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.     

COVID-19 hospitalization rates rise exponentially with age,inversely proportional to thymic T-cell production

Here, we report that COVID-19 hospitalization rates follow an exponential relationship with age, doubling for every 16 years of age or equivalently increasing by 4.5% per year of life (R² = 0.98). This mirrors the well-studied exponential decline of both thymus volume and T-cell production, which halve every 16 years. COVID-19 can therefore be added to the list of other diseases with this property, including those caused by methicillin-resistant Staphylococcus aureus, MERS-CoV, West Nile virus, Streptococcus pneumoniae and certain cancers, such as chronic myeloid leukaemia and brain cancers. In addition, the incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. Since these properties are shared with some non-contagious diseases, we hypothesized that the age dependence does not come from social-mixing patterns, i.e. that the probability of hospitalization given infection rises exponentially, doubling every 16 years. A Bayesian analysis of daily hospitalizations, incorporating contact matrices, found that this relationship holds for every age group except for the under 20s. While older adults have fewer contacts than young adults, our analysis suggests that there is an approximate cancellation between the effects of fewer contacts for the elderly and higher infectiousness due to a higher probability of developing severe disease. Our model fitting suggests under 20s have 49–75% additional immune protection beyond that predicted by strong thymus function alone, consistent with increased juvenile cross-immunity from other viruses. We found no evidence for differences between age groups in susceptibility to infection or infectiousness to others (given disease state), i.e. the only important factor in the age dependence of hospitalization rates is the probability of hospitalization given infection. These findings suggest the existence of a T-cell exhaustion threshold, proportional to thymic output and that clonal expansion of peripheral T-cells does not affect disease risk. The strikingly simple inverse relationship between risk and thymic T-cell output adds to the evidence that thymic involution is an important factor in the decline of the immune system with age and may also be an important clue in understanding disease progression, not just for COVID-19 but other diseases as well.     

Project to develop school education services in Delhi, India

There are many ways in which quantitative decision models can be applied in project management. The introduction of a project evaluation review technique network model to the development of a school education service in the city of Delhi, India, is described. The reasons for choosing this method, its advantages and limitations are discussed. Examples of the information obtained from the model are presented and explained.     

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)     

Coupled-mode theory of overmoded cylindrical metal bragg-reflectors

A coupled-mode theory of overmoded, cylindrical metal Bragg-reflectors is presented. The first-order Bragg coupling constants are derived for TE → TE, TM → TM, TE → TM, and TM → TE mode conversions. Reflectivities and transverse modeQ-factors are computed for a Bragg-reflector resonator. The results illustrate important competition effects between nearly-degenerate-transverse-modes occurring within both the Bragg-reflectors and the resonator.     

Longitudinal bone mineral density changes in early rheumatoid arthritis

A prospective longitudinal study of patients with early RA was performed to examine the influence of disease duration, disease activity and physical activity on bone loss. Sixty-seven patients with non-steroid treated RA of less than 5 yr duration, including 16 patients with disease duration less than 6 months, had BMD measurements of the femoral neck and the lumbar spine over a 12-month period using dual energy X-ray absorptiometry. The BMD changes were compared with values from 72 control patients and were also correlated with serial measurements of disease activity (measured by the Stoke Index) and disability [measured by the Health Assessment Questionnaire (HAQ) score], at 3-monthly intervals over the 12-month period. No significant differences in BMD changes were found between RA patients and controls overall. Patients with disease duration of less than 6 months had significantly greater loss of BMD at the femoral neck (-3.9%, S.E.M. 1.5) than the remainder of the cohort (-0.2%, S.E.M. 0.7) (P = 0.02) and controls (-0.8%, S.E.M. 0.6). Lumbar spine BMD changes correlated with the initial Stoke Index (Rs-0.373, P = 0.01) but not mean Stoke Indices. There was no correlation of BMD changes with age or HAQ scores. These findings suggest that significant bone loss occurs within the first few months of disease in patients with RA.     

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)