Life Sciences Commons^™

Interactions Between Connected Half-Sarcomeres Produce Emergent Mechanical Behavior In A Mathematical Model Of Muscle, Kenneth S. Campbell

Physiology Faculty Publications

Most reductionist theories of muscle attribute a fiber's mechanical properties to the scaled behavior of a single half-sarcomere. Mathematical models of this type can explain many of the known mechanical properties of muscle but have to incorporate a passive mechanical component that becomes approximately 300% stiffer in activating conditions to reproduce the force response elicited by stretching a fast mammalian muscle fiber. The available experimental data suggests that titin filaments, which are the mostly likely source of the passive component, become at most approximately 30% stiffer in saturating Ca2+ solutions. The work described in this manuscript used computer modeling to …

Expression Of Sorl1 And A Novel Sorl1 Splice Variant In Normal And Alzheimers Disease Brain, Karrie E. Grear, I-Fang Ling, James F. Simpson, Jennifer L. Furman, Christopher R. Simmons, Shawn L. Peterson, Frederick A. Schmitt, William R. Markesbery, Qiang Liu, Julia E. Crook, Steven G. Younkin, Guojun Bu, Steven Estus

Physiology Faculty Publications

BACKGROUND: Variations in sortilin-related receptor (SORL1) expression and function have been implicated in Alzheimers Disease (AD). Here, to gain insights into SORL1, we evaluated SORL1 expression and splicing as a function of AD and AD neuropathology, neural gene expression and a candidate single nucleotide polymorphism (SNP).

RESULTS: To identify SORL1 splice variants, we scanned each of the 46 internal SORL1 exons in human brain RNA samples and readily found SORL1 isoforms that lack exon 2 or exon 19. Quantification in a case-control series of the more abundant isoform lacking exon 2 (delta-2-SORL1), as well as the "full-length" SORL1 (FL-SORL1) isoform …

Tumor Necrosis Factor-Alpha (Tnf-Α) Enhances Functional Thermal And Chemical Responses Of Trp Cation Channels In Human Synoviocytes, Mikhail Y. Kochukov, Terry A. Mcnearney, Huaizhi Yin, Liping Zhang, Fei Ma, Larissa Ponomareva, Sarah Abshire, Karin N. Westlund

Physiology Faculty Publications

Background: We have shown functional expression of several TRP channels on human synovial cells, proposing significance in known calcium dependent proliferative and secretory responses in joint inflammation. The present study further characterizes synoviocyte TRP expression and activation responses to thermal and osmotic stimuli after pre-treatment with proinflammatory mediator tumor necrosis factor alpha (TNF-α, EC50 1.3221 x 10^-10 g/L).

Results: Fluorescent imaging of Fura-2 loaded human SW982 synoviocytes reveals immediate and delayed cytosolic calcium oscillations elicited by (1) TRPV1 agonists capsaicin and resiniferatoxin (20-40% of cells), (2) moderate and noxious temperature change, and (3) osmotic stress TRPV4 activation (11.5% of …

Passive Limb Movement Augments Ventilatory Response To Co2 Via Sciatic Inputs In Anesthetized Rats, Jianguo Zhuang, Fadi Xu, Cancan Zhang, Donald T. Frazier

Physiology Faculty Publications

Passive limb movement (PLM) in humans induces a phasic hyperpnea, but the underlying physiological mechanisms remain unclear. We asked whether PLM in anesthetized rats would produce a similar phasic hyperpnea associated with an augmented ventilatory (V̇_E) response to CO₂ that is dependent on sciatic afferents. The animals underwent 5 min threshold PLM, 3 min hypercapnia (5% CO₂), and their combination (CO₂ exposure at the end of 2^nd min of 5-min PLM) before and after bilateral transection of the sciatic nerves. We found that a threshold PLM evoked a phasic hyperpnea, similar to …

Reactive Oxygen Species Mediate Tnfr1 Increase After Trpv1 Activation In Mouse Drg Neurons, Fei Ma, Liping Zhang, Karin N. Westlund

Physiology Faculty Publications

Background: Transient receptor potential vanilloid subtype 1 (TRPV1) is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor α (TNF-α), a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1) activation. Reactive oxygen species (ROS) production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG) neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and …

Lrp1 Shedding In Human Brain: Roles Of Adam10 And Adam17, Qiang Liu, Juan Zhang, Hien Tran, Marcel M. Verbeek, Karina Reiss, Steven Estus, Guojun Bu

Physiology Faculty Publications

BACKGROUND: The low-density lipoprotein receptor-related protein 1 (LRP1) plays critical roles in lipid metabolism, cell survival, and the clearance of amyloid-beta (Abeta) peptide. Functional soluble LRP1 (sLRP1) has been detected in circulating human placenta; however, whether sLRP1 is also present in the central nervous system is unclear.

RESULTS: Here we show that abundant sLRP1 capable of binding its ligands is present in human brain tissue and cerebral spinal fluid (CSF). Interestingly, the levels of sLRP1 in CSF are significantly increased in older individuals, suggesting that either LRP1 shedding is increased or sLRP1 clearance is decreased during aging. To examine potential …