Hope College

CUL5 acts as the scaffold protein of the E3 ligase complex in ubiquitin-dependent protein degradation pathways. Overexpression of CUL5 inhibits cellular proliferation, whereas inhibition of CUL5 expression induces proliferation and may contribute to clinical disorders including cancer. The effects of CUL5 depend on its post-translational modification by NEDD8 (neddylation), a process that represents a potential therapeutic target. This study explores the structure-function relationship between CUL5 and its neddylation status in vitro. CUL5 was mutated at the putative neddylation site Lys (K) 724 to Arg (K724RCUL5) and at three potential neddylation sites K724, K727, and K728 (K724R/K727R/K728RCUL5). Because mutation of the PKA phosphorylation site Ser (S) 730 (S730ACUL5) was previously shown to induce neddylation, a K724R/S730ACUL5 mutant was also generated. Mutant and wild-type constructs were expressed in rat endothelial cells (RAMEC), T47D cancer cells, and COS-1 cells. Cellular proliferation, MAPK phosphorylation, ERα expression, and CUL5 neddylation status were analyzed, including treatment with the neddylation inhibitor MLN4924. Expression of wild-type CUL5 attenuated cell growth in RAMEC, T47D, and COS-1 cells. In contrast, expression of K724RCUL5 and K724R/S730ACUL5 mutants induced cellular growth, whereas the K724R/K727R/K728RCUL5 mutant had no significant effect on proliferation. In T47D cells, MAPK phosphorylation and estrogen receptor (ERα) expression were directly correlated with the neddylation status of CUL5. Western blot analysis of COS-1 cells treated with MLN4924 demonstrated that CUL5 remained neddylated in all mutant cell lines. These findings suggest that modification of CUL5 by NEDD8 may occur at multiple lysine residues and that multi-site neddylation may contribute to the diverse regulatory effects of CUL5 on cellular signaling and proliferation.

This pilot study examined the implicit racial biases of pre-service teachers using the Race-based Implicit Association Test (RA-IAT) administered before and after a course focused on racial inequity and the unseen power structures that sustain systemic oppression in schools and society.Paired-samples t-tests and ANCOVA results did not yield statistically significant changes in RA-IAT dscores for the intervention group of pre-service teachers.However, the intervention group demonstrated a more consistent trend toward reduced bias, suggesting that the absence of significant findings may reflect the small effect sizes typically associated with shifts in implicit measures, particularly within a restricted range of scores and the limited statistical power in a modest sample size.The emerging pattern of bias reduction is encouraging and highlights the need for future research with larger cohorts.

Mathematical creativity remains a complex and often contested construct, with its definition and measurement still subject to debate. While the four classic indicators—elaboration, flexibility, fluency, and originality have provided a foundation for research, they alone cannot resolve the field’s conceptual “fuzziness.” This paper examines mathematical creativity through three intersecting lenses: intelligence, intellect, and education. Intelligence is viewed as cognitive capacity, providing the mental resources for abstraction, problem transformation, and reasoning. Education offers the conceptual tools, heuristics, and domain knowledge necessary for productive problem solving. Intellect—closely associated with the personality trait of openness—supports curiosity, tolerance for ambiguity, and exploration. We argue that the interaction among these three factors influences the likelihood of producing mathematically creative processes and products. Drawing on contemporary research, we propose a model that integrates cognitive ability, educational attainment, and personality characteristics to better predict creative potential. This model highlights how educational environments can either foster or inhibit creativity and suggests that creativity is not a fixed trait but a dynamic outcome shaped by opportunity, knowledge, and affect. We conclude by discussing implications for assessment, curriculum design, and future research, encouraging a more nuanced approach to cultivating mathematical creativity across diverse educational and cultural contexts.

The primary aims of this study were to determine acute and longitudinal relationships between static flexibility measures and running economy(RE). Seventy-one healthy recreational runners (34 males/37 females, age: 36.4 [12.4]y, body mass index: 23.3 [3.1]kg/m2) completed an aerobic fitness assessment (VO2max) based on self-selected half-marathon race pace (RP) and flexibility testing (standing toe-touch test and weight-bearing lunge test) at baseline and 2 to 3weeks prior to an endurance running or multisport race (70 [21]d apart). Participants resumed self-selected training and physical activity between laboratory visits. Hierarchical linear regressions were used to assess relationships between flexibility and RE across timepoints, and pre-post changes in flexibility and RE. Interactions between age and flexibility, and experience and flexibility were also investigated. No significant differences (P > .05) were found between flexibility measurements and RE at RP from visit 1 to visit 2, nor were there any significant associations between RE at RP and scores on the weight-bearing lunge test or standing toe-touch test. However, there was a significant interaction between age and the weight-bearing lunge test on RE at RP (ß = -0.0270, P = .018) such that older runners with less flexibility and younger runners with greater flexibility were less economical at RP at baseline. Our findings suggest that reduced flexibility may decrease the energetic cost of running for older runners to a greater extent than it does for younger runners. When prescribing run training intensity and mileage, coaches and clinicians working with masters runners should be cognizant of the potential performance benefits of decreased ankle joint flexibility as well as the overall greater risk of calf injury in this population. Future research should consider the underlying mechanism by which age enhances the beneficial effects of decreased flexibility on RE.

ABSTRACT Objective This study evaluated the psychometric properties of the Scales for Outcomes in Parkinson’s Disease – Sleep Scale (SCOPA-Sleep) in a sample of patients with fibromyalgia syndrome (FMS), and examined the unique and interactive associations between sleep problems, daytime fatigue, and quality of life. Method A total of 79 adults diagnosed with FMS according to the 2010 American College of Rheumatology criteria completed measures assessing sleep problems, daytime fatigue (SCOPA-Sleep), and health-related quality of life (EuroQOL-5D). Exploratory factor analysis (EFA) and internal consistency analyses assessed the dimensionality and reliability of the SCOPA-Sleep. Multiple linear regression examined confounding and moderation effects of sleep problems and fatigue on quality of life, controlling for sociodemographic variables. Results EFA supported a two-factor structure of the SCOPA-Sleep reflecting distinct subscales for nighttime sleep problems and daytime fatigue. The subscales were uncorrelated, and both demonstrated strong internal consistency (α = .87 and .84, respectively). Regression analyses revealed that daytime fatigue was not significantly associated with quality of life after adjusting for covariates. However, sleep problems were a significant predictor of reduced quality of life (β = – .33, p < .01). No significant interaction between sleep problems and fatigue was observed. Conclusions The SCOPA-Sleep may be a useful brief screening tool for sleep-related impairments in clinical FMS assessment. However, given the relatively small and homogeneous sample (predominantly middle-aged women not currently employed), the generalizability of these findings is limited. Future research should replicate these results in larger and more diverse FMS populations.

Capsaicin (CAP), a bioactive compound in chili peppers, activates transient receptor potential vanilloid 1 channels, leading to calcium efflux, which may enhance muscle contraction and make heavy resistance exercises (RE) easier to perform. Additionally, CAP may amplify muscle swelling caused by fluid accumulation during RE due to its mechanistic effects. PURPOSE: Examine the impact of acute CAP ingestion and RE on ratings of perceived exertion (RPE) and muscle swelling in resistance-trained men. METHODS: 10 recreationally resistance-trained men (age: 21 ± 2 years, mass: 79.3 ± 9.9 kg; height: 176.6 ± 6.1 cm) completed 2 identical lower body RE sessions. Participants consumed either 2.4 mg CAP or placebo (PL; microcrystalline cellulose) 45 minutes (m) before RE. Each RE session included 5 sets of 10 repetitions at 80% of 1-repetition maximum on leg press followed by knee extension with 2 weeks separating the conditions. Ratings of perceived exertion (RPE) were recorded after each set, and muscle ultrasounds were taken before RE (PRE), immediately (IP), 10 m, 15 m, and 30 m post-RE to analyze for rectus femoris cross-sectional area (CSA) and thickness (RT). Repeated measures ANOVA were used to analyze the effect of CAP on RPE, CSA, and RT. RESULTS: Results indicated a significant (p < 0.05) condition x set effect for RPE, with PL showing higher RPE (8 ± 0) than CAP (7 ± 0) in the first set. Leg Press exercises (7 ± 0) trended to have lower RPE than knee extensions (8 ± 0; p = 0.07) with CAP. While no significant (p > 0.05) differences were observed between PL and CAP conditions for CSA and RT, both measures increased over time. For CSA, PRE (6.06 ± 0.21 cm2) had a smaller CSA than IP (7.46 ± 0.28 cm2),10 m (7.63 ± 0.23 cm2),15 m (7.33 ± 0.21 cm2), and 30 m (6.95 ± 0.16 cm2) post-RE. For RT, PRE (1.77 ± 0.07 cm) had less thickness than IP (2.33 ± 0.08 cm),10 m (2.29 ± 0.09 cm), 15 m (2.21 ± 0.08 cm), and 30 m (2.09 ± 0.08 cm) post-RE. CONCLUSION: CAP ingestion appears to reduce early RPE during RE, suggesting it may lower initial fatigue and enable a stronger start in high-intensity workouts. CSA and RT increased regardless of supplementation, likely due to similar metabolic stress from the identical RE, which may explain why overall RPE changes were not significant. Future studies should explore CAP's effect on muscle swelling in repetitions performed to failure.

This study evaluates the long-term financial outcomes of Roth and traditional IRAs, with their different tax advantages. Global applicability to countries with similar types of retirement plans is emphasized. A full factorial simulation assessed 54 unique combinations of IRA type, investment mix, and tax rates during working and retirement years. Results indicate that investment type plays a more critical role than IRA type in determining outcomes. Portfolios with significant exposure to the S&amp;P 500 consistently achieved higher ending balances and longer-lasting funds compared to portfolios relying on lower-yield investments. Traditional IRAs, leveraging frontend tax advantages, performed best when tax savings were reinvested, though Roth IRAs provided tax-free withdrawals, maximizing backend benefits.Key findings include the importance of starting early, maintaining significant equity exposure throughout life for higher returns, and understanding that IRA type often has a marginal impact relative to investment strategy. The study highlights that the most effective strategy is situational, influenced by factors such as tax rates and market conditions. These insights, while grounded in U.S. data, offer guidance for retirement planning systems globally. Policymakers and individuals are encouraged to prioritize early, consistent, and aggressive investment strategies to optimize retirement outcomes.