@article{enomoto_castro_hash_thomson_nakanishi-hester_perry_aker_haupt_opperman_roe_et al._2024, title={Prevalence of radiographic appendicular osteoarthritis and associated clinical signs in young dogs}, volume={14}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-52324-9}, abstractNote={AbstractThis study aimed to determine the prevalence of osteoarthritis (OA) and associated clinical signs in young dogs. Owners of dogs aged 8 months–4 years from a single practice, were contacted in random order, to participate in a general health screen. Clinical and orthopedic examinations were performed. Each joint was scored for pain reactions (0–4). Orthogonal radiographs of all joints were made under sedation. Each joint was scored for radiographic OA (rOA) severity on an 11-point scale. Clinical OA (cOA) was defined as an overlap of rOA and joint pain in ≥ 1 joint. Owners completed OA questionnaires. The owners of 123 dogs agreed to participate. Overall, 39.8% (49/123) of dogs had rOA in ≥ 1 joint, and 16.3% (20/123) or 23.6% (29/123) dogs had cOA, depending on the cut-off value of joint pain; moderate (2), or mild (1), respectively. Owners of dogs with cOA observed signs of impairment in approximately 30% of cases. Only 2 dogs with cOA were receiving OA pain management. The most commonly affected joints in descending order of frequency were elbow, hip, tarsus, and stifle. Radiographically visible OA is common in young dogs, and 40–60% of dogs with rOA had cOA. However, OA-pain appears underdiagnosed and undertreated in young dogs.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Enomoto, Masataka and Castro, Nicholas and Hash, Jonathan and Thomson, Andrea and Nakanishi-Hester, Aoi and Perry, Erin and Aker, Savannah and Haupt, Emily and Opperman, Logan and Roe, Simon and et al.}, year={2024}, month={Feb} }
 @article{enomoto_hash_cole_sanchez_thomson_perry_aker_nakanishi-hester_haupt_opperman_et al._2024, title={Response to treatment with grapiprant as part of a standard multimodal regimen in young dogs with appendicular joint osteoarthritis associated pain}, volume={11}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2024.1461628}, abstractNote={The response to medical management of young dogs with osteoarthritis (OA) associated pain has not been evaluated. Using an open-label design, the effectiveness, over a 4-month period, of standardized management (grapiprant/fish oil/exercise) for treating OA pain in young dogs was evaluated.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Enomoto, Masataka and Hash, Jonathan and Cole, Tracey and Sanchez, Maria D. Porcel and Thomson, Andrea and Perry, Erin and Aker, Savannah and Nakanishi-Hester, Aoi and Haupt, Emily and Opperman, Logan and et al.}, year={2024}, month={Oct} }
 @article{nakanishi-hester_sai_ninomiya-tsuji_2024, title={The Mechanism and Roles of TAK1 hyperactivation in the Alzheimer's Disease Mouse Model}, volume={300}, ISSN={["1083-351X"]}, DOI={10.1016/j.jbc.2024.106732}, abstractNote={Neuroinflammation in the hippocampus is causally associated with Alzheimer's Disease (AD). However, the precise mechanisms of how inflammatory signaling in each cell type, neuron, oligodendrocyte, astrocyte, microglia, etc. impacts neuronal function remain elusive. Oligodendrocytes (OLGs), known for myelin formation and neuron support, emerge as potential contributors to chronic neuroinflammation. Unlike neurons, OLGs can regenerate throughout the lifespan, making them viable targets for understanding and potentially mitigating AD. We found that mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, a central player in intracellular inflammation signaling, is hyperactivated in the hippocampus of aged and AD model mice. We previously demonstrated that neuron lineage specific Tak1 gene deletion ameliorated neuron loss and cognitive impairment. These results suggest that TAK1-driven inflammatory signaling promotes AD. In our current study, my objectives are to elucidate the mechanism of TAK1 hyperactivation and its role, particularly, in OLGs. We found that compound stimulation of an inflammatory cytokine, TNF and a neurotransmitter glutamate-calcium influx activates TAK1. In addition, calcium calmodulin kinase II (CaMKII) is found to be involved in TAK1 activation by binding to and modulates TAK1 binding protein 2, TAB2. TAB2 serves a dual role in the regulation of TAK1 as it can recruit activators and deactivators of TAK1 and deleting Tab2 gene hyperactivates TAK1. These results collectively suggest that calcium-CaMKII-TAB2 blockade together with TNF hyperactivates TAK1. We are currently analyzing mice with OLG-specific Tab2 deletion (TAK1 hyper-activation). We found that Tab2 deletion blocks OLG differentiation, suggesting that TAK1 hyperactivation impairs OLG-derived support for neurons. Our results uncovered the importance of TAK1 in AD pathogenesis, offering potential avenues for therapeutic intervention. The study is funded by National Institute of Health, R35GM139601, 2019-AARG-NTF-641347.}, number={3}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Nakanishi-Hester, Aoi and Sai, Kazuhito and Ninomiya-Tsuji, Jun}, year={2024}, month={Mar}, pages={S556–S556} }
 @article{sai_nakanishi_scofield_tokarz_linder_cohen_ninomiya-tsuji_2023, title={Aberrantly activated TAK1 links neuroinflammation and neuronal loss in Alzheimer?s disease mouse models}, volume={136}, ISSN={["1477-9137"]}, url={http://dx.doi.org/10.1242/jcs.260102}, DOI={10.1242/jcs.260102}, abstractNote={ABSTRACT
               Neuroinflammation is causally associated with Alzheimer's disease (AD) pathology. Reactive glia cells secrete various neurotoxic factors that impair neuronal homeostasis eventually leading to neuronal loss. Although the glial activation mechanism in AD has been relatively well studied, how it perturbs intraneuronal signaling, which ultimately leads to neuronal cell death, remains poorly understood. Here, we report that compound stimulation with the neurotoxic factors TNF and glutamate aberrantly activates neuronal TAK1 (also known as MAP3K7), which promotes the pathogenesis of AD in mouse models. Glutamate-induced Ca2+ influx shifts TNF signaling to hyper-activate TAK1 enzymatic activity through Ca2+/calmodulin-dependent protein kinase II, which leads to necroptotic cellular damage. Genetic ablation and pharmacological inhibition of TAK1 ameliorated AD-associated neuronal loss and cognitive impairment in the AD model mice. Our findings provide a molecular mechanism linking cytokines, Ca2+ signaling and neuronal necroptosis in AD.}, number={6}, journal={JOURNAL OF CELL SCIENCE}, publisher={The Company of Biologists}, author={Sai, Kazuhito and Nakanishi, Aoi and Scofield, Kimberly M. and Tokarz, Debra A. and Linder, Keith E. and Cohen, Todd J. and Ninomiya-Tsuji, Jun}, year={2023}, month={Mar} }
 @article{nakanishi_lascelles_allen_case_gearing_enomoto_2022, title={A Pilot, Open-Label Study to Evaluate the Efficacy of Intra-Articular Administration of a Caninized TNF Receptor Fc Fusion Protein as a Treatment for Osteoarthritis-Associated Joint Pain}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.836709}, abstractNote={Tumor necrosis factor-α (TNF-α) is a potential target for osteoarthritis (OA) treatment. In several recent clinical studies in human OA, anti-TNF-α therapy showed promising results; however, these were open-label and based on patient-reported outcome measures. In this study, we developed a caninized TNF-α receptor-Fc (caTNFR-Fc) fusion protein and conducted a non-randomized, open-label, pilot study in dogs with OA using objectively measured ground reaction forces and activity. The aims of the study were to assess the efficacy of the intra-articular (IA) injection of the caTNFR-Fc fusion protein as a treatment for OA pain, and additionally to evaluate TNF concentrations in synovial fluid (SF) between joints with/without OA in dogs. Dogs (n = 12) with single-limb lameness due to single joint appendicular OA were recruited. All dogs received caTNFR-Fc fusion protein injection into the affected joint under sedation. Objective kinetic gait analysis using force plate was performed prior to (baseline), and at 14- and 28-days following treatment. Additionally, SF samples were collected from OA joints (n = 69) and non-OA joints (n = 79) in a different cohort of dogs and TNF-α were measured using enzyme-linked immunosorbent assay. No significant treatment effects on the limb use, activity, and the questionnaire were found. The concentration of TNF-α was significantly higher in OA joints than in healthy joints (p = 0.0019), but TNF-α was detected in only 10/69 OA samples. The IA injection of caTNFR-Fc fusion protein provided no benefit in terms of objective limb use and activity data in dogs with OA in this pilot study. Although the SF concentration of TNF-α was significantly higher in OA joints, few OA joints had measurable TNF-α. Collectively, the data indicate TNF-α may not be a good therapeutic target in canine OA.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Nakanishi, Aoi and Lascelles, B. Duncan X. and Allen, Julie and Case, Beth and Gearing, David and Enomoto, Masataka}, year={2022}, month={Jun} }
 @article{prefarrow fat supplementation impact on piglet survival, reproduction_2022, url={https://www.nationalhogfarmer.com/nutrition/prefarrow-fat-supplementation-impact-piglet-survival-reproduction}, journal={National Hog Farmer}, year={2022}, month={May} }
 @article{summer body condition at farrowing influences litter size_2022, url={https://www.nationalhogfarmer.com/livestock/summer-body-condition-farrowing-influences-litter-size}, journal={National Hog Farmer}, year={2022}, month={Sep} }
 @article{2021 adsa undergraduate scholarship recognition awards _2021, url={https://www.sciencedirect.com/science/article/pii/S0022030221010067}, journal={Journal of Dairy Science}, year={2021}, month={Nov} }
 @article{abstracts‐posters_2021, volume={19}, url={http://dx.doi.org/10.1111/vco.12764}, DOI={10.1111/vco.12764}, number={S1}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, year={2021}, month={Sep}, pages={4–24} }