Modulation of the β-Catenin Signaling Pathway by the Dishevelled-Associated Protein Hipk1

BACKGROUND:Wnts are evolutionarily conserved ligands that signal through beta-catenin-dependent and beta-catenin-independent pathways to regulate cell fate, proliferation, polarity, and movements during vertebrate development. Dishevelled (Dsh/Dvl) is a multi-domain scaffold protein required for virtually all known Wnt signaling activities, raising interest in the identification and functions of Dsh-associated proteins. METHODOLOGY:We conducted a yeast-2-hybrid screen using an N-terminal fragment of Dsh, resulting in isolation of the Xenopus laevis ortholog of Hipk1. Interaction between the Dsh and Hipk1 proteins was confirmed by co-immunoprecipitation assays and mass spectrometry, and further experiments suggest that Hipk1 also complexes with the transcription factor Tcf3. Supporting a nuclear function during X. laevis development, Myc-tagged Hipk1 localizes primarily to the nucleus in animal cap explants, and the endogenous transcript is strongly expressed during gastrula and neurula stages. Experimental manipulations of Hipk1 levels indicate that Hipk1 can repress Wnt/beta-catenin target gene activation, as demonstrated by beta-catenin reporter assays in human embryonic kidney cells and by indicators of dorsal specification in X. laevis embryos at the late blastula stage. In addition, a subset of Wnt-responsive genes subsequently requires Hipk1 for activation in the involuting mesoderm during gastrulation. Moreover, either over-expression or knock-down of Hipk1 leads to perturbed convergent extension cell movements involved in both gastrulation and neural tube closure. CONCLUSIONS:These results suggest that Hipk1 contributes in a complex fashion to Dsh-dependent signaling activities during early vertebrate development. This includes regulating the transcription of Wnt/beta-catenin target genes in the nucleus, possibly in both repressive and activating ways under changing developmental contexts. This regulation is required to modulate gene expression and cell movements that are essential for gastrulation

GCRE Critical-Assembly Studies

Critical-assembly studies were made to provide engineering and physics data to aid in developing the Gas Cooled Reactor Experiment-1 (GCRE-l). Measurements of critical mass, flux and power distributions, and shutdown worth of the GCRE-1 mock-up safety and control blades were obtained. The critical assembly consists of aluminum tubes containing four concentric stainless steel cylinders wrapped wtth highly enriched uranium foil. These tubes are supported at each end by grid plates aiid arranged to approximate a right circular cylinder. The entire core structure is supported within a tank which can be filled remotely with moderator water. A void beneath the core structure and the air above it represent the gas plenums of the GCRE-1 reactor. Critical mass and flux power distributions were determined for several cases of four basic cores. The thermal utilization, measured in two core configurations, was 0.780 for the reactor wtthout burnable poison or a lead reflector. The temperature coefficient of reactivity, measured in two cores, was positive at room temperature but negative in the proposed operatingtemperature range. The total reactivity effect in going from 20 to 80 deg C was a positive 0.22% DELTA k/k. The worth of control and safety-shutdown blades of several compositions and sizes in various locations was determined for a number of core configurations; blades having a sandwich construction of cadmium, tungsten, and indium had the greatest shutdown worth. To date these studies have resulted in a 61-element core (critical with 54 elements) with a 4-in. lead reflector which has 2.5% DELTA k/k excess reactivity for startup and for override of poison and burnup. A mock-up blade configuration has been determined which will control the excess reactivity introduced by flooding the elements with mineral oil (to simulate water flooding when fuel elements are changed in GCRE-1). (auth

Case Report of a Child after Hematopoietic Cell Transplantation with Acute Aspergillus Tracheobronchitis as a Cause for Respiratory Failure

Rapid respiratory failure due to invasive mycosis of the airways is an uncommon presentation of Aspergillus infection, even in immunocompromised patients, and very few pediatric cases have been reported. Patients with Aspergillus tracheobronchitis present with nonspecific symptoms, and radiologic studies are often noninformative, leading to a delay in diagnosis. Prompt initiation of adequate antifungal therapies is of utmost importance to improve outcome. We report the case of a 9-year-old girl with chronic myelogenous leukemia who developed respiratory distress 41 days after hematopoietic cell transplantation and rapidly deteriorated despite multiple interventions and treatment modalities

Case Report of a Child after Hematopoietic Cell Transplantation with Acute Aspergillus Tracheobronchitis as a Cause for Respiratory Failure

Rapid respiratory failure due to invasive mycosis of the airways is an uncommon presentation of Aspergillus infection, even in immunocompromised patients, and very few pediatric cases have been reported. Patients with Aspergillus tracheobronchitis present with nonspecific symptoms, and radiologic studies are often noninformative, leading to a delay in diagnosis. Prompt initiation of adequate antifungal therapies is of utmost importance to improve outcome. We report the case of a 9-year-old girl with chronic myelogenous leukemia who developed respiratory distress 41 days after hematopoietic cell transplantation and rapidly deteriorated despite multiple interventions and treatment modalities