Faculty Research
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Item Short-term, highfat diet accelerates disuse atrophy and protein degradation in a muscle-specific manner in mice(BioMed Central (Nutrition & Metabolism), 2015) Roseno, Stephen L.; Davis, Patrick R.; Bollinger, Lance M.; Powell, Jonathan S.; Witczak, Carol A.; Brault, JeffreyBackground: A short-term high-fat diet impairs mitochondrial function and the ability of skeletal muscle to respond to growth stimuli, but it is unknown whether such a diet alters the ability to respond to atrophy signals. The purpose of this study was to determine whether rapid weigh gain induced by a high-fat (HF) diet accelerates denervation-induced muscle atrophy. Methods: Adult, male mice (C57BL/6) were fed a control or HF (60 % calories as fat) diet for 3 weeks (3wHF). Sciatic nerve was sectioned unilaterally for the final 5 or 14 days of the diet. Soleus and extensor digitorum longus (EDL) muscles were removed and incubated in vitro to determine rates of protein degradation and subsequently homogenized for determination of protein levels of LC3, ubiquitination, myosin heavy chain (MHC) distribution, and mitochondrial subunits. Results: When mice were fed the 3wHF diet, whole-body fat mass more than doubled, but basal (innervated) muscle weights, rates of protein degradation, LC3 content, mitochondrial protein content, and myosin isoform distribution were not significantly different than with the control diet in either soleus or EDL. However in the 14 day denervated soleus, the 3wHF diet significantly augmented loss of mass, proteolysis rate, amount of the autophagosome marker LC3 II, and the amount of overall ubiquitination as compared to the control fed mice. On the contrary, the 3wHF diet had no significant effect in the EDL on amount of mass loss, proteolysis rate, LC3 levels, or ubiquitination. Fourteen days denervation also induced a loss of mitochondrial proteins in the soleus but not the EDL, regardless of the diet. Conclusions: Taken together, a short-term, high-fat diet augments denervation muscle atrophy by induction of protein degradation in the mitochondria-rich soleus but not in the glycolytic EDL. These findings suggest that the denervation-induced loss of mitochondria and HF diet-induced impairment of mitochondrial function may combine to promote skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]Item Unleashing shear: Role of intercellular traction and cellular moments in collective cell migration(Biochemical and Biophysical Research Communications, 2020-02-05) Alvarez, Diego F.; Patel, Neel G.; Nguyen, Alyson; Xu, Ningyong; Ananthasekar, Shivani; Stevens, Troy; Tambe, Dhananjay T.In the field of endothelial biology, the term “shear forces” is tied to the forces exerted by the flowing blood on the quiescent cells. But endothelial cells themselves also exert physical forces on their immediate and distant neighbors. Specific factors of such intrinsic mechanical signals most relevant to immediate neighbors include normal (Fn) and shear (Fs) components of intercellular tractions, and those factors most relevant to distant neighbors include contractile or dilatational (Mc) and shear (Ms) components of the moments of cytoskeletal forces. However, for cells within a monolayer, Fn, Fs, Mc, and Ms remain inaccessible to experimental evaluation. Here, we present an approach that enables quantitative assessment of these properties. Remarkably, across a collectively migrating sheet of pulmonary microvascular endothelial cells, Fs was of the same order of magnitude as Fn. Moreover, compared to the normal components (Fn, Mc) of the mechanical signals, the shear components (Fs, Ms) were more distinctive in the cells closer to the migration front. Individual cells had an innately collective tendency to migrate along the axis of maximum contractile moment e a collective migratory process we referred to as cellular plithotaxis. Notably, larger Fs and Ms were associated with stronger plithotaxis, but dilatational moment appeared to disengage plithotactic guidance. Overall, cellular plithotaxis was more strongly associated with the “shear forces” (Fs, Ms) than with the “normal forces” (Fn, Mc). Finally, the mechanical state of the cells with fast migration speed and those with highly circular shape were reminiscent of fluid-like and solid-like matter, respectively. The results repeatedly pointed to neighbors imposing shear forces on a cell as a highly significant event, and hence, the term “shear forces” must include not just the forces from flowing fluid but also the forces from the substrate and neighbors. Collectively, these advances set the stage for deeper understanding of mechanical signaling in cellular monolayers.Item Validity of the Somatic Complaints Scales of the MMPI‑2‑RF in an Outpatient Chronic Pain Clinic(Journal of Clinical Psychology in Medical Settings, 2021-02-22) Mickens, Lauren; Nghiem, Duyen; Wygant, Dustin; Umlauf, Robert; Marek, RyanChronic pain has become a significant medical issue. The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a broadband psychological test that has been validated for use across various medical settings and can aid in the assessment and treatment planning of chronic pain. In the current investigation, it was hypothesized that the somatic complaints scales of the MMPI-2-RF would demonstrate good convergent validity from a structured psychodiagnostic interview and other measures of pain and somatization, and lack gender bias. Patients (n = 200) who produced valid MMPI-2-RFs in an outpatient chronic pain clinic were included in the study. Patients were also administered the Modified Somatic Perception Questionnaire (MSPQ), Pain Disability Index (PDI), and the Structured Clinical Interview for DSM-IVTR (SCID). Zero-order and partial correlations (controlling for gender) were calculated between MMPI-2-RF scale scores and other criteria. Stepdown hierarchical regression analyses were used to detect bias. By and large, higher scale scores on the somatic/cognitive scales of the MMPI-2-RF were modestly or substantially correlated with MSPQ scores, PDI scores, and SCID Somatization symptom count, even after controlling for gender. Regression analyses suggested that the MMPI- 2-RF scale scores were not biased as a function of gender. These findings support the validity of specific MMPI-2-RF scales to help identify somatization and psychosocial functioning among patients with chronic pain. Identification of somatization early within the course of treatment of chronic pain may help focus treatment targets, including referrals for psychological interventions such as cognitive behavior therapy for chronic pain.