Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord

Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.     

Arboreality predicts Batrachochytrium dendrobatidis infection level in tropical direct-developing frogs

Pathogen-mediated changes in host behaviour can result from hosts altering their habitat preferences. Although infection risk with pathogenic fungus Batrachochytrium dendrobatidis in amphibians is associated with environments favouring its growth, the relationship with microhabitat use has not been examined. Here, we aim to determine if microhabitats used by frogs during their nocturnal activity predict B. dendrobatidis prevalence and infection intensity. Our focal host, Eleutherodactylus coqui, is a habitat generalist that uses multiple habitats from the forest floor to the canopy. We analysed data on B. dendrobatidis occurrence in 157 adults and 122 juveniles at El Yunque National forest in Puerto Rico. We categorized each individual’s nocturnal microhabitat as forest floor, curled palm fronds in the floor, arboreal bromeliads and foliage or tree trunks 50 cm to 2.5 m above ground. We found that frogs on the forest floor had the greatest B. dendrobatidis prevalence (73%), compared with those active in vegetation above ground (55%). Overall, the probability of B. dendrobatidis infection in frogs using microhabitats on the forest floor was twice as great as for those on arboreal substrates. Differences in B. dendrobatidis prevalence and intensity in E. coqui may be explained by specific abiotic conditions of microenvironments (temperature and humidity) affecting both pathogen and host, and by the age-specific ecological requirements of hosts. Adults were found to be most active in microhabitats where individuals had lower infection burdens, suggesting pathogen-modulated habitat choice. This work has important implications for the evolutionary dynamics of enzootic diseases and provides data that may inform potential mitigation strategies against a generalist amphibian pathogen.     

Extensive characterization of sphere models established from colorectal cancer cell lines

Links between cancer and stem cells have been proposed for many years. As the cancer stem cell (CSC) theory became widely studied, new methods were developed to culture and expand cancer cells with conserved determinants of “stemness”. These cells show increased ability to grow in suspension as spheres in serum-free medium supplemented with growth factors and chemicals. The physiological relevance of this phenomenon in established cancer cell lines remains unclear. Cell lines have traditionally been used to explore tumor biology and serve as preclinical models for the screening of potential therapeutic agents. Here, we grew cell-forming spheres (CFS) from 25 established colorectal cancer cell lines. The molecular and cellular characteristics of CFS were compared to the bulk of tumor cells. CFS could be isolated from 72 % of the cell lines. Both CFS and their parental CRC cell lines were highly tumorigenic. Compared to their parental cells, they showed similar expression of putative CSC markers. The ability of CRC cells to grow as CFS was greatly enhanced by prior treatment with 5-fluorouracil. At the molecular level, CFS and parental CRC cells showed identical gene mutations and very similar genomic profiles, although microarray analysis revealed changes in CFS gene expression that were independent of DNA copy-number. We identified a CFS gene expression signature common to CFS from all CRC cell lines, which was predictive of disease relapse in CRC patients. In conclusion, CFS models derived from CRC cell lines possess interesting phenotypic features that may have clinical relevance for drug resistance and disease relapse.     

Competition for food and space in a heteromyid community in the Great Basin Desert

A series of removal experiments were performed on Dipodomys merriami, D. microps, and Perognathus longimembris to test for the importance of competition for food and microhabitats in a heteromyid community in the Great Basin Desert. Each of these species was removed singly to determine the short-term effects on the microhabitat preferences of the remaining species. We correctly predicted, based on differences in diet, that the removal of D. microps (a foliovore) would have no effect on D. merriami or P. longimembris (granivores). Using the dominance hierarchy theory, we correctly predicted that removal of a larger heteromyid, D. merriami, would have an effect on the microhabitat use of the smaller P. longimembris, but not vice versa. While our results offer strong evidence of competition for food and microhabitats, the short-term reactions were weak compared to the long-term reactions found in other studies of heteromyids.     

Commentary: Reflections on Co-operative Inquiry in This Historic Moment

Systemic Practice and Action Research - My reading of the six accounts of co-operative inquiry in this volume comes during a historic moment for action research in which the tensions of celebration...     

Effect of 723-1723-1723-1on ethanol withdrawal in mice

Summary ⁹ (10 mg/kg, i.p.) administered to mice immediately after withdrawal from a 3-day exposure to ethanol vapor was found to intensify withdrawal reactions. No effect was seen when ⁹ was administered chronically during the exposure to ethanol.     

Hidden depths: Halley, hell and other people

During the long eighteenth century, boundaries between theology and natural philosophy, between imaginary and factual travel narratives, between fiction and social commentary, were far more fluid than they are today. To explore these relationships, this paper links Mary Shelley’s Frankenstein—a book often hailed as the first science fiction novel—to two earlier works which are now less well known: Edmond Halley’s article about terrestrial magnetism, in which he suggested that God had created inhabited illuminated cavities inside the earth; and a satirical fantasy voyage written by the Danish author Ludvig Holberg, but published anonymously as Niels Klim’s journey to the underground and immediately translated into many languages. Attention is focussed on how the ambiguous presentation of these and other texts blurs any straightforward classification of genres. The aim of examining these writers together is not to search for direct mappings from one project to another, but instead to introduce Holberg’s unfamiliar yet important book and also to cast new light on Frankenstein, one of England’s most famous works of literature.     

Basic proteins of mouse ova and blastocysts

Zusammenfassung Mit einer speziellen Färbetechnik auf basische Proteine wird gezeigt, dass die Intensität und damit auch die Quantität der basischen Proteine beim übergang vom 4-Zell-Stadium zum 8-Zell-Stadium im Cytoplasma stark zunimmt. Daraus wird der Schluss gezogen, dass erst zu diesem Zeitpunkt die genetische Information für die Proteinsynthese wirksam wird.     

Collagen treated with (+)-catechin becomes resistant to the action of mammalian collagenase

Summary Treatment of radioactively labeled guinea-pig skin soluble collagen or calf skin collagen with the flavonoid (+)-catechin makes the collagen resistant to the action of mammalian collagenase but not to the action of bacterial collagenase. Complete resistance to the action of the mammalian enzyme may be achieved by incubating 0.6 mg of collagen (dry weight) with 0.1 mM (+)-catechin, followed by dialysis to remove the unbound flavonoid. Since incubation of the mammalian enzyme with (+)-catechin does not inhibit its activity, it is postulated that (+)-catechin binds tightly to collagen and modifies its structure sufficiently to make it resistant to enzyme degradation.Acknowledgments. This work was supported by grants from the Easter Seal Research Foundation of the National Easter Seal Society for Crippled Children and Adults (R-7821), and the National Institutes of Health (HL-20447). (+)-Catechin was a generous gift from Zyma SA, CH-1260 Nyon, Switzerland.