presence or absence of a (national) partnership-centered relationship determines propensities to bring political issues to court. As such, well beyond change in groups\u27 legal capacity and resources, current increases in levels of political litigation suggest more fundamental transformations in the structure and meaning of relations between citizen groups and the state

Patient characteristics of Medicare beneficiaries who report not getting influenza and pneumococcal vaccinations, 2001–2013

Background: Despite long standing recommendations of pneumococcal and influenza vaccination for adults age 65 years and older and wide-spread availability to vaccination services, vaccination coverage in the United states is low. We sought to explore reasons patients reportedly did not receive these vaccines. Methods: We used publicly available data from the Medicare Current Beneficiary Survey, a continuous panel survey of a representative sample of the Medicare population, as well as Medicare enrollment data. We explored questions pertaining to influenza and pneumococcal vaccination status, self-reported reasons for being unvaccinated and patient perspectives toward health care utilization. Results: The majority of the respondents who did not receive vaccines for influenza or pneumococcal disease reported that they did not know it was needed or that their doctor did not recommend it. Respondents who were not vaccinated against influenza reported concerns about side effects. Coverage for both vaccines was lower among respondents in the Southeast region and among those who are dual-eligible or less engaged in healthcare utilization. Little difference was observed by gender, urban status, or Part C enrollment for influenza respondents. Higher pneumococcal vaccine coverage was found among females as well as those living in urban settings or enrolled in Medicare Part C. Conclusions: Implementation of the national guidelines calling for all health care professions – whether they provide vaccinations or not – to take steps to help ensure adults are fully immunized is critical. Tailored communication to beneficiaries that addresses the importance of both vaccines as well as key barriers, like side effects, is also needed

Influenza vaccination coverage estimates in the fee-for service Medicare beneficiary population 2006 – 2016: Using population-based administrative data to support a geographic based near real-time tool

Older adults are at great risk of developing serious complications from seasonal influenza. We explore vaccination coverage estimates in the Medicare population through the use of administrative claims data and describe a tool designed to help shape outreach efforts and inform strategies to help raise influenza vaccination rates. This interactive mapping tool uses claims data to compare vaccination levels between geographic (i.e., state, county, zip code) and demographic (i.e., race, age) groups at different points in a season. Trends can also be compared across seasons. Utilization of this tool can assist key actors interested in prevention – medical groups, health plans, hospitals, and state and local public health authorities – in supporting strategies for reaching pools of unvaccinated beneficiaries where general national population estimates of coverage are less informative. Implementing evidence-based tools can be used to address persistent racial and ethnic disparities and prevent a substantial number of influenza cases and hospitalizations

Patterns of seasonal influenza activity in U.S. core-based statistical areas, described using prescriptions of oseltamivir in Medicare claims data

Using Medicare claims data on prescriptions of oseltamivir dispensed to people 65 years old and older, we present a descriptive analysis of patterns of influenza activity in the United States for 579 core-based statistical areas (CBSAs) from the 2010–2011 through the 2015–2016 influenza seasons. During this time, 1,010,819 beneficiaries received a prescription of oseltamivir, ranging from 45,888 in 2011–2012 to 380,745 in 2014–2015. For each season, the peak weekly number of prescriptions correlated with the total number of prescriptions (Pearson’s r ≥ 0.88). The variance in peak timing decreased with increasing severity (p < 0.0001). Among these 579 CBSAs, neither peak timing, nor relative timing, nor severity of influenza seasons showed evidence of spatial autocorrelation (0.02 ≤ Moran’s I ≤ 0.23). After aggregating data to the state level, agreement between the seasonal severity at the CBSA level and the state level was fair (median Cohen’s weighted κ = 0.32, interquartile range = 0.26–0.39). Based on seasonal severity, relative timing, and geographic place, we used hierarchical agglomerative clustering to join CBSAs into influenza zones for each season. Seasonal maps of influenza zones showed no obvious patterns that might assist in predicting influenza zones for future seasons. Because of the large number of prescriptions, these data may be especially useful for characterizing influenza activity and geographic distribution during low severity seasons, when other data sources measuring influenza activity are likely to be sparse. Keywords: Antivirals, Influenza, Medicar