Internalization of Formyl Peptide Receptor in Leukocytes Subject to Fluid Stresses

Human leukocytes retract pseudopods under normal physiologic levels of fluid shear stress even in the absence of any other mediator. To gain more detailed understanding of the mechanisms that regulate this cell behavior, we exposed leukocytes to a steady state laminar shear field in a flow chamber and computed the fluid stresses distribution on the surface of individual cells with and without pseudopod. The surface fluid stress distribution on such cell is quite inhomogeneous. We hypothesized that the local fluid stresses on the cell surface serve to regulate pseudopod retraction by way of membrane receptors, especially the formyl peptide receptor (FPR). Comparison of the receptor distribution and the stress distribution over the surface of the cells indicates that the membrane fluid stress alone is not directly correlated with the extent of regional pseudopod retraction, giving further support to the hypothesis that membrane receptors are involved in the mechanotransduction of leukocytes. We observed that after exposure to fluid shear the FPR was internalized to a small intracellular compartment. This internalization appears to be independent of the original location of the receptor on the surface of the cell and the FPR appears to be more derived from multiple locations on the cell, with both higher and lower fluid stresses. The evidence suggests that FPR involvement in the pseudopod-retraction process is not limited to cell surface regions with the highest fluid shear stress, but rather a more global occurrence over the majority of the cell membrane

Mammograms on-the-go—predictors of repeat visits to mobile mammography vans in St Louis, Missouri, USA: A case–control study

OBJECTIVES: Among women, breast cancer is the most common non-cutaneous cancer and second most common cause of cancer-related death. The purpose of this study was to determine the extent to which women use mobile mammography vans for breast cancer screening and what factors are associated with repeat visits to these vans. DESIGN: A case–control study. Cases are women who had a repeat visit to the mammography van. (n=2134). PARTICIPANTS: Women who received a mammogram as part of Siteman Cancer Center's Breast Health Outreach Program responded to surveys and provided access to their clinical records (N=8450). Only visits from 2006 to 2014 to the mammography van were included. OUTCOME MEASURES: The main outcome is having a repeat visit to the mammography van. Among the participants, 25.3% (N=2134) had multiple visits to the mobile mammography van. Data were analysed using χ(2) tests, logistic regression and negative binomial regression. RESULTS: Women who were aged 50–65, uninsured, or African-American had higher odds of a repeat visit to the mobile mammography van compared with women who were aged 40–50, insured, or Caucasian (OR=1.135, 95% CI 1.013 to 1.271; OR=1.302, 95% CI 1.146 to 1.479; OR=1.281, 95% CI 1.125 to 1.457), respectively. However, the odds of having a repeat visit to the van were lower among women who reported a rural ZIP code or were unemployed compared with women who provided a suburban ZIP code or were employed (OR=0.503, 95% CI 0.411 to 0.616; OR=.868, 95% CI 0.774 to 0.972), respectively. CONCLUSION: This study has identified key characteristics of women who are either more or less likely to use mobile mammography vans as their primary source of medical care for breast cancer screening and have repeat visits

Differential Regulation of Primitive Myelopoiesis in the Zebrafish by Spi-1/Pu.1 and C/ebp1

The zebrafish has become a powerful tool for analysis of vertebrate hematopoiesis. Zebrafish, unlike mammals, have a robust primitive myeloid pathway that generates both granulocytes and macrophages. It is not clear how this unique primitive myeloid pathway relates to mammalian definitive hematopoiesis. In this study, we show that the two myeloid subsets can be distinguished using RNA in situ hybridization. Using a morpholino-antisense gene knockdown approach, we have characterized the hematopoietic defects resulting from knockdown of the myeloid transcription factor gene pu.1 and the unique zebrafish gene c/ebp1. Severe reduction of pu.1 resulted in complete loss of primitive macrophage development, with effects on granulocyte development only with maximal knockdown. Reduction of c/ebp1 did not ablate initial macrophage or granulocyte development, but resulted in loss of expression of the secondary granule gene lys C. These data reveal strong functional conservation of pu.1 between zebrafish primitive myelopoiesis and mammalian definitive myelopoiesis. Further, these results are consistent with a conserved role between c/ebp1 and mammalian C/EBPE, whose ortholog in zebrafish has not been identified. These studies validate the examination of zebrafish primitive myeloid development as a model for human myelopoiesis, and form a framework for identification and analysis of myeloid mutants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63190/1/zeb.2007.0505.pd

Systematic image-driven analysis of the spatial Drosophila embryonic expression landscape

We created innovative virtual representation for our large scale Drosophila insitu expression dataset. We aligned an elliptically shaped mesh comprised of small triangular regions to the outline of each embryo. Each triangle defines a unique location in the embryo and comparing corresponding triangles allows easy identification of similar expression patterns.The virtual representation was used to organize the expression landscape at stage 4-6. We identified regions with similar expression in the embryo and clustered genes with similar expression patterns.We created algorithms to mine the dataset for adjacent non-overlapping patterns and anti-correlated patterns. We were able to mine the dataset to identify co-expressed and putative interacting genes.Using co-expression we were able to assign putative functions to unknown genes

Converging identities: dimensions of acculturation and personal identity status among immigrant college students

The present study was designed to ascertain the extent to which dimensions of acculturation would differ across personal identity statuses in a sample of 2,411, first and second generation immigrant college‐attending emerging adults. Participants from 30 colleges and universities around the United States completed measures of personal identity processes as well as of heritage and American cultural practices, values, and identifications. Cluster‐analytic procedures were used to classify participants into personal identity statuses based on the personal identity processes. Results indicated that, across ethnic groups, individuals in the achieved and searching moratorium statuses reported the greatest endorsement of heritage and American cultural practices, values, and identifications; and individuals in the carefree diffusion status reported the lowest endorsement of all the cultural variables under study. These results are discussed in terms of the convergence between personal identity and cultural identity processes

Meaning in life in emerging adulthood: a person-oriented approach

The present study investigated naturally occurring profiles based on two dimensions of meaning in life: Presence of Meaning and Search for Meaning. Cluster analysis was used to examine meaning-in-life profiles, and subsequent analyses identified different patterns in psychosocial functioning for each profile. A sample of 8,492 American emerging adults (72.5% women) from 30 colleges and universities completed measures on meaning in life, and positive and negative psychosocial functioning. Results provided support for five meaningful yet distinguishable profiles. A strong generalizability of the cluster solution was found across age, and partial generalizability was found across gender and ethnicity. Furthermore, the five profiles showed specific patterns in relation to positive and negative psychosocial functioning. Specifically, respondents with profiles high on Presence of Meaning showed the most adaptive psychosocial functioning, whereas respondents with profiles where meaning was largely absent showed maladaptive psychosocial functioning. The present study provided additional evidence for prior research concerning the complex relationship between Presence of Meaning and Search for Meaning, and their relation with psychosocial functioning. Our results offer a partial clarification of the nature of the Search for Meaning process by distinguishing between adaptive and maladaptive searching for meaning in life

Relative Health Effects of Education, Socioeconomic Status and Domestic Gender Inequity in Sweden: A Cohort Study

Introduction: Limited existing research on gender inequities suggests that for men workplace atmosphere shapes wellbeing while women are less susceptible to socioeconomic or work status but vulnerable to home inequities. Methods: Using the 2007 Northern Swedish Cohort (n = 773) we identified relative contributions of perceived gender inequities in relationships, financial strain, and education to self-reported health to determine whether controlling for sex, examining interactions between sex and other social variables, or sex-disaggregating data yielded most information about sex differences. Results and Discussion: Men had lower education but also less financial strain, and experienced less gender inequity. Overall, low education and financial strain detracted from health. However, sex-disaggregated data showed this to be true for women, whereas for men only gender inequity at home affected health. In the relatively egalitarian Swedish environment where women more readily enter all work arenas and men often provide parenting, traditional primacy of the home environment (for women) and the work environment (for men) in shaping health is reversing such that perceived domestic gender inequity has a significant health impact on men, while for women only education and financial strain are contributory. These outcomes were identified only when data were sex-disaggregated

Mechanism of efficient double-strand break repair by a long non-coding RNA.

Mechanistic studies in DNA repair have focused on roles of multi-protein DNA complexes, so how long non-coding RNAs (lncRNAs) regulate DNA repair is less well understood. Yet, lncRNA LINP1 is over-expressed in multiple cancers and confers resistance to ionizing radiation and chemotherapeutic drugs. Here, we unveil structural and mechanistic insights into LINP1's ability to facilitate non-homologous end joining (NHEJ). We characterized LINP1 structure and flexibility and analyzed interactions with the NHEJ factor Ku70/Ku80 (Ku) and Ku complexes that direct NHEJ. LINP1 self-assembles into phase-separated condensates via RNA-RNA interactions that reorganize to form filamentous Ku-containing aggregates. Structured motifs in LINP1 bind Ku, promoting Ku multimerization and stabilization of the initial synaptic event for NHEJ. Significantly, LINP1 acts as an effective proxy for PAXX. Collective results reveal how lncRNA effectively replaces a DNA repair protein for efficient NHEJ with implications for development of resistance to cancer therapy