Social Network Types and Acute Stroke Preparedness Behavior

Objectives: Presence of informal social networks has been associated with favorable health and behaviors, but whether different types of social networks impact on different health outcomes remains largely unknown. We examined the associations of different social network types (marital dyad, household, friendship, and informal community networks) with acute stroke preparedness behavior. We hypothesized that marital dyad best matched the required tasks and is the most effective network type for this behavior. Methods: We collected in-person interview and medical record data for 1,077 adults diagnosed with stroke and transient ischemic attack. We used logistic regression analyses to examine the association of each social network with arrival at the emergency department (ED) within 3 h of stroke symptoms. Results: Adjusting for age, race-ethnicity, education, gender, transportation type to ED and vascular diagnosis, being married or living with a partner was significantly associated with early arrival at the ED (odds ratio = 2.0, 95% confidence interval: 1.2–3.1), but no significant univariate or multivariate associations were observed for household, friendship, and community networks. Conclusions: The marital/partnership dyad is the most influential type of social network for stroke preparedness behavior

Structure of the active form of human Origin Recognition Complex and its ATPase motor module

Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double-layered shallow corkscrew, with the AAA+ and AAA+-like domains forming one layer, and the winged-helix domains (WHDs) forming a top layer. CDC6 fits easily between ORC1 and ORC2, completing the ring and the DNA-binding channel, forming an additional ATP hydrolysis site. Analysis of the ATPase activity of the complex provides a basis for understanding ORC activity as well as molecular defects observed in Meier-Gorlin Syndrome mutations

The dynamic nature of the human origin recognition complex revealed through five cryoEM structures

Genome replication is initiated from specific origin sites established by dynamic events. The Origin Recognition Complex (ORC) is necessary for orchestrating the initiation process by binding to origin DNA, recruiting CDC6, and assembling the MCM replicative helicase on DNA. Here we report five cryoEM structures of the human ORC (HsORC) that illustrate the native flexibility of the complex. The absence of ORC1 revealed a compact, stable complex of ORC2-5. Introduction of ORC1 opens the complex into several dynamic conformations. Two structures revealed dynamic movements of the ORC1 AAA+ and ORC2 winged-helix domains that likely impact DNA incorporation into the ORC core. Additional twist and pinch motions were observed in an open ORC conformation revealing a hinge at the ORC5·ORC3 interface that may facilitate ORC binding to DNA. Finally, a structure of ORC was determined with endogenous DNA bound in the core revealing important differences between human and yeast origin recognition

Evolution of DNA replication origin specification and gene silencing mechanisms.

DNA replication in eukaryotic cells initiates from replication origins that bind the Origin Recognition Complex (ORC). Origin establishment requires well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. A 3.9 Å structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed that a loop within Orc2 inserts into a DNA minor groove and an α-helix within Orc4 inserts into a DNA major groove. Using a massively parallel origin selection assay coupled with a custom mutual-information-based modeling approach, and a separate analysis of whole-genome replication profiling, here we show that the Orc4 α-helix contributes to the DNA sequence-specificity of origins in S. cerevisiae and Orc4 α-helix mutations change genome-wide origin firing patterns. The DNA sequence specificity of replication origins, mediated by the Orc4 α-helix, has co-evolved with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA interference

Language barriers between physicians and patients are not associated with thrombolysis of stroke mimics

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To belong is to matter: sense of belonging enhances meaning in life

In four methodologically diverse studies (N = 644), we found correlational (Study 1), longitudinal (Study 2), and experimental (Studies 3 and 4) evidence that a sense of belonging predicts how meaningful life is perceived to be. In Study 1 (n = 126), we found a strong positive correlation between sense of belonging and meaningfulness. In Study 2 (n = 248), we found that initial levels of sense of belonging predicted perceived meaningfulness of life, obtained 3 weeks later. Furthermore, initial sense of belonging predicted independent evaluations of participants essays on meaning in life. In Studies 3 (n = 105) and 4 (n = 165), we primed participants with belongingness, social support, or social value and found that those primed with belongingness (Study 3) or who increased in belongingness (Study 4) reported the highest levels of perceived meaning. In Study 4, belonging mediated the relationship between experimental condition and meaning

Family as a salient source of meaning in young adulthood

Five studies demonstrated the role of family relationships as an important source of perceived meaning in life. In Study 1 (n=450), 68% participants reported that their families were the single most significant contributor to personal meaning. Study 2 (n=231) participants ranked family above 12 likely sources of meaning. Studies 3 (n=87) and 4 (n=130) demonstrated that participants' reports of their closeness to family (Study 3) and support from family (Study 4) predicted perceived meaning in life, even when controlling for several competing variables. Study 5 (n=261) ruled out social desirability as an alternative explanation to the proposed relationship between family and meaning. We conclude that for young adults, family relationships are a primary source of meaning in life and they contribute to their sense of meaning