Inositol 1,4,5-trisphosphate is not effective in releasing calcium from skeletal sarcoplasmic reticulum microsomes

Regulation of many cell systems has been shown to be mediated by Inositol 1,4,5-trisphosphate which causes a release of calcium from intracellular sites. We have shown that release of Ca2+ from sarcoplasmic reticulum microsomes was not stimulated by IP3. The phorbol ester, TPA, also had no effect on Ca2+ release or Ca2+ ATPase activity. Thus, it is unlikely that the breakdown of polyphosphatidylinositides serves as a second messenger to mediate release of Ca2+ in skeletal muscle.     

Direct Comparisons of 2D and 3D Dental Microwear Proxies in Extant Herbivorous and Carnivorous Mammals

The analysis of dental microwear is commonly used by paleontologists and anthropologists to clarify the diets of extinct species, including herbivorous and carnivorous mammals. Currently, there are numerous methods employed to quantify dental microwear, varying in the types of microscopes used, magnifications, and the characterization of wear in both two dimensions and three dimensions. Results from dental microwear studies utilizing different methods are not directly comparable and human quantification of wear features (e.g., pits and scratches) introduces interobserver error, with higher error being produced by less experienced individuals. Dental microwear texture analysis (DMTA), which analyzes microwear features in three dimensions, alleviates some of the problems surrounding two-dimensional microwear methods by reducing observer bias. Here, we assess the accuracy and comparability within and between 2D and 3D dental microwear analyses in herbivorous and carnivorous mammals at the same magnification. Specifically, we compare observer-generated 2D microwear data from photosimulations of the identical scanned areas of DMTA in extant African bovids and carnivorans using a scanning white light confocal microscope at 100x magnification. Using this magnification, dental microwear features quantified in 2D were able to separate grazing and frugivorous bovids using scratch frequency; however, DMTA variables were better able to discriminate between disparate dietary niches in both carnivorous and herbivorous mammals. Further, results demonstrate significant interobserver differences in 2D microwear data, with the microwear index remaining the least variable between experienced observers, consistent with prior research. Overall, our results highlight the importance of reducing observer error and analyzing dental microwear in three dimensions in order to consistently interpret diets accurately.     

Verapamil as a co-mutagen in the Salmonella/mammalian microsome mutagenicity test

Verapamil is a calcium-channel blocking agent, commonly used for chronic treatment of heart conditions. We have previously demonstrated that verapamil acts as a co-mutagen in a bacterial mutagenicity test for some experimental anilinoacridine antitumour drugs. Within the anilinoacridines series there are several compounds which are apparently non-mutagenic (or very weak mutagens) in the absence of verapamil, but strong mutagens in its presence. We have now tested a wider range of materials for verapamil enhancement of mutagenicity, to include some of those to which persons on verapamil therapy might be exposed through life-style or occupation. Some verapamil enhancement of mutagenicity was seen with most mutagenic compounds including anticancer drugs, antiparasitic agents, one biological stain and one hair dye. A number of tricyclic antidepressants and biological stains were tested and found to be non-mutagenic. If these results extrapolate to mammalian cells, long-term verapamil therapy could potentially increase the effects of certain environmental mutagens.     

Changes in the Gut Microbiome of the Sea Lamprey during Metamorphosis

Vertebrate metamorphosis is often marked by dramatic morphological and physiological changes of the alimentary tract, along with major shifts in diet following development from larva to adult. Little is known about how these developmental changes impact the gut microbiome of the host organism. The metamorphosis of the sea lamprey (Petromyzon marinus) from a sedentary filter-feeding larva to a free-swimming sanguivorous parasite is characterized by major physiological and morphological changes to all organ systems. The transformation of the alimentary canal includes closure of the larval esophagus and the physical isolation of the pharynx from the remainder of the gut, which results in a nonfeeding period that can last up to 8 months. To determine how the gut microbiome is affected by metamorphosis, the microbial communities of feeding and nonfeeding larval and parasitic sea lamprey were surveyed using both culture-dependent and -independent methods. Our results show that the gut of the filter-feeding larva contains a greater diversity of bacteria than that of the blood-feeding parasite, with the parasite gut being dominated by Aeromonas and, to a lesser extent, Citrobacter and Shewanella. Phylogenetic analysis of the culturable Aeromonas from both the larval and parasitic gut revealed that at least five distinct species were represented. Phenotypic characterization of these isolates revealed that over half were capable of sheep red blood cell hemolysis, but all were capable of trout red blood cell hemolysis. This suggests that the enrichment of Aeromonas that accompanies metamorphosis is likely related to the sanguivorous lifestyle of the parasitic sea lamprey.     

Mutagenic and clastogenic activity of nitracrine analogues in cultured V79 Chinese hamster cells

Nitracrine is used clinically as an antitumour agent, and analogues are actively being developed in some laboratories. The mutagenic activity of 9-[(3-dimethylaminopropyl)amino]-acridine and its 1-nitro (nitracrine), 2-, 3- and 4-nitro derivatives was evaluated at the 6-thioguanine and ouabain resistance loci in cultured Chinese hamster fibroblasts (V79-171b cell line). The des-nitro, 2- and 3-nitro caused no statistically significant mutagenic activity at either locus. Each of these 3 compounds weakly increased (approximately 2-fold) the incidence of micronuclei in the same cell line when tested at cytotoxic doses. Both the 1- and 4-nitro compounds increased the incidence of 6-thioguanine resistant cells from around 1 in 10(-6) to approximately 1 in 10(-4). The former compound significantly increased the frequency of ouabain-resistant cells. Both of these compounds were potent inducers of micronuclei in V79-171b cells, indicating high clastogenic activity. It would appear prudent to regard both of these compounds as potential human carcinogens.     

Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

Background  

Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited.     

The karyotype of Alligator mississippiensis,and chromosomal mapping of the ZFY/X homologue,Zfc

Comparative mapping studies of X-linked genes in mammals have provided insights into the evolution of the X chromosome. Many reptiles including the American alligator, Alligator mississippiensis, do not appear to possess heteromorphic sex chromosomes, and sex is determined by the incubation temperature of the egg during embryonic development. Mapping of homologues of mammalian X-linked genes in reptiles could lead to a greater understanding of the evolution of vertebrate sex chromosomes. One of the genes used in the mammalian mapping studies was ZFX, an X-linked copy of the human ZFY gene which was originally isolated as a candidate for the mammalian testis-determining factor (TDF). ZFX is X-linked in eutherians, but maps to two autosomal locations in marsupials and monotremes, close to other genes associated with the eutherian X. The alligator homologue of the ZFY/ZFX genes, Zfc, has been isolated and described previously. A detailed karyotype of A. mississippiensis is presented, together with chromosomal in situ hybridisation data localising the Zfc gene to chromosome 3. Further chromosomal mapping studies using eutherian X-linked genes may reveal conserved chromosomal regions in the alligator that have become part of the eutherian X chromosome during evolution.