Modifiers of mammary tumor progression and metastasis on mouse Chromosomes 7, 9, and 17

Tumor progression, the growth and dissemination of primary tumor to secondary sites, is of critical clinical importance since the vast majority of patients succumb to metastatic disease rather than to the primary tumor. Many factors are likely to influence this process, including the primary oncogenic events, environmental exposures and stress and progressive stochastic mutations. Previously, our laboratory demonstrated that an additional factor, the genetic background on which tumors arose, had a significant effect on metastatic efficiency. Using a highly metastatic transgene-induced mammary tumor model, a locus modulating metastatic efficiency, Mtes1, was localized on proximal mouse Chromosome 19. In addition, a number of additional suggestive loci were observed on several other chromosomes. To confirm the presence of these additional loci before initiating cloning strategies, chromosomal substitution strains have been constructed and assayed for modification of the cancer phenotypes. Using the chromosomal substitution strains, an additional modifier modulating tumor latency was confirmed, as well as three new modifier genes that alter the kinetics of tumor progression. Identification and analysis of these loci will likely present interesting and novel information about cancer heterogeneity in the human population.     

Inference of phylogenetic relationships within Fabriciidae (Sabellida,Annelida) using molecular and morphological data

Cladistic relationships among fabriciids have to date been explored in the context of adult morphology, but resolution has been declining as more species are described. In this study, we incorporated data on the reproductive system, including features related to the male sperm and sperm storage by females, to supplement existing data on adult morphology (for a total of 50 characters). Three nuclear DNA markers (18S rDNA approximately 1800 bp, the D1 region of 28S rDNA approximately 320 bp, and histone H3 approximately 330 bp) were sequenced from 21 species of fabriciids. We assessed the phylogeny of Fabriciidae based on an integrative analysis of these morphological and molecular characters. Our results show that, in addition to three previously recovered apomorphies for Fabriciidae (absence of ventral lips, modification of abdominal uncini to an elongate manubrium, and presence of branchial hearts), six more apomorphies associated with the reproductive system can be used to support this clade—spermiogenesis only in the thorax, spermiogenesis in large clusters with a central cytophore, single dorsal sperm duct, sperm nuclear projection, thickening of the sperm nuclear membrane and the sperm extra‐axonemal sheath. The results require the erection of two new genera and two new species, which are described. © The Willi Hennig Society 2010.     

Behavioral fingerprints predict insecticide and anthelmintic mode of action

Novel invertebrate‐killing compounds are required in agriculture and medicine to overcome resistance to existing treatments. Because insecticides and anthelmintics are discovered in phenotypic screens, a crucial step in the discovery process is determining the mode of action of hits. Visible whole‐organism symptoms are combined with molecular and physiological data to determine mode of action. However, manual symptomology is laborious and requires symptoms that are strong enough to see by eye. Here, we use high‐throughput imaging and quantitative phenotyping to measure Caenorhabditis elegans behavioral responses to compounds and train a classifier that predicts mode of action with an accuracy of 88% for a set of ten common modes of action. We also classify compounds within each mode of action to discover substructure that is not captured in broad mode‐of‐action labels. High‐throughput imaging and automated phenotyping could therefore accelerate mode‐of‐action discovery in invertebrate‐targeting compound development and help to refine mode‐of‐action categories.     

The reproductive system of Osedax (Annelida,Siboglinidae): ovary structure,sperm ultrastructure,and fertilization mode

Osedax is a genus of siboglinid annelids in which the females live on dead vertebrate bones on the seafloor. These females have a posterior end that lies within the bone and contains the ovarian tissue, as well as the “roots” involved with bone degradation and nutrition. The males are microscopic and live as “harems” in the lumen of the gelatinous tube that surrounds the female trunk, well away from the ovary. Females are known to spawn fertilized primary oocytes, suggesting internal fertilization. However, little is known about sperm transfer, sperm storage, or the location of fertilization, and the morphology of the female reproductive system has not been described and compared with the reproductive systems of other siboglinids. A 3D‐reconstruction of the ovisac of Osedax showed ovarian tissue with multiple lobes and mature oocytes stored in a “uterus” before being released through the single oviduct. The oviduct emerges as a gonopore on the trunk and travels along the trunk to finally open to the seawater as a thin cylindrical tube among the crown of palps. Light and transmission electron microscopy of mature Osedax sperm revealed elongate heads consisting of a nucleus with helical grooves occupied by mitochondria. In contrast to other Siboglinidae, Osedax sperm are not packaged into spermatophores or spermatozeugmata, and Osedax females lack a discrete region for sperm storage. Transmission electron microscopy and fluorescence microscopy allowed detection of sperm associated with ovarian tissue of the female ovisac of four different Osedax species. This provides the first evidence for the site of internal fertilization in Osedax. A heart body was found in the circulatory system, as seen in other siboglinids and some other annelids. The possible presence of nephridia in the anterior ovisac region was also documented. These morphological features provide new insights for comparing the regionalization of Osedax females in relation to other siboglinids.