Energy expenditure estimation from respiration variables

Abstract The aim of this study was to develop and cross-validate two models to estimate total energy expenditure (TEE) based on respiration variables in healthy subjects during daily physical activities. Ninety-nine male and female subjects systematically varying in age (18–60 years) and body mass index (BMI; 17–36 kg*m−2) completed eleven aerobic activities with a portable spirometer as the criterion measure. Two models were developed using linear regression analyses with the data from 67 randomly selected subjects (50.0% female, 39.9 ± 11.8 years, 25.1 ± 5.2 kg*m−2). The models were cross-validated with the other 32 subjects (49% female, 40.4 ± 10.7 years, 24.7 ± 4.6 kg*m−2) by applying equivalence testing and Bland-and-Altman analyses. Model 1, estimating TEE based solely on respiratory volume, respiratory rate, and age, was significantly equivalent to the measured TEE with a systematic bias of 0.06 kJ*min−1 (0.22%) and limits of agreement of ±6.83 kJ*min−1. Model 1 was as accurate in estimating TEE as Model 2, which incorporated further information on activity categories, heart rate, sex, and BMI. The results demonstrated that respiration variables and age can be used to accurately determine daily TEE for different types of aerobic activities in healthy adults across a broad range of ages and body sizes

Genetic and pharmacological inhibition of TTK impairs pancreatic cancer cell line growth by inducing lethal chromosomal instability

Pancreatic ductal adenocarcinoma, which accounts for the majority of pancreatic cancers, is a lethal disease with few therapeutic options. Genomic profiling of pancreatic ductal adenocarcinoma has identified a complex and heterogeneous landscape. Understanding the molecular characteristics of pancreatic ductal adenocarcinoma will facilitate the identification of potential therapeutic strategies. We analyzed the gene expression profiles of primary tumors from patients compared to normal pancreas and identified high co-overexpression of core components of the spindle assembly checkpoint, including the protein kinase TTK (also known as MPS-1). We found overexpression of TTK protein in a subset of pancreatic ductal adenocarcinoma primary tumors and cell lines. siRNA-mediated depletion or catalytic inhibition of TTK resulted in an aberrant cell cycle profile, multi- and micro-nucleation, induction of apoptosis, and decreased cell proliferation and transformed growth. Selective catalytic inhibition of TTK caused override of the spindle assembly checkpoint-induced cell cycle arrest. Interestingly, we identified ubiquitin specific peptidase 16 (Usp16), an ubiquitin hydrolase, as a phosphorylation substrate of TTK. Usp16 regulates chromosomal condensation and G2/M progression by deubiquitinating histone H2A and polo-like kinase 1. Phosphomimetic mutants of Usp16 show enhanced proteosomal degradation and may prolong the G2/M transition allowing for correction of replication errors. Taken together, our results suggest a critical role for TTK in preventing aneuploidy-induced cell death in pancreatic cancer