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.     

A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from Conus purpurascens venom

A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).     

Review of The parent-child connection.

[Correction Notice: An erratum for this article was reported in Vol 31(2) of Canadian Psychology Psychologie Canadienne (see record 2007-08913-001). In the October 1989 issue (Vol. 30, No. 4, p. 697), Arnold Rincover's affiliation with the Ontario Institute for Studies in Education was incorrectly given as Associate Professor. He has been an Extramural Instructor at O.I.S.E.] Reviews the book, The parent-child connection by Arnold Rincover (1988). The parent-child connection is a well written book that offers valuable advice to help parents of young children evaluate and understand their children's behaviour. It also offers useful suggestions on managing child behaviour, although these parenting tips are most likely to be useful to those parents who least need them (i.e., those with numerous personal and social resources, whose children are presenting only minor behavioural difficulties). The two general themes of the book, child behaviour as communication and developmental norms as guidelines for deciding if behaviour is problematic, are well-suited to the purposes of a parent reference book. They offer an appropriate framework for discussing specific child behaviours and helping parents to determine if these behaviours are problematic in their children. This book is a welcome addition to the list of available parenting books, and may prove particularly useful for younger parents in need of accurate and understandable information about normal child development and behaviour. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Depression in ethnically diverse women: Implications for treatment in primary care settings.

What do health care practitioners need to know about providing adequate care for depressed minority women? This article examined the prevalence of depressive symptoms and clinical depression in ethnic minorities, the extent to which current health service utilization is congruent with needs, and the effectiveness of treatments provided to ethnic minorities in the primary care setting. The impact of ethnic minority women's sociocultural context on symptom expression and help-seeking behavior is also discussed. Finally, the clinical implications for accurate assessment and treatment of ethnic minority women by both medical and mental health practitioners working in the primary care sector are addressed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Negative priming in associative learning: Evidence from a serial-conditioning procedure.

Three experiments investigated the suggestion that a predicted or primed stimulus commands less processing and consequently elicits a weaker CR than a stimulus that is not primed. In each experiment rats received initial training in which the presentation of each of 2 serial compounds, A-X and B-Y, was followed by the delivery of food. Subsequently, X's capacity to elicit the CR, approaching the site of food delivery, was assessed when X was preceded by Stimulus A (i.e., primed) or was presented after Stimulus B. Stimulus X elicited a more vigorous response when it was presented after B than when it followed A. These results show that the ability of one event to elicit its CR is reduced if its presentation has been predicted by some other event. This negative priming effect supports one aspect of A. R. Wagner's (1981) model of Pavlovian conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.     

Kanga(ROO): Handling the micro-DST of the BaBar experiment with ROOT

A system based on ROOT for handling the micro-DST of the BaBar experiment is described. The purpose of the Kanga system is to have micro-DST data available in a format well suited for data distribution within a world-wide collaboration with many small sites. The design requirements, implementation and experience in practice after three years of data taking by the BaBar experiment are presented.     

Effects of cross-phase modulation in wavelength-multiplexed SCMvideo transmission systems

Channel crosstalk effects in wavelength-multiplexed subcarrier-multiplexing video transmission systems due to cross-phase modulation are investigated. The crosstalk level depends on the spacing of optical channels. For analogue CATV transmissions in the 1.5 μm window using normal singlemode fibre, it is shown that the number of achievable optical channels is severely limited by cross-phase modulation for typical system parameters