59 research outputs found

    The G-quartet containing FMRP binding site in FMR1 mRNA is a potent exonic splicing enhancer

    Get PDF
    The fragile X mental retardation protein (FMRP) is a RNA-binding protein proposed to post-transcriptionally regulate the expression of genes important for neuronal development and synaptic plasticity. We previously demonstrated that FMRP binds to its own FMR1 mRNA via a guanine-quartet (G-quartet) RNA motif. However, the functional effect of this binding on FMR1 expression was not established. In this work, we characterized the FMRP binding site (FBS) within the FMR1 mRNA by a site directed mutagenesis approach and we investigated its importance for FMR1 expression. We show that the FBS in the FMR1 mRNA adopts two alternative G-quartet structures to which FMRP can equally bind. While FMRP binding to mRNAs is generally proposed to induce translational regulation, we found that mutations in the FMR1 mRNA suppressing binding to FMRP do not affect its translation in cellular models. We show instead that the FBS is a potent exonic splicing enhancer in a minigene system. Furthermore, FMR1 alternative splicing is affected by the intracellular level of FMRP. These data suggest that the G-quartet motif present in the FMR1 mRNA can act as a control element of its alternative splicing in a negative autoregulatory loop

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

    Get PDF
    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    The relationship between psychological Suzhi and social anxiety among Chinese adolescents: the mediating role of self-esteem and sense of security

    No full text
    Abstract Background High incidence and morbidity rates are found among adolescents with social anxiety disorder, a severe and harmful form of social phobia. Extensive research has been conducted to uncover the underlying psychological factors associated with the development and continuation of this disorder. Previous research has focused on single individual difference variables such as personality, cognition, or emotion; thus, the effect of an individual’s full psychological profile on social anxiety has rarely been studied. Psychological suzhi is a comprehensive psychological quality that has been promoted in Chinese quality-oriented education. This research aimed to explore how psychological suzhi affects Chinese adolescents’ social anxiety. Methods A cross-sectional survey study was carried out among 1459 middle school students (683 boys and 776 girls) from various middle schools in seven provinces of China. Psychological suzhi, self-esteem, sense of security, and social anxiety were measured via four self-reported questionnaires: the Brief Psychological Suzhi Questionnaire for middle school students, the Chinese version of the Rosenberg Self-Esteem Scale, the Security Questionnaire, and the Social Avoidance and Distress Scale. Results Analyses showed that psychological suzhi is positively related to self-esteem and sense of security, and it is negatively correlated with social anxiety. The results also revealed that self-esteem partially mediates the relationship between adolescents’ psychological suzhi and social anxiety, with self-esteem and sense of security serving as chain mediators in the relationship between psychological suzhi and social anxiety. Conclusions Results highlight that psychological suzhi is a protective factor against social anxiety. It can directly protect adolescents from social anxiety, and it also can protect them through affecting their self-esteem and sense of security. These results are discussed from the viewpoints of school leaders, psychology teachers, and school counsellors, who provide support to students to improve their social functioning within the school context. The findings of this study may provide new perspectives regarding the prevention and treatment of social anxiety

    The Relationship between Childhood Abuse and Suicidal Ideation among Chinese College Students: The Mediating Role of Core Self-Evaluation and Negative Emotions

    No full text
    Childhood abuse is a significant risk factor for suicidal ideation. However, the underlying mediation mechanism necessitates further exploration. This study investigated the mediating role of core self-evaluation and negative emotions in the relationship between childhood abuse and suicide ideation in young adults. A sample of 3103 college students from 11 universities across 8 provinces in China was analyzed. Childhood abuse, core self-evaluation, negative emotions, and suicidal ideation were assessed using the Childhood Trauma Questionnaire (CTQ-CF), Core Self-Evaluation Scale, Affect Scale, and Beck Suicidal Ideation Scale (BSI-CV), respectively. Data analysis was conducted using SPSS 19.0 and SPSS Macro Process. We found that high scores for childhood abuse were associated with elevated levels of suicidal ideation, whereas low scores for core self-evaluation were closely linked to heightened levels of negative emotions and suicidal ideation. Furthermore, core self-evaluation and negative emotions mediated the relationship between childhood abuse and suicidal ideation through three significant paths. The results demonstrate that childhood abuse can directly impact suicidal ideation in young adulthood and indirectly influence suicidal ideation by affecting core self-evaluation and negative emotions. They suggest that addressing core self-evaluation and negative emotions in individuals who have experienced childhood abuse may help prevent or treat suicidal ideation

    Research on Basic Characteristics and Bidding Strategy of Thermal Power Units in Fujian Spot Market

    No full text
    In the electricity market environment, thermal power units have changed from the executors of power production under the monopoly mechanism to the decision-makers of production and operation under the competitive environment. The merits and demerits of bidding schemes for thermal power units are directly related to self-interest of themselves. The bidding decisions of power plants are not only affected by economic factors, but also by technical factors peculiar to the power system and the electric generator. In recent years, research on bidding strategies of thermal power units based on the power market environment has been paid more and more attention in the field of electric market. This paper first introduces the basic peak regulation and frequency modulation technical characteristics of thermal power units and cost calculation. Then, from the angle of quotation, paper analyzes characteristics of quotation mechanism of units in Fujian Electric Power day-ahead, real-time and peak regulation auxiliary service market. Furthermore, the research status of bidding strategies of thermal power units participating in electricity market at home and abroad in cost analysis, market clearing price prediction, game theory and so on are summarized. Finally, the bidding strategy for units in Fujian Spot Market is put forward

    Influences on Shotcrete Rebound from Walls with Random Roughness

    No full text
    Concrete slurry can be sprayed on walls for reinforcement; however, there is a certain amount of rebound which is hazardous, lowers production quality, and wastes material. To investigate this problem, we studied single slurry droplets at the mesoscopic level. We deduced the factors influencing droplet spreading and wall adhesion to create models of shotcrete rebound. Then, a numerical simulation orthogonal experiment investigating droplet-wall impacts was performed. The relationship between the spreading coefficient and each influencing factor is discussed, and numerical models are presented. Finally, the obtained models are verified by physical experiments. The results show that the spreading coefficient can be used to better characterize the effect of slurry droplet adhesion to walls. Modeled and experimentally observed droplet-wall impacts showed good consistency. The influence of each factor on the spreading coefficient was determined in the following order of strength: droplet velocity and viscosity, wall roughness, and surface tension. The spreading coefficient increases with velocity, decreases with viscosity and roughness, and increases first and then decreases with surface tension. This study improves the fluid dynamics-based theory of multiphase flow in concrete slurry and provides a theoretical basis for mitigating shotcrete rebound

    Appendicular skeletal muscle mass: A more sensitive biomarker of disease severity than BMI in adults with mitochondrial diseases.

    No full text
    The study aimed to evaluate the body composition of patients with mitochondrial diseases (MD) and correlate it with disease severity. Overall, 89 patients (age ≥ 18 years) with MD were recruited, including 49 with chronic progressive external ophthalmoplegia (CPEO) and 40 with mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). Body composition, including fat mass index (FMI), fat-free mass index (FFMI), skeletal muscle mass index (SMI), and appendicular skeletal muscle mass index (ASMI), were examined using multifrequency bioelectric impedance analysis. Clinical assessments, including muscle strength, usual gait speed, and disease severity determined by the Newcastle Mitochondrial Disease Adult Scale score (NMDAS), were performed. The comparisons between patients group and age- and gender-matched healthy controls, as well as the correlations between anthropometric measurements, body composition, and disease severity were analyzed. Height, weight, body mass index (BMI), FFMI, SMI, and ASMI were significantly lower in patients with MD than in healthy controls. Notably, low muscle mass was noted in 69.7% (62/89) of MD patients, with 22 patients also presenting with compromised physical performance as indicated by decreased gait speed, resulting in 24.7% satisfied the sarcopenia diagnostic criteria. Disease severity was more negatively correlated with ASMI than it was with height, weight, and BMI. Subgroup analysis showed that in the MELAS subgroup, disease severity was negatively correlated with height, weight, and ASMI; whereas in the CPEO subgroup, it was only negatively correlated with ASMI and SMI. Additionally, ASMI was positively associated with muscle strength. Altogether, compared with BMI, ASMI is a more sensitive biomarker predicting disease severity of MD, both in MELAS and CPEO patients
    corecore