This paper deals with a number of conceptual and theoretical issues that underlie the proposal to employ narrative explanations in science education: What is narrative? What is explanation? and What is narrative explanation? In answering these questions, we develop a framework of narrative elements and characteristics of narrative explanations. Two possible examples of narrative explanation are presented and examined in light of the framework. This examination brings to light various conceptual and empirical questions related to the examples and to the larger issue of the use of examples like them in science instruction. The value of the framework lies partly in its power to point to such questions. The questions can guide a program of theoretical and empirical research into the psychological reality of the narrative form of explanation, the existence of narrative explanations in science, the use of narrative explanations in science teaching, and the nature and extent of the narrative effect upon which proposals for the use of narrative often are justified.

Phosphoinositides play key regulatory roles in vesicular transport pathways in eukaryotic cells. Clathrin-mediated membrane trafficking has been shown to require phosphoinositides, but little is known about the enzyme(s) responsible for their formation. Here we report that clathrin functions as an adaptor for the class II PI 3-kinase C2alpha (PI3K-C2alpha), binding to its N-terminal region and stimulating its catalytic activity, especially toward phosphorylated inositide substrates. Further, we show that endogenous PI3K-C2alpha is localized in coated pits and that exogenous expression affects clathrin-mediated endocytosis and sorting in the trans-Golgi network. These findings provide a mechanistic basis for localized inositide generation at sites of clathrin-coated bud formation, which, with recruitment of inositide binding proteins and subsequent synaptojanin-mediated phosphoinositide hydrolysis, may regulate coated vesicle formation and uncoating.

In recent years, a large family of phosphoinositide 3-kinase (PI3K) isozymes has been characterized and cloned. Several of these PI3K enzymes have overlapping tissue distributions and it remains unclear if and how their 3-phosphoinositide products elicit differential, intracellular effects. One possibility is that the PI3K enzymes display a restricted distribution within the cell to produce their 3-phospholipid products in specific, subcellular compartments. In the present study we characterize the subcellular distribution of the novel class II PI3K isozyme PI3K-C2␣ in several mammalian cell types. Differential centrifugation of COS-1 and U937 cells together with Western blot analysis demonstrated that PI3K-C2␣ is constitutively associated with phospholipid membranes. Centrifugation of rat brain homogenates and Western blotting revealed that in contrast to the class IA PI3K enzymes, PI3K-C2␣ could be copurified with a population of clathrin-coated vesicles (CCVs). Furthermore, a PI3K activity refractory to wortmannin treatment was detected in CCV preparations consistent with the presence of the PI3K-C2␣ isozyme. These biochemical observations were supported by immunofluorescence analysis that revealed PI3K-C2␣ to have a punctate distribution and an enrichment of immunoreactivity within a perinuclear site consistent with its presence in the endoplasmic reticulum or Golgi apparatus. Dual label immunofluorescence demonstrated that in this region, the distribution of PI3K-C2␣ closely paralleled that of ␥-adaptin, a component of the AP-1 adaptor that is present in the trans-Golgi and the trans-Golgi network (TGN) resident protein TGN-46. Neither the phospholipid association nor the subcellular localization of PI3K-C2␣ was dependent upon either its COOH-terminal PX or C2 domains. Mutants lacking these domains demonstrated a similar distribution to the wild type enzyme when expressed as recombinant proteins. Treatment of cells with brefeldin A disrupted the perinuclear staining pattern of both PI3K-C2␣ and the AP-1 complex demonstrating that the localization of both molecules at the TGN is dependent upon ADP-ribosylation factor GTPase activity.Phosphoinositide 3-kinase (PI3K) 1 was originally isolated from bovine brain as a heterodimeric complex consisting of an 85-kDa regulatory subunit and a 110-kDa catalytic subunit. Since then, additional purification strategies and reverse transcriptase-polymerase chain reaction-based approaches have identified seven other mammalian PI3K catalytic subunits. On

Experiences of profound existential or spiritual significance can be triggered reliably through psychopharmacological means using psychedelic substances. However, little is known about the benefits of religious, spiritual, or mystical experiences (RSMEs) prompted by psychedelic substances, as compared with those that occur through other means. In this study, 739 self-selected participants reported the psychological impact of their RSMEs and indicated whether they were induced by a psychedelic substance. Experiences induced by psychedelic substances were rated as more intensely mystical (d = .75, p < .001), resulted in a reduced fear of death (d = .21, p < .01), increased