α-Catenin and vinculin cooperate to promote high E-cadherin-based adhesion strength.

Maintaining cell cohesiveness within tissues requires that intercellular adhesions develop sufficient strength to support traction forces applied by myosin motors and by neighboring cells. Cadherins are transmembrane receptors that mediate intercellular adhesion. The cadherin cytoplasmic domain recruits several partners, including catenins and vinculin, at sites of cell-cell adhesion. Our study used force measurements to address the role of αE-catenin and vinculin in the regulation of the strength of E-cadherin-based adhesion. αE-catenin-deficient cells display only weak aggregation and fail to strengthen intercellular adhesion over time, a process rescued by the expression of αE-catenin or chimeric E-cadherin·αE-catenins, including a chimera lacking the αE-catenin dimerization domain. Interestingly, an αE-catenin mutant lacking the modulation and actin-binding domains restores cadherin-dependent cell-cell contacts but cannot strengthen intercellular adhesion. The expression of αE-catenin mutated in its vinculin-binding site is defective in its ability to rescue cadherin-based adhesion strength in cells lacking αE-catenin. Vinculin depletion or the overexpression of the αE-catenin modulation domain strongly decreases E-cadherin-mediated adhesion strength. This supports the notion that both molecules are required for intercellular contact maturation. Furthermore, stretching of cell doublets increases vinculin recruitment and α18 anti-αE-catenin conformational epitope immunostaining at cell-cell contacts. Taken together, our results indicate that αE-catenin and vinculin cooperatively support intercellular adhesion strengthening, probably via a mechanoresponsive link between the E-cadherin·ß-catenin complexes and the underlying actin cytoskeleton.

The relationship between local public health agency characteristics and performance of partnership-related essential public health services.

OBJECTIVE: The relationships between characteristics of local public health agencies and their self-reported scores on partnership-related indicators of the Ten Essential Public Health Services were examined. DESIGN: A retrospective cross-sectional study using secondary data from the National Public Health Performance Standards Program (NPHPSP) and the 2005 Profile of Local Public Health Agencies from the National Association of City and County Health Organizations (NACCHO) was completed. Participants. Local public health systems that participated in both the NPHPSP and the NACCHO surveys. MAIN OUTCOME MEASURES: Partnership-related elements from the NPHPSP data set were used as dependent variables, whereas combined focused elements from the NPHPSP and the NACCHO surveys served as independent variables. RESULTS: Local public health agencies' increase in partnerships over the preceding 3 years and involvement in a community health improvement process were significantly related to numerous partnership performance scores--more so than other agency characteristics. Involvement in the Mobilizing Action through Planning and Partnerships process was inversely related to some partnership performance scores. CONCLUSIONS: Future research must continue to identify and explore additional community- and agency-level predictors of partnership performance.

Force measurements in E-cadherin-mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42.

We have used a modified, dual pipette assay to quantify the strength of cadherin-dependent cell-cell adhesion. The force required to separate E-cadherin-expressing paired cells in suspension was measured as an index of intercellular adhesion. Separation force depended on the homophilic interaction of functional cadherins at the cell surface, increasing with the duration of contact and with cadherin levels. Severing the link between cadherin and the actin cytoskeleton or disrupting actin polymerization did not affect initiation of cadherin-mediated adhesion, but prevented it from developing and becoming stronger over time. Rac and Cdc42, the Rho-like small GTPases, were activated when E-cadherin-expressing cells formed aggregates in suspension. Overproduction of the dominant negative form of Rac or Cdc42 permitted initial E-cadherin-based adhesion but affected its later development; the dominant active forms prevented cell adhesion outright. Our findings highlight the crucial roles played by Rac, Cdc42, and actin cytoskeleton dynamics in the development and regulation of strong cell adhesion, defined in terms of mechanical forces.

Medical Evaluation Board for Mental Health Condition: U.S. Army Officer Medical Evaluation Board Data by Branch and Component.

OBJECTIVE: A retrospective review of Medical Evaluation Board (MEB) data to determine the effect of career field or Army component on the relative risk for mental health (MH) related MEBs among Army Officers, may identify specific populations for enhanced screening before accession, or groups that may require targeted preventive resources during their careers. METHOD: 4 years' of data available on Army Officers from the Department of the Army's Electronic Disability Evaluation System database, contained specific information on the officers' physical profiles, career fields, and service component. This information was compared with a dataset provided by the Defense Manpower Data Center (DMDC), reporting documented force strength by career field and service component for the corresponding years, allowing for calculation and comparison of MEB and MH-MEB rates between Army components and between career fields. RESULTS: Significant differences in MEB and MH-MEB rates were found between Army components, but database gaps make this assessment uncertain. When comparing MEB and MH-MEB rates between career fields (regardless of service component), 9 career fields had statistically significant higher risk rates of MEB and/or MH-MEB, whereas 13 career fields showed significantly lower rates of MEB and/or MH-MEB. CONCLUSION: Frequency of Army Officer MEBs and/or MH-MEBs were variable and career field dependent; the underlying causes of these variations warrant further research. The use of the Electronic Disability Evaluation System database for the Integrated Disability Evaluation System process is a rich source of data for in-depth analysis, but the program itself and the procedures for its use need to be improved to obtain more complete information.

Evaluating a deer-targeted acaricide applicator for area-wide suppression of blacklegged ticks, Ixodes scapularis (Acari: Ixodidae), in Rhode Island.

Over a 5-year period, September 1997 through May 2002, as many as 25 U.S. Department of Agriculture-Agricultural Research Service "4-Poster" acaricide applicators were distributed in areas of high deer activity throughout a 518-hectare area in a rural Rhode Island community. Corn consumption and acaricide levels for each device were monitored weekly during each treatment season to assess the degree of deer use. The efficacy of acaricide treatment was determined by comparing relative blacklegged tick (Ixodes scapularis) densities in the 4-Poster treatment site to a separate, similar-sized nontreatment area. The tendency of white-tailed deer to use the 4-Poster was variable temporally, and appeared to be largely dependent on the availability of alternative food sources. Total corn consumption was nearly fourfold lower during large oak masting years when compared with no/low mast years. Moreover, habitat characteristics, such as the presence of maintained hay lands consisting of alfalfa and clover, also appeared to influence the frequency and amount of 4-Poster use. After 2 years of adequate treatment (nearly 12,000 kg of corn consumed), we achieved nearly 50% control of nymphal blacklegged ticks within the treatment site compared with tick abundance levels in the nontreated area. Moreover, that level of tick control was maintained for 1 year after removal of the 4-Poster devices but began to wane 2 years after treatment ended.

Prototypical type I E-cadherin and type II cadherin-7 mediate very distinct adhesiveness through their extracellular domains.

Using a dual pipette assay that measures the force required to separate adherent cell doublets, we have quantitatively compared intercellular adhesiveness mediated by Type I (E- or N-cadherin) or Type II (cadherin-7 or -11) cadherins. At similar cadherin expression levels, cells expressing Type I cadherins adhered much more rapidly and strongly than cells expressing Type II cadherins. Using chimeric cadherins, we found that the extracellular domain exerts by far the dominant effect on cell adhesivity, that of E-cadherin conferring high adhesivity, and that of cadherin-7 conferring low adhesivity. Type I cadherins were incorporated to a greater extent into detergent-insoluble cytoskeletal complexes, and their cytoplasmic tails were much more effective in disrupting strong adherent junctions, suggesting that Type II cadherins form less stable complexes with beta-catenin. The present study demonstrates compellingly, for the first time, that cadherins are dramatically different in their ability to promote intercellular adhesiveness, a finding that has profound implications for the regulation of tissue morphogenesis.