Neuropeptide signaling regulates the susceptibility of developing C. elegans to anoxia

Inadequate delivery of oxygen to organisms during development can lead to cell dysfunction/death and life-long disabilities. Although the susceptibility of developing cells to low oxygen conditions changes with maturation, the cellular and molecular pathways that govern responses to low oxygen are incompletely understood. Here we show that developing Caenorhabditis elegans are substantially more sensitive to anoxia than adult animals and that this sensitivity is controlled by nervous system generated hormones (e.g., neuropeptides). A screen of neuropeptide genes identified and validated nlp-40 and its receptor aex-2 as a key regulator of anoxic survival in developing worms. The survival-promoting action of impaired neuropeptide signaling does not rely on five known stress resistance pathways and is specific to anoxic insult. Together, these data highlight a novel cell non-autonomous pathway that regulates the susceptibility of developing organisms to anoxia

Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway

A productive angiogenic response must couple to the survival machinery of endothelial cells to preserve the integrity of newly formed vessels. Angiopoietin-1 (Ang-1) is an endothelium-specific ligand essential for embryonic vascular stabilization, branching morphogenesis, and post-natal angiogenesis, but its contribution to endothelial cell survival has not been completely elucidated. Here we show that Ang-1 acting via the Tie 2 receptor induces phosphorylation of the survival serine-threonine kinase, Akt (or protein kinase B). This is associated with up-regulation of the apoptosis inhibitor, survivin, in endothelial cells and protection of endothelium from death-inducing stimuli. Moreover, dominant negative survivin negates the ability of Ang-1 to protect cells from undergoing apoptosis. The activation of anti-apoptotic pathways mediated by Akt and survivin in endothelial cells may contribute to Ang-1 stabilization of vascular structures during angiogenesis, in vivo

Self-Assembly of Actin Scaffolds at Ponticulin-Containing Supported Phospholipid Bilayers

Phospholipid vesicles containing ponticulin have been used to form solid supported and tethered bilayer lipid membranes. The ponticulin serves as both a nucleation site for actin polymerization as well as a binding site for F-actin. Studies of F-actin binding to such bilayers have demonstrated the formation of an in vitro actin scaffold. The dissociation constant for the binding of F-actin filaments to a ponticulin-containing tethered bilayer was found to be 11 ± 5 nM, indicative of high affinity binding

A Generalized duality symmetry for nonabelian Yang-Mills fields

It is shown that classical nonsupersymmetric Yang-Mills theory in 4 dimensions is symmetric under a generalized dual transform which reduces to the usual dual *-operation for electromagnetism. The parallel phase transport $\tilde{A}_\mu(x)$ constructed earlier for monopoles is seen to function also as a potential in giving full description of the gauge field, playing thus an entirely dual symmetric role to the usual potential $A_\mu(x)$. Sources of $A$ are monopoles of $\tilde{A}$ and vice versa, and the Wu-Yang criterion for monopoles is found to yield as equations of motion the standard Wong and Yang-Mills equations for respectively the classical and Dirac point charge; this applies whether the charge is electric or magnetic, the two cases being related just by a dual transform. The dual transformation itself is explicit, though somewhat complicated, being given in terms of loop space variables of the Polyakov type.Comment: Latex file, 26 pages, 3 figures and 2 charts not included but supplied on reques