GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

Analysis of Combined Systems of Two Endoreversible Engines

A single endoreversible engine can operate as a cooler, a true heat engine, a heat pump, or a refrigerator. We investigate how many different modes of operation a combined system of two endoreversible engines may display. Special attention is paid to the independent combined system which neither consumes nor supplies power.     

An alcohol expectancy-challenge prevention program for at risk college women.

Alcohol expectancy-challenge programs are effective in changing expectancies and reducing drinking in college men (J. Darker & M. S. Goldman. 1993. 1998); however, recent evidence suggests this protocol might not be effective for women (M. E. Dunn, C. Lau, & I. Y. Cruz, 2000). This study was designed to reevaluate the effectiveness of a social/sexual expectancy-challenge intervention in college women reporting moderate to heavy alcohol use. Forty-six undergraduate women were randomly assigned to the prevention or control condition. Participants reported alcohol expectancies at pre- and posttest and monitored their drinking patterns daily for 6 weeks. The program was effective in changing some expectancies but did not reduce drinking. This further confirms differences in the mechanisms by which expectancy-challenge programs function for men and women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An Investigation of the Reduction and Reoxidation of Isolated Vanadate Sites Supported on MCM-48

The reduction and subsequent reoxidation of isolated vanadate species supported on silica was investigated using temperature-programmed reduction and oxidation, along with in-situ XANES and Raman spectroscopy. Approximately 70–80% of the vanadium was reduced to V³⁺ after reduction in H₂ at temperatures up to 923 K. Upon reduction, the vanadyl oxygen was removed and the three remaining V–O bonds are lengthened by 0.2 Å. The vanadate species are rapidly reoxidized when exposed to O₂, with the amount of oxygen uptake matching well with the amount removed during reduction. In-situ Raman spectroscopy during reoxidation in ¹⁸O₂ showed that significant scrambling occurs between gas phase oxygen and surface oxygen species during the reoxidation of the vanadate species.     

The lipid composition of selected tissues from a Mediterranean monk seal,Monachus monachus

The lipid composition of blubber, brain, muscle and heart from a Mediterranean monk sealMonachus monachus (an endangered species) were examined to allow comparisons with more common species of seals. Only neutral lipids (mainly triacylglycerols) were detectable in the blubber lipids, whereas polar lipids predominated in the heart and in the brain. Neutral and polar lipids comprised almost equal proportions in both liver and muscle. Choline glycerophospholipids (CGP) were the major polar lipids, followed by ethanolamine glycerophospholipids (EGP) in the liver, heart and muscle. Cerebrosides accounted for 28.8% of the brain lipids. All lipid classes of the liver contained high levels (31–47%) of polyunsaturated fatty acids (PUFA), with the exception of phosphatidylserine. The total proportion of n−6 PUFA exceeded that of n−3 PUFA in all lipid classes of the liver, due mainly to the high levels of 20∶4n−6. The highest level of 20∶4n−6 occurred in phosphatidylinositol, where it comprised 32.4% of the total fatty acids. The CGP and EGP of the brain contained lower levels of PUFA than those of the liver, muscle and heart. Alkenyl ethers accounted for 35.8% of the total long-chain moieties in brain EGP. The fatty acid composition of blubber triacylglycerols differed from those of the lipid classes from other tissues in that it had a very low ratio of n−6 to n−3 PUFA (0.3) as a result of a lower content of 20∶4n−6.     

Mechanical simulations of SANDIA II tests OECD ISP 48 benchmark

This paper illustrates the work carried out by EDF within the framework of ISP 48 post-test analysis of NUPEC/NRC 1:4-scale model of a prestressed pressure containment vessel of a nuclear power plant [Hessheimer, M.F., Klamerus, E.W., Rightly, G.S., Lambert, L.D., Dameron, R.A., 2003. Overpressurization test of a 1:4-scale prestressed concrete containment vessel model. NUREG/CR-6810, SAND2003-0840P. Sandia National Laboratories, Albuquerque, NM]. EDF as a participant of the International Standard Problem no. 48 [Mathet, E., Hessheimer, M., Ali, S., Tegeler, B., 2005. An international standard problem: analysis of 1:4-scale prestressed concrete containment vessel model under severe accident conditions. Proceedings of 18th International Conference on Structural Mechanics in Reactor Technology. SMiRT 18. Beijing, China] has participated in this program, within the framework of its research and development program on the simulation of non-linear behaviour of nuclear power plant prestressed concrete pressure containment vessels. EDF performed several simulations to determine the ultimate response of the scale model. To determine the most influent parameters in such an analysis several studies were carried out. A full 3D mesh of the entire structure was then created. The mesh was built using a parametric tool to measure the influence of discretization on results. To represent the cracking of concrete, two material laws were then used. The purpose of this paper is to illustrate the ultimate behaviour of SANDIA II model obtained by Code_Aster^® finite element platform, with comparison to tests records, and also to share the lessons learned from the parametric computations and underline precautions that must be taken in such studies.     

Six Synthesis Methods for Reversible Logic

The (2 ^w )! reversible transformations on w wires, i.e. reversible logic circuits with w inputs and w outputs, together with the action of cascading, form a group, isomorphic to the symmetric group S ₂ ^w . Therefore, we investigate the group S _n as well as one of its subgroups isomorphic to S _n/2 × S _n/2. We then consider the left cosets, the right cosets, and the double cosets generated by the subgroup. Each element of a coset can function as the representative of the coset. The coset can then be considered as the set of all group elements that differ from the representative by merely multiplying (either to the left or to the right or to both sides) by an arbitrary element of the subgroup. Different choices of the coset space and different choices of the coset representatives lead to six different syntheses for implementing an arbitrary reversible logic operation into hardware. Evaluation of all six methods, by means of three different cost functions (gate cost, switch cost, and quantum cost), leads to a best choice.     

Leiomyosarcoma of the esophagus: results of surgical treatment

BACKGROUND: This study examined the results of surgical treatment of leiomyosarcoma of the esophagus. METHODS: Between January 1920 and December 1996, 17 patients (9 men and 8 women) with leiomyosarcoma of the esophagus were treated surgically at the Mayo Clinic. Median age was 58 years and ranged from 26 to 76 years. Symptoms included dysphagia in 11 patients (64.7%) and odynophagia in 6 (35.3%). The tumor was located in the middle third of the esophagus in 10 patients (58.8%) and in the cervical esophagus in 7 (41.2%). Procedures performed included esophagogastrectomy in 9 patients (Ivor Lewis in 5, left thoracoabdominal in 3, and transhiatal in 1), enucleation in 3, transgastric excision in 1, and exploration without resection in 4. RESULTS: The procedure was considered curative in 11 patients (64.7%). There was one operative death (mortality, 5.9%). Complications occurred in 3 patients (17.6%) and included anastomotic leak in 2 and bleeding requiring reoperation in 1. Growth pattern was infiltrating in 7, polypoid in 5, and intramural in 5. Histologically, the tumor was grade 1 in 6 patients, grade 2 in 2, grade 3 in 7, and grade 4 in 2. The tumor was postsurgically classified as stage I in 2 patients, stage IIA in 7, stage IIB in 1, stage IIIA in 5, stage IV in 1, and unknown in 1. Six patients (35.3%) received adjuvant treatment. Follow-up was complete in 16 patients (94.1%) and ranged from 1 to 182 months (median, 48 months). Five- and 10-year actuarial survivals were 47.0% and 31.0%, respectively. Seven patients (41.2%) are currently alive (median survival, 72 months); all underwent curative resection. Factors affecting survival included completeness of resection, growth pattern, postsurgical stage, tumor grade, and tumor location (p < 0.05). CONCLUSIONS: We conclude that leiomyosarcoma of the esophagus is rare. Complete resection provides long-term survival.     

Prevalence and role of anticardiolipin antibodies in Crohn disease

OBJECTIVES: Anticardiolipin antibodies belong to the group of antiphospholid antibodies, and may be seen in association with endothelial damage and recurrent vascular thrombosis. The aim of our study was to determine in patients with Crohn's disease the frequency of anticardiolipin antibodies, and to correlate their presence with clinical activity and treatment of the disease. METHODS: One hundred and thirty-eight sera from patients with Crohn's disease and 118 from age-matched controls were tested for IgG anticardiolipin antibodies. In the Crohn's disease group, we determined whether the patients had a past history of vascular thrombosis, a clinically active intestinal disease, or a current immunosuppressive therapy (steroids or azathioprine). RESULTS: Anticardiolipin antibodies were found significantly more often in patients with Crohn's disease than in controls: 11.0% versus 2.5%, P < 0.02. Three patients with Crohn's disease had a past history of vascular thrombosis, but none of them had anticardiolipin antibodies. The presence of anticardiolipin antibodies was not correlated with the fact that patients had a clinically active disease (P = 0.77), or a current immunosuppressive therapy at the time of the serological test (P = 0.95). CONCLUSIONS: There is a significantly high prevalence of patients with anticardiolipin antibodies during Crohn's disease. The positivity of the test does not seem to be correlated to the existence of a past history of vascular thrombosis, nor to the clinical activity of the disease.