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second model, the two main conditions were parametrically modulated by the two categories, respectively (SOM, S5.1). The activation of the precuneus was higher for hard dominance-solvable games than for easy ones ( Fig. 4A and table S10). The activation of the insula was higher for the highly focal coordination games than for less focal ones ( Fig. 4B and table S11). Previous studies also found that precuneus activity increased when the number of planned moves increased (40, 41). The higher demand for memory-related imagery and memory retrieval may explain the greater precuneus activation in hard dominance-solvable games. In highly focal coordination games, the participants may have felt quite strongly that the pool students must notice the same salient feature. This may explain why insula activation correlates with NCI.Participants might have disagreed about which games were difficult. We built a third model to investigate whether the frontoparietal activation correlates with how hard a dominance-solvable game is and whether the activation in insula and ACC correlates with how easy a coordination game is. Here, the two main conditions were parametrically modulated by each participant's probability of obtaining a reward in each game (SOM, S2.2 and S5.2). We found a negative correlation between the activation of the precuneus and the participant's probability of obtaining a reward in dominance-solvable games ( Fig. 4C and table S12), which suggests that dominance-solvable games that yielded lower payoffs presented harder mental challenges. In a previous study on working memory, precuneus activity positively correlated with response times, a measure of mental effort (24). Both findings are consistent with the interpretation that subjective measures reflecting harder tasks (higher efforts) correlate with activation in precuneus. A positive correlation between insula activation and the participant's probability of obtaining a reward again suggests that coordination games with a highly salient feature strongly activated the "gut feeling" reported by many participants (Fig. 4D and table S13). A previous study found that the subjective rating of "chills intensity" in music correlates with activation of insula (42). Both findings are consistent with the interpretation that the subjective intensity of how salient a stimulus is correlates with activation in insula.As mentioned, choices were made significantly faster in coordination games than in dominancesolvable games. The results of the second and third models provide additional support for the idea that intuitive and deliberative mental processes have quite different properties. The "slow and effortful" process was more heavily taxed when the dominance-solvable games were harder. The "fast and effortless" process was more strongly activated when coordination was easy.

Glucose is the preferred carbon source for most eukaryotic cells and has profound effects on many cellular functions. How Snf3p. We identified a dominant mutation in RGT2 that causes constitutive expression of several ILT genes, even in the absence of the inducer glucose. This same mutation introduced into SNF3 also causes glucoseindependent expression of ILT genes. Thus, the Rgt2p and Snf3p glucose transporters appear to act as glucose receptors that generate an intracellular glucose signal, suggesting that glucose signaling in yeast is a receptor-mediated process.inhibited in glucose-grown cells, leading to derepression of the HXT genes.

Subcellular distributions of the five human Arf proteins were examined, using a set of isoform-specific polyclonal and a pan-Arf monoclonal antibodies. Subcellular fractionation of cultured mammalian cells allowed the demonstration that Arf6 is uniquely localized to the plasma membranes of Chinese hamster ovary cells. The plasma membrane distrubution was unaffected by either GTP␥S (guanosine 5-O-(3-thio)triphosphate) or brefeldin A, an activator and inhibitor of Arf activities, respectively. In contrast, Arf proteins 1, 3, 4, and 5 were predominantly cytosolic but could be recruited to a variety of intracellular membranes, but not plasma membranes, upon incubation in the presence of GTP␥S. The GTP␥S-promoted binding of the cytosolic Arf proteins to membranes was blocked by brefeldin A. The stable association of Arf6 with plasma membranes and the insensitivity of its localization to either GTP␥S or brefeldin A revealed a clear distinction between Arf6 and the other Arf isoforms. Localization of Arf6 to the plasma membrane suggests a unique cellular role for this isoform at the plasma membrane, but failure to find endogenous Arf6 on endocytic structures, including clathrin-coated vesicles, appears inconsistent with the proposed role of Arf6 in assembly of coat structures or endosomes in transfected fibroblasts (1, 2).The ADP-ribosylation factor (Arf) 1 family is a group of structurally related proteins that form a subset of the Ras superfamily of regulatory GTP-binding proteins (for a recent review, see Ref. 3). In addition to serving as cofactors for cholera toxin-catalyzed ADP-ribosylation, Arf proteins have more recently been associated with a wide array of functions. These include acting as regulators of the binding of coat proteins and adaptins to intracellular membranes (4, 5), activators of phospholipase D (6, 7), regulators of ER and Golgi morphology and function (8, 9), and cytosolic factors conferring sensitivity to GTP␥S in cell-free assays of intra-Golgi (10 -12) and ER-Golgi transport (13), and endosome (14) and nuclear membrane fusion (15, 16).The importance of Arf proteins in both membrane traffic and organelle organization was manifest due to the sensitivities of most Arf proteins to both GTP␥S, a slowly hydrolyzable GTP analog, and to brefeldin A (BFA), a fungal metabolite capable of inhibiting guanine nucleotide exchange on Arf in a crude system (17-19). The activation (GTP binding) and deactivation (GTP hydrolysis) cycle of Arf action in cells is thought to coincide with its binding and release, respectively, from intracellular membranes. In this model, activation of a soluble Arf protein results in its translocation to a membrane and the recruitment, through unknown mechanisms, of coat proteins or adaptor complexes to that membrane. It remains unclear how, or even if, Arf-mediated activation of phospholipase D or cholera toxin relate to mechanisms of regulation of membrane transport by Arf proteins.

Genomics is not only essential for students to understand biology but also provides unprecedented opportunities for undergraduate research. The goal of the Genomics Education Partnership (GEP), a collaboration between a growing number of colleges and universities around the country and the Department of Biology and Genome Center of Washington University in St. Louis, is to provide such research opportunities. Using a versatile curriculum that has been adapted to many different class settings, GEP undergraduates undertake projects to bring draft-quality genomic sequence up to high quality and/or participate in the annotation of these sequences. GEP undergraduates have improved more than 2 million bases of draft genomic sequence from several species of Drosophila and have produced hundreds of gene models using evidence-based manual annotation. Students appreciate their ability to make a contribution to ongoing research, and report increased independence and a more active learning approach after participation in GEP projects. They show knowledge gains on pre- and postcourse quizzes about genes and genomes and in bioinformatic analysis. Participating faculty also report professional gains, increased access to genomics-related technology, and an overall positive experience. We have found that using a genomics research project as the core of a laboratory course is rewarding for both faculty and students.