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11.
Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2–94.7% high-grade CIN and in 59.3–100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection.  相似文献   
12.
BackgroundIt has been suggested that a higher intra-individual variability benefits the motor learning of wheelchair propulsion. The present study evaluated whether feedback-induced variability on wheelchair propulsion technique variables would also enhance the motor learning process. Learning was operationalized as an improvement in mechanical efficiency and propulsion technique, which are thought to be closely related during the learning process.Methods17 Participants received visual feedback-based practice (feedback group) and 15 participants received regular practice (natural learning group). Both groups received equal practice dose of 80 min, over 3 weeks, at 0.24 W/kg at a treadmill speed of 1.11 m/s. To compare both groups the pre- and post-test were performed without feedback. The feedback group received real-time visual feedback on seven propulsion variables with instruction to manipulate the presented variable to achieve the highest possible variability (1st 4-min block) and optimize it in the prescribed direction (2nd 4-min block). To increase motor exploration the participants were unaware of the exact variable they received feedback on. Energy consumption and the propulsion technique variables with their respective coefficient of variation were calculated to evaluate the amount of intra-individual variability.ResultsThe feedback group, which practiced with higher intra-individual variability, improved the propulsion technique between pre- and post-test to the same extent as the natural learning group. Mechanical efficiency improved between pre- and post-test in the natural learning group but remained unchanged in the feedback group.ConclusionThese results suggest that feedback-induced variability inhibited the improvement in mechanical efficiency. Moreover, since both groups improved propulsion technique but only the natural learning group improved mechanical efficiency, it can be concluded that the improvement in mechanical efficiency and propulsion technique do not always appear simultaneously during the motor learning process. Their relationship is most likely modified by other factors such as the amount of the intra-individual variability.  相似文献   
13.
Dual-task performance is often impaired after stroke. This may be resolved by enhancing patients’ automaticity of movement. This study sets out to test the constrained action hypothesis, which holds that automaticity of movement is enhanced by triggering an external focus (on movement effects), rather than an internal focus (on movement execution). Thirty-nine individuals with chronic, unilateral stroke performed a one-leg-stepping task with both legs in single- and dual-task conditions. Attentional focus was manipulated with instructions. Motor performance (movement speed), movement automaticity (fluency of movement), and dual-task performance (dual-task costs) were assessed. The effects of focus on movement speed, single- and dual-task movement fluency, and dual-task costs were analysed with generalized estimating equations. Results showed that, overall, single-task performance was unaffected by focus (p = .341). Regarding movement fluency, no main effects of focus were found in single- or dual-task conditions (p’s ≥ .13). However, focus by leg interactions suggested that an external focus reduced movement fluency of the paretic leg compared to an internal focus (single-task conditions: p = .068; dual-task conditions: p = .084). An external focus also tended to result in inferior dual-task performance (β = -2.38, p = .065). Finally, a near-significant interaction (β = 2.36, p = .055) suggested that dual-task performance was more constrained by patients’ attentional capacity in external focus conditions. We conclude that, compared to an internal focus, an external focus did not result in more automated movements in chronic stroke patients. Contrary to expectations, trends were found for enhanced automaticity with an internal focus. These findings might be due to patients’ strong preference to use an internal focus in daily life. Future work needs to establish the more permanent effects of learning with different attentional foci on re-automating motor control after stroke.  相似文献   
14.
In this study, we explore the potential to reconstruct lake-level (and groundwater) fluctuations from tree-ring chronologies of black alder (Alnus glutinosa L.) for three study lakes in the Mecklenburg Lake District, northeastern Germany. As gauging records for lakes in this region are generally short, long-term reconstructions of lake-level fluctuations could provide valuable information on past hydrological conditions, which, in turn, are useful to assess dynamics of climate and landscape evolution. We selected black alder as our study species as alder typically thrives as riparian vegetation along lakeshores. For the study lakes, we tested whether a regional signal in lake-level fluctuations and in the growth of alder exists that could be used for long-term regional hydrological reconstructions, but found that local (i.e. site-specific) signals in lake level and tree-ring chronologies prevailed. Hence, we built lake/groundwater-level reconstruction models for the three study lakes individually. Two sets of models were considered based on (1) local tree-ring series of black alder, and (2) site-specific Standardized Precipitation Evapotranspiration Indices (SPEI). Although the SPEI-based models performed statistically well, we critically reflect on the reliability of these reconstructions, as SPEI cannot account for human influence. Tree-ring based reconstruction models, on the other hand, performed poor. Combined, our results suggest that, for our study area, long-term regional reconstructions of lake-level fluctuations that consider both recent and ancient (e.g., archaeological) wood of black alder seem extremely challenging, if not impossible.  相似文献   
15.
The evolution of increased competitive ability (EICA) hypothesis predicts that escape from intense herbivore damage may enable invasive plants to evolve higher competitive ability in the invasive range. Below-ground root herbivory can have a strong impact on plant performance, and invasive plants often compete with multiple species simultaneously, but experimental approaches in which EICA predictions are tested with root herbivores and in a community setting are rare. Here, we used Brassica nigra plants from eight invasive- and seven native-range populations to test whether the invasive-range plants have evolved increased competitive ability when competing with Achillea millefolium and with a community (both with and without A. millefolium). Further, we tested whether competitive interactions depend on root herbivory on B. nigra by the specialist Delia radicum. Without the community, competition with A. millefolium reduced biomass of invasive- but not of native-range B. nigra. With the community, invasive-range B. nigra suffered less than native-range B. nigra. Although the overall effect of root herbivory was not significant, it reduced the negative effect of the presence of the community. The community produced significantly less biomass when competing with B. nigra, irrespective of the range of origin, and independent of the presence of A. millefolium. Taken together, these results offer no clear support for the EICA hypothesis. While native-range B. nigra plants appear to be better in dealing with a single competitor, the invasive-range plants appear to be better in dealing with a more realistic multi-species community. Possibly, this ability of tolerating multiple competitors simultaneously has contributed to the invasion success of B. nigra in North America.  相似文献   
16.
At large attitudes are built on earlier experience with the attitude object. If earlier experiences are not available, as is the case for unfamiliar attitude objects such as new technologies, no stored evaluations exist. Yet, people are still somehow able to construct attitudes on the spot. Depending on the familiarity of the attitude object, attitudes may find their basis more in affect or cognition. The current paper investigates differences in reliance on affect or cognition in attitude formation toward familiar and unfamiliar realistic attitude objects. In addition, individual differences in reliance on affect (high faith in intuition) or cognition (high need for cognition) are taken into account. In an experimental survey among Dutch consumers (N = 1870), we show that, for unfamiliar realistic attitude objects, people rely more on affect than cognition. For familiar attitude objects where both affective and cognitive evaluations are available, high need for cognition leads to more reliance on cognition, and high faith in intuition leads to more reliance on affect, reflecting the influence of individually preferred thinking style. For people with high need for cognition, cognition has a higher influence on overall attitude for both familiar and unfamiliar realistic attitude objects. On the other hand, affect is important for people with high faith in intuition for both familiar and unfamiliar attitude objects and for people with low faith in intuition for unfamiliar attitude objects; this shows that preferred thinking style is less influential for unfamiliar objects. By comparing attitude formation for familiar and unfamiliar realistic attitude objects, this research contributes to understanding situations in which affect or cognition is the better predictor of overall attitudes.  相似文献   
17.
A commonly used paradigm to study motor imagery is the hand laterality judgment task. The present study aimed to determine which strategies young children employ to successfully perform this task. Children of 5 to 8 years old (N = 92) judged laterality of back and palm view hand pictures in different rotation angles. Response accuracy and response duration were registered. Response durations of the trials with a correct judgment were fitted to a-priori defined predictive sinusoid models, representing different strategies to successfully perform the hand laterality judgment task. The first model predicted systematic changes in response duration as a function of rotation angle of the displayed hand. The second model predicted that response durations are affected by biomechanical constraints of hand rotation. If observed data could be best described by the first model, this would argue for a mental imagery strategy that does not involve motor processes to solve the task. The second model reflects a motor imagery strategy to solve the task. In line with previous research, we showed an age-related increase in response accuracy and decrease in response duration in children. Observed data for both back and palm view showed that motor imagery strategies were used to perform hand laterality judgments, but that not all the children use these strategies (appropriately) at all times. A direct comparison of response duration patterns across age sheds new light on age-related differences in the strategies employed to solve the task. Importantly, the employment of the motor imagery strategy for successful task performance did not change with age.  相似文献   
18.
19.
Characterization of host-pathogen interactions is a fundamental approach in microbiological and immunological oriented disciplines. It is commonly accepted that host cells start to change their phenotype after engulfing pathogens. Techniques such as real time PCR or ELISA were used to characterize the genes encoding proteins that are associated either with pathogen elimination or immune escape mechanisms. Most of such studies were performed in vitro using primary host cells or cell lines. Consequently, the data generated with such approaches reflect the global RNA expression or protein amount recovered from all cells in culture. This is justified when all host cells harbor an equal amount of pathogens under experimental conditions. However, the uptake of pathogens by phagocytic cells is not synchronized. Consequently, there are host cells incorporating different amounts of pathogens that might result in distinct pathogen-induced protein biosynthesis. Therefore, we established a technique able to detect and quantify the number of pathogens in the corresponding host cells using immunofluorescence-based high throughput analysis. Paired with multicolor staining of molecules of interest it is now possible to analyze the infection profile of host cell populations and the corresponding phenotype of the host cells as a result of parasite load.  相似文献   
20.
The association between experienced victimization and students'' psychological and social adjustment depends on the intensity of victimization. We examined how frequency and multiplicity of victimization, and the number of bullies involved, account for differences in students’ psychosocial well-being and social standing in the classroom. Multilevel analyses were conducted on the control group of an intervention study among students in grades 3–6 of Dutch elementary schools (N = 2859 students from 124 classes and 33 schools; ages 8–12; 49.6% boys). It was found that victims of frequent and multiple victimization, and victims who were victimized by several bullies, had higher levels of psychosocial adjustment problems than victims of less frequent and non-multiple victimization, and victims with only one bully. Moreover, these more severe victims turned out to be least accepted and most rejected among their classmates. The findings illustrate that it can be fruitful to use several measures of victimization so that (differences in) adjustment problems can be better understood. Moreover, the results suggest that it is important to find out who is victimized, in what ways, and by whom. Anti-bullying interventions should provide resources to do this.  相似文献   
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