Purpose We sought to describe leisure-time, aerobic, and muscle strengthening physical activity (PA) patterns in U.S. Asian Indians, in comparison to other races/ethnicities. Design, Setting, and Sample We utilized the 2011–2018 National Health Interview Surveys, a set of cross-sectional, nationally representative surveys of the U.S. noninstitutionalized population. Our study population included 257 652 adults who answered PA questions. Measures PA was classified per 2008 U.S. guidelines and continuously per estimated metabolic equivalents (METs). Race was classified into White, Black, Asian Indian, Other Asian, and American Indian/Alaskan Native/Multiracial. Analysis We used survey design-adjusted, multivariable logistic regression to determine odds of sufficient and highly active physical activity levels, adjusting for predisposing, enabling, need, and health care service factors as guided by the Anderson Model. We also used linear regression to determine racial differences in average MET-minutes/week. Analysis was additionally stratified by comorbidity status. Results While Asian Indians (N = 3049) demonstrated similar odds of sufficient aerobic PA as Whites (aOR [95% CI]: .97 [.88,1.07]), Asian Indians had 22% lower odds of meeting highly active aerobic PA levels (.78 [.71,0.87]) and 18% lower odds of meeting sufficient muscle strengthening PA levels (.82 [.73,0.91]). This translated to an average 172 (95% CI: 45 300) fewer MET-minutes. Furthermore, this decrease in MET-minutes/week was especially apparent in those without hypertension (β[95% CI]: −164 [-314,-15]) without diabetes (−185 [-319,-52]), and low/normal BMI (−422 [-623,-222]). Conclusion Asian Indians, especially those without comorbidities, are less likely to engage in high-intensity physical activity than Whites.

Late-infantile neuronal ceroid lipofuscinosis (LINCL) is a neurodegenerative lysosomal storage disorder caused by mutations in the gene encoding the protease tripeptidyl-peptidase 1 (TPP1). Progression of LINCL can be slowed or halted by enzyme replacement therapy, where recombinant human TPP1 is administered to patients. In this study, we utilized protein engineering techniques to increase the stability of recombinant TPP1 with the rationale that this may lengthen its lysosomal half-life, potentially increasing the potency of the therapeutic protein. Utilizing multiple structure-based methods that have been shown to increase the stability of other proteins, we have generated and evaluated over 70 TPP1 variants. The most effective mutation, R465G, increased the melting temperature of TPP1 from 55.6°C to 64.4°C and increased its enzymatic half-life at 60°C from 5.4 min to 21.9 min. However, the intracellular half-life of R465G and all other variants tested in cultured LINCL patient-derived lymphoblasts was similar to that of WT TPP1. These results provide structure/function insights into TPP1 and indicate that improving in vitro thermal stability alone is insufficient to generate TPP1 variants with improved physiological stability. This conclusion is supported by a proteome-wide analysis that indicates that lysosomal proteins have higher melting temperatures but also higher turnover rates than proteins of other organelles. These results have implications for similar efforts where protein engineering approaches, which are frequently evaluated in vitro, may be considered for improving the physiological properties of proteins, particularly those that function in the lysosomal environment.

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