Browsing by Subject "cell biology"

Now showing 1 - 6 of 6
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    Angiogenic potential of skeletal muscle derived extracellular vesicles differs between oxidative and glycolytic muscle tissue in mice
    (Nature, 2023-11) Kargl, Christopher K.; Jia, Zhihao; Shera, Deborah A.; Sullivan, Brian P.; Burton, Lundon C.; Kim, Kun Ho; Nie, Yaohui; Hubal, Monica J.; Shannahan, Jonathan H.; Kuang, Shihuan; Gavin, Timothy P.; Exercise & Kinesiology, School of Health and Human Sciences
    Skeletal muscle fibers regulate surrounding endothelial cells (EC) via secretion of numerous angiogenic factors, including extracellular vesicles (SkM-EV). Muscle fibers are broadly classified as oxidative (OXI) or glycolytic (GLY) depending on their metabolic characteristics. OXI fibers secrete more pro-angiogenic factors and have greater capillary densities than GLY fibers. OXI muscle secretes more EV than GLY, however it is unknown whether muscle metabolic characteristics regulate EV contents and signaling potential. EVs were isolated from primarily oxidative or glycolytic muscle tissue from mice. MicroRNA (miR) contents were determined and endothelial cells were treated with OXI- and GLY-EV to investigate angiogenic signaling potential. There were considerable differences in miR contents between OXI- and GLY-EV and pathway analysis identified that OXI-EV miR were predicted to positively regulate multiple endothelial-specific pathways, compared to GLY-EV. OXI-EV improved in vitro angiogenesis, which may have been mediated through nitric oxide synthase (NOS) related pathways, as treatment of endothelial cells with a non-selective NOS inhibitor abolished the angiogenic benefits of OXI-EV. This is the first report to show widespread differences in miR contents between SkM-EV isolated from metabolically different muscle tissue and the first to demonstrate that oxidative muscle tissue secretes EV with greater angiogenic signaling potential than glycolytic muscle tissue.
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    Antiremodeling Agents Influence Osteoblast Activity Differently in Modeling and Remodeling Sites of Canine Rib
    (Calcified Tissue International, 2006-10-10) Allen, Matthew R.; Follet, Helene; Khurana, M.; Sato, M.; Burr, David B.; Department of Anatomy & Cell Biology, IU School of Medicine
    Antiremodeling agents reduce bone loss in part through direct actions on osteoclasts. Their effects on osteoblasts and bone formation activity are less clear and may differ at sites undergoing modeling vs. remodeling. Skeletally mature intact beagles, 1–2 years old at the start of the study, were treated daily with clinically relevant doses of alendronate (0.10 or 0.20 mg/kg), risedronate (0.05 or 0.10 mg/kg), raloxifene (0.50 mg/kg), or vehicle (1 mL/kg). Dynamic bone formation parameters were histologically assessed on periosteal, endocortical/trabecular, and intracortical bone envelopes of the rib. Raloxifene significantly increased periosteal surface mineral apposition rate (MAR), a measure of osteoblast activity, compared to all other treatments (+108 to +175%, P < 0.02), while having no significant effect on MAR at either the endocortical/trabecular or intracortical envelope. Alendronate (both 0.10 and 0.20 doses) and risedronate (only the 0.10 dose) significantly (P ≤ 0.05) suppressed MAR on the endocortical/trabecular envelope, while none of the bisphosphonate doses significantly altered MAR at either the periosteal or intracortical envelopes compared to vehicle. Based on these results, we conclude that (1) at clinically relevant doses the two classes of antiremodeling agents, bisphosphonates and selective estrogen receptor modulators, exert differential effects on osteoblast activity in the canine rib and (2) this effect depends on whether modeling or remodeling is the predominant mechanism of bone formation.
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    Cell Biology: Function Guides Form of Auditory Sensory Cells
    (Elsevier, 2020-02) McGrath, Jamis; Perrin, Benjamin J.; Biology, School of Science
    Mechanosensory bundles on auditory sensory cells are composed of stereocilia that grow in rows of decreasing height. This pattern depends on the specification of the eventual tallest row, then the assignment of distinct molecular identities to the shorter rows. Mechanotransduction refines and maintains row identity, thus instructing the form of the bundle.
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    Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells
    (Nature Publishing Group, 2016-05-24) Liu, Xiao-Ping; Koehler, Karl R.; Mikosz, Andrew M.; Hashino, Eri; Holt, Jeffrey R.; Department of Otolaryngology—Head & Neck Surgery, IU School of Medicine
    Inner ear sensory epithelia contain mechanosensitive hair cells that transmit information to the brain through innervation with bipolar neurons. Mammalian hair cells do not regenerate and are limited in number. Here we investigate the potential to generate mechanosensitive hair cells from mouse embryonic stem cells in a three-dimensional (3D) culture system. The system faithfully recapitulates mouse inner ear induction followed by self-guided development into organoids that morphologically resemble inner ear vestibular organs. We find that organoid hair cells acquire mechanosensitivity equivalent to functionally mature hair cells in postnatal mice. The organoid hair cells also progress through a similar dynamic developmental pattern of ion channel expression, reminiscent of two subtypes of native vestibular hair cells. We conclude that our 3D culture system can generate large numbers of fully functional sensory cells which could be used to investigate mechanisms of inner ear development and disease as well as regenerative mechanisms for inner ear repair.
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    Sequestration of host metabolism by an intracellular pathogen
    (eLife Sciences Organisation, Ltd., 2016) Gehre, Lena; Gorgette, Olivier; Perrinet, Stéphanie; Prevost, Marie-Christine; Ducatez, Mathieu; Giebel, Amanda M.; Nelson, David E.; Ball, Steven G.; Subtil, Agathe; Department of Microbiology and Immunology, IU School of Medicine
    For intracellular pathogens, residence in a vacuole provides a shelter against cytosolic host defense to the cost of limited access to nutrients. The human pathogen Chlamydia trachomatis grows in a glycogen-rich vacuole. How this large polymer accumulates there is unknown. We reveal that host glycogen stores shift to the vacuole through two pathways: bulk uptake from the cytoplasmic pool, and de novo synthesis. We provide evidence that bacterial glycogen metabolism enzymes are secreted into the vacuole lumen through type 3 secretion. Our data bring strong support to the following scenario: bacteria co-opt the host transporter SLC35D2 to import UDP-glucose into the vacuole, where it serves as substrate for de novo glycogen synthesis, through a remarkable adaptation of the bacterial glycogen synthase. Based on these findings we propose that parasitophorous vacuoles not only offer protection but also provide a microorganism-controlled metabolically active compartment essential for redirecting host resources to the pathogens.
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    Using Zebrafish to implement a Course-Based Undergraduate Research Experience (CURE) to study Teratogenesis in Two Biology Laboratory Courses
    (Office of the Vice Chancellor for Research, 2015-04-17) Sarmah, S.; Chism, G.W.; Vaughan, M. A.; Muralidharan, P.; Marrs, J.A.; Marrs, Kathleen A.
    Abstract: Two related course-based undergraduate research experiences (CUREs) were introduced into a freshman introductory biology and a sophomore level cell biology class. In fall 2013, first semester freshman students were introduced to scientific research in an introductory biology laboratory course. Students were mentored to develop and execute original research projects investigating embryonic nicotine and caffeine exposure effects on development, particularly on heart development and function, using zebrafish embryos. In spring 2014, sophomore level cell biology students extended these studies and analyzed the effects of nicotine and caffeine at precise times in gastrulation. The freshman research experience was repeated in fall 2014 where a new group of students expanded the earlier research to investigate effects of additional toxicants on development. Students designed new protocols, made measurements, documented data, presented results and generated novel, high quality preliminary data that will be further studied in successive semesters. Student researchers identified novel effects of nicotine exposure on gastrulation and heart morphogenesis. Student surveys showed the greatest gains in ability to (1) design experiments, (2) analyze data, and (3) make scientific presentations. This CURE approach generated excitement and engagement that translated into high student satisfaction and enhanced learning.