Natural killer (NK) cells play critical roles defending against tumors and pathogens. We show that mice lacking both transcription factors Eomesodermin (Eomes) and T-bet failed to develop NK cells. ...Developmental stability of immature NK cells constitutively expressing the death ligand TRAIL depended on T-bet. Conversely, maturation characterized by loss of constitutive TRAIL expression and induction of Ly49 receptor diversity and integrin CD49b (DX5
+) required Eomes. Mature NK cells from which Eomes was deleted reverted to phenotypic immaturity if T-bet was present or downregulated NK lineage antigens if T-bet was absent, despite retaining expression of Ly49 receptors. Fetal and adult hepatic hematopoiesis restricted Eomes expression and limited NK development to the T-bet-dependent, immature stage, whereas medullary hematopoiesis permitted Eomes-dependent NK maturation in adult mice. These findings reveal two sequential, genetically separable checkpoints of NK cell maturation, the progression of which is metered largely by the anatomic localization of hematopoiesis.
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► NK cells are absent in mice lacking both T-bet and Eomes ► T-bet is essential to stabilize immature, TRAIL
+ NK cells ► Eomes is required to develop and partially maintain mature, DX5
+ NK cells ► NK cells lose NK antigens after deletion of T-bet and Eomes
We hypothesize that a major macroeconomic crisis triggers four alternative responses among nascent entrepreneurs: disengagement, delay, compensation, and adaptation. We also suggest that commitment ...and ambition (or “high potential”) moderate these responses. Our most important finding is the relative absence of behavioral crisis responses. However, crises may make high–tech founders become more likely to disengage, whereas the opposite holds for founders far into the process. Our study sheds light on the mechanisms behind aggregate effects of crises on the number and type of start–ups in an economy, and can guide future research on the effect of crises on nascent entrepreneurship.
Interleukin-15 (IL-15) is a pleiotropic cytokine that classically acts to support the development, maintenance, and function of killer lymphocytes. IL-15 is abundant in the uterus prior to and during ...pregnancy, but it is subject to tight spatial and temporal regulation. Both mouse models and human studies suggest that homeostasis of IL-15 is essential for healthy pregnancy. Dysregulation of IL-15 is associated with adverse outcomes of pregnancy. Herein, we review producers of IL-15 and responders to IL-15, including non-traditional responders in the maternal uterus and fetal placenta. We also review regulation of IL-15 at the maternal-fetal interface and propose mechanisms of action of IL-15 to facilitate additional study of this critical cytokine in the context of pregnancy.
Longitudinal panel studies of large, random samples of business start-ups captured at the preoperational stage allow researchers to address core issues for entrepreneurship research, namely, the ...processes of creation of new business ventures as well as their antecedents and outcomes. Here, we perform a methods-orientated review of all 83 journal articles that have used this type of data set, our purpose being to assist users of current data sets as well as designers of new projects in making the best use of this innovative research approach. Our review reveals a number of methods issues that are largely particular to this type of research. We conclude that amidst exemplary contributions, much of the reviewed research has not adequately managed these methods challenges, nor has it made use of the full potential of this new research approach. Specifically, we identify and suggest remedies for context-specific and interrelated methods challenges relating to sample definition, choice of level of analysis, operationalization and conceptualization, use of longitudinal data and dealing with various types of problematic heterogeneity. In addition, we note that future research can make further strides towards full utilization of the advantages of the research approach through better matching (from either direction) between theories and the phenomena captured in the data, and by addressing some under-explored research questions for which the approach may be particularly fruitful.
High density lipoproteins (HDL) are a heterogeneous family of particles that contain distinct complements of proteins that define their function. Thus, it is important to accurately and sensitively ...identify proteins associated with HDL. Here we highlight the HDL Proteome Watch Database which tracks proteomics studies from different laboratories across the world.
In 45 published reports, almost 1000 individual proteins have been detected in preparations of HDL. Of these, 251 have been identified in at least three different laboratories. The known functions of these consensus HDL proteins go well beyond traditionally recognized roles in lipid transport with many proteins pointing to HDL functions in innate immunity, inflammation, cell adhesion, hemostasis and protease regulation, and even vitamin and metal binding.
The HDL proteome derived across multiple studies using various methodologies provides confidence in protein identifications that can offer interesting new insights into HDL function. We also point out significant issues that will require additional study going forward.
This book explores the rationales for religious silence in early medieval abbeys, and the use of sign language among monks when rules of silence forbade them from speaking. It provides a full-length ...study of the silent language of hand signs employed by the monks of the Abbey of Cluny in France.
Abstract High density lipoproteins (HDL) represent a compositionally diverse population of particles in the circulation, containing a wide variety of lipids and proteins. Gene ontology functional ...analysis of the 96 commonly identified HDL binding proteins reveals that almost half of these proteins are either proteases or have known roles in protease regulation. Here, we discuss the activities of some of these proteins in regard to their roles in regulating proteases involved in inflammation, coagulation, and complement activation, particularly in the context of atherosclerosis. The overall goal of this review is to discuss potential functional roles of HDL in protease regulatory pathways based on current literature and known functions of HDL binding proteins and to promote the consideration of HDL as a global modulator of proteolytic equilibrium.
HDL cholesterol (HDL-C) is a commonly used lipid biomarker for assessing cardiovascular health. While a central focus has been placed on the role of HDL in the reverse cholesterol transport (RCT) ...process, our appreciation for the other cardioprotective properties of HDL continues to expand with further investigation into the structure and function of HDL and its specific subfractions. The development of novel assays is empowering the research community to assess different aspects of HDL function, which at some point may evolve into new diagnostic tests.
This review discusses our current understanding of the formation and maturation of HDL particles via RCT, as well as the newly recognized roles of HDL outside RCT. The antioxidative, antiinflammatory, antiapoptotic, antithrombotic, antiinfective, and vasoprotective effects of HDL are all discussed, as are the related methodologies for assessing these different aspects of HDL function. We elaborate on the importance of protein and lipid composition of HDL in health and disease and highlight potential new diagnostic assays based on these parameters.
Although multiple epidemiologic studies have confirmed that HDL-C is a strong negative risk marker for cardiovascular disease, several clinical and experimental studies have yielded inconsistent results on the direct role of HDL-C as an antiatherogenic factor. As of yet, our increased understanding of HDL biology has not been translated into successful new therapies, but will undoubtedly depend on the development of alternative ways for measuring HDL besides its cholesterol content.
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