Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by deficiency of the protein dystrophin and affects approximately 1/3500 boys. Basic/translational studies of exercise effects in DMD have been conducted for decades, but with often contradictory results concerning benefit vs. detriment especially for cardiac muscle. However, these studies have been exclusively performed in a mouse model which does not fully recapitulate the DMD cardiac phenotype. Here we present the first known characterization of exercise and physical function in a new DMD mdx rat model that better mimics human DMD. DMD mdx rats (n=6) and healthy, sibling wild types (WT, n=9) were compared in this study. I performed a battery of functional and exercise tests  when the rats were at 14-15 weeks of age, including max treadmill endurance, volitional wheel running distance, forelimb grip strength, and in-vivo hindlimb force testing. Total work performed in treadmill endurance testing was lower for DMD mdx (2.6±0.3 Kpm) vs. WT (29.3±2.2 Kpm), p<0.001. 24-hr wheel running distance was lower for DMD mdx (702±65m) vs. WT (1038±66m), p<0.001. Forelimb grip strength was lower for DMD mdx (211±16g) vs. WT (318±13g), p<0.001. Finally, in electrically-stimulated in-vivo hindlimb force testing, both muscular endurance (% of initial force at 200-s) and peak torque (at 120Hz) were less in DMDmdx (55±2%, 0.33±0.02nM*m/g) vs. WT (69±2%, 0.45±0.030nM*m/g) p<0.01. Capacity for volitional and forced exercise is severely impaired in the novel DMD rat, congruent with limitations observed in functional muscular strength and endurance. Ongoing work is examining exercise adaptations and cardiac responses in this model which may better represent training responses in DMD patients and be useful for establishing exercise guidelines in this population.

In this study we developed a nonhuman primate model of simian immunodeficiency virus (SIV)-Zika virus (ZIKV) co-infection to understand how HIV infection impacts ZIKV pathogenesis and test our hypothesis that ZIKV pathogenesis is enhanced in people living with untreated HIV. Previously, we have found delayed viral clearance, as well as delayed and dampened expansion of whole blood monocytes, the ZIKV cellular targets, during SIV infection. Here, we sought to further characterize the innate immune responses of SIV-ZIKV co-infection, by assessing cytokine and chemokine release. Pigtail macaques (n=7) were infected with SIVmac239M and co-infected with ZIKV at 9 weeks post-SIV infection. Co-infected animals were compared to control animals (n=7) infected with ZIKV only. Longitudinal plasma and cerebral spinal fluid (CSF) were collected at timepoints pre- and post-infection and assayed using a multiplex immunoassay to quantify 24 different cytokine and chemokines ex vivo. SIV and ZIKV both induced pro-inflammatory responses, characterized by transient increases in interleukin-17 (IL-17A) and monocyte chemoattractant protein-1 (MCP-1), with no major differences between experimental groups. Plasma MCP-1 concentrations were also found to be consistent with dampened and delayed whole blood monocyte frequencies. Pro-inflammatory interleukin-8 (IL-8), a chemokine needed for recruitment of neutrophils, increased in the plasma during SIV infection but not following ZIKV infection, a result that is in contrast to our previous findings. Transient increases in IL-8 were detected in a few animals in the CSF after ZIKV infection, which may be evidence for neuroinflammation. Overall, no significant differences between SIV+ vs SIV- groups were found for any analytes detected in plasma or CSF during ZIKV infection. Collectively, our results demonstrate that both SIV and ZIKV infections induce a pro-inflammatory response, that is not enhanced by SIV-ZIKV co-infection. This suggests SIV induced immunosuppression does not impair pro-inflammatory cytokine responses during ZIKV infection.

As the impacts of climate change begin to increase in urgency, new techniques for natural disaster mitigation must be invented to protect communities and ecosystems everywhere – especially in coastal environments where they’ll be affected most quickly and dramatically. It’s possible that the solution might come from a radical decolonization in our approach to landscape architecture, land and resource management and environmental planning. How can implementing Indigenous land stewardship techniques in coastal communities help mitigate the impacts of climate change? This project explores Indigenous land and resource management and considers how they might be best integrated into contemporary ecological design in the Western Washington shoreline region while confronting colonial perceptions and interpretations of Indigenous knowledge. Methods include researching global approaches to Indigenous land stewardship integration, a case study on issues relating to the ancestral land of the Olympic Peninsula’s Makah and Quinault peoples, and development of printmaking techniques in monotype, linoleum and lithography. Products will include a research paper with best practice recommendations, artistic landscape representations in the form of prints and an informational zine to make built environment issues collaborative and accessible, with which net proceeds will be contributed back to collaborating tribal communities. Through collective action, working towards decolonizing ecological design and planning might offer sacred land the chance it needs to heal.