Unconventional myosin proteins of the MyTH-FERM superclass are involved in intrafilopodial trafficking, are thought to be mediators of membrane-cytoskeleton interactions, and are linked to several forms of deafness in mammals. Here we show that the Drosophila myosin XV homolog, Sisyphus, is expressed at high levels in leading edge cells and their cellular protrusions during the morphogenetic process of dorsal closure. Sisyphus is required for the correct alignment of cells on opposing sides of the fusing epithelial sheets, as well as for adhesion of the cells during the final zippering/fusion phase. We have identified several putative Sisyphus cargos, including DE-cadherin (also known as Shotgun) and the microtubule-linked proteins Katanin-60, EB1, Milton and aPKC. These cargos bind to the Sisyphus FERM domain, and their binding is in some cases mutually exclusive. Our data suggest a mechanism for Sisyphus in which it maintains a balance between actin and microtubule cytoskeleton components, thereby contributing to cytoskeletal cross-talk necessary for regulating filopodial dynamics during dorsal closure.

Objective-Social norms have been associated with a wide range of health behaviors. In this study, we examined whether the social norms of HIV risk behaviors are clustered within social networks and whether the norms of network members are linked to the risk behaviors of their social network members.Design-Data were collected from the baseline assessment of 354 networks with 933 participants in a network oriented HIV prevention intervention targeting injection drug users (IDUs) in the Philadelphia, US and Chiang Mai, Thailand.Main Outcome Measures-Four descriptive HIV risk norms of sharing needles, cookers, and cotton and front or back-loading among friends who inject were assessed.Results-Three of four injection risk norms (sharing needle, cookers, and cotton) were found to be significantly clustered. In Philadelphia, one network member's (the index participant) norms of sharing needles and front or back-loading were found to be significantly associated with the network members' risk behaviors, and the norm of sharing cotton was marginally associated. Conclusion-The results of this study suggest that among injection drug users, social norms are clustered within networks; social networks are a meaningful level of analyses for understanding how social norms lead to risk behaviors, providing important data for intervening to reduce injection related HIV risks. In this study, we examined how social norms of HIV risk behaviors are structured within social networks and how these norms may be linked to subsequent risk behavior. A critical issue in altering health behaviors is how individual-level behavior change can be leveraged into group or community level change. How can a minority of individuals who have adopted a new set of health behaviors lead to acceptance and adoption of these behaviors within the larger community (Prislin & Christensen, 2005)? One conceptual approach to community level change is through social diffusion, wherein prominent individuals within a group, known as early adopters, first embrace a new behavior (Rogers, 2003). It has been hypothesized that successful social diffusion early adopters lead others to change their behavior. In this manner, the new behavior is diffused through the community. Social diffusion has been used to evaluate changes in antibiotic prescribing practices, uptake of medical technology, and the spread of fads and new commercial products (Jacobsen & Guastello, 2007;Hashimoto et al., 2006;Van den Bulte & Lilien, 2001). KeywordsInvestigators have utilized the process of social diffusion information for planned behavioral interventions. Opinion leader models of health behavior change have utilized influential individuals to diffuse changes in health behaviors. In the field of HIV prevention, community opinion leaders' models of behavior change have been successful in reducing risk behaviors in many but not all studies (Elford, Bolding, & Sherr, 2004;Kelly et al., 1991;Sikkema et al, 2005). Although several opinion leader interventions have been successful in alterin...

Integration of patterning cues via transcriptional networks to coordinate gene expression is critical during morphogenesis and misregulated in cancer. Using DNA adenine methyltransferase (Dam)ID chromatin profiling, we identified a protein-protein interaction between the Drosophila Myc oncogene and the Groucho corepressor that regulates a subset of direct dMyc targets. Most of these shared targets affect fate or mitosis particularly during neurogenesis, suggesting the dMyc-Groucho complex may coordinate fate acquisition with mitotic capacity during development. We find an antagonistic relationship between dMyc and Groucho that mimics the antagonistic interactions found for EGF and Notch signaling: dMyc is required to specify neuronal fate and enhance neuroblast mitosis, whereas Groucho is required to maintain epithelial fate and inhibit mitosis. Our results suggest that the dMyc-Groucho complex defines a previously undescribed mechanism of Myc function and may serve as the transcriptional unit that integrates EGF and Notch inputs to regulate early neuronal development.neurogenesis ͉ Drosophila ͉ stem cell ͉ cell fate ͉ mitosis

ELF5, an Ets family transcription factor found exclusively in epithelial cells, is expressed in the distal lung epithelium during embryogenesis, then becomes restricted to proximal airways at the end of gestation and postnatally. To test the hypothesis that ELF5 represses distal epithelial differentiation, we generated a transgenic mouse model in which a doxycycline inducible HA-tagged mouse Elf5 transgene was placed under the control of the lung epithelium-specific human SFTPC promoter. We found that expressing high levels of ELF5 during early lung development disrupted branching morphogenesis and produced a dilated epithelium. The effects of ELF5 on morphogenesis were stage-dependent, since inducing the transgene on E16.5 had no effect on branching. ELF5 reduced expression of the distal lung epithelial differentiation markers Erm, Napsa and Sftpc, and type II cell ultrastructural differentiation was immature. ELF5 overexpression did not induce the proximal airway epithelial markers Ccsp and Foxj1, but did induce expression of p63, a marker of basal cells in the trachea and esophagus. High ELF5 levels also induced the expression of genes found in other endodermal epithelia but not normally associated with the lung. These results suggest that precise levels of ELF5 regulate the specification and differentiation of epithelial cells in the lung.