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https://www.readbyqxmd.com/read/27926853/a-dynamical-threshold-for-cardiac-delayed-afterdepolarization-mediated-triggered-activity
#1
Michael B Liu, Christopher Y Ko, Zhen Song, Alan Garfinkel, James N Weiss, Zhilin Qu
Ventricular myocytes are excitable cells whose voltage threshold for action potential (AP) excitation is ∼-60 mV at which INa is activated to give rise to a fast upstroke. Therefore, for a short stimulus pulse to elicit an AP, a stronger stimulus is needed if the resting potential lies further away from the INa threshold, such as in hypokalemia. However, for an AP elicited by a long duration stimulus or a diastolic spontaneous calcium release, we observed that the stimulus needed was lower in hypokalemia than in normokalemia in both computer simulations and experiments of rabbit ventricular myocytes...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926840/calcium-dependent-structural-dynamics-of-a-spin-labeled-ryr-peptide-bound-to-calmodulin
#2
Cheng Her, Jesse E McCaffrey, David D Thomas, Christine B Karim
We have used chemical synthesis, electron paramagnetic resonance (EPR), and circular dichroism to detect and analyze the structural dynamics of a ryanodine receptor (RyR) peptide bound to calmodulin (CaM). The skeletal muscle calcium release channel RyR1 is activated by Ca(2+)-free CaM and inhibited by Ca(2+)-bound CaM. To probe the structural mechanism for this regulation, wild-type RyRp and four spin-labeled derivatives were synthesized, each containing the nitroxide probe 2,2,6,6-tetramethyl-piperidine-1-oxyl-4-amino-4-carboxylic acid substituted for a single amino acid...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27923697/layer-by-layer-nanoparticle-platform-for-cancer-active-targeting
#3
Min Sung Suh, Jie Shen, Liisa T Kuhn, Diane J Burgess
Nanoparticles as drug delivery carriers have been investigated over the last few decades, particularly for cancer treatment. The rationale in developing such nanoparticles is to maximize drug efficacy while minimizing toxic side effects. This can be most effectively achieved through target specific drug delivery. A novel biocompatible nanoparticle platform prepared using the core-shell self-assembly technique is reported. The core consists of calcium phosphate which is biocompatible and pH-sensitive, and the shell is composed of biocompatible polymers (hyaluronic acid, CD44 targeting moiety; and chitosan, physical cross-linker)...
December 3, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27920337/effect-of-epigallocatechin-3-gallate-on-acrylamide-induced-oxidative-stress-and-apoptosis-in-pc12-cells
#4
Y He, D Tan, Y Mi, B Bai, D Jiang, X Zhou, S Ji
Acrylamide (ACR) is a chemical intermediate utilized in industry. ACR is also formed during heating of foods containing carbohydrates and amino acids. Therefore, humans are widely exposed to ACR, and ACR neurotoxicity in humans is a significant public health issue attracting wide attention. In this study, we investigated the potential neuroprotective effects of epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic compound in green tea, in PC12 cells treated with ACR. ACR-treated PC12 cells pretreated with various concentrations of EGCG (2...
December 5, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27919911/in-vitro-activation-of-coagulation-by-human-neutrophil-dna-and-histone-proteins-but-not-neutrophil-extracellular-traps
#5
Denis F Noubouossie, Matthew F Whelihan, Yuan-Bin Yu, Erica Sparkenbaugh, Rafal Pawlinski, Dougald M Monroe, Nigel S Key
NETosis is a physiological process in which neutrophils release their nuclear material in the form of neutrophil extracellular traps (NETs). NETs have been reported to directly promote thrombosis in animal models. Although the effects of purified NET components including DNA, histone proteins and neutrophil enzymes on coagulation have been characterized, the mechanism by which intact NETs promote thrombosis is largely unknown. In this study, human neutrophils were stimulated to produce NETs in platelet-free plasma (PFP) or in buffer using PMA or calcium ionophore...
December 5, 2016: Blood
https://www.readbyqxmd.com/read/27919025/ip3-still-on-the-move-but-now-in-the-slow-lane
#6
REVIEW
Luc Leybaert
In this issue of Science Signaling, Dickinson et al show that the intracellular messenger inositol 1,4,5-trisphosphate (IP3), which triggers the release of calcium (Ca(2+)) from the endoplasmic reticulum, is a slowly diffusing local signal, rather than a rapidly diffusing global one. These findings have implications for the understanding of the mechanisms of Ca(2+) wave propagation, especially long-range, cell-to-cell propagating Ca(2+) waves.
November 8, 2016: Science Signaling
https://www.readbyqxmd.com/read/27916928/the-effect-of-lupinus-albus-and-calcium-chloride-on-growth-performance-body-composition-plasma-biochemistry-and-meat-quality-of-male-pigs-immunized-against-gonadotrophin-releasing-factor
#7
Karen Moore, Bruce Mullan, Jae Cheol Kim, Frank Dunshea
Two hundred and ninety-four pigs were used to assess the effect of two ingredients (Lupinus albus (albus lupins) or a combination of calcium chloride and sodium tri-polyphosphate (mineral salts)) on growth performance, body composition and objective meat quality of pigs immunized against gonadotrophin releasing factor (immunocastrates) and entire male pigs in the late finishing phase. Pigs fed mineral salts ate less feed than those fed the control diet with no effect on growth rate (p > 0.05), backfat (p > 0...
December 1, 2016: Animals: An Open Access Journal From MDPI
https://www.readbyqxmd.com/read/27914700/microvesicle-transfer-of-kinin-b1-receptors-is-a-novel-inflammatory-mechanism-in-vasculitis
#8
Robin Kahn, Maria Mossberg, Anne-Lie Ståhl, Karl Johansson, Ingrid Lopatko Lindman, Caroline Heijl, Mårten Segelmark, Matthias Mörgelin, L M Fredrik Leeb-Lundberg, Diana Karpman
During vasculitis, activation of the kinin system induces inflammation, whereby the kinin B1-receptor is expressed and activated after ligand binding. Additionally, activated blood cells release microvesicles into the circulation. Here we determined whether leukocyte-derived microvesicles bear B1-kinin receptors during vasculitis, and if microvesicles transfer functional B1-receptors to recipient cells, thus promoting inflammation. By flow cytometry, plasma from patients with vasculitis were found to contain high levels of leukocyte-derived microvesicles bearing B1-receptors...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27913210/trpv4-activation-of-endothelial-nitric-oxide-synthase-resists-nonalcoholic-fatty-liver-disease-by-blocking-cyp2e1-mediated-redox-toxicity
#9
Ratanesh K Seth, Suvarthi Das, Diptadip Dattaroy, Varun Chandrashekaran, Firas Alhasson, Gregory Michelotti, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Darwin P Bell, Wolfgang Liedtke, Saurabh Chatterjee
NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for effective treatment. NAFLD progression is strongly linked to a balance between liver injury, tissue regeneration and the functioning of endogenous defense mechanisms. The failure of the defense pathways to resist the tissue damage arising from redox stress, one of the "multiple hits" in disease progression, give rise to heightened inflammation and occasional fibrosis...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27912872/anti-allergic-potential-of-typhonium-blumei-inhibition-of-degranulation-via-suppression-of-pi3k-plc%C3%AE-2-phosphorylation-and-calcium-influx
#10
Michal Korinek, Kuan-Ming Chen, Yu-Han Jiang, Mohamed El-Shazly, Joel Stocker, Chon-Kit Chou, Tsong-Long Hwang, Yang-Chang Wu, Bing-Hung Chen, Fang-Rong Chang
BACKGROUND: Typhonium blumei Nicolson & Sivadasan (Araceae) is a traditional Chinese medicinal herb possessing detumescent, detoxifying, and anti-inflammatory activities. It is used in Taiwan as a folk medicine to treat cancer and inflammatory diseases. Typhonium blumei is usually not distinguished from Typhonium roxburghii Schott and they are commonly used interchangeably. PURPOSE: To evaluate and compare the anti-allergic and anti-inflammatory properties of T...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27911759/neurotransmitter-release-can-be-stabilized-by-a-mechanism-that-prevents-voltage-changes-near-the-end-of-action-potentials-from-affecting-calcium-currents
#11
Stephen G Clarke, Matthew S Scarnati, Kenneth G Paradiso
: At chemical synapses, presynaptic action potentials (APs) activate voltage-gated calcium channels, allowing calcium to enter and trigger neurotransmitter release. The duration, peak amplitude, and shape of the AP falling phase alter calcium entry, which can affect neurotransmitter release significantly. In many neurons, APs do not immediately return to the resting potential, but instead exhibit a period of depolarization or hyperpolarization referred to as an afterpotential. We hypothesized that presynaptic afterpotentials should alter neurotransmitter release by affecting the electrical driving force for calcium entry and calcium channel gating...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911331/excitation-contraction-coupling-alterations-in-myopathies
#12
Isabelle Marty, Julien Fauré
During the complex series of events leading to muscle contraction, the initial electric signal coming from motor neurons is transformed into an increase in calcium concentration that triggers sliding of myofibrils. This process, referred to as excitation-contraction coupling, is reliant upon the calcium-release complex, which is restricted spatially to a sub-compartment of muscle cells ("the triad") and regulated precisely. Any dysfunction in the calcium-release complex leads to muscle impairment and myopathy...
November 29, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#13
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906053/attenuated-ca-2-release-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2a
#14
Marino DiFranco, Irina Kramerova, Julio L Vergara, Melissa Jan Spencer
BACKGROUND: Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 knockout (C3KO) mice) leads to reduced ryanodine receptor (RyR1) expression and abnormal Ca2+/calmodulin-dependent protein kinase II (Ca-CaMKII)-mediated signaling. We previously reported that Ca(2+) release measured by fura2-FF imaging in response to single action potential stimulation was reduced in old C3KO mice; however, the use of field stimulation prevented investigation of the mechanisms underlying this impairment...
February 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906050/the-sh3-and-cysteine-rich-domain-3-stac3-gene-is-important-to-growth-fiber-composition-and-calcium-release-from-the-sarcoplasmic-reticulum-in-postnatal-skeletal-muscle
#15
Xiaofei Cong, Jonathan Doering, Davi A G Mazala, Eva R Chin, Robert W Grange, Honglin Jiang
BACKGROUND: The SH3 and cysteine-rich domain 3 (Stac3) gene is specifically expressed in the skeletal muscle. Stac3 knockout mice die perinatally. In this study, we determined the potential role of Stac3 in postnatal skeletal muscle growth, fiber composition, and contraction by generating conditional Stac3 knockout mice. METHODS: We disrupted the Stac3 gene in 4-week-old male mice using the Flp-FRT and tamoxifen-inducible Cre-loxP systems. RESULTS: RT-qPCR and western blotting analyses of the limb muscles of target mice indicated that nearly all Stac3 mRNA and more than 70 % of STAC3 protein were deleted 4 weeks after tamoxifen injection...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905548/neurexin-regulates-nighttime-sleep-by-modulating-synaptic-transmission
#16
Huawei Tong, Qian Li, Zi Chao Zhang, Yi Li, Junhai Han
Neurexins are cell adhesion molecules involved in synaptic formation and synaptic transmission. Mutations in neurexin genes are linked to autism spectrum disorders (ASDs), which are frequently associated with sleep problems. However, the role of neurexin-mediated synaptic transmission in sleep regulation is unclear. Here, we show that lack of the Drosophila α-neurexin homolog significantly reduces the quantity and quality of nighttime sleep and impairs sleep homeostasis. We report that neurexin expression in Drosophila mushroom body (MB) αβ neurons is essential for nighttime sleep...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903742/p2y6-receptor-antagonist-mrs2578-inhibits-neutrophil-activation-and-aggregated-neutrophil-extracellular-trap-formation-induced-by-gout-associated-monosodium-urate-crystals
#17
Payel Sil, Craig P Hayes, Barbara J Reaves, Patrick Breen, Shannon Quinn, Jeremy Sokolove, Balázs Rada
Human neutrophils (polymorphonuclear leukocytes [PMNs]) generate inflammatory responses within the joints of gout patients upon encountering monosodium urate (MSU) crystals. Neutrophil extracellular traps (NETs) are found abundantly in the synovial fluid of gout patients. The detailed mechanism of MSU crystal-induced NET formation remains unknown. Our goal was to shed light on possible roles of purinergic signaling and neutrophil migration in mediating NET formation induced by MSU crystals. Interaction of human neutrophils with MSU crystals was evaluated by high-throughput live imaging using confocal microscopy...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27901382/assessment-of-in-vitro-release-of-carboplatin-from-six-carrier-media
#18
Marije Risselada, Denis J Marcellin-Little, Kristen M Messenger, Emily Griffith, Gigi S Davidson, Mark G Papich
OBJECTIVE To investigate in vitro carboplatin release from 6 carrier media. SAMPLE 6 carboplatin-containing carrier media. PROCEDURES An in vitro release study was performed with 6 commercially available carrier media: a hemostatic gelatin sponge, a poloxamer copolymer gel, and 2 sizes (3 and 4.8 mm in diameter) of beads molded from each of 2 commercial calcium sulfate products. All carrier media contained 10 mg of carboplatin. Carrier media specimens were placed in 37°C PBS solution for 96 hours. Carboplatin concentrations in PBS solution were measured by use of high-performance liquid chromatography at 15 time points to calculate the amount and proportion of carboplatin released from each specimen...
December 2016: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/27896815/how-and-why-are-calcium-currents-curtailed-in-the-skeletal-muscle-voltage-gated-calcium-channels
#19
Bernhard E Flucher, Petronel Tuluc
Voltage-gated calcium channels represent the sole mechanism converting electrical signals of excitable cells into cellular functions such as contraction, secretion, and gene regulation. Specific voltage-sensing domains detect changes in membrane potentials and control channel gating. Calcium ions entering through the channel function as second messengers regulating cell functions; with the exception of skeletal muscle, where CaV 1.1 is essentially not functioning as channel but activates calcium release from intracellular stores...
November 29, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27896810/multiple-pathways-for-elevating-extracellular-adenosine-in-the-rat-hippocampal-ca1-region-characterized-by-adenosine-sensor-cells
#20
Kunihiko Yamashiro, Yuki Fujii, Shohei Maekawa, Mitsuhiro Morita
Extracellular adenosine in the brain, which modulates various physiological and pathological processes, fluctuates in a complicated manner that reflects the circadian cycle, neuronal activity, metabolism, and disease states. The dynamics of extracellular adenosine in the brain are not fully understood, largely because of the lack of simple and reliable methods of measuring time-dependent changes in tissue adenosine distribution. This study describes the development of a biosensor, designated an adenosine sensor cell, expressing adenosine A1 receptor, and a genetically modified G protein...
November 5, 2016: Journal of Neurochemistry
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