المؤلفون: Peirce-Cottler, Shayn M, Sander, Edward A, Fisher, Matthew B, Deymier, Alix C, LaDisa, John F, O'Connell, Grace, Corr, David T, Han, Bumsoo, Singh, Anita, Wilson, Sara E, Lai, Victor K, Clyne, Alisa Morss

المصدر: Journal of Biomechanical Engineering. 146(4)

مصطلحات موضوعية: Engineering, Biomedical Engineering, Bioengineering, Quality Education, Humans, Biomechanical Phenomena, Biophysics, Systems Analysis, Mechanical Engineering, Biomedical engineering

الوصف: The human body represents a collection of interacting systems that range in scale from nanometers to meters. Investigations from a systems perspective focus on how the parts work together to enact changes across spatial scales, and further our understanding of how systems function and fail. Here, we highlight systems approaches presented at the 2022 Summer Biomechanics, Bio-engineering, and Biotransport Conference in the areas of solid mechanics; fluid mechanics; tissue and cellular engineering; biotransport; and design, dynamics, and rehabilitation; and biomechanics education. Systems approaches are yielding new insights into human biology by leveraging state-of-the-art tools, which could ultimately lead to more informed design of therapies and medical devices for preventing and treating disease as well as rehabilitating patients using strategies that are uniquely optimized for each patient. Educational approaches can also be designed to foster a foundation of systems-level thinking.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/01k20804Test

المؤلفون: Kuper, Tracy J., Islam, Mohammad Mazharul, Peirce-Cottler, Shayn M., Papin, Jason A., Ford, Roseanne M

المساهمون: Scott, Matthew, National Institute of Allergy and Infectious Diseases, National Institutes of Health

المصدر: PLOS Computational Biology ; volume 20, issue 4, page e1012031 ; ISSN 1553-7358

الوصف: With the generation of spatially resolved transcriptomics of microbial biofilms, computational tools can be used to integrate this data to elucidate the multi-scale mechanisms controlling heterogeneous biofilm metabolism. This work presents a Multi-scale model of Metabolism In Cellular Systems (MiMICS) which is a computational framework that couples a genome-scale metabolic network reconstruction (GENRE) with Hybrid Automata Library (HAL), an existing agent-based model and reaction-diffusion model platform. A key feature of MiMICS is the ability to incorporate multiple -omics-guided metabolic models, which can represent unique metabolic states that yield different metabolic parameter values passed to the extracellular models. We used MiMICS to simulate Pseudomonas aeruginosa regulation of denitrification and oxidative stress metabolism in hypoxic and nitric oxide (NO) biofilm microenvironments. Integration of P . aeruginosa PA14 biofilm spatial transcriptomic data into a P . aeruginosa PA14 GENRE generated four PA14 metabolic model states that were input into MiMICS. Characteristic of aerobic, denitrification, and oxidative stress metabolism, the four metabolic model states predicted different oxygen, nitrate, and NO exchange fluxes that were passed as inputs to update the agent’s local metabolite concentrations in the extracellular reaction-diffusion model. Individual bacterial agents chose a PA14 metabolic model state based on a combination of stochastic rules, and agents sensing local oxygen and NO. Transcriptome-guided MiMICS predictions suggested microscale denitrification and oxidative stress metabolic heterogeneity emerged due to local variability in the NO biofilm microenvironment. MiMICS accurately predicted the biofilm’s spatial relationships between denitrification, oxidative stress, and central carbon metabolism. As simulated cells responded to extracellular NO, MiMICS revealed dynamics of cell populations heterogeneously upregulating reactions in the denitrification pathway, which may function to ...

الإتاحة: https://doi.org/10.1371/journal.pcbi.1012031Test

المؤلفون: Harris, Alexandra R., Esparza, Savieay, Azimi, Mohammad S., Cornelison, Robert, Azar, Francesca N., Llaneza, Danielle C., Belanger, Maura, Mathew, Alexander, Tkachenko, Svyatoslav, Perez, Matthew J., Rosean, Claire Buchta, Bostic, Raegan R., Cornelison, R. Chase, Tate, Kinsley M., Peirce-Cottler, Shayn M., Paquette, Cherie, Mills, Anne, Landen, Charles N., Saucerman, Jeff, Dillon, Patrick M., Pompano, Rebecca R., Rutkowski, Melanie A., Munson, Jennifer M.

مصطلحات موضوعية: platinum, chemotherapy, lymphangiogenesis, metastasis, breast cancer, ovarian cancer, lymphatic endothelial cells, anti-VEGFR3 therapy

الوصف: Chemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma, unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drugs drain via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used class of chemotherapeutics, to directly induce systemic lymphangiogenesis and activation. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We found similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increased cancer metastasis as compared to no pre-treatment. These platinum-induced phenomena could be blocked by VEGFR3 inhibition. These findings have implications for cancer patients receiving platinums and may support the inclusion of anti-VEGFR3 therapy into treatment regimens or differential design of treatment regimens to alter these potential effects. ; Published version

وصف الملف: application/pdf

العلاقة: 801764; http://hdl.handle.net/10919/111216Test; https://doi.org/10.3389/fonc.2022.801764Test; 12

الإتاحة: https://doi.org/10.3389/fonc.2022.801764Test
http://hdl.handle.net/10919/111216Test

المؤلفون: Suarez‐Martinez, Ariana Diandra, Peirce‐Cottler, Shayn M., Isakson, Brant, Scallan, Joshua, Murfee, Walter Lee

المساهمون: National Institutes of Health

المصدر: The FASEB Journal ; volume 32, issue S1 ; ISSN 0892-6638 1530-6860

الوصف: Ex Vivo biomimetic models have emerged as powerful experimental tools for basic science discovery and pre‐clinical drug testing. A challenge for microvascular research is recapitulating the complexity associated with intact networks in real tissue scenarios. To meet this challenge, our laboratory recently introduced the rat mesentery culture model, which enables the real‐time investigation of multicellular interactions during angiogenesis and lymphangiogenesis at the same time. The impact of this approach could be increased with the use of analogous transgenic mouse tissue. However, mouse mesentery is normally avascular raising the question: Can we induce microvascular growth into the mouse mesentery? Preliminary observations of mesenteric tissues harvested from mice treated with tamoxifen for conditional knockout studies suggests that vascularization in the mouse mesentery might be possible. The objective of this study was to test the hypothesis that tamoxifen treatment causes microvascular growth into avascular mouse mesenteric tissue. Female C57BL/6 mice were given a daily IP injection of 0.1 mL for 5 consecutive days containing the following experimental groups: Saline, Sunflower Seed Oil (Oil), and Tamoxifen (Tmx) dissolved in sunflower seed oil (10 mg/mL). Following 21 days post the last injection, mesenteric tissues were harvested and labeled with anti‐mouse platelet endothelial cell adhesion molecule (PECAM), neuron‐glial antigen 2 (NG2), and alpha‐smooth muscle actin (a‐SMA) antibodies to identify endothelial cells, pericytes, and smooth muscle cells, respectively. Zero tissues (0/8) from the Saline group contained a branching microvascular network. In contrast, all tissues from the Oil (8/8) and Tmx (8/8) groups contained networks with arterioles, venules, and capillaries. Smooth muscle cells and pericytes were present in their expected wrapping morphologies and locations along the hierarchy of the networks. In contrast to Saline tissues, Oil and Tmx treated tissues also contained branching ...

الإتاحة: https://doi.org/10.1096/fasebj.2018.32.1_supplement.573.6Test

المؤلفون: Awojoodu, Anthony O., Ogle, Molly E., Sefcik, Lauren S., Bowers, Daniel T., Martin, Kyle, Brayman, Kenneth L., Lynch, Kevin R., Peirce-Cottler, Shayn M., Botchwey, Edward

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2013 Aug . 110(34), 13785-13790.

الوصول الحر: https://www.jstor.org/stable/42713003Test

المؤلفون: Adamson, Samantha E., Meher, Akshaya K., Chiu, Yu-hsin, Sandilos, Joanna K., Oberholtzer, Nathaniel P., Walker, Natalie N., Hargett, Stefan R., Seaman, Scott A., Peirce-Cottler, Shayn M., Isakson, Brant E., McNamara, Coleen A., Keller, Susanna R., Harris, Thurl E., Bayliss, Douglas A., Leitinger, Norbert

المساهمون: National Institutes of Health

المصدر: Molecular Metabolism ; volume 4, issue 9, page 610-618 ; ISSN 2212-8778

مصطلحات موضوعية: Cell Biology, Molecular Biology

الإتاحة: https://doi.org/10.1016/j.molmet.2015.06.009Test
https://api.elsevier.com/content/article/PII:S2212877815001337?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2212877815001337?httpAccept=text/plainTest

المؤلفون: Okutsu, Mitsuharu, Call, Jarrod A., Lira, Vitor A., Zhang, Mei, Donet, Jean A., French, Brent A., Martin, Kyle S., Peirce-Cottler, Shayn M., Rembold, Christopher M., Annex, Brian H., Yan, Zhen

المصدر: Circulation: Heart Failure ; volume 7, issue 3, page 519-530 ; ISSN 1941-3289 1941-3297

الوصف: Background— Congestive heart failure (CHF) is a leading cause of morbidity and mortality, and oxidative stress has been implicated in the pathogenesis of cachexia (muscle wasting) and the hallmark symptom, exercise intolerance. We have previously shown that a nitric oxide–dependent antioxidant defense renders oxidative skeletal muscle resistant to catabolic wasting. Here, we aimed to identify and determine the functional role of nitric oxide–inducible antioxidant enzyme(s) in protection against cardiac cachexia and exercise intolerance in CHF. Methods and Results— We demonstrated that systemic administration of endogenous nitric oxide donor S -nitrosoglutathione in mice blocked the reduction of extracellular superoxide dismutase (EcSOD) protein expression, as well as the induction of MAFbx/Atrogin-1 mRNA expression and muscle atrophy induced by glucocorticoid. We further showed that endogenous EcSOD, expressed primarily by type IId/x and IIa myofibers and enriched at endothelial cells, is induced by exercise training. Muscle-specific overexpression of EcSOD by somatic gene transfer or transgenesis (muscle creatine kinase [MCK]-EcSOD) in mice significantly attenuated muscle atrophy. Importantly, when crossbred into a mouse genetic model of CHF (α-myosin heavy chain–calsequestrin), MCK-EcSOD transgenic mice had significant attenuation of cachexia with preserved whole body muscle strength and endurance capacity in the absence of reduced HF. Enhanced EcSOD expression significantly ameliorated CHF-induced oxidative stress, MAFbx/Atrogin-1 mRNA expression, loss of mitochondria, and vascular rarefaction in skeletal muscle. Conclusions— EcSOD plays an important antioxidant defense function in skeletal muscle against cardiac cachexia and exercise intolerance in CHF.

الإتاحة: https://doi.org/10.1161/circheartfailure.113.000841Test

المؤلفون: Harris, Alexandra R., Azimi, Mohammad S., Cornelison, Robert, Azar, Francesca N., Llaneza, Danielle C., Belanger, Maura, Mathew, Alexander, Tkachenko, Svyatoslav, Esparza, Savieay, Perez, Matthew J., Rosean, Claire Buchta, Bostic, Raegan R., Cornelison, R. Chase, Tate, Kinsley M., Peirce-Cottler, Shayn M., Paquette, Cherie, Mills, Anne, Landen, Charles N., Saucerman, Jeff, Dillon, Patrick M., Pompano, Rebecca R., Rutkowski, Melanie A., Munson, Jennifer M.

الوصف: Chemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drug drains via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used chemotherapeutic, to directly induce systemic VEGFR3-dependent lymphangiogenesis. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We saw similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment results in lymphatic hyperplasia and secretion of pro-chemotactic factors in lymph nodes. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increases cancer metastasis. These findings have broad-reaching implications for cancer patients receiving platinums and support the inclusion of anti-VEGFR3 therapy into treatment regimens. Summary Platinum chemotherapy induces lymphangiogenesis priming tissues for metastasis of breast cancer. Inhibition of VEGFR3 via antibody blockade can reverse these effects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=sharebioRxiv::c8d0dba5294a9407d7f180a88656d793Test

المؤلفون: Hashambhoy, Yasmin L., Chappell, John C., Peirce-Cottler, Shayn M., Bautch, Victoria L., Mac Gabhann, Feilim

المصدر: Frontiers in Physiology ; volume 2 ; ISSN 1664-042X

مصطلحات موضوعية: Physiology (medical), Physiology

الإتاحة: https://doi.org/10.3389/fphys.2011.00062Test

المؤلفون: Peirce-Cottler, Shayn M., Marsden, Alison

المصدر: Current Opinion in Biomedical Engineering ; volume 11, page A1-A3 ; ISSN 2468-4511

مصطلحات موضوعية: Biomedical Engineering, Biomaterials, Medicine (miscellaneous), Bioengineering

الإتاحة: https://doi.org/10.1016/j.cobme.2019.12.001Test
https://api.elsevier.com/content/article/PII:S246845111930073X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S246845111930073X?httpAccept=text/plainTest