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Increased remodeling of the extracellular matrix in malignant tumors has been shown to correlate with tumor aggressiveness and a poor prognosis. This remodeling involves degradation of the original extracellular matrix (ECM) and deposition of a new tumor-supporting ECM. The main constituent of the ECM is collagen and collagen turnover mainly occurs in a sequential manner, where initial proteolytic cleavage of the insoluble fibers is followed by cellular internalization of large well-defined collagen fragments for lysosomal degradation. However, despite extensive research in the field, a lack of consensus on which cell types within the tumor microenvironment express the involved proteases still exists. Furthermore, the relative contribution of different cell types to collagen internalization is not well-established. Here, we developed quantitative ex vivo collagen degradation assays and show that the proteases responsible for the initial collagen cleavage in two murine syngeneic tumor models are matrix metalloproteinases produced by cancer-associated fibroblasts and that collagen degradation fragments are endocytosed primarily by tumor-associated macrophages and cancer-associated fibroblasts from the tumor stroma. Using tumors from mannose receptor-deficient mice, we show that this receptor is essential for collagen-internalization by tumor-associated macrophages. Together, these findings identify the cell types responsible for the entire collagen degradation pathway, from initial cleavage to endocytosis of fragments for intracellular degradation.
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The preschool environment exerts an important influence on children's behaviour, including physical activity (PA). However, information is lacking regarding where and when most of children's PA is undertaken. This study aimed to describe PA and sedentary time (SED) during preschool hours and time out-of-care, and on weekdays and weekend days, and to investigate differences in PA patterns according to sex, age, and MVPA levels. From September 2015 to June 2016, we measured PA levels of 1109 children (age range, 2.7-6.5â¯years; mean age 4.7â¯years; boys, 52%) using ActiGraph GT3X+ accelerometers for up to 14 consecutive days. We applied a linear mixed model to analyse associations and interactions between total PA (counts per minute [cpm]), light PA (LPA), moderate-to-vigorous PA (MVPA), SED, sex, age, and overall MVPA regardless of setting, during preschool hours versus time out-of-care, and on weekdays versus weekend days. Children undertook more PA and less SED on weekdays compared to weekend days (pâ¯<â¯0.01). For boys, MVPA levels were higher during preschool hours than during time out-of-care (pâ¯<â¯0.05). Differences in total PA and MVPA between preschool hours versus time out-of-care, and between weekdays and weekend days, were greater in boys, older children, and highly active children than in girls, younger children, and children with lower overall MVPA levels (pâ¯<â¯0.01). The preschool arena is important for children's PA. Concerning MVPA, this study showed that boys, older children, and highly active children benefit more from this environment compared to girls, younger preschoolers, and children with lower MVPA levels.
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INTRODUCTION: Encouraging walking during the daily commute is a potential strategy for increasing physical activity levels. This study aimed: (i) to examine, and compare by travel mode, the objectively measured physical activity of a working adult population, and, (ii) to identify associations between mode of travel to work and a range of individual, interpersonal, organisational and environmental characteristics. METHODS: Employees (n=654) recruited from 87 workplaces in geographically distinct areas provided data through accelerometers, Global Positioning System (GPS) receivers, travel diaries and questionnaires. Separate multivariable logistic regression models were developed to examine factors associated with physical activity during the commute and mode of travel to work. RESULTS: In comparison to car users (7.3â¯minutes±Standard Deviation 7.6), walkers (34.3±18.6) and public transport users (25.7±14.0) accrued substantially higher levels of daily moderate to vigorous physical activity during the commute. Combined accelerometer and GPS data showed that participants who walked at least ten minutes during their commute were more likely to have a shorter commute distance (p<0.001), occupy a sedentary job (p<0.01), and be classified as 'underweight or normal weight' (p<0.03). No car access (p<0.001), and absence of free work car parking (p<0.01) were independently related to walking to work and using public transport. Shorter commuting distances were also related to walking to work (p<0.001). Public transport users were more likely to be younger (p=0.04), have more positive environmental perceptions (p=0.01), and less likely to combine their commute with caring responsibilities (p=0.03). CONCLUSIONS: This study shows that walking to work and using public transport are important contributors to physical activity levels in a working population. Planning, transport and behavioural interventions to promote walking during the commute should take into account the wider determinants. Reducing availability of free work car parking is one possible strategy to discourage car use.
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Strategies for increasing adherence to physical activity assessments are often linked to extra financial or personal effort. This paper aims to investigate the influence of the recruitment strategy on participants' adherence to accelerometry and resulting PA data. Data were used from two previous studies conducted in 2013 and 2016 in Cologne, Germany, differing in recruitment strategy (Nâ¯=â¯103, 40.8% male, mean age 20.9⯱â¯3.7â¯years, mean BMI 23.7⯱â¯4.1â¯kg/m2). In the passive recruitment (PR) group, vocational students took part in the accelerometry (ActiGraph GT3X+) in line with the main study unless they denied participation. In the active recruitment (AR) group, vocational students were invited to actively volunteer for the accelerometry. Impact of recruitment strategy on adherence and PA data was examined by regression analysis. Average adherence to the accelerometry was 66.7% (AR) and 74.0% (PR). No statistically significant influence of recruitment strategy on adherence and resulting PA was found (all pâ¯>â¯0.05). The difference in recruitment strategy did not affect adherence to accelerometry. The data imply that AR may be applicable. Future studies using larger sample sizes and diverse populations should further investigate these trends.
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Sedentary behaviour is an independent risk factor for adverse health conditions. Adults with intellectual disabilities spend a high proportion of their day engaged in sedentary behaviour, however, there is limited evidence on potential correlates of objectively measured sedentary behaviour in this population group. In Glasgow, UK from July to September 2017, a secondary analysis of pooled baseline accelerometer data from two randomised controlled trials of lifestyle behaviour change programmes was conducted. Backwards linear regression was used to investigate the associations between demographic, biological, and environmental correlates and objective measure of sedentary behaviour (percentage of time spent sedentary). One-hundred and forty-three participants provided valid accelerometer data. Mean percentage time spent sedentary (adjusted for wear time) was 72.9% [Standard Deviation (SD) = 8.7] per day. In the final model, physical and mental health problems were significantly (p < 0.05) associated with increased percentage time spent sedentary. This is the first study to provide evidence on multi-level, demographic, biological, and environmental correlates of objectively measured sedentary behaviour in adults with intellectual disabilities. To inform the development of interventions to modify sedentary behaviours in adults with intellectual disabilities, further research is required including a wide range of socio-ecological correlates.
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OBJECTIVE: To study the associations between: 1) number of permanent outdoor play facilities per pupil and 2) the size of the outdoor play area per pupil with sedentary time and physical activity (PA) during school hours in six-, nine-, and 15-year olds. We conducted a cross-sectional study of nationally representative samples of Norwegian six- (n = 1071), nine- (n = 1421) and 15-year-olds (n = 1106) in 2011 (the Physical Activity Among Norwegian Children Study). The participation rates were 56.4%, 73.1% and 57.8% for six-, nine- and 15-year olds, respectively. We assessed PA objectively for seven consecutive days using accelerometers, the size of a school's outdoor play area (SOPA) using an online map service and the permanent play facility (PPF) provision using a standardized form during school site visits. We successfully measured SOPA and PPF in 99 schools, from which 3040 participants provided valid accelerometer data. We used generalized least-squares random-effects models with robust variance estimation to assess associations. Our results indicate that better provision of permanent play facilities may reduce sedentary time and increase time spent in light PA among six-year-olds. Permanent play facility provision was not associated with sedentary time or PA among nine- and 15-year-olds. Associations found between outdoor play area size, physical activity and sedentary time were negligible. Future research should investigate what types of permanent play facilities may be associated with physical activity in both children and adolescents.
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INTRODUCTION: Hepatocellular Carcinoma (HCC) is one of most lethal cancers worldwide. The prognosis is very poor and therapeutic options are limited. The aim of this study was to determine the correlation of the [(18)F]FDG uptake profile of three HCC cell lines with p53 and glucose transporters (GLUTs) 1, 2, 3, 5 and 12 expression and with the glucose level present in the cell culture medium. METHODS: Cell lines used are HepG2 (wp53), HuH7 (overexpress p53) and Hep3B2.1-7 (p53null). An immunocytochemical analysis was performed to evaluate p53 expression. Through uptake studies were analyzed the [(18)F]FDG uptake profiles of all cell lines under study. The expression of GLUTs were quantified by flow cytometry. The [(18)F]FDG uptake studies GLUTs expression analysis were performed on cells that grew in a high and low glucose medium in order to determine the effect of glucose concentration on GLUTs expression and on [(18)F]FDG uptake. RESULTS: Immunocytochemical analysis confirmed the p53 expression profiles of all cell lines. It was found out that for all cell lines, [(18)F]FDG uptake is higher when cells grow in low glucose medium, however, the glucose level doesn't affect mostly the GLUTs expression. The Hep3B2.1-7 (p53null) is always the one that have higher [(18)F]FDG uptake. It was found that not always GLUT1 and GLUT3 are the most expressed by these cell lines. CONCLUSIONS: Our results shown that the p53 expression influences [(18)F]FDG uptake. This suggests that [(18)F]FDG may be used in HCC diagnosis, and may even provide some information about the genetic profile of the tumor.
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BACKGROUND: Neighborhood attributes are modifiable determinants of physical activity (PA) and sedentary behavior (SB). We tested whether the objectively-assessed built and social environment was associated with PA and SB in Swiss youth and whether sex, age and the socioeconomic position (Swiss-SEP) modified such associations. METHODS: We combined data of 1742 youth (ages 4 to 17) from seven studies conducted within Switzerland between 2005-2010. All youth provided accelerometer data and a home address, which was linked to objective environmental data and the Swiss-SEP-index. Associations between neighborhood attributes and PA were analyzed by multivariable multilevel regression analyses. RESULTS: The extent of green areas and building density was positively associated with PA in the total sample (p < 0.05). Factors representing centrally located areas, and more schoolchildren living nearby tended to increase PA in secondary schoolchildren, boys and those from lower-ranked socioeconomic areas. In primary schoolchildren, the extent of green areas was positively associated with PA (p = 0.05). Associations between neighborhood attributes and PA were more pronounced in youth from low socioeconomic areas. CONCLUSIONS: The results indicate that some associations between neighborhood attributes and PA differ by age, sex and socioeconomic area. This should be taken into account when planning interventions to increase childhood PA.
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Bowen-Conradi syndrome (BCS) is a lethal autosomal recessive disorder caused by a D86G substitution in the protein, Essential for Mitotic Growth 1 (EMG1). EMG1 is essential for 18S rRNA maturation and 40S ribosome biogenesis in yeast, but no studies of its role in ribosome biogenesis have been done in mammals. To assess the effect of the EMG1 mutation on cell growth and ribosomal biogenesis in humans, we employed BCS patient cells. The D86G substitution did not interfere with EMG1 nucleolar localization. In BCS patient lymphoblasts, cells accumulated in G2/M, resulting in reduced proliferation rates; however, patient fibroblasts showed normal proliferation. The rate of 18S rRNA processing was consistently delayed in patient cells, although this did not lead to a difference in the levels of 40S ribosomes, or a change in protein synthesis rates. These results demonstrate that as in yeast, EMG1 in mammals has a role in ribosome biogenesis. The obvious phenotype in lymphoblasts compared to fibroblasts suggests a greater need for EMG1 in rapidly dividing cells. Tissue-specific effects have been seen in other ribosomal biogenesis disorders, and it seems likely that the impact of EMG1 deficiency would be larger in the rapidly proliferating cells of the developing embryo.