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Background/Objective: Movement and walking are huge facets in how we go about our lives and experience the world. Gait is compromised in numerous conditions, from injury and chronic pain to neurological conditions and arthritis. Movement biomechanics have therefore been studied extensively in humans for decades. Although animal models are often used to examine the progression of various health conditions, translational gait research in animal models are less complete, and there is limited information on gait changes as mice grow. Methods: We recorded video segments of wild-type C57Bl/6J mice during skeletal growth (5 weeks to 16 weeks) walking (n = 4 Female, n = 2 Male) at 20 cm/s on the DigiGait system, a transparent treadmill equipped with a high-speed camera. Videos captured a ventral view of the mouse and were processed using DigiGait Analysis software, which uses local thresholding and position-finding algorithms to examine paw placement on the treadmill belt. Manual adjustments were made to eliminate artifacts and confirm heel-strike and toe-off times. After these corrections, the software returns stride parameters that were compared between sexes. Results: Over 30 gait metrics, including stride length, frequency, stance/swing times, and stance width, were calculated for all four limbs per animal for several time points. Stride length increased from 4.5 ± .5 cm at week 5 to 5.0 ± .8 cm at week 16, and frequency decreased from 4.6 ± .6 to 4.2 ± .6 steps per second. No notable changes in stance width, symmetry, or stance/swing ratio were identified. Conclusion and Potential Impact: Future directions for this research include conducting a principal component analysis to investigate the variability within the gait data. Identifying trends in gait parameters will help create a more complete picture of gait maturation. Establishing this baseline data allows for its comparison against treatment groups and the potentially meaningful investigation of translatable therapeutics and interventions.

Cell spreading and migration play central roles in many physiological and pathophysiological processes. We have previously shown that MFN2 regulates the migration of human neutrophillike cells via suppressing Rac activation. Here, we show that in mouse embryonic fibroblasts, MFN2 suppresses RhoA activation and supports cell polarization. After the initial spreading period, the wild-type cells polarize and migrate, whereas the Mfn2-/- cells maintain a circular shape. Increased cytosolic Ca2+ resulting from the loss of Mfn2 is directly responsible for this phenotype, which can be rescued by expressing an artificial tether to bring mitochondria and ER to close vicinity. Elevated cytosolic Ca2+ activates Ca2+/calmodulin-dependent protein kinase II, RhoA, and Myosin light-chain kinase, causing an over-activation of non-muscle myosin II and a formation of a prominent F-actin ring at the cell periphery and increased cell contractility. The formation of the peripheral actin band alters cell physics and is dependent on substrate rigidity.Our results provide a novel molecular basis to understand how MFN2 regulates distinct signaling pathways in different cells and tissue environments, which is instrumental in understanding and treating MFN2-related diseases.

Hiring practices in academia have critically limited the entry of individuals from historically excluded groups (e.g., people who identify as Black/African American, Hispanic/Latino, American Indian/Alaskan Native, LGBTQ+, people with disabilities) into our biomedical engineering faculty. Excluding such individuals has hindered our profession’s research impact and ability to equitably educate our students. With many departments committed to “do better,” we now need to embrace a new mindset and gain the skills necessary to rectify injustices in our faculty hiring processes. Here, we offer a faculty hiring roadmap that departments can leverage to eliminate many barriers of entry to members of historically excluded groups as faculty in biomedical engineering. We call on our colleagues to recognize the failings of our current hiring practices and adopt the guidelines provided here to diversify biomedical engineering departments so that we might collectively accelerate the impact, innovation, and power of our profession.

Background and Hypothesis Bacterial vaginosis, which is the imbalance of normal vaginal microbiota, contributes to preterm delivery, vaginitis, and decreased drug efficacy. Despite metronidazole efficacy in reducing BV contributing organisms, BV continues to recur in 50% of patients. Previous studies showing imidazole propionate’s role in the pathogenesis of type II diabetes suggest that similar metabolite-regulated pathways in vaginal microbiomes may be the key in pathogenesis of uterine diseases such as BV. Thus, the purpose of this study was to observe the relationship between vaginal metabolites, host or microbiome-derived, and transcriptomic responses in vaginal epithelial tissues stratified by vaginal microbiome composition (“microbiome group”). The hypothesis was that differences in vaginal microbiome composition result in differential regulation of metabolite-host pathway functional relationships. Project Methods Transcript levels and metabolite concentrations precollected from 23 East African women were processed and analyzed via R. Transcriptomic data were converted into KEGG pathway enrichment scores via ssGSEA2.0, a package within R. Enrichment scores were correlated (Spearman) with metabolite levels by microbiome group and lactobacillus dominant phenotypes, and relationships were visualized via Heatmap3 and Cytoscape. Results: The results showed varying strengths in correlation among metabolites and KEGG pathway enrichment scores after filtering for strong correlations (R > |0.5|) and significance (p< 0.05). Nonlactobacillus dominant microbiomes showed fewer strongly associated metabolite-KEGG pathway relationships compared to the lactobacillus dominant microbiome group, specifically the imidazole-related networks. Conclusion: In this study, variations in significant correlations among metabolites and KEGG pathways suggests that microbiome diversity may contribute to how metabolites regulate host pathways in vaginal epithelial cells. The reduced pathway interactions observed in imidazole compounds suggests that dysregulation may contribute to recurrence of bacterial vaginosis. This method of modelling could be used to characterize the regulation of critical pathways associated with the pathogenesis of bacterial vaginosis.

Articular cartilage lines the load-bearing surfaces of long bones and undergoes compositional and structural degeneration during osteoarthritis progression. Contrast enhanced microcomputed tomography (μCT) is being applied to a variety of preclinical models, including the mouse, to map structural and compositional properties in 3-D. The thinness (~30–50 μm) and high cellularity of mouse articular cartilage presents a significant imaging challenge. Our group previously showed that mouse articular cartilage and proteoglycan (PG) content can be assessed by μCT with the ioxagalate-based contrast agent Hexabrix, but the voxel size used (6 μm) was deemed to be barely adequate. The objective of the present study is to assess the utility of a novel contrast agent, CA4+, to quantify mouse articular cartilage morphology and composition with high resolution μCT imaging (3 μm voxels) and to compare the sensitivity of CA4+ and Hexabrix to detect between-group differences. While both contrast agents are iodine-based, Hexabrix is anionic and CA4+ is cationic so they interact differently with negatively charged PGs. With CA4+, a strong correlation was found between non-calcified articular cartilage thickness measurements made with histology and μCT (R2 = 0.72, p < 0.001). Cartilage degeneration – as assessed by loss in volume, thickness and PG content – was observed in 34-week old mice when compared to both 7- and 12-week old mice. High measurement precision was observed with CA4+, with the coefficient of variation after repositioning and re-imaging samples equaling 2.8%, 4.5%, 7.4% and 5.9% for attenuation, thickness, volume, and PG content, respectively. Use of CA4+ allowed increased sensitivity for assessing PG content compared to Hexabrix, but had no advantage for measurement of cartilage thickness or volume. This improvement in imaging should prove useful in preclinical studies of cartilage degeneration and regeneration.