MEN,destruction and separation: mechanistic links between mitotic exit and cytokinesis in budding yeast

Cellular events must be executed in a certain sequence during the cell division in order to maintain genome integrity and hence ensure a cell's survival. In M phase, for instance, chromosome segregation always precedes mitotic exit (characterized by mitotic kinase inactivation via cyclin destruction); this is then followed by cytokinesis. How do cells impose this strict order? Recent findings in budding yeast have suggested a mechanism whereby partitioning of chromosomes into the daughter cell is a prerequisite for the activation of mitotic exit network (MEN). So far, however, a regulatory scheme that would temporally link the initiation of cytokinesis to the execution of mitotic exit has not been determined. We propose that the requirement of MEN components for cytokinesis, their translocation to the mother–daughter neck and triggering of this translocation by inactivation of the mitotic kinase may be the three crucial elements that render initiation of cytokinesis dependent on mitotic exit. BioEssays 24: 659–666, 2002. © 2002 Wiley Periodicals, Inc.     

The Impact of Dyspepsia on Symptom Severity and Quality of Life in Adults with Headache

Background

Dyspepsia and headache frequently co-exist, but the clinical implication of this association is uncertain. We planned to examine the prevalence and impact of dyspepsia in adults with headache.

Methods

A cross-sectional study was conducted in a secondary care setting. Clinical, psychological and health-related quality of life (HRQOL) data were compared between subjects with headache and controls (non-headache subjects). The impact of dyspepsia was analysed further in subjects with headache alone.

Results

280 subjects (93 cases with headache and 187 matched controls) were recruited. The following baseline characteristics of subjects were as follows: mean age 45.0±17.3 years, 57.0% females and ethnic distribution—Malaysian = 45 (48.4%), Chinese n = 24 (25.8%) and Indians n = 24 (25.8%). Headache sub-types among cases with headache were as follows: tension-type headache (TTH) n = 53 (57.0%) and migraine n = 40 (43.0%). Dyspepsia was more prevalent in cases with headache compared to controls (25.8% vs 12.8%, p = 0.011), and headache was independently associated with dyspepsia (OR 2.75, 95% CI 1.39–5.43). Among cases with headache, there was a trend towards a higher prevalence of dyspepsia in those with migraine (27.5%) compared to TTH (24.5%). Subjects with headache and dyspepsia, compared to those with headache alone, had a greater severity of headache symptoms (63.67±22.85 mm vs 51.20 ±24.0 mm VAS, p = 0.029). Overall HRQOL scores were lower in headache subjects with dyspepsia (EQ-5D summary score 0.82±0.18 vs 0.90 ±0.16, p = 0.037 and EQ-5D VAS 62.08±17.50 mm vs 72.62 ±18.85 mm, p = 0.018), compared to those without dyspepsia.

Conclusion

Dyspepsia is associated with more severe headache symptoms and results in a lower HRQOL in patients with headache.     

Tyrosine phosphorylation profiling in FGF-2 stimulated human embryonic stem cells

The role of fibroblast growth factor-2 (FGF-2) in maintaining undifferentiated human embryonic stem cells (hESC) was investigated using a targeted phosphoproteomics approach to specifically profile tyrosine phosphorylation events following FGF-2 stimulation. A cumulative total number of 735 unique tyrosine phosphorylation sites on 430 proteins were identified, by far the largest inventory to date for hESC. Early signaling events in FGF-2 stimulated hESC were quantitatively monitored using stable isotope dimethyl labeling, resulting in temporal tyrosine phosphorylation profiles of 316 unique phosphotyrosine peptides originating from 188 proteins. Apart from the rapid activation of all four FGF receptors, trans-activation of several other receptor tyrosine kinases (RTKs) was observed as well as induced tyrosine phosphorylation of downstream proteins such as PI3-K, MAPK and several Src family members. Both PI3-K and MAPK have been linked to hESC maintenance through FGF-2 mediated signaling. The observed activation of the Src kinase family members by FGF-2 and loss of pluripotent marker expression post Src kinase inhibition may point to the regulation of cytoskeletal and actin depending processes to maintain undifferentiated hESC.     

Joint Association of Sitting Time and Physical Activity with Metabolic Risk Factors among Middle-Aged Malays in a Developing Country: A Cross-Sectional Study

Background

Prolonged sitting is associated with increased weight and higher risks for abdominal obesity, dyslipidaemia, hyperglycaemia and hypertension among the adult population. This has been well documented in the West, but studies on these associations are lacking in developing countries, including Malaysia.

Objective

This cross-sectional study aimed to examine the joint association of sitting time and physical activity with metabolic risk factors among middle-aged working adults.

Methodology

A total of 686 Malay men and women participated (mean age 45.9±6.5 years). Metabolic syndrome was diagnosed from the modified NCEP ATP III criteria. Self-reported sitting time was obtained with the validated Malay version of the International Physical Activity Questionnaire. Participants were asked about their time spent sitting during travel in a motor vehicle, e.g., car, motorcycle or bus, over the preceding 7 days. Logistic regression was used to estimate the odds ratio with the confidence interval for the combined effects of sitting quartiles and physical activity categories with metabolic risk factors.

Results/Significance

The prevalence of metabolic syndrome among our participants was 31.9%. Their average total sitting time (including transportation) was 7.6±2.4 h/day. After we adjusted for gender and educational level, higher sitting quartiles and physically inactive groups were associated with higher odds for metabolic syndrome compared with the referent group (sitting <6 h/day and physically active). In the physically active stratum, the odds for metabolic syndrome in participants who sat ≥9.3 h/day was 3.8 times that of participants who sat <6 h/day. Both higher sitting quartiles and insufficient physical activity were associated with adverse effects on abdominal obesity, hypertriglyceridemia and hyperglycaemia.

Conclusion

In joint analyses of sitting time and physical activity, higher sitting time and insufficient physical activity were deleteriously associated with odds for metabolic risk factors in middle-aged Malay men and women.     

Eating Behaviour among Multi-Ethnic Adolescents in a Middle-Income Country as Measured by the Self-Reported Children’s Eating Behaviour Questionnaire

Background

Escalating weight gain among the Malaysian paediatric population necessitates identifying modifiable behaviours in the obesity pathway.

Objectives

This study describes the adaptation and validation of the Children’s Eating Behaviour Questionnaire (CEBQ) as a self-report for adolescents, investigates gender and ethnic differences in eating behaviour and examines associations between eating behaviour and body mass index (BMI) z-scores among multi-ethnic Malaysian adolescents.

Methodology

This two-phase study involved validation of the Malay self-reported CEBQ in Phase 1 (n = 362). Principal Axis Factoring with Promax rotation, confirmatory factor analysis and reliability tests were performed. In Phase 2, adolescents completed the questionnaire (n = 646). Weight and height were measured. Gender and ethnic differences in eating behaviour were investigated. Associations between eating behaviour and BMI z-scores were examined with complex samples general linear model (GLM) analyses, adjusted for gender, ethnicity and maternal educational level.

Results

Exploratory factor analysis revealed a 35-item, 9-factor structure with ‘food fussiness’ scale split into two. In confirmatory factor analysis, a 30-item, 8-factor structure yielded an improved model fit. Reliability estimates of the eight factors were acceptable. Eating behaviours did not differ between genders. Malay adolescents reported higher Food Responsiveness, Enjoyment of Food, Emotional Overeating, Slowness in Eating, Emotional Undereating and Food Fussiness 1 scores (p<0.05) compared to Chinese and Indians. A significant negative association was observed between BMI z-scores and Food Fussiness 1 (‘dislike towards food’) when adjusted for confounders.

Conclusion

Although CEBQ is a valuable psychometric instrument, adjustments were required due to age and cultural differences in our sample. With the self-report, our findings present that gender, ethnic and weight status influenced eating behaviours. Obese adolescents were found to display a lack of dislike towards food. Future longitudinal and qualitative studies are warranted to further understand behavioural phenotypes of obesity to guide prevention and intervention strategies.