Genomic Analysis of Homotypic Vacuole Fusion

Yeast vacuoles undergo fission and homotypic fusion, yielding one to three vacuoles per cell at steady state. Defects in vacuole fusion result in vacuole fragmentation. We have screened 4828 yeast strains, each with a deletion of a nonessential gene, for vacuole morphology defects. Fragmented vacuoles were found in strains deleted for genes encoding known fusion catalysts as well as 19 enzymes of lipid metabolism, 4 SNAREs, 12 GTPases and GTPase effectors, 9 additional known vacuole protein-sorting genes, 16 protein kinases, 2 phosphatases, 11 cytoskeletal proteins, and 28 genes of unknown function. Vacuole fusion and vacuole protein sorting are catalyzed by distinct, but overlapping, sets of proteins. Novel pathways of vacuole priming and docking emerged from this deletion screen. These include ergosterol biosynthesis, phosphatidylinositol (4,5)-bisphosphate turnover, and signaling from Rho GTPases to actin remodeling. These pathways are supported by the sensitivity of the late stages of vacuole fusion to inhibitors of phospholipase C, calcium channels, and actin remodeling. Using databases of yeast protein interactions, we found that many nonessential genes identified in our deletion screen interact with essential genes that are directly involved in vacuole fusion. Our screen reveals regulatory pathways of vacuole docking and provides a genomic basis for studies of this reaction

The Rho GDI Rdi1 regulates Rho GTPases by distinct mechanisms

© 2008 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0).The small guanosine triphosphate (GTP)-binding proteins of the Rho family are implicated in various cell functions, including establishment and maintenance of cell polarity. Activity of Rho guanosine triphosphatases (GTPases) is not only regulated by guanine nucleotide exchange factors and GTPase-activating proteins but also by guanine nucleotide dissociation inhibitors (GDIs). These proteins have the ability to extract Rho proteins from membranes and keep them in an inactive cytosolic complex. Here, we show that Rdi1, the sole Rho GDI of the yeast Saccharomyces cerevisiae, contributes to pseudohyphal growth and mitotic exit. Rdi1 interacts only with Cdc42, Rho1, and Rho4, and it regulates these Rho GTPases by distinct mechanisms. Binding between Rdi1 and Cdc42 as well as Rho1 is modulated by the Cdc42 effector and p21-activated kinase Cla4. After membrane extraction mediated by Rdi1, Rho4 is degraded by a novel mechanism, which includes the glycogen synthase kinase 3β homologue Ygk3, vacuolar proteases, and the proteasome. Together, these results indicate that Rdi1 uses distinct modes of regulation for different Rho GTPases.Deutsche Forschungsgemeinschaf

Sport, and use of anabolic androgenic steroids among Icelandic high school students: a critical test of three perspectives

<p>Abstract</p> <p>Background</p> <p>This study investigates the use of anabolic androgenic steroids (AAS) among a national representative sample of high school students in Iceland. We test several hypotheses drawn from three perspectives. The first perspective focuses on the use of AAS as an individual phenomenon motivated by the desire to succeed in sport. The second perspective views the use of AAS as shaped by norms and values embedded in social relationships of formally organized sport. The third perspective suggests that factors outside sport, which have been shown to correlate with the use of other substances, predict the use of AAS.</p> <p>Method</p> <p>We use logistic regression and predicted probabilities to analyze data from a national representative survey of 11031 Icelandic high school students.</p> <p>Results</p> <p>Our results indicated that the use of AAS is not significantly related to participation in formally organized sports. However, it positively relates to fitness and physical training in informal contexts. We found a relatively strong relationship between the use of AAS and the use of illicit substances and a moderate relationship between AAS use and alcohol and tobacco consumption. We also found a significant negative relationship between AAS use and school integration and school achievement, and a significant positive relationship between AAS use and school anomie. The relation between AAS use and family-related variables was weaker. Finally, we found that the relationship between sport participation, physical exercise, and AAS use varies across levels of anomie and integration.</p> <p>Conclusion</p> <p>Our findings suggest that the use of AAS and especially illegal substances should be considered more as a social and a health problem rather than a sport specific issue. We found that high school students participating in fitness and informal training outside of formally organized sport clubs are the main risk group and should be the target of prevention efforts. However, this should not be done at the expense of general risk factors that affect AAS and other substances used by the general population. Finally, we suggest that prevention efforts should target both groups and individuals.</p

Spectatorship and Social Cognition: Per Persson's Understanding Cinema

This paper places Per Persson's book Understanding Cinema in relation to cognitive film theory and the increasing necessity of it to further engage with the psychological and anthropological literature on social cognition. This paper focuses upon Persson's ability to integrate cognitive and cultural perspectives when explaining a spectator's comprehension of point‐of‐view editing, variable framing and character psychology. It is argued that Persson's theoretical framework would have been more explanatorily complete if it had adopted an analytical dualist stance as a means to theorise the ontologically mixed nature of the psychological processes in question