Objective: The current study aims to validate the PERMA-Profiler, a well-known well-being measure, among a sample of student veterans. Participants: A sample of 205 student veterans were recruited ...from universities across the United States. Method: Cross-sectional research design was used in this study. Measurement structure of the PERMA-Profiler was evaluated using exploratory factor analysis (EFA). Convergent, divergent, and criterion-related validity was tested using Pearson correlation coefficients and Kruskal-Wallis test. Results: The EFA results yielded a two-factor solution for student veterans. Factors are named as emotional character strengths and performance character strengths. Conclusions: The PERMA-Profiler is a multidimensional scale with good reliability and acceptable levels of convergent, divergent, and criterion-related validity. The PERMA-Profiler can help researchers and practitioners better gauge well-being in student veterans. Implications will be discussed.
Upstream open reading frames (uORFs) are known to negatively affect translation of the downstream ORF. The regulatory proteins involved in relieving this inhibition are however poorly characterized. ...In response to cellular stress, eIF2α phosphorylation leads to an inhibition of global protein synthesis, while translation of specific factors such as CHOP is induced. We analyzed a 105‐nt inhibitory uORF in the transcript of human CHOP (huORFchop) and found that overexpression of the zebrafish or human ENDOU poly(U)‐endoribonuclease (Endouc or ENDOU‐1, respectively) increases CHOP mRNA translation also in the absence of stress. We also found that Endouc/ENDOU‐1 binds and cleaves the huORFchop transcript at position 80G‐81U, which induces CHOP translation independently of phosphorylated eIF2α. However, both ENDOU and phospho‐eIF2α are nonetheless required for maximal translation of CHOP mRNA. Increased levels of ENDOU shift a huORFchop reporter as well as endogenous CHOP transcripts from the monosome to polysome fraction, indicating an increase in translation. Furthermore, we found that the uncapped truncated huORFchop‐69‐105‐nt transcript contains an internal ribosome entry site (IRES), facilitating translation of the cleaved transcript. Therefore, we propose a model where ENDOU‐mediated transcript cleavage positively regulates CHOP translation resulting in increased CHOP protein levels upon stress. Specifically, CHOP transcript cleavage changes the configuration of huORFchop thereby releasing its inhibition and allowing the stalled ribosomes to resume translation of the downstream ORF.
SYNOPSIS
Heat or ER stress trigger a stress response involving eIF2α phosphorylation and induction of the transcription factor CHOP. Here, stress‐induced poly(U)‐specific endoribonuclease is found to specifically cleave CHOP mRNA, thereby releasing a uORF‐associated inhibitory structure and allowing its selective translation.
Zebrafish Endouc and its human orthologue ENDOU positively regulate CHOP translation independently of phosphorylated eIF2α.
Both ENDOU and phospho‐eIF2α are required for maximal translation of CHOP upon heat shock or ER stress.
ENDOU binds the 105‐nt upstream uORF of the human CHOP transcript and cleaves it at position 80G‐81U.
The truncated huORFchop‐81‐105 transcript does not contain IRES activity, while uncapped truncated huORFchop‐69‐105 transcript does.
Cleavage of CHOP transcripts by zebrafish Endouc and its human orthologue ENDOU positively regulates translation by inducing a conformational change in the inhibitory structure that allows stalled ribosomes to progress.
Our previous study demonstrated that myc, mitochondrial oxidative phosphorylation, mTOR, and stemness are independently responsible for chemoresistance in acute myeloid leukemia (AML) cells. This ...study aimed to identify potential mechanisms of chemoresistance of the “7 + 3” induction in AML by using a single‐cell RNA sequencing (scRNA‐seq) approach. In the present study, 13 untreated patients with de novo AML were enrolled and stratified into two groups: complete remission (CR; n = 8) and non‐CR (n = 5). Single‐cell RNA sequencing was used to analyze genetic profiles of 28,950 AML cells from these patients; results were validated using a previously published bulk RNA‐seq dataset. Our study results showed chemoresistant AML cells had premature accumulation during early hematopoiesis. Hematopoietic stem cell‐like cells from the non‐CR group expressed more leukemic stem cell markers (CD9, CD82, IL3RA, and IL1RAP) than those from the CR group. Chemoresistant progenitor cells had impaired myeloid differentiation owing to early arrest of hematopoiesis. Notably, AML cells analyzed by scRNA‐seq and bulk RNA‐seq harbored a comparable myeloid lineage cell fraction, which internally validated our results. Using the TCGA database, our analysis demonstrated that patients with AML with higher expression of chemoresistant genetic markers (IL3RA and IL1RAP) had a worse overall survival (p < 0.01 for IL3RA; p < 0.05 for IL1RAP). In conclusion, AML cells responsive and resistant to the “7 + 3” induction were derived from a diverse cancerous hematopoietic stem cell population, as indicated by the specific genetic biomarkers obtained using scRNA‐seq approach. Furthermore, arrest of hematopoiesis was shown to occur earlier in chemoresistant AML cells, furthering the current understanding of chemoresistance in AML.
Background: Self-determination theory (SDT) and self-efficacy theory (SET) can be used to conceptualize self-determined motivation to engage in mental health and vocational rehabilitation (VR) ...services and to predict recovery. To incorporate SDT and SET as a framework for vocational recovery, developing and validating SDT/SET measures in vocational rehabilitation is warranted. Outcome expectancy is an important SDT/SET variable affecting rehabilitation engagement and recovery.
Aims: The purpose of this study was to validate the Vocational Outcome Expectancy Scale (VOES) for use within the SDT/SET vocational recovery framework.
Methods: One hundred and twenty-four individuals with serious mental illness (SMI) participated in this study. Measurement structure of the VOES was evaluated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA).
Results: Both EFA and CFA results supported a two-factor structure: (a) positive outcome expectancy, and (b) negative outcome expectancy. The internal consistency reliability coefficients for both factors were acceptable. In addition, positive outcome expectancy correlated stronger than negative outcome expectancy with other SDT/SET constructs in the expected directions.
Conclusions: The VOES is a brief, reliable and valid instrument for assessing vocational outcome expectancy in individuals with SMI that can be integrated into SDT/SET as a vocational rehabilitation engagement and recovery model in psychiatric rehabilitation.
The clearest career path to the middle class generally involves access, and completion, of postsecondary education. However, persons with disabilities are less likely to enroll or graduate from ...college compared with their same-age peers without disabilities. The quality of life of students with disabilities, and their well-being, may be a root cause of low graduation rates. To flourish in life is to both feel good and function effectively. Seligman developed the Positive Emotion, Engagement, Relationships, Meaning, and Accomplishment (PERMA) model that may be useful in understanding the well-being of individuals. The purpose of this study is to examine the factorial structure of the PERMA model in sample college students with disabilities and then examine the model’s relationship with outcomes important to college adjustment such as academic achievement, relationship problems, stress, life satisfaction, and core self-evaluation. Ninety-seven college students with disabilities enrolled in Science, Technology, Engineering, and Mathematics (STEM) were recruited for the study. Findings support a one-factor solution for the PERMA measurement model. Furthermore, PERMA was negatively correlated with factors associated with college difficulty and positively associated with factors linked to college success. The PERMA model also demonstrated that well-being mediates the relationship between functional disability and life satisfaction. Implications for rehabilitation researchers and practitioners are reviewed.
Ethnocultural empathy is one of the most important multicultural competencies in counseling psychology. Wang et al. developed the Scale of Ethnocultural Empathy (SEE) for counseling psychology ...educators as an outcome variable to evaluate multicultural counseling competencies of counselors-in-training. The purpose of this study was to evaluate the measurement structure of the SEE in a sample of undergraduate and graduate students in rehabilitation. Confirmatory factor analysis results indicated that the four-factor intercorrelated model fit the data very well. The four factors are (a) empathic feeling and expression, (b) empathic perspective taking, (c) empathic awareness, and (d) acceptance of cultural differences. The SEE can be an invaluable tool for rehabilitation counselor educators to evaluate their students’ level of multicultural rehabilitation counseling competency and as an outcome variable for multicultural rehabilitation counseling training.
Silver nanowires were synthesized using a polyol process by employing ethylene glycol, poly(N-vinylpyrrolidone), and silver nitrate as precursors. The concentration of silver nitrate was varied to ...study the resulting changes in aspect ratios of silver nanowires. The experimental results indicated that the growth characteristics of silver nanowires were affected by the synthesis temperature, the concentration of silver nitrate, and the rate at which silver nitrate was added. Field-emission scanning electron microscopy, UV–visible spectrophotometry, and X-ray diffractometry were employed to characterize the silver nanowires. As the concentration of silver nitrate was reduced, the diameters of the silver nanowires decreased, increasing the aspect ratio. The optimal diameter and length of the silver nanowires were 100nm and 20μm, respectively. A thin film composed of silver nanowires exhibited average transmittance of 92.15% at visible wavelengths and a sheet resistance of 20Ω/sq; such a film could be used as a transparent conductive film in commercial applications.
•Using a polyol method to synthesize of silver nanowire•Concentration effect of silver nitrate on the synthesis was discussed.•Seed precursors are not used during the silver nanowire synthesizing.•The silver nanowire diameter and length were 100nm and 20μm, respectively.•High transmittance and low sheet resistance of silver nanowire film can be obtained.
Community participation and autonomy are two of the vital treatments and rehabilitation outcomes for people with chronic health conditions and disabilities, including people with cancer. The purpose ...of this study is to investigate psychometric properties of the Impact on Participation and Autonomy Scale (IPA) in a sample of Turkish cancer survivors. An exploratory factor analysis was used to analyze data collected from 186 cancer survivors who completed the IPA, Health Care Climate Questionnaire, Satisfaction with Life Scale, and the Role Functioning subscale of the EORTC Core Quality of Life Questionnaire. In contrast to the original five-factor solution, the results provided a better fit for a three-factor correlated model (Activities of Daily Living ADL/Instrumental ADL, social relations, and employment and education). The IPA factors were significantly associated with supportive healthcare climate, role functioning, and life satisfaction in the theoretically expected directions, providing support for the nomological construct validity of the Turkish version of the IPA. Overall, the Turkish version of the IPA is a psychometrically sound measure of participation and autonomy that can be used to assess cancer survivors’ levels of community participation for treatment planning and selection of evidence-based healthcare and psychosocial interventions for cancer survivors.
Many studies suggest that far-infrared (FIR) therapy can reduce the frequency of some vascular-related diseases. The non-thermal effect of FIR was recently found to play a role in the long-term ...protective effect on vascular function, but its molecular mechanism is still unknown. In the present study, we evaluated the biological effect of FIR on vascular endothelial growth factor (VEGF)-induced proliferation in human umbilical vein endothelial cells (HUVECs). We found that FIR ranging 3∼10 µm significantly inhibited VEGF-induced proliferation in HUVECs. According to intensity and time course analyses, the inhibitory effect of FIR peaked at an effective intensity of 0.13 mW/cm(2) at 30 min. On the other hand, a thermal effect did not inhibit VEGF-induced proliferation in HUVECs. FIR exposure also inhibited the VEGF-induced phosphorylation of extracellular signal-regulated kinases in HUVECs. FIR exposure further induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO generation in VEGF-treated HUVECs. Both VEGF-induced NO and reactive oxygen species generation was involved in the inhibitory effect of FIR. Nitrotyrosine formation significantly increased in HUVECs treated with VEGF and FIR together. Inhibition of phosphoinositide 3-kinase (PI3K) by wortmannin abolished the FIR-induced phosphorylation of eNOS and Akt in HUVECs. FIR exposure upregulated the expression of PI3K p85 at the transcriptional level. We further found that FIR exposure induced the nuclear translocation of promyelocytic leukemia zinc finger protein (PLZF) in HUVECs. This induction was independent of a thermal effect. The small interfering RNA transfection of PLZF blocked FIR-increased PI3K levels and the inhibitory effect of FIR. These data suggest that FIR induces the nuclear translocation of PLZF which inhibits VEGF-induced proliferation in HUVECs.
Although immature differentiation and uncontrolled proliferation of hematopoietic stem cells are thought to be the primary mechanisms of acute myeloid leukemia (AML), the pathophysiology in most ...cases remains unclear. Dinaciclib, a selective small molecule targeting multiple cyclin-dependent kinases (CDKs), is currently being evaluated in oncological clinical trials. Despite the proven anticancer potential of dinaciclib, the differential molecular mechanisms by which it inhibits the growth of different AML cell lines remain unclear. In the current study, we treated HL-60 and KG-1 AML cell lines with dinaciclib and investigated the potential mechanisms of dinaciclib-induced AML cell growth inhibition using flow cytometry and western blotting assays. Data from HL-60 and KG-1 AML cells were validated using human primary AML cells. The results showed that the growth inhibitory effect of dinaciclib was more sensitive in HL-60 cells (IC50: 8.46 nM) than in KG-1 cells (IC50: 14.37 nM). The protein decline in Cyclin A/B and CDK1 and cell cycle arrest in the G2/M phase were more profound in HL-60 cells, corresponding to its growth inhibition. Although the growth inhibition of KG-1 cells by dinaciclib was still pronounced, the cell cycle-associated proteins were relatively insensitive. In addition to cell cycle regulation, the activation/expression of ERK1/STAT3/MYC signaling was significantly reduced by dinaciclib in KG-1 cells compared with that in HL-60 cells. Regarding the results of primary AML cells, we observed ERK1/STAT3/MYC inhibition and cell cycle regulation in different patients. These findings suggest that the cell cycle-associated and ERK1/STAT3/MYC signaling pathways might be two distinct mechanisms by which dinaciclib inhibits AML cells, which could facilitate the development of combination therapy for AML in the future.
Display omitted
•Our study indicates that dinaciclib might inhibit AML cell growth through specific CDK inhibition or an alternative ERK1/STAT3/MYC pathway. This finding may contribute to the development of future therapeutic strategies for AML.
PDF
