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    Abstract: The transcription factor c-MYC regulates a multiplicity of genes involved in cellular growth, proliferation, metabolism and DNA damage response and its overexpression is a hallmark of many tumours. Since MYC promotes apoptosis under conditions of stress, such as limited availability of nutrients or cytokines, MYC-driven cells are very much dependent on signals that inhibit cell death. Stress signals trigger apoptosis via the pathway regulated by opposing fractions of the BCL-2 protein family and previous genetic studies have shown that the development of B lymphoid tumours in Emicro-Myc mice is critically dependent on expression of pro-survival BCL-2 relatives MCL-1, BCL-W and, to a lesser extent, BCL-XL, but not BCL-2 itself, and that sustained growth of these lymphomas is dependent on MCL-1. Using recently developed mice that lack expression of all three functional pro-survival A1 genes, we show here that the kinetics of lymphoma development in Emicro-Myc mice and the competitive repopulation capacity of Emicro-Myc haemopoietic stem and progenitor cells is unaffected by the absence of A1. However, conditional loss of a single remaining functional A1 gene from transplanted A1-a(-/-)A1-b (fl/fl) A1-c(-/-) Emicro-Myc lymphomas slowed their expansion, significantly extending the life of the transplant recipients. Thus, A1 contributes to the survival of malignant Emicro-Myc-driven B lymphoid cells. These results strengthen the case for BFL-1, the human homologue of A1, being a valid target for drug development for MYC-driven tumours.
    Type of Publication: Journal article published
    PubMed ID: 29339775
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  • 3
    Keywords: CANCER ; RISK ; ASSOCIATION ; HUMANS ; nutrition ; INSULIN-RESISTANCE ; metabolic syndrome ; WOMENS HEALTH ; FISH INTAKE ; DAIRY CONSUMPTION
    Abstract: OBJECTIVE: The long-term association between dietary protein and type 2 diabetes incidence is uncertain. We aimed to investigate the association between total, animal, and plant protein intake and the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from eight European countries, with an average follow-up time of 12.0 years. Pooled country-specific hazard ratios (HRs) and 95% CI of prentice-weighted Cox regression analyses were used to estimate type 2 diabetes incidence according to protein intake. RESULTS: After adjustment for important diabetes risk factors and dietary factors, the incidence of type 2 diabetes was higher in those with high intake of total protein (per 10 g: HR 1.06 [95% CI 1.02-1.09], Ptrend 〈 0.001) and animal protein (per 10 g: 1.05 [1.02-1.08], Ptrend = 0.001). Effect modification by sex (P 〈 0.001) and BMI among women (P 〈 0.001) was observed. Compared with the overall analyses, associations were stronger in women, more specifically obese women with a BMI 〉30 kg/m(2) (per 10 g animal protein: 1.19 [1.09-1.32]), and nonsignificant in men. Plant protein intake was not associated with type 2 diabetes (per 10 g: 1.04 [0.93-1.16], Ptrend = 0.098). CONCLUSIONS: High total and animal protein intake was associated with a modest elevated risk of type 2 diabetes in a large cohort of European adults. In view of the rapidly increasing prevalence of type 2 diabetes, limiting iso-energetic diets high in dietary proteins, particularly from animal sources, should be considered.
    Type of Publication: Journal article published
    PubMed ID: 24722499
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  • 4
    ISSN: 1399-3054
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: The above-ground parts of two years old seedlings of Douglas fir (Pseudotsuga menziesii) were exposed to filtered air, NH3, NO2+, SO2 (66, 96 and 95 μg m−3, respectively), to a mixture of NO2+NH3 (55 + 82 μg m−3) or SO2+NO2 (128 + 129 μg m−3), for 8 months in fumigation chambers. Both chlorophyll fluorescence and gas exchange measurements were carried out on shoots which had sprouted at the beginning of the exposure period. The chlorophyll fluorescence measurements were performed after 3 and 5 months of exposure (average shoot age 70 and 140 days, respectively). Light response curves of electron transport rate (J) were determined, in which J was deduced from chlorophyll fluorescence. In addition, light response curves of net CO2 assimilation were determined after 5 months of exposure. After 3 months of exposure (average shoot age 70 days) all exposure treatments showed a lower maximum electron transport rate (Jmax) as compared to the control shoots (filtered air). A large reduction (45%) was observed for shoots exposed to SO2+NO2. During the exposure period between 3 and 5 months (average shoot age 70 and 140 days, respectively) a decrease of Jmax was observed for all treatments. Jmax had further declined some time after termination of the exposure, when average shoot age was 310 days.Shoots exposed to SO2 and SO2+NO2 also showed a reduction in maximum net CO2 assimilation (Pmax) as compared to the control shoots. However, shoots exposed to NO2 showed no reduction and even a higher Pmax was observed for shoots exposed to NH3 or NO2+NH3. Needles of these treatments also showed a higher chlorophyll content which might explain the contradictory results obtained for these treatments: the increased amount of photosynthetic units counteracts the reduction in Jmax and consequently no reduction in Pmax is measured. Shoots exposed to SO2 and SO2+NO2 also showed a reduction in maximum stomatal conductance (gs). However, the stomatal opening was larger than could be expected on basis of their (maximum) CO2 assimilation rate. Consequently, water use efficiency of these shoots was lower than that of the control shoots. Also shoots exposed to NO2 had a lower water use efficiency due to a significantly higher maximum gs. Shoots exposed to NH3 showed a high transpiration rate in the dark, indicating imperfect stomatal closure.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1439-6327
    Keywords: Key words Exercise intensity ; Physical activity ; Insulin sensitivity ; Insulin tolerance test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to evaluate the role of exercise intensity in the effect of physical training on insulin sensitivity. The insulin tolerance test (ITT) was applied to quantify insulin sensitivity. Eighteen healthy, young, untrained men and women participated in a 4-week, five times per week, 1-h per session bicycle-ergometer training program. Training consisted of 3-min bouts of cycling interspersed with 2 min at a lower exercise intensity. Intensities were 80 and 40% of pretraining maximal power output (W˙ max) in the high-intensity (HI) and 40 and 20% W˙ max in the low-intensity (LI) group. The insulin sensitivity index (ISindex) was similar in the HI and LI group before the training intervention [mean (SD) −0.1898 (0.058) and −0.1892 (0.045), respectively]. After training, the ISindex was −0.2358 (0.051) (P = 0.005 vs pretraining) in the HI group and −0.2050 (0.035) (P = 0.099 against pretraining) in the LI group. We conclude that improvements in insulin sensitivity are more pronounced with high-intensity training, when exercise frequency and duration are kept similar. We further conclude that the ITT is suitable for use in intervention studies.
    Type of Medium: Electronic Resource
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