EphrinB phosphorylation and reverse signaling: regulation by Src kinases and PTP-BL phosphatase

Ephrins are cell surface-associated ligands for Eph receptors and are important regulators of morphogenic processes such as axon guidance and angiogenesis. Transmembrane ephrinB ligands act as "receptor-like" signaling molecules, in part mediated by tyrosine phosphorylation and by engagement with PDZ domain proteins. However, the underlying cell biology and signaling mechanisms are poorly understood. Here we show that Src family kinases (SFKs) are positive regulators of ephrinB phosphorylation and phosphotyrosine-mediated reverse signaling. EphB receptor engagement of ephrinB causes rapid recruitment of SFKs to ephrinB expression domains and transient SFK activation. With delayed kinetics, ephrinB ligands recruit the cytoplasmic PDZ domain containing protein tyrosine phosphatase PTP-BL and are dephosphorylated. Our data suggest the presence of a switch mechanism that allows a shift from phosphotyrosine/SFK-dependent signaling to PDZ-dependent signaling.

Aurora kinases as anticancer drug targets

The human aurora family of serine-threonine kinases comprises three members, which act in concert with many other proteins to control chromosome assembly and segregation during mitosis. Aurora dysfunction can cause aneuploidy, mitotic arrest, and cell death. Aurora kinases are strongly expressed in a broad range of cancer types. Aurora A expression in tumors is often associated with gene amplification, genetic instability, poor histologic differentiation, and poor prognosis. Aurora B is frequently expressed at high levels in a variety of tumors, often coincidently with aurora A, and expression level has also been associated with increased genetic instability and clinical outcome. Further, aurora kinase gene polymorphisms are associated with increased risk or early onset of cancer. The expression of aurora C in cancer is less well studied. In recent years, several small-molecule aurora kinase inhibitors have been developed that exhibit preclinical activity against a wide range of solid tumors. Preliminary clinical data from phase I trials have largely been consistent with cytostatic effects, with disease stabilization as the best response achieved in solid tumors. Objective responses have been noted in leukemia patients, although this might conceivably be due to inhibition of the Abl kinase. Current challenges include the optimization of drug administration, the identification of potential biomarkers of tumor sensitivity, and combination studies with cytotoxic drugs. Here, we summarize the most recent preclinical and clinical data and discuss new directions in the development of aurora kinase inhibitors as antineoplastic agents.

An Isopach Map and Discussion of the Marine Jurassic of Western United Sates and Canada

Recent demands for petroleum to carry on the war effort have resulted in widespread prospecting in the northern Great Plains. Nearly all oil wells now drilled are of a depth to penetrate the marine Jurassic formations. It is known that these strata differ in thickness from place to place, but information of distribution, thickness, and lithology has not yet been compiled.

A Discussion of the Geology and an Isopach Map of the Pennsylvanian System in Wyoming and Adjacent Areas

Pennsylvanian strata in Wyoming and adjacent areas have been the subject of much work and discussion. Most of the work has been due to the economic importance of the system as an oil producer in this region. Oil production from strata of Pennsylvanian age is rather recent history; and therefore, much of the available information is local­ized and incomplete.

An Isopach Map and a Discussion of the Permian in Wyoming and Adjacent Areas

The accelerated post-war demand for petroleum products with resultant high prices and dwindling reserves has spurred producers to an extensive search for new fields and for ad­ditional production in known fields. Exploration and discov­ery is dependent on the collection and correlation of vast amounts of data both in the field and that found in liter­ature.

An Isopach Map and a Discussion of the Cambrian Strata in the Central Cordilleran Area

In the past few years intensive studies have been going on concerning Cambrian formations as a locale for orebodies. Many of the dolomites and limestones of southwestern Montana are susceptible to replacement by mineralizing solutions, especially when overlain by a rather impervious layer of shale, as is the Pilgrim limestone of Upper Cambrian time.

An Isopach Map and Discussion of Triassic Strata in Southern Montana and Wyoming

Oil and gas have been found in the Triassic strata of Wyoming. Although the Triassic has not as yet proven to be a large producing horizon it is very probable that ad­ditional oil will be found in Triassic strata in the future, and it is one of the goals at which oil well drillers aim their tools.

Modulus method and radial stretch map in the Heisenberg group

We develop a modulus method for surface families inside a domain in the Heisenberg group and we prove that the stretch map between two Heisenberg spherical rings is a minimiser for the mean distortion among the class of contact quasiconformal maps between these rings which satisfy certain boundary conditions.

A bone-thickness map as a guide for bone-anchored port implantation surgery in the temporal bone

The bone-anchored port (BAP) is an investigational implant, which is intended to be fixed on the temporal bone and provide vascular access. There are a number of implants taking advantage of the stability and available room in the temporal bone. These devices range from implantable hearing aids to percutaneous ports. During temporal bone surgery, injuring critical anatomical structures must be avoided. Several methods for computer-assisted temporal bone surgery are reported, which typically add an additional procedure for the patient. We propose a surgical guide in the form of a bone-thickness map displaying anatomical landmarks that can be used for planning of the surgery, and for the intra-operative decision of the implant’s location. The retro-auricular region of the temporal and parietal bone was marked on cone-beam computed tomography scans and tridimensional surfaces displaying the bone thickness were created from this space. We compared this method using a thickness map (n = 10) with conventional surgery without assistance (n = 5) in isolated human anatomical whole head specimens. The use of the thickness map reduced the rate of Dura Mater exposition from 100% to 20% and OPEN ACCESS Materials 2013, 6 5292 suppressed sigmoid sinus exposures. The study shows that a bone-thickness map can be used as a low-complexity method to improve patient’s safety during BAP surgery in the temporal bone.