Oligodendrocyte progenitor cells proliferate and survive in an immature state following treatment with an axolemma-enriched fraction

The ability of an AEF (axolemma-enriched fraction) to influence the proliferation, survival and differentiation of OPC (oligodendrocyte progenitor cells) was evaluated. Following addition of AEF to cultured OPC, the AEF associated with the outer surface of OPC so that subsequent metabolic events were likely mediated by direct AEF-OPC contact. Addition of AEF to the cultured OPC resulted in a dose- and time-dependent increase in proliferation that was partially dependent on Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) activation. The major mitogen in an AEF-SE (soluble 2.0 M NaCl extract of the AEF) was identified as aFGF (acidic fibroblast growth factor) and accounted for 50% of the mitogenicity. The remaining 50% of the mitogenicity had properties consistent with bFGF (basic fibroblast growth factor) but was not unequivocally identified. Under conditions that limit the survival of OPC in culture, AEF treatment prolonged the survival of the OPC. Antigenic and morphological examination of the AEF-treated OPC indicated that the AEF treatment helped the OPC survive in a more immature state. The potential downstream metabolic pathways potentially activated in OPC by AEF and the consequences of these activated pathways are discussed. The results of these studies are consistent with the view that direct contact of axons with OPC stimulates their proliferation and survival while preventing their differentiation.     

Inhibition of rhythmic spiking by colored noise in neural systems

We study the effect of colored noise on the rhythmic spiking activity of neural systems in this paper. The phenomenon of the so-called inverse stochastic resonance , that is, noise with appropriate intensity suppresses the spiking activity in neural systems, is clearly observed in a special parameter regime. We find that the inhibition effect of colored noise is stronger than that of Gaussian white noise. Furthermore, our simulation results show that the inhibition effect of colored noise provides a useful mechanism for the generation of synchronized burst in type-2 mixed-feed-forward-feedback loop neuronal network motif, which indicates that such inhibition effect might have some biological implications.     

In vitro differentiation of mouse ES cells into hepatocytes with coagulation factors VIII and IX expression profiles

Coagulation factors II, V, VII, VIII, IX and X are produced by hepatocytes. So factors VIII and IX deficiencies, which result in hemophilia A and B, have the potential to respond to cellular replacement therapy. Embryonic stem (ES) cells provide a unique source for therapeutic applications. Here, E14 mouse ES cells have been induced into hepatocytes in vitro. Morphology revealed that ES-derived hepatic-like cells were round or polyhedral shaped with distinct boundary of individual cells, and some arranged in trabeculae. These cells expressed endodermal-or liver-specific mRNA—transthyretin (TTR), α1-anti-trypsin (AAT), α-fetoprotein (AFP), albumin (ALB), glucose-6-phoshpatase (G6P) and tyrosine aminotransferase (TAT). Approximately (85.1±0.5)% of the ES-derived cells was stained positive green with ICG uptake. These cells were also stained magenta as a result of PAS reaction. In this paper, expression of coagulation factors VIII and IX mRNA in the ES-derived cells is documented. Therefore, ES cells might be developed as substitute donor cells for the therapy of coagulation factor deficiencies.     

Resistance of fast- and slow-growing subalpine fir to pheromone-induced attack by western balsam bark beetle (Coleoptera: Scolytinae)

Abstract 1 We investigated the resistance of fast‐ and slow‐growing subalpine fir to pheromone‐induced attack by western balsam bark beetle at two sites in the interior of British Columbia, Canada. 2 Attack success by the beetle and subsequent tree mortality were higher in slow‐growing trees than in fast‐growing trees. 3 Fast‐growing trees were more likely to produce secondary resin, and in greater quantities, than slow‐growing trees after attack. 4 Host vigour (indicated by recent radial growth) was positively related to the induced defense response and resistance of subalpine fir to bark beetle attack. These results are discussed in the context of plant defense and plant–herbivore interaction hypotheses. 5 Given the preference of western balsam bark beetle for weakened trees, as well as the reduced defenses and increased mortality rates in less vigorous trees, effective management tactics for this beetle may include strategies that increase the growth and vigour of its subalpine fir host.     

Asymmetry in sexual development of gonads in intersex rainbow trout

Large‐scale sampling of spontaneous rainbow trout Oncorhynchus mykiss intersexes indicated a strong asymmetry of gonad differentiation in XX females; the right gonad was more sensitive to the mutation‐induced masculinization than the left one.     

Functional engineering of hepatocytes via heterocellular presentation of a homoadhesive molecule, E-cadherin.

Engineering functional activity of liver cell cultures requires the modulation of specific cell-cell interactions. We have investigated the quantitative role of systematically varied presentation of the cell-cell adhesion molecule, E-cadherin, on the differentiated function of cocultured parenchymal liver cells, hepatocytes. Specifically, we incorporated different proportions of E-cadherin transfected L-929 chaperone cells and untransfected chaperone cells, within cultures of primary rat hepatocytes on a collagen substrate. By using a strongly adhesive substrate that restricted cadherin-induced variations in cell spreading and growth-arresting chaperone cells, we could carefully isolate the potential role of cell-cell adhesion on cell differentiation. Using immunofluorescence microscopy, we confirmed that cadherins expressed at hepatocyte-hepatocyte contacts as well as hepatocyte-chaperone contacts were crossreactive. However, hepatocytes cocultured with cadherin-presenting chaperone cells had a 55-65% increase in longterm function over hepatocytes cocultured with control, nonpresenting chaperone cells. Notably, the cadherin-induced increase in function occurred over and above the basal, coculture-induced functional elevation. Further, we quantified the stoichiometric importance of cadherin contacts by comparing established markers of hepatocyte functional activity across a graded range of E-cadherin presentation. At low levels of cadherin-mediated contacts, the induction of differentiated function was weak, while high levels of contacts elicited a marked increase in function. Thus, hepatocyte biochemical functions (albumin and urea secretion) were biphasically governed by the degree of cadherin-based contacts presented during culture. Overall, our results demonstrate the unequivocal role of cell-cell adhesion molecules in hepatocyte functional engineering, through the graded use of cadherin presentation from functionally incompetent, heterotypic chaperone cells.     

THE ORIGIN OF AN ORGAN: PHYLOGENETIC ANALYSIS OF EVOLUTIONARY INNOVATION IN THE DIGESTIVE TRACT OF FLIES (INSECTA: DIPTERA)

The cardia, a prominent digestive tract organ consisting of several specialized cell types, occurs throughout the “higher” or muscoid flies, division Schizophora of order Diptera. Phylogenetic analysis of cellular organization in 65 insect species from 36 families indicates that this organ originated within the order Diptera from ancestrally undifferentiated tissues. “Lower” flies, suborder “Nematocera,” display little or no epithelial cell specialization at the corresponding site. Scorpionflies of the outgroup order Mecoptera are similarly unspecialized. Intermediate levels of cellular specialization occur in Tabanomorpha, Asilomorpha and Aschiza, dipteran taxa that diverge between “Nematocera” and Schizophora. The distribution of epithelial characteristics suggests that the cardia evolved through a sequence of simple tissue transformations, combining changes in epithelial configuration with local differentiation of cell structure and function. The evolution of locally specialized cell types implies the emergence of structural genes and regulatory mechanisms through the modification of an ancestral genome that had not supported such extensive differentiation. Comparison of localized gene expression in Drosophila melanogaster with that in other fly species having greater or lesser degrees of cell specialization may provide a practical model system for studying specific patterns of mutation associated with such evolutionary innovation.     

Origin of the phyla and cancer

Multicelled animals with specialized cells (metazoans) emerged shortly after rising oxygen levels in the seas permitted formation of collagen-family molecules. Certain unicells then formed 3-D clusters, some with disc- or ball-like shapes that happened to resemble blastulas. These became unstable beyond a certain size due to contrasting metabolic styles among their component cells. For whereas cells near their exteriors could employ oxygen respiration, cells closer to the oxygen-deprived interiors were obliged to rely on anaerobic metabolism (fermentation), a process that produces waste molecules that, if retained within cells, cause disproportionate cell growth. Unstable blastula-like forms would either disintegrate or reorganize along surfaces of relative weakness in a process that may be likened to gastrulation. Initial cell-differentiation depended on the quantity and diversity of retained fermentation products and on the pumping of molecules from cell to cell by the consequent electro-chemical gradients. In subsequent contexts, oxygen deprivation, fermentation, excess cell growth, and disintegration or reorganization of tissues produce cancer.     

Variation in body size and trophic morphology within and among genetically differentiated populations of the cichlid fish, Metriaclima zebra, from Lake Malawi

1. The cichlid fish Metriaclima zebra , common in Lake Malawi, feeds by filtering plankton from the water and by brushing items from sediment covered substrata. It inhabits isolated rocky reefs among which community structure, resource availability and gene pools are likely to differ. We speculated that body size and trophic morphology of M. zebra might vary concomitantly.
2. We quantified the extent of genetic, body size and trophic variation within and between populations of M. zebra from southern Lake Malawi. Specifically, we tested the hypotheses that: (i) local populations are genetically differentiated, (ii) local populations differ in jaw morphology, dentition and standard length (SL), and (iii) variation in size is correlated with variation in trophic morphology.
3. Local populations of M. zebra differed in mean SL and were genetically differentiated. Moreover, populations exhibited dissimilar oral jaw morphologies and dentitions, perhaps related to differences in feeding biology. Variation in jaw shape was largely restricted to the curvature of the distal tip of the dentary. Populations were characterised by individuals with oblique, upward or downward directed gapes. Dental patterns differed in the proportion of unicuspid teeth in all rows of each jaw (dentaries and premaxillae) and the spacing of teeth in affected rows.
4. Within populations, jaw and tooth shapes were correlated with body size. Smaller individuals possessed upward curving jaws and closely packed multicusped teeth, while larger individuals exhibited relatively downward-directed jaws with increasing numbers of widely spaced unicuspid teeth.
5. Metriaclima zebra populations have increased in mean SL over the last decade, in contrast to a decline among Lake Malawi pelagic cichlids. Differences in size may contribute to variation in trophic morphology and may track local environmental dynamics in this lacustrine system.     

Docosahexaenoic acid-containing phosphatidylethanolamine enhances HL-60 cell differentiation by regulation of c-jun and c-myc expression

18:1/docosahexaenoic acid (DHA)-containing phosphatidylethanolamine (PE) enhanced cell differentiation and growth inhibition of HL-60 induced by dibutyryl cAMP (dbcAMP) in a dose-dependent manner. The combined treatment of 200 μM dbcAMP and 50 μM 18:1/DHA-PE increased the NBT reducing activity, which is as an indicator of cell differentiation, to more than 75% from 40% of cells treated with 200 μM dbcAMP alone. In HL-60 cells treated with 50 μM 18:1/DHA-PE and 200 μM dbcAMP for 24 h, the expression level of c-jun mRNA and c-Jun protein were remarkably elevated compared to cells treated with dbcAMP alone. In contrast, there was no difference in the expression levels of c-fos mRNA and c-Fos protein between the combination of 18:1/DHA-PE + dbcAMP or dbcAMP alone. On the other hand, the combine treatment of 18:1/DHA-PE and dbcAMP markedly reduced the expression level of c-myc oncogene during 48 h incubation. The decreases of c-myc mRNA by 18:1/DHA-PE and/or dbcAMP was correlated with growth inhibition effect. Thus, 18:1/DHA-PE might enhance dbcAMP-induced HL-60 cell differentiation and growth inhibition by regulation of c-jun and c-myc mRNA and their products.