Biology subjects

Stout, J. R.

Publications and source records attributed to Stout, J. R..

3 recordsLinked to original sources

bioRxiv2024

CHANGES IN MUSCLE QUALITY FOLLOWING SHORT-TERM RESISTANCE TRAINING IN OLDER ADULTS: A COMPARISON OF ECHO INTENSITY AND TEXTURE ANALYSIS

BackgroundSkeletal muscle echo intensity (EI) is associated with functional outcomes in older adults, but resistance training interventions have shown mixed results. Texture analysis has been proposed as a novel approach for assessing muscle quality, as it captures spatial relationships between pixels. PurposeTo examine changes in first-order (EI) and second-order (texture) features of muscle quality following lower-body resistance training in older adults. MethodsTwelve older adults (2 males, 10 females; mean {+/-} SD age = 70 {+/-} 5 years) completed 6 weeks of progressive resistance training, consisting of twice-weekly sessions at 85% of estimated 1RM. Pre- and post-intervention assessments included ultrasound imaging of the rectus femoris (RF) and vastus lateralis (VL), 5-repetition maximum (5RM) leg extension strength, and maximal voluntary isometric contraction (MVIC) force. Ultrasound images were analyzed for EI and texture features using gray-level co-occurrence matrix (GLCM) analysis. ResultsLarge improvements were observed in 5RM leg extension strength (p < 0.001, d = 2.09), MVIC force (p = 0.006, d = 0.969), and RF EI (uncorrected: p = 0.003, d = 0.727; corrected: p = 0.012, d = 0.864). No significant changes were observed in muscle size, VL EI, or texture features for either muscle. ConclusionsShort-term resistance training improved strength and RF muscle quality as measured by EI. However, texture analysis features were not sensitive to changes following training. These findings suggest that traditional EI measures may be more appropriate than texture analysis for tracking changes in muscle quality following resistance training in older adults. NEW & NOTEWORTHYWe studied muscle quality changes after 6 weeks of resistance training in older adults, comparing traditional EI to texture analysis. Despite significant strength gains, only RF EI improved, with minimal changes in muscle size, VL EI, or texture parameters. Surprisingly, texture analysis was less sensitive than traditional EI in detecting muscle quality changes. Our results suggest that conventional EI measures may be more suitable for evaluating short-term adaptations to resistance training in older adults.

physiology↗

bioRxiv2023

MCAK Inhibitors Induce Aneuploidy in Triple Negative Breast Cancer Models

Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC50 for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target. Simple SummaryTriple negative breast cancer (TNBC) is the most lethal breast cancer subtype with few treatment options available. Standard of care for TNBC involves the use of taxanes, which are initially effective, but dose limiting toxicities are common, and patients often relapse with resistant tumors. Specific drugs that produce taxane-like effects may be able to improve patient quality of life and prognosis. In this study we identify three novel inhibitors of the Kinesin-13 MCAK. MCAK inhibition induces aneuploidy; similar to cells treated with taxanes. We demonstrate that MCAK is upregulated in TNBC and is associated with poorer prognoses. These MCAK inhibitors reduce the clonogenic survival of TNBC cells, and the most potent of the three inhibitors, C4, sensitizes TNBC cells to taxanes, similar to the effects of MCAK knockdown. This work will expand the field of precision medicine to include aneuploidy-inducing drugs that have the potential to improve patient outcomes.

cancer biology↗

bioRxiv2018

RESISTANCE TRAINING DOES NOT INDUCE UNIFORM ADAPTATIONS TO QUADRICEPS MUSCLES

Resistance training may differentially affect morphological adaptations along the length of uni-articular and bi-articular muscles. The purpose of this study was to compare changes in muscle morphology along the length of the rectus femoris (RF) and vastus lateralis (VL) in response to resistance training. Following a 2-wk preparatory phase, 15 resistance-trained men (24.0 {+/-} 3.0 y, 90.0 {+/-} 13.8 kg, 174.9 {+/-} 20.7 cm) completed pre-training (PRE) assessments of muscle thickness (MT), pennation angle (PA), cross-sectional area (CSA), and echo-intensity in the RF and VL at 30, 50, and 70% of each muscles length; fascicle length (FL) was estimated from respective measurements of MT and PA within each muscle and region. Participants then began a high intensity, low volume (4 x 3 - 5 repetitions, 3min rest) lower-body resistance training program, and repeated all PRE-assessments after 8 weeks (2 d {middle dot} wk-1) of training (POST). Although three-way (muscle [RF, VL] x region [30, 50, 70%] x time [PRE, POST]) repeated measures analysis of variance did not reveal significant interactions for any assessment of morphology, significant simple (muscle x time) effects were observed for CSA (p = 0.002) and FL (p = 0.016). Specifically, average CSA changes favored the VL (2.96 {+/-} 0.69 cm2, pp < 0.001) over the RF (0.59 {+/-} 0.20 cm2, p = 0.011), while significant decreases in average FL were noted for the RF (-1.03 {+/-} 0.30 cm, p = 0.004) but not the VL (-0.05 {+/-} 0.36 cm, p = 0.901). No other significant differences were observed. The findings of this study demonstrate the occurrence of non-homogenous adaptations in RF and VL muscle size and architecture following 8 weeks of high-intensity resistance training in resistance-trained men. However, training does not appear to influence region-specific adaptations in either muscle.

physiology↗