Open Access. Powered by Scholars. Published by Universities.®

Physical Sciences and Mathematics Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 9 of 9

Full-Text Articles in Physical Sciences and Mathematics

Restoration Of Frequency-Dependent Depression Of The H-Reflex By Passive Exercise In Spinal Rats, N. B. Reese, R. D. Skinner, D. Mitchell, C. C. Yates, Christina B. Cooley, T. S. Kiser, E. E. García-Rill Jun 2019

Restoration Of Frequency-Dependent Depression Of The H-Reflex By Passive Exercise In Spinal Rats, N. B. Reese, R. D. Skinner, D. Mitchell, C. C. Yates, Christina B. Cooley, T. S. Kiser, E. E. García-Rill

Christina B Cooley

Hyper-reflexia, measured as a decrease of low frequency-dependent depression of the H-reflex, is known to occur in both humans and animals after spinal cord injury (SCI). Previous studies have shown that passive exercise for 3 months could be used to restore low frequency-dependent depression of the H-reflex after SCI. To determine the effects of various periods of time on the ability of passive exercise to restore low frequency-dependent depression of the H-reflex. Spinal Cord Injury Mobilization Program of the Center for Translational Neuroscience, the research arm of the Jackson T Stephens Spine and Neuroscience Institute, Little Rock, AR, USA. Adult …


Unfolded Protein Response Activation Reduces Secretion And Extracellular Aggregation Of Amyloidogenic Immunoglobulin Light Chain, Christina B. Cooley, L. M. Ryno, L. Plate, G. J. Morgan, J. D. Hulleman, J. W. Kelly, R. L. Wiseman Jun 2019

Unfolded Protein Response Activation Reduces Secretion And Extracellular Aggregation Of Amyloidogenic Immunoglobulin Light Chain, Christina B. Cooley, L. M. Ryno, L. Plate, G. J. Morgan, J. D. Hulleman, J. W. Kelly, R. L. Wiseman

Christina B Cooley

Light-chain amyloidosis (AL) is a degenerative disease characterized by the extracellular aggregation of a destabilized amyloidogenic Ig light chain (LC) secreted from a clonally expanded plasma cell. Current treatments for AL revolve around ablating the cancer plasma cell population using chemotherapy regimens. Unfortunately, this approach is limited to the ∼70% of patients who do not exhibit significant organ proteotoxicity and can tolerate chemotherapy. Thus, identifying new therapeutic strategies to alleviate LC organ proteotoxicity should allow AL patients with significant cardiac and/or renal involvement to subsequently tolerate established chemotherapy treatments. Using a small-molecule screening approach, the unfolded protein response (UPR) was …


Small Molecule Proteostasis Regulators That Reprogram The Er To Reduce Extracellular Protein Aggregation, L. Plate, Christina B. Cooley, J. J. Chen, R. J. Paxman, C. M. Gallagher, F. Madoux, J. C. Genereux, W. Dobbs, D. Garza, T. P. Spicer, L. Scampavia, S. J. Brown, H. Rosen, E. T. Powers, P. Hodder, R. L. Wiseman, J. W. Kelly Jun 2019

Small Molecule Proteostasis Regulators That Reprogram The Er To Reduce Extracellular Protein Aggregation, L. Plate, Christina B. Cooley, J. J. Chen, R. J. Paxman, C. M. Gallagher, F. Madoux, J. C. Genereux, W. Dobbs, D. Garza, T. P. Spicer, L. Scampavia, S. J. Brown, H. Rosen, E. T. Powers, P. Hodder, R. L. Wiseman, J. W. Kelly

Christina B Cooley

Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy …


Beyond Cell Penetrating Peptides: Designed Molecular Transporters, P. A. Wender, Christina B. Cooley, E. I. Geihe Jun 2019

Beyond Cell Penetrating Peptides: Designed Molecular Transporters, P. A. Wender, Christina B. Cooley, E. I. Geihe

Christina B Cooley

Inspired originally by peptides that traverse biological barriers, research on molecular transporters has since identified the key structural requirements that govern cellular entry, leading to new, significantly more effective and more readily available agents. These new drug delivery systems enable or enhance cellular and tissue uptake, can be targeted and provide numerous additional advantages of significance in imaging, diagnostics and therapy.


Broadly Applicable Methodology For The Rapid And Dosable Small Molecule-Mediated Regulation Of Transcription Factors In Human Cells, M. D. Shoulders, L. M. Ryno, Christina B. Cooley, J. W. Kelly, R. L. Wiseman Jun 2019

Broadly Applicable Methodology For The Rapid And Dosable Small Molecule-Mediated Regulation Of Transcription Factors In Human Cells, M. D. Shoulders, L. M. Ryno, Christina B. Cooley, J. W. Kelly, R. L. Wiseman

Christina B Cooley

Direct and selective small molecule control of transcription factor activity is an appealing avenue for elucidating the cell biology mediated by transcriptional programs. However, pharmacologic tools to modulate transcription factor activity are scarce because transcription factors are not readily amenable to small molecule-mediated regulation. Moreover, existing genetic approaches to regulate transcription factors often lead to high nonphysiologic levels of transcriptional activation that significantly impair our ability to understand the functional implications of transcription factor activity. Herein, we demonstrate that small molecule-mediated conformational control of protein degradation is a generally applicable, chemical biological methodology to obtain small molecule-regulated transcription factors that …


Fluorogenic Atom Transfer Radical Polymerization In Aqueous Media As A Strategy For Detection, Zachary T. Allen, Jemima R. Sackey-Addo, Madeline P. Hopps, Danyal Tahseen, Joseph T. Anderson, Tyler A. Graf, Christina B. Cooley Jun 2019

Fluorogenic Atom Transfer Radical Polymerization In Aqueous Media As A Strategy For Detection, Zachary T. Allen, Jemima R. Sackey-Addo, Madeline P. Hopps, Danyal Tahseen, Joseph T. Anderson, Tyler A. Graf, Christina B. Cooley

Christina B Cooley

The development of novel approaches to signal amplification in aqueous media could enable new diagnostic platforms for the detection of water-soluble analytes, including biomolecules. This paper describes a fluorogenic polymerization approach to amplify initiator signal by the detection of visible fluorescence upon polymerization in real-time. Fluorogenic monomers were synthesized and co-polymerized by atom transfer radical polymerization (ATRP) in water to reveal increasing polymer fluorescence as a function of both reaction time and initiator concentration. Optimization of the fluorogenic ATRP reaction conditions allowed for the quantitative detection of a small-molecule initiator as a model analyte over a broad linear concentration range …


Designed Guanidinium-Rich Amphipathic Oligocarbonate Molecular Transporters Complex, Deliver And Release Sirna In Cells, E. I. Geihe, Christina B. Cooley, J. R. Simon, M. K. Kiesewetter, J. A. Edward, R. P. Hickerson, R. L. Kaspar, J. L. Hedrick, R. M. Waymouth, P. A. Wender Jun 2019

Designed Guanidinium-Rich Amphipathic Oligocarbonate Molecular Transporters Complex, Deliver And Release Sirna In Cells, E. I. Geihe, Christina B. Cooley, J. R. Simon, M. K. Kiesewetter, J. A. Edward, R. P. Hickerson, R. L. Kaspar, J. L. Hedrick, R. M. Waymouth, P. A. Wender

Christina B Cooley

The polyanionic nature of oligonucleotides and their enzymatic degradation present challenges for the use of siRNA in research and therapy; among the most notable of these is clinically relevant delivery into cells. To address this problem, we designed and synthesized the first members of a new class of guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver, and release siRNA in cells, resulting in robust knockdown of target protein synthesis in vitro as determined using a dual-reporter system. The organocatalytic oligomerization used to synthesize these co-oligomers is step-economical and broadly tunable, affording an exceptionally quick strategy to explore chemical space for optimal …


Oligocarbonate Molecular Transporters: Oligomerization-Based Syntheses And Cell-Penetrating Studies, Christina B. Cooley, B. M. Trantow, F. Nederberg, M. K. Kiesewetter, J. L. Hedrick, R. M. Waymouth, P. A. Wender Jun 2019

Oligocarbonate Molecular Transporters: Oligomerization-Based Syntheses And Cell-Penetrating Studies, Christina B. Cooley, B. M. Trantow, F. Nederberg, M. K. Kiesewetter, J. L. Hedrick, R. M. Waymouth, P. A. Wender

Christina B Cooley

A new family of guanidinium-rich molecular transporters featuring a novel oligocarbonate backbone with 1,7-side chain spacing is described. Conjugates can be rapidly assembled irrespective of length in a one-step oligomerization strategy that can proceed with concomitant introduction of probes (or by analogy drugs). The new transporters exhibit excellent cellular entry as determined by flow cytometry and fluorescence microscopy, and the functionality of their drug delivery capabilities was confirmed by the delivery of the bioluminescent small molecule probe luciferin and turnover by its intracellular target enzyme.


Developmental Changes In Pedunculopontine Nucleus (Ppn) Neurons, T. Kobayashi, C. Good, J. Biedermann, Christina B. Cooley, R. D. Skinner, E. E. García-Rill Jun 2019

Developmental Changes In Pedunculopontine Nucleus (Ppn) Neurons, T. Kobayashi, C. Good, J. Biedermann, Christina B. Cooley, R. D. Skinner, E. E. García-Rill

Christina B Cooley

The developmental decrease in rapid-eye-movement (REM) sleep in man occurs between birth and after puberty. We hypothesize that if this decrease in REM sleep does not occur, lifelong increases in REM sleep drive may ensue. Such disorders are characterized by hypervigilance and sensory-gating deficits, such as are present in postpubertal onset disorders like schizophrenia, panic attacks (a form of anxiety disorder), and depression. The decrease in REM sleep in the rat occurs between 10 and 30 days of age. We studied changes in size and physiological properties of pedunculopontine nucleus (PPN) cells involved in the control of arousal, i.e., waking …