Role of Notch pathway in terminal follicle cell differentiation during Drosophila oogenesis

 During Drosophila oogenesis the body axes are determined by signaling between the oocyte and the somatic follicle cells that surround the egg chamber. A key event in the establishment of oocyte anterior-posterior polarity is the differential patterning of the follicle cell epithelium along the anterior-posterior axis. Both the Notch and epithelial growth factor (EGF) receptor pathways are required for this patterning. To understand how these pathways act in the process we have analyzed markers for anterior and posterior follicle cells accompanying constitutive activation of the EGF receptor, loss of Notch function, and ectopic expression of Delta. We find that a constitutively active EGF receptor can induce posterior fate in anterior but not in lateral follicle cells, showing that the EGF receptor pathway can act only on predetermined terminal cells. Furthermore, Notch function is required at both termini for appropriate expression of anterior and posterior markers, while loss of both the EGF receptor and Notch pathways mimic the Notch loss-of-function phenotype. Ectopic expression of the Notch ligand, Delta, disturbs EGF receptor dependent posterior follicle cell differentiation and anterior-posterior polarity of the oocyte. Our data are consistent with a model in which the Notch pathway is required for early follicle cell differentiation at both termini, but is then repressed at the posterior for proper determination of the posterior follicle cells by the EGF receptor pathway. Received: 5 November 1998 / Accepted: 14 December 1998     

Determination of the absolute configuration of Anisotome irregular diterpenes: application of CD and NMR methods

Several Anisotome diterpene derivatives were synthesized in an attempt to obtain a crystalline compound for X-ray analysis. Although we were unable to obtain a suitable crystal, the absolute configuration of the irregular diterpene skeleton was determined using two other techniques: a circular dichroism (CD) protocol based on a tetraarylporphyrin molecular tweezer that allowed prediction of the absolute stereochemistry on a microscale level, and a method employing differences in NMR shifts from derivatization of the naturally occurring acid 1 with enantiomers of a phenylglycine methyl ester (PGME) chiral anisotropic reagent. The excellent agreement between the CD and NMR methods led to the assignment of a 2S-absolute configuration for anisotomenoic acid 1.     

Relative sensitivities of repair-deficient mammalian cells for clonogenic survival after alpha-particle irradiation

The clonogenic survival of cells of the radiation-sensitive hamster cell lines irs1, irs2, irs3 and xrs5, representing different DNA repair pathways, was compared to that of their parent lines after alpha-particle irradiation. Measurements of nuclear area were made to calculate the probability of surviving a single alpha-particle traversal, the average number of lethal lesions per track and per unit dose, along with the "intrinsic radiosensitivity" of these cells, allowing for the potential of multiple lethal lesions per traversal. For all cell lines studied, alpha particles were found to be more biologically effective per unit absorbed dose than X rays at inducing cell inactivation. The repair-deficient cells showed an enhanced sensitivity to alpha particles compared to their parent line, but the degree of enhancement was less than for X rays. The reduction in additional sensitivity for alpha-particle irradiation was shown not to be due predominantly to differences in cell geometry limiting the probability of a cell nucleus being traversed. The results suggest that both the nonhomologous end-joining pathway and to a lesser extent the homologous recombination repair pathway play a role in successful repair of alpha-particle-induced damage, although a large proportion of damage is not repaired by either pathway.     

Sex ratio at birth, polygyny, and fertility: a cross-national study

The sex ratio at birth may reflect frequency of intercourse that affects the timing of conception. If so, cross-national variation in polygyny and fertility might account for country differences in secondary sex ratios. Consistent with the timing of intercourse hypothesis, the birth sex ratios of 148 countries declined with total fertility rates and polygyny intensity, and increased with contraception use in correlational analysis. Regression analysis confirmed that polygyny was a negative predictor of the sex ratio (and contraception was a positive predictor), with level of economic development and mother's age controlled, but the effects disappeared with total fertility added to the equation. The sex ratio evidently declines with increases in fertility because more children are born at a later birth order when frequency of intercourse is lower.     

In vivo measurement of the dynamic 3-D kinematics of the ovine stifle joint

The ovine stifle joint is a promising animal model for investigation of joint mechanobiology. A method for in vivo measurement of dynamic 3-D kinematics of the ovine stifle joint is described (accuracy: 0.36 +/- 0.39 mm). Inter-subject variability in kinematics is greater than both intra-subject and inter-session variability. For future studies in which joint kinematics are measured prior to and following controlled orthopaedic interventions, pooling of data should be avoided and each subject should act as its own control.     

Physiological concentrations of bile salts inhibit recovery of ischemic-injured porcine ileum

We have previously shown rapid in vitro recovery of barrier function in porcine ischemic-injured ileal mucosa, attributable principally to reductions in paracellular permeability. However, these experiments did not take into account the effects of luminal contents, such as bile salts. Therefore, the objective of this study was to evaluate the role of physiological concentrations of deoxycholic acid in recovery of mucosal barrier function. Porcine ileum was subjected to 45 min of ischemia, after which mucosa was mounted in Ussing chambers and exposed to varying concentrations of deoxycholic acid. The ischemic episode resulted in significant reductions in transepithelial electrical resistance (TER), which recovered to control levels of TER within 120 min, associated with significant reductions in mucosal-to-serosal (3)H-labeled mannitol flux. However, treatment of ischemic-injured tissues with 10(-5) M deoxycholic acid significantly inhibited recovery of TER with significant increases in mucosal-to-serosal (3)H-labeled mannitol flux, whereas 10(-6) M deoxycholic acid had no effect. Histological evaluation at 120 min revealed complete restitution regardless of treatment, indicating that the breakdown in barrier function was due to changes in paracellular permeability. Similar effects were noted with the application of 10(-5) M taurodeoxycholic acid, and the effects of deoxycholic acid were reversed with application of the Ca(2+)-mobilizing agent thapsigargin. Deoxycholic acid at physiological concentrations significantly impairs recovery of epithelial barrier function by an effect on paracellular pathways, and these effects appear to be Ca(2+) dependent.     

Early birds

Concern is growing about the impact of climate change on organisms but there's much uncertainty about its effects. A new European study of two bird species does not provide good news.     

The role of G-protein coupled receptors and associated proteins in receptor tyrosine kinase signal transduction

It is well established that stimulation of G-protein coupled receptors (GPCRs) can activate signalling from receptor tyrosine kinases by a process termed transactivation. Indeed, in recent years, it has become apparent that transactivation is a general phenomenon that has been demonstrated for many unrelated GPCRs and receptor tyrosine kinases. In this case the GPCR/G-protein participation is up-stream of the receptor tyrosine kinase. Substantial research has addressed these findings but meanwhile another mechanism of cross talk has been slowly emerging. For over a decade, a growing body of evidence has demonstrated that numerous growth factors use G-proteins and attendant signalling molecules such as beta-arrestins that participate down-stream of the receptor tyrosine kinase to signal to effectors, such as p42/p44 MAPK. This review highlights this novel mechanism of cross talk between receptor tyrosine kinases and GPCRs, which is distinct from growth factor receptor transactivation by GPCRs.