Biology subjects

Troy, K.

Publications and source records attributed to Troy, K..

5 recordsLinked to original sources

bioRxiv2023

Young adults accelerate their arms significantly faster and earlier than old adults resulting in improved center of mass dynamics during an overground slip perturbation

Arm motions reduce the likelihood of falling from a slip in young adults, and injuries to older adults from falls are known to occur from a frontal plane fall. Therefore, the purpose of this study was to quantify the frontal plane trunk and arm motion in older and younger adults during a slip. Eleven older adults (age: 72.0 {+/-} 5.0) and 11 younger adults (age: 25.17 {+/-} 5.94) were subjected to a slip during walking. 27% of the older adults and 11% of the younger adults experienced a fall from the slip incident. The arm excursion did not significantly differ between groups, however younger adults average peak arm abduction occurred 310 ms prior to older adults (p = 0.03). There were no significant differences in peak trunk between groups. The arm abduction acceleration was significantly higher in younger adults compared to older adults (3593.2 {+/-} 1144.8 vs. 2309.8 {+/-} 1428.5 degrees/s2, p = 0.03). Furthermore, young adults exhibited a significantly reduced CoM excursion compared to old adults (4.55 {+/-} 3.45 vs. 10.27 {+/-} 6.62 cm, p < 0.01). Young adults may have exhibited lower fall rates due to the significantly higher acceleration of their arms compared to old adults.

bioengineering↗

bioRxiv2021

Dominant and nondominant distal radius microstructure: predictors of asymmetry and effects of a unilateral mechanical loading intervention

Most information about distal radius microstructure is based on the non-dominant forearm, with little known about the factors that contribute to bilateral asymmetries in the general population, or what factors may influence bilateral changes over time. Here, we analyzed bilateral longitudinal high resolution peripheral quantitative computed tomography (HRpQCT) data collected over a 12-month period as part of a clinical trial that prescribed a well-controlled, compressive loading task to the nondominant forearm. Baseline data from 102 women age 21-40, and longitudinal data from 66 women who completed the 12-month trial, were examined to determine factors responsible for side-to-side asymmetries in bone structure and change in structure over time. Cross-sectionally, the dominant radius had 2.4%-2.7% larger cross-sectional area, trabecular area, and bone mineral content than the nondominant radius, but no other differences were noted. Those who more strongly favored their dominant arm had significantly more, thinner, closely spaced trabecular struts in their dominant versus nondominant radius. Individuals assigned to a loading intervention had significant bilateral gains in total bone mineral density (2.0% and 1.2% in the nondominant versus dominan sides), and unilateral gains in cortical area (3.1%), thickness (3.0%), bone mineral density (1.7%) and inner trabecular density (1.3%). Each of these gains were significantly predicted by loading dose, a metric that included bone strain, number of cycles, and strain rate. Within individuals, change was negatively associated with age, meaning that women closer to age 40 experienced less of a gain in bone versus those closer to age 21. We believe that dominant/nondominant asymmetries in bone structure reflect differences in habitual loads during growth and past ability to adapt, while response to loading reflects current individual physiologic capacity to adapt.

physiology↗

bioRxiv2020

Relating Bone Strain to Local Changes in Radius Microstructure Following 12 Months of Axial Forearm Loading in Women

Work in animal models suggest that bone structure adapts to local bone strain, but this relationship has not been comprehensively studied in humans. Here, we quantified the influence of strain magnitude and gradient on bone adaptation in the forearm of premenopausal women performing compressive forearm loading (n=11) and non-loading controls (n=10). High resolution peripheral quantitative computed tomography (HRpQCT) scans of the distal radius acquired at baseline and 12 months of a randomized controlled experiment were used to identify local sites of bone formation and resorption. Bone strain was estimated using validated finite element (FE) models. Trabecular strain magnitude and gradient were higher near (within 200 {micro}m) formation versus resorption (p<0.05). Trabecular formation and resorption occurred preferentially near very high (>95th percentile) versus low (<5th percentile) strain magnitude and gradient elements, and very low strain elements were more likely to be near resorption than formation (p<0.05). In the cortical compartment, strain gradient was higher near formation versus resorption (p<0.05), and both formation and resorption occurred preferentially near very high versus low strain gradient elements (p<0.05). At most, 54% of very high and low strain elements were near formation or resorption only, and similar trends were observed in the control and load groups. These findings suggest that strain, likely in combination with other physiological factors, influences adaptation under normal loads and in response to a novel loading intervention, and represents an important step toward defining exercise interventions to maximize bone strength.

bioengineering↗

bioRxiv2019

Super-resolution imaging reveals the evolution of higher-order chromatin folding in early carcinogenesis

Aberrant chromatin structure is a hallmark in cancer cells and has long been used for clinical diagnosis of cancer. However, underlying higher-order chromatin folding during malignant transformation remains elusive, due to the lack of molecular scale resolution. Using optimized stochastic optical reconstruction microscopy (STORM) for pathological tissue (PathSTORM), we uncovered a gradual decompaction and fragmented higher-order chromatin folding throughout all stages of carcinogenesis in multiple tumor types, even prior to the tumor formation. Our integrated imaging, genomic, and transcriptomic analyses reveal the functional consequences in enhanced formation of transcription factories, spatial juxtaposition with relaxed nanosized chromatin domains and impaired genomic stability. We also demonstrate the potential of imaging higher-order chromatin decompaction to detect high-risk precursors that cannot be distinguished by conventional pathology. Taken together, our findings reveal the gradual decompaction and fragmentation of higher-order chromatin structure as an enabling characteristic in early carcinogenesis to facilitate malignant transformation, which may improve cancer diagnosis, risk stratification, and prevention.\n\nSIGNIFICANCEGenomic DNA is folded into a higher-order structure that regulates transcription and maintains genomic stability. Although much progress has been made on understanding biochemical characteristics of epigenetic modifications in cancer, the higher-order folding of chromatin structure remains largely unknown. Using optimized super-resolution microscopy, we uncover de-compacted and fragmented chromatin folding in tumor initiation and stepwise progression in multiple tumor types, even prior to the presence of tumor cells. This study underlines the significance of unfolding higher-order chromatin structure as an enabling characteristic to promote tumorigenesis, which may facilitate the development and evaluation of new preventive strategies. The potential of imaging higher-order chromatin folding to improve cancer detection and risk stratification is demonstrated by detecting high-risk precursors that cannot be distinguished by conventional pathology.

cancer biology↗

bioRxiv2018

Do mechanical strain magnitude and rate drive bone adaptation in adult women? A 12-month prospective study.

Although there is strong evidence that certain activities can increase bone density and structure in some individuals, it is unclear what specific mechanical factors govern the response. This is important because understanding the effect of mechanical signals on bone could contribute to more effective osteoporosis prevention methods and efficient clinical trial design. The degree to which strain rate and magnitude govern bone adaptation in humans has never been prospectively tested. Here, we studied the effects of a voluntary upper extremity compressive loading task in healthy adult women during a twelve month prospective period. One hundred and two women age 21-40 participated in one of two experiments. (1): low (n=21) and high (n=24) strain magnitude. (2): low (n=21) and high (n=20) strain rate. Control: (n=16): no intervention. Strains were assigned using subject-specific finite element models. Load cycles were recorded digitally. The primary outcome was change in ultradistal integral bone mineral content (iBMC), assessed with QCT. Interim timepoints and secondary outcomes were assessed with high resolution pQCT (HRpQCT). Sixty-six subjects completed the intervention, and interim data were analyzed for 77 subjects. Both the low and high strain rate groups had significant 12-month increases to ultradistal iBMC (change in control: -1.3{+/-}2.7%, low strain rate: 2.7{+/-}2.1%, high strain rate: 3.4{+/-}2.2%), total iBMC, and other measures. \"Loading dose\" was positively related to 12-month change in ultradistal iBMC, and interim changes to total BMD, cortical thickness and inner trabecular BMD. Subjects who gained the most bone completed, on average, 130 loading bouts of (mean strain) 550 {varepsilon} at 1805 {varepsilon}/s. Those with the greatest gains had the highest loading dose. We conclude that signals related to strain magnitude, rate, and number of loading bouts contribute to bone adaptation in healthy adult women, but only explain a small amount of variance in bone changes.

physiology↗