Gβ1 controls collective cell migration by regulating the protrusive activity of leader cells in the posterior lateral line primordium

Collective cell migration is critical for normal development, tissue repair and cancer metastasis. Migration of the posterior lateral line primordium (pLLP) generates the zebrafish sensory organs (neuromasts, NMs). This migration is promoted by the leader cells at the leading edge of the pLLP, which express the G protein-coupled chemokine receptor Cxcr4b and respond to the chemokine Cxcl12a. However, the mechanism by which Cxc112a/Cxcr4b signaling regulates pLLP migration remains unclear. Here we report that signal transduction by the heterotrimeric G protein subunit Gβ1 is essential for proper pLLP migration. Although both Gβ1 and Gβ4 are expressed in the pLLP and NMs, depletion of Gβ1 but not Gβ4 resulted in an arrest of pLLP migration. In embryos deficient for Gβ1, the pLLP cells migrated in an uncoordinated fashion and were unable to extend protrusions at the leading front, phenocopying those in embryos deficient for Cxcl12a or Cxcr4b. A transplantation assay showed that, like Cxcr4b, Gβ1 is required only in the leader cells of the pLLP. Analysis of F-actin dynamics in the pLLP revealed that whereas wild-type leader cells display extensive actin polymerization in the direction of pLLP migration, counterparts defective for Gβ1, Cxcr4b or Cxcl12a do not. Finally, synergy experiments revealed that Gβ1 and Cxcr4b interact genetically in regulating pLLP migration. Collectively, our data indicate that Gβ1 controls migration of the pLLP, likely by acting downstream of the Cxcl12a/Cxcr4b signaling. This study also provides compelling evidence for functional specificity among Gβ isoforms in vivo.     

Methylene amine substituted arylindenopyrimidines as potent adenosine A2A/A1 antagonists

A novel series of arylindenopyrimidines were identified as A_2A and A₁ receptor antagonists. The series was optimized for in vitro activity by substituting the 8- and 9-positions with methylene amine substituents. The compounds show excellent activity in mouse models of Parkinson’s disease when dosed orally.     

Owlifier: Creating OWL-DL ontologies from simple spreadsheet-based knowledge descriptions

Discovery and integration of data is important in many ecological studies, especially those that concern broad-scale ecological questions. Data discovery and integration are often difficult and time consuming tasks for researchers, which is due in part to the use of informal, ambiguous, and sometimes inconsistent terms for describing data content. Ontologies offer a solution to this problem by providing consistent definitions of ecological concepts that in turn can be used to annotate, relate, and search for data sets. However, unlike in molecular biology or biomedicine, few ontology development efforts exist within ecology. Ontology development often requires considerable expertise in ontology languages and development tools, which is often a barrier for ontology creation in ecology. In this paper we describe an approach for ontology creation that allows ecologists to use common spreadsheet tools to describe different aspects of an ontology. We present conventions for creating, relating, and constraining concepts through spreadsheets, and provide software tools for converting these ontologies into equivalent OWL-DL representations. We also consider inverse translations, i.e., to convert ontologies represented using OWL-DL into our spreadsheet format. Our approach allows large lists of terms to be easily related and organized into concept hierarchies, and generally provides a more intuitive and natural interface for ontology development by ecologists.     

Postpartum Group Cohesion of Sympatric Deer in Texas

ABSTRACT Postpartum behavior of maternal deer may be specific to species of deer and predators. We captured sympatric white-tailed deer (Odocoileus virginianus) and mule deer (O. hemionus eremicus) fawns from radiocollared adult females in 2004–2006 on rangelands of west central Texas, USA, where predators larger than bobcats (Lynx rufus) were absent. Our objective was to determine whether differences in postpartum antipredator behavior existed between deer species, and if so, examine efficacy of those strategies. We collected postpartum group cohesion data in 2004 and 2005 by using radiotelemetry and examined dead fawns for cause of mortality. During fawns' hider phase, <3 weeks postpartum, mule deer females kept fawns closer to themselves (95% CI = 39−66 m) and twins closer to each other (95% CI = 25–49 m) than did white-tailed deer females (95% CIs = 152–234 m and 163–255 m, respectively). After 30 days postpartum, familial group cohesion was similarly tight for both species. During hider phases from 2004 to 2006, predated carcasses of white-tailed deer fawns (11 of 11) were dismembered or consumed more than mule deer fawns (7 of 13, P = 0.016), which was one line of evidence for maternal defense by mule deer adults. During hider phases in 2004 and 2005, predation rate of mule deer fawns was lower than that for white-tailed deer fawns. In 2006, predation rate increased for mule deer but was similar for white-tailed deer fawns compared with previous years. The tight cohesion strategy of mule deer exhibited in 2004 and 2005 seemed successful at thwarting small predators. Without large predators, the loose cohesion strategy of white-tailed deer females was maladaptive. When meso-predators are abundant due to extermination of larger predators, predation on fawns could increase if a deer species has relatively fixed postpartum maternal antipredator behavior.