A Boolean Model of the Gene Regulatory Network Underlying Mammalian Cortical Area Development

The cerebral cortex is divided into many functionally distinct areas. The emergence of these areas during neural development is dependent on the expression patterns of several genes. Along the anterior-posterior axis, gradients of Fgf8, Emx2, Pax6, Coup-tfi, and Sp8 play a particularly strong role in specifying areal identity. However, our understanding of the regulatory interactions between these genes that lead to their confinement to particular spatial patterns is currently qualitative and incomplete. We therefore used a computational model of the interactions between these five genes to determine which interactions, and combinations of interactions, occur in networks that reproduce the anterior-posterior expression patterns observed experimentally. The model treats expression levels as Boolean, reflecting the qualitative nature of the expression data currently available. We simulated gene expression patterns created by all possible networks containing the five genes of interest. We found that only of these networks were able to reproduce the experimentally observed expression patterns. These networks all lacked certain interactions and combinations of interactions including auto-regulation and inductive loops. Many higher order combinations of interactions also never appeared in networks that satisfied our criteria for good performance. While there was remarkable diversity in the structure of the networks that perform well, an analysis of the probability of each interaction gave an indication of which interactions are most likely to be present in the gene network regulating cortical area development. We found that in general, repressive interactions are much more likely than inductive ones, but that mutually repressive loops are not critical for correct network functioning. Overall, our model illuminates the design principles of the gene network regulating cortical area development, and makes novel predictions that can be tested experimentally.     

Ruthenium ammine complexes as electron acceptors for growth stimulation by plasma membrane electron transport

Ammineruthenium(III) complexes have been found to act as electron acceptors for the transplasmalemma electron transport system of animal cells. The active complexes hexaammineruthenium(III), pyridine pentaammineruthenium(III), and chloropentaammineruthenium(III) range in redox potential (E ₀) from 305 to –42 mV. These compounds also act as electron acceptors for the NADH dehydrogenase of isolated plasma membranes. Stimulation of HeLa cell growth, in the absence of calf serum, by these compounds provides evidence that growth stimulation by the transplasma membrane electron transport system is not entirely based on reduction and uptake of iron.     

Estimating the number of genetic elements that defer senescence inDrosophila

Summary Although many different physiological and biochemical changes characterize the process of senescence, little is understood of the genetic elements that determine its age of onset. We provide here the first estimates of the number of genetic factors that extend longevity inDrosophila melanogaster. Life span was measured in F₁, F₂ and backcrosses of true-breeding long and short-lived stocks ofD. melanogaster, established by selection. Estimates of the number of effective factors delaying senescence range from about 0.3 to 1.5, indicating control by a single factor. The distribution of longevity shows this to arise as selection acts on the short-lived parental stock. Life span is extended at the cost of early fecundity.     

Evidence that the enoyl-CoA hydratase bifunctional protein of mouse liver peroxisomes is identical with the 70,000 dalton peroxisomal membrane protein

Peroxisomal enoyl-CoA hydratase was purified from livers of mice treated with di-(2-ethylhexyl)phthalate and its properties compared with those of the 70 kDa protein present in the membranes prepared by carbonate extraction of peroxisomes. The two proteins had identical subunit molecular masses, of about 70,000 daltons. Limited proteolysis of these proteins using the V8 proteinase of S. aureus yielded identical peptide maps, with these peptides crossreacting with antiserum raised against the 70 kDa membrane protein. These data are consistent with the proposal that the peroxisomal 70 kDa membrane protein and the peroxisomal enoyl-CoA hydratase are the same protein.