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Search Results for all work with filters:

  • Engineering, Biomedical

Work 1-10 of 1969

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Article

Endothelial Dysfunction, Arterial Stiffening, and Intima-Media Thickening in Large Arteries from HIV-1 Transgenic Mice

by Laura Hansen; Ivana Parker; Roy Sutliff; Manu Omar Platt; Rudolph L. Gleason, Jr.

2013

Subjects
  • Engineering, Biomedical
  • Health Sciences, Medicine and Surgery
  • File Download
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Abstract:Close

HIV patients on highly active antiretroviral therapy (HAART) exhibit elevated incidence of cardiovascular disease (CVD), including a higher risk of myocardial infarction and prevalence of atherosclerotic lesions, as well as increases in markers of subclinical atherosclerosis including increased carotid artery intima-media thickness (c-IMT), increased arterial stiffness, and impaired flow-mediated dilation. Both HAART and HIV-infection are independent risk factors for atherosclerosis and myocardial infarction. Studies implicate the HIV proteins tat, gp120, vpu, and nef in early on-set atherosclerosis. The objective of this study was to quantify the role of expression of HIV-1 proteins on the vascular function, biomechanics, and geometry of common carotid arteries and aortas. This study employed NL4-3Δ gag/pol transgenic mice (HIV-Tg), which contain the genetic sequence for the HIV-1 proteins env, tat, nef, rev, vif, vpr, and vpu but lacks the gag and pol genes and reports that HIV-Tg mice have impaired aortic endothelial function, increased c-IMT, and increased arterial stiffness. Further, HIV-Tg arteries show decreased elastin content, increased cathepsin K and cathepsin S activity, and increased mechanical residual stress. Thus, mice that express HIV proteins exhibit pre-clinical markers of atherosclerosis and these markers correlate with changes in markers of vascular remodeling. These findings are consistent with the hypothesis that HIV-proteins, independent of HAART treatment or HIV infection, could play a role in of the development of CVD.

Article

Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle

by Asha Shekaran; Jose R. Garcia; Amy Y. Clark; Taylor E. Kavanaugh; Angela S. Lin; Robert E. Guldberg; Andres J. Garcia

2014

Subjects
  • Engineering, Biomedical
  • File Download
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Abstract:Close

Non-healing bone defects present tremendous socioeconomic costs. Although successful in some clinical settings, bone morphogenetic protein (BMP) therapies require supraphysiological dose delivery for bone repair, raising treatment costs and risks of complications. We engineered a protease-degradable poly(ethylene glycol) (PEG) synthetic hydrogel functionalized with a triple helical, α2β1 integrin-specific peptide (GFOGER) as a BMP-2 delivery vehicle. GFOGER-functionalized hydrogels lacking BMP-2 directed human stem cell differentiation and produced significant enhancements in bone repair within a critical-sized bone defect compared to RGD hydrogels or empty defects. GFOGER functionalization was crucial to the BMP-2-dependent healing response. Importantly, these engineered hydrogels outperformed the current clinical carrier in repairing non-healing bone defects at low BMP-2 doses. GFOGER hydrogels provided sustained invivo release of encapsulated BMP-2, increased osteoprogenitor localization in the defect site, enhanced bone formation and induced defect bridging and mechanically robust healing at low BMP-2 doses which stimulated almost no bone regeneration when delivered from collagen sponges. These findings demonstrate that GFOGER hydrogels promote bone regeneration in challenging defects with low delivered BMP-2 doses and represent an effective delivery vehicle for protein therapeutics with translational potential.

Article

Self-regenerating giant hyaluronan polymer brushes

by Wenbin Wei; Jessica L. Faubel; Hemaa Selvakumar; Daniel T. Kovari; Joanna Tsao; Felipe Rivas; Amar T. Mohabir; Michelle Krecker; Elaheh Rahbar; Adam R. Hall; Michael A. Filler; Jennifer L. Washburn; Paul H. Weigel; Jennifer Curtis

2019

Subjects
  • Engineering, Biomedical
  • Physics, General
  • Chemistry, Biochemistry
  • File Download
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Tailoring interfaces with polymer brushes is a commonly used strategy to create functional materials for numerous applications. Existing methods are limited in brush thickness, the ability to generate high-density brushes of biopolymers, and the potential for regeneration. Here we introduce a scheme to synthesize ultra-thick regenerating hyaluronan polymer brushes using hyaluronan synthase. The platform provides a dynamic interface with tunable brush heights that extend up to 20 microns – two orders of magnitude thicker than standard brushes. The brushes are easily sculpted into micropatterned landscapes by photo-deactivation of the enzyme. Further, they provide a continuous source of megadalton hyaluronan or they can be covalently-stabilized to the surface. Stabilized brushes exhibit superb resistance to biofilms, yet are locally digested by fibroblasts. This brush technology provides opportunities in a range of arenas including regenerating tailorable biointerfaces for implants, wound healing or lubrication as well as fundamental studies of the glycocalyx and polymer physics.

Article

Art for Reward's Sake: Visual Art Recruits the Ventral Striatum

by Simon A Lacey; Henrik Hagtvedt; Vanessa M. Patrick; Amy Anderson; Randall Stilla; Gopikrishna Deshpande; Xiaoping P Hu; João R. Sato; Srinivas Reddy; Krish Sathian

2011

Subjects
  • Engineering, Biomedical
  • Mathematics
  • Biology, Neuroscience
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A recent study showed that people evaluate products more positively when they are physically associated with art images than similar non-art images. Neuroimaging studies of visual art have investigated artistic style and esthetic preference but not brain responses attributable specifically to the artistic status of images. Here we tested the hypothesis that the artistic status of images engages reward circuitry, using event-related functional magnetic resonance imaging (fMRI) during viewing of art and non-art images matched for content. Subjects made animacy judgments in response to each image. Relative to non-art images, art images activated, on both subject- and item-wise analyses, reward-related regions: the ventral striatum, hypothalamus and orbitofrontal cortex. Neither response times nor ratings of familiarity or esthetic preference for art images correlated significantly with activity that was selective for art images, suggesting that these variables were not responsible for the art-selective activations. Investigation of effective connectivity, using time-varying, wavelet-based, correlation-purged Granger causality analyses, further showed that the ventral striatum was driven by visual cortical regions when viewing art images but not non-art images, and was not driven by regions that correlated with esthetic preference for either art or non -art images. These findings are consistent with our hypothesis, leading us to propose that the appeal of visual art involves activation of reward circuitry based on artistic status alone and independently of its hedonic value.

Article

Mechanically Induced Catalytic Amplification Reaction for Readout of Receptor-Mediated Cellular Forces

by Victor Pui-Yan Ma; Yang Liu; Dr. Kevin Yehl; Kornelia Galior; Yun Zhang; Khalid Salaita

2016

Subjects
  • Chemistry, General
  • Engineering, Biomedical
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Mechanics play a fundamental role in cell biology, but detecting piconewton (pN) forces is challenging because of a lack of accessible and high throughput assays. A mechanically induced catalytic amplification reaction (MCR) for readout of receptor-mediated forces in cells is described. Mechanically labile DNA duplexes presenting ligands are surface immobilized such that specific receptor forces denature the duplex and thus expose a blocked primer. Amplification of primers is achieved using an isothermal polymerization reaction and quantified by fluorescence readout. As a proof of concept, the assay was used to test the activity of a mechanomodulatory drug and integrin adhesion receptor antibodies. To the best of our knowledge, this is the first example of a catalytic reaction triggered in response to molecular piconewton forces. The MCR may transform the field of mechanobiology by providing a new facile tool to detect receptor specific mechanics with the convenience of the polymerase chain reaction (PCR).

Article

Twitchin kinase inhibits muscle activity

by Yohei Matsunaga; Hyundoo Hwang; Barbara Franke; Rhys Williams; McKenna Penley; Hiroshi Qadota; Hong Yi; Levi Morran; Hang Lu; Olga Mayans; Guy Benian

2017

Subjects
  • Health Sciences, Pathology
  • Engineering, Biomedical
  • Biology, Physiology
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© 2017 Matsunaga et al. Muscle sarcomeres contain giant polypeptides composed of multiple immunoglobulin and fibronectin domains and one or two protein kinase domains. Although binding partners for a number of this family's kinase domains have been identified, the catalytic necessity of these kinase domains remains unknown. In addition, various members of this kinase family are suspected pseudokinases with no or little activity. Here we address catalytic necessity for the first time, using the prototypic invertebrate representative twitchin (UNC-22) from Caenorhabditis elegans. In in vitro experiments, change of a conserved lysine (K) that is involved in ATP coordination to alanine (A) resulted in elimination of kinase activity without affecting the overall structure of the kinase domain. The same mutation, unc-22(sf21), was generated in the endogenous twitchin gene. The unc-22(sf21) worms have well-organized sarcomeres. However, unc-22(sf21) mutants move faster than wild-type worms and, by optogenetic experiments, contract more. Wild-type nematodes exhibited greater competitive fitness than unc-22(sf21) mutants. Thus the catalytic activity of twitchin kinase has a role in vivo, where it inhibits muscle activity and is likely maintained by selection.

Article

Smartphone app for non-invasive detection of anemia using only patient-sourced photos

by Robert G. Mannino; David R Myers; Erika A. Tyburski; Christina Caruso; Jeanne Boudreaux; Traci Leong; Gari D. Clifford; Wilbur Lam

2018

Subjects
  • Engineering, Biomedical
  • Biology, Biostatistics
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We introduce a paradigm of completely non-invasive, on-demand diagnostics that may replace common blood-based laboratory tests using only a smartphone app and photos. We initially targeted anemia, a blood condition characterized by low blood hemoglobin levels that afflicts >2 billion people. Our app estimates hemoglobin levels by analyzing color and metadata of fingernail bed smartphone photos and detects anemia (hemoglobin levels <12.5 g dL−1) with an accuracy of ±2.4 g dL−1 and a sensitivity of 97% (95% CI, 89–100%) when compared with CBC hemoglobin levels (n = 100 subjects), indicating its viability to serve as a non-invasive anemia screening tool. Moreover, with personalized calibration, this system achieves an accuracy of ±0.92 g dL−1 of CBC hemoglobin levels (n = 16), empowering chronic anemia patients to serially monitor their hemoglobin levels instantaneously and remotely. Our on-demand system enables anyone with a smartphone to download an app and immediately detect anemia anywhere and anytime.

Article

Covarying ionic conductances to emulate phase maintenance in stomatogastric neurons

by Wafa Soofi; Astrid A Prinz

2010

Subjects
  • Biology, General
  • Engineering, Biomedical
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Neuronal networks produce reliable functional output throughout the lifespan of an animal despite ceaseless molecular turnover and a constantly changing environment. Central pattern generators, such as that of the crustacean stomatogastric ganglion (STG), robustly maintain their functionality over a wide range of burst periods [1]. Extracellular recordings of the LP neuron of the STG have demonstrated that as the burst period varies over time, the interspike intervals change proportionally, so that the spike phases are relatively invariant.

Article

VEGF-A regulates angiogenesis during osseointegration of Ti implants via paracrine/autocrine regulation of osteoblast response to hierarchical microstructure of the surface

by Andrew L Raines; Michael B Berger; Nehal Patel; Sharon L Hyzy; Barbara Boyan; Zvi Schwartz

2019

Subjects
  • Engineering, Biomedical
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Establishment of a patent vasculature at the bone–implant interface plays a significant role in determining overall success of orthopedic and dental implants. Osteoblasts produce vascular endothelial growth factor-A (VEGF-A), an important regulator of angiogenesis during bone formation and healing, and the amount secreted is sensitive to titanium (Ti) surface microtopography and surface energy. The purpose of this study was to determine if surface properties modulate cellular response to VEGF-A. MG63 osteoblast-like cells were transfected with shRNA targeting VEGF-A at >80% knockdown. Cells stably silenced for VEGF-A secreted reduced levels of osteocalcin, osteoprotegerin, FGF-2, and angiopoietin-1 when cultured on grit-blasted/acid-etched (SLA) and hydrophilic SLA (modSLA) Ti surfaces and conditioned media from these cultures caused reduced angiogenesis in an endothelial tubule formation assay. Treatment of MG63 cells with 20 ng/mL rhVEGF-A165 rescued production in silenced cells and increased production of osteocalcin, osteoprotegerin, FGF-2, and angiopoietin-1, with greatest effects on control cells cultured on modSLA. Addition of a neutralization antibody against VEGF receptor 2 (VEGFR2; Flk-1) resulted in a significant increase in VEGF-A production. Overall, this study indicates that VEGF-A has two roles in osseointegration: enhanced angiogenesis and an autocrine/paracrine role in maturation of osteoblast-like cells in response to Ti surface properties. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 423–433, 2019.

Article

17Beta-Estradiol Promotes Aggressive Laryngeal Cancer Through Membrane-Associated Estrogen Receptor-Alpha 36

by Nofrat Schwartz; Reyhaan A Chaudhri; Agreen Hadadi; Zvi Schwartz; Barbara Boyan

2014

Subjects
  • Health Sciences, Oncology
  • Engineering, Biomedical
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17β-estradiol (E2) plays a key role in tumorigenesis by enhancing cell survivability and metastasis through its cytoplasmic receptors. Recently, a variant of estrogen receptor alpha, ERα36 has been implicated as a substantial mediator of E2's proliferative and antiapoptotic effects through rapid membrane-associated signaling, and cancers previously regarded as hormone-independent due to the absence of traditional receptors, may in fact be susceptible to E2. Despite rising from a secondary sex organ and having a clear gender disposition, laryngeal cancer is not uniformly accepted as hormone dependent, even in the face of compelling evidence of E2 responsiveness. The aim of this study was to further elucidate the role of E2 in the tumorigenesis of laryngeal cancer, both in vitro and in vivo. ERα36 presence was evaluated in membranes of the laryngeal carcinoma cell line, Hep2, as well as in laryngeal tumor samples. In vitro ERα36 was found to mediate rapid activation of protein kinase C and phospholipase D by E2, leading to increased proliferation and protection against chemotherapy-induced apoptosis. Furthermore, in response to E2 activation of ERα36, an upregulation of angiogenic and metastatic factors was observed. Clinical analysis of laryngeal tumors revealed a similar association between the amount of ERα36 and VEGF and indicated a role in lymph node metastasis. These findings present compelling evidence of ERα36-dependent E2 signaling in laryngeal cancer. Thus, targeting ERα36 may reduce the deleterious effects of E2 in laryngeal cancer, ultimately suggesting the importance of antiestrogen therapy or the production of novel drugs that specifically target ERα36. © 2013 Springer Science+Business Media New York.
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