MicroRNAs (miRNAs) circulate in the bloodstream in a highly stable, extracellular form and are being developed as blood-based biomarkers for cancer and other diseases. However, the mechanism underlying their remarkable stability in the RNase-rich environment of blood is not well understood. The current model in the literature posits that circulating miRNAs are protected by encapsulation in membrane-bound vesicles such as exosomes, but this has not been systematically studied. We used differential centrifugation and size-exclusion chromatography as orthogonal approaches to characterize circulating miRNA complexes in human plasma and serum. We found, surprisingly, that the majority of circulating miRNAs cofractionated with protein complexes rather than with vesicles. miRNAs were also sensitive to protease treatment of plasma, indicating that protein complexes protect circulating miRNAs from plasma RNases. Further characterization revealed that Argonaute2 (Ago2), the key effector protein of miRNA-mediated silencing, was present in human plasma and eluted with plasma miRNAs in size-exclusion chromatography. Furthermore, immunoprecipitation of Ago2 from plasma readily recovered non-vesicle-associated plasma miRNAs. The majority of miRNAs studied copurified with the Ago2 ribonucleoprotein complex, but a minority of specific miRNAs associated predominantly with vesicles. Our results reveal two populations of circulating miRNAs and suggest that circulating Ago2 complexes are a mechanism responsible for the stability of plasma miRNAs. Our study has important implications for the development of biomarker approaches based on capture and analysis of circulating miRNAs. In addition, identification of extracellular Ago2-miRNA complexes in plasma raises the possibility that cells release a functional miRNA-induced silencing complex into the circulation.icroRNAs (miRNAs) are a class of approximately 22 nucleotide noncoding RNAs that mediate posttranscriptional gene regulation by binding to and repressing specific messenger RNA targets. We and others previously demonstrated that miRNAs are present in the human circulation in a cell-free form and that altered plasma and serum miRNA profiles are observed in cancer and other diseases (1-9). This, along with the finding that miRNAs are remarkably stable in plasma despite high circulating RNase activity (1), suggests that miRNAs may be developed into a powerful new class of blood-based biomarkers.The mechanism underlying the unexpected stability of cell-free miRNAs in the RNase-rich environment of blood has not been systematically investigated, although it has important implications for miRNA biomarker development and for potential biological functions of circulating miRNAs (10). Currently, the dominant model for circulating miRNA stability is that miRNAs are released from cells in membrane-bound vesicles, which protect them from blood RNase activity. Vesicles proposed as carriers of circulating miRNAs include exosomes, which are 50-to 90-nm vesicles arising from multivesicular bodie...

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An unprecedented number of human sexuality studies have been initiated in response to the acquired immune deficiency syndrome (AIDS) epidemic. Unfortunately, methodological developments in the field of sex research have been slow in meeting the demands of AIDS investigations focusing on the diverse populations at risk for infection with the human immunodeficiency virus (e.g., adolescents, gay men, intravenous-drug users, ethnic minorities, elderly transfusees). In this article, we review and integrate current literature on measurement error and participation bias in sex research, with an emphasis on collecting sexual information in the context of AIDS. The relevance of these findings for AIDS-related sex research is discussed, and recommendations are made to guide future investigations.

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Current strategic human resource management theory suggests that HR flexibility is a dynamic capability facilitating a firm's rapid response to changing economic environments, thus creating value. However, the components of HR flexibility and their potential relationship to firm performance have not been empirically examined. We hypothesize that flexibility of employee skills, employee behaviors, and HR practices represent critical sub-dimensions of HR flexibility and are related to superior firm performance. Results based on perceptual measures of HR flexibility and accounting measures of firm performance support this prediction. While skill, behavior, and HR practice flexibility are significantly associated with an index of firm financial performance, we find that only skill flexibility contributes to cost efficiency.

While previous literature tends to focus on role models as significant other people, particularly in one's early life, this study finds that individuals tend to construe their role models as a selection process of attributes from others throughout their career. I discovered that individuals primarily construe their role models along positive/negative, global/specific, close/distant, and hierarchically superior/peer-subordinate dimensions, and that across the career span, the tendency to observe role models did not change. Rather, the emphasis placed on different dimensions of role models changes. Early-stage respondents who are working on creating a viable self-concept were more likely to construe their role models as positive, close, and sources of a range of attributes. Middle- and late-stage respondents were more likely to see their role models as sources of specific, and often negative, attributes. The study suggests that these observed patterns are related to individuals' increasing confidence in their professional self-concept. In early stages, individuals pay attention to role models to create a viable self-concept; in middle stages, they seek to refine their self-concept, and in late stages, they seek to enhance and affirm their self-concept.

Organizations are rife with situations likely to cause employee anger, including complex relationships, chronic pressure, high stakes, and factors beyond individual control. The importance of this discrete emotion has led to a range of studies exploring the implications of anger for critical organizational phenomena, including emotion norms, leadership, gender issues, status and power, and cross-cultural differences. Despite the dramatic increase in scholarly attention over the past decade to understanding anger experience and expression in organizations, there exist few current reviews and little integration of this diverse literature. By combining a psychological perspective of anger as an episodic process with an organizational perspective emphasizing contextual effects and norms, this review will summarize current research in this vital area, provide a model for understanding and integrating this work, and propose themes for future research.

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