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https://www.readbyqxmd.com/read/28525756/immunization-elicited-broadly-protective-antibody-reveals-ebolavirus-fusion-loop-as-a-site-of-vulnerability
#1
Xuelian Zhao, Katie A Howell, Shihua He, Jennifer M Brannan, Anna Z Wec, Edgar Davidson, Hannah L Turner, Chi-I Chiang, Lin Lei, J Maximilian Fels, Hong Vu, Sergey Shulenin, Ashley N Turonis, Ana I Kuehne, Guodong Liu, Mi Ta, Yimeng Wang, Christopher Sundling, Yongli Xiao, Jennifer S Spence, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, Kartik Chandran, John M Dye, Xiangguo Qiu, Yuxing Li, M Javad Aman
While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28522805/nitric-oxide-donor-protects-against-acetic-acid-induced-gastric-ulcer-in-rats-via-s-nitrosylation-of-trpv1-on-vagus-nerve
#2
Ting Han, Yan Tang, Jing Li, Bing Xue, Liping Gong, Jingxin Li, Xiao Yu, Chuanyong Liu
This study was conducted to investigate the effects of nitric oxide (NO) in acetic acid-induced gastric ulcer of rats and the underlying mechanisms. We found that peritoneal injection of sodium nitroprusside (SNP), a NO donor, decreased the ulcer area, inflammatory cell infiltration and MPO degree in acetic acid-induced gastric ulcer in rats. This effect was abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist or prior subdiaphragmatic vagotomy. SNP increased the jejunal mesenteric afferent discharge in a dose-depended manner, which was largely diminished by pretreatment of S-nitrosylation blocker N-ethylmaleimide, TRPV1 antagonist capsazepine, genetic deletion of TRPV1, or vagotomy...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28516122/two-electrode-voltage-clamp-recordings-in-xenopus-laevis-oocytes-reconstitution-of-abscisic-acid-activation-of-slac1-anion-channel-via-pyl9-aba-receptor
#3
Cun Wang, Jingbo Zhang, Julian I Schroeder
Two-Electrode Voltage-Clamp (TEVC) recording in Xenopus laevis oocytes provides a powerful method to investigate the functions and regulation of ion channel proteins. This approach provides a well-known tool to characterize ion channels or transporters expressed in Xenopus laevis oocytes. The plasma membrane of the oocyte is impaled by two microelectrodes, one for voltage sensing and the other one for current injection. Here we list a protocol that allows robust reconstitution of multi-component signaling pathways...
January 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28514017/isopimaric-acid-a-multi-targeting-ion-channel-modulator-reducing-excitability-and-arrhythmicity-in-a-spontaneously-beating-mouse-atrial-cell-line
#4
Sajjad Salari, Malin Silverå Ejneby, Johan Brask, Fredrik Elinder
AIM: Atrial fibrillation is the most common persistent cardiac arrhythmia, and it is not well controlled by present drugs. Because some resin acids open voltage-gated potassium channels and reduce neuronal excitability, we explored the effects of the resin acid isopimaric acid (IPA) on action potentials and ion currents in cardiomyocytes. METHODS: Spontaneously beating mouse atrial HL-1 cells were investigated with the whole-cell patch-clamp technique. RESULTS: 1-25 μmol L(-1) IPA reduced the action potential frequency by up to 50%...
May 17, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28513773/attenuation-of-renal-ischemic-reperfusion-injury-by-salvianolic-acid-b-via-suppressing-oxidative-stress-and-inflammation-through-pi3k-akt-signaling-pathway
#5
Z G Ma, H Q Xia, S L Cui, J Yu
Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250-300 g) were obtained and split into four groups with ten rats in each group...
May 15, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28511915/altered-ionic-currents-and-amelioration-by-igf-1-and-pacap-in-motoneuron-derived-cells-modelling-sbma
#6
Aura M Jiménez Garduño, Leon J Juárez-Hernández, María J Polanco, Laura Tosatto, Daniela Michelatti, Daniele Arosio, Manuela Basso, Maria Pennuto, Carlo Musio
Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a motor neuron disease caused by the expansion of a polymorphic CAG tandem repeat encoding a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is triggered by the binding of mutant AR to its natural ligands, testosterone and dihydrotestosterone (DHT). To investigate the neuronal alterations of motor neuron cell models of SBMA, we applied patch-clamp methods to verify how polyQ expansions in the AR alter cell ionic currents...
May 10, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28508747/voltage-gated-na-currents-in-human-dorsal-root-ganglion-neurons
#7
Xiulin Zhang, Birgit T Priest, Inna Belfer, Michael S Gold
Available evidence indicates voltage-gated Na(+) channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons...
May 16, 2017: ELife
https://www.readbyqxmd.com/read/28506097/a-computational-model-of-the-ca-2-transients-and-influence-of-buffering-in-guinea-pig-urinary-bladder-smooth-muscle-cells
#8
Vijay Dave, Rohit Manchanda
Many cellular events including electrical activity and muscle contraction are regulated and coordinated by intracellular [Formula: see text] concentration ([[Formula: see text]][Formula: see text]. In detrusor smooth muscle (DSM) cells, [[Formula: see text]]i is normally maintained at very low levels and rises transiently during signalling processes as a result of (i) influx from the extracellular space (mainly via L-type and T-type [Formula: see text] channels) and (ii) [Formula: see text] release from sarcoplasmic reticulum (SR) into the cytoplasm...
April 20, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/28500173/tgf-%C3%AE-1-transforming-growth-factor-%C3%AE-1-plays-a-pivotal-role-in-cardiac-myofibroblast-arrhythmogenicity
#9
Nicolò Salvarani, Ange Maguy, Stefano A De Simone, Michele Miragoli, Florian Jousset, Stephan Rohr
BACKGROUND: TGF-β1 (transforming growth factor-β1) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β1 alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro. METHODS AND RESULTS: Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β1, applied for 24 to 48 hours at clinically relevant concentrations (≤2...
May 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28499969/corticotropin-releasing-hormone-modulates-airway-vagal-preganglionic-neurons-of-sprague-dawley-rats-at-multiple-synaptic-sites-via-activation-of-its-type-1-receptors-implications-for-stress-associated-airway-vagal-excitation
#10
Yuhong Guo, Xianxia Yan, Xingxin Chen, Ding He, Ming Zeng, Yonghua Chen, Chunmei Xia, Dongying Qiu, Jijiang Wang
Corticotropin-releasing hormone release is the final common pathway of stress-associated neuroendocrine responses. This study tested how corticotropin-releasing hormone modulates airway vagal preganglionic neurons. Airway vagal preganglionic neurons in neonatal rats were retrogradely labeled with fluorescent dye and identified in medullary slices, and their responses to corticotropin-releasing hormone (200nmolL(-1)) were examined using whole-cell patch clamp. The results show that under current clamp, corticotropin-releasing hormone (200nmolL(-1)) depolarized airway vagal preganglionic neurons and significantly increased the rate of their spontaneous firing...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28499095/trpm7-is-involved-in-volume-regulation-in-salivary-glands
#11
J M Kim, S Choi, K Park
Under hypotonic conditions, the regulatory volume decrease (RVD) is essential to maintain physiological homeostasis and functions in diverse biological systems. Intracellular Ca(2+) has been reported as an important mediator of this response, but the underlying Ca(2+) mechanism responsible for RVD is still controversial. Here we investigate the role of Ca(2+) in the RVD response using live-cell imaging, microspectrofluorimetry, and a patch-clamp technique. A typical RVD was observed in submandibular gland acinar cells after swelling in a hypotonic solution, whereas intracellular Ca(2+) chelation completely inhibited the RVD response...
May 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28498927/efficacy-and-safety-of-carbetocin-given-as-an-intravenous-bolus-compared-with-short-infusion-for-caesarean-section-double-blind-double-dummy-randomized-controlled-non-inferiority-trial
#12
S Dell-Kuster, I Hoesli, O Lapaire, E Seeberger, L A Steiner, H C Bucher, T Girard
Background: Carbetocin is a synthetic oxytocin-analogue, which should be administered as bolus according to manufacturer's recommendations. A higher speed of oxytocin administration leads to increased cardiovascular side-effects. It is unclear whether carbetocin administration as short infusion has the same efficacy on uterine tone compared with bolus administration and whether haemodynamic parameters differ. Methods: In this randomized, double-blind, non-inferiority trial, women undergoing planned or unplanned Caesarean section (CS) under regional anaesthesia received a bolus and a short infusion, only one of which contained carbetocin 100 mcg (double dummy)...
May 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28498410/neuropeptide-y-suppresses-epileptiform-discharges-by-regulating-ampa-receptor-glur2-subunit-in-rat-hippocampal-neurons
#13
Wei Bu, Wen-Qing Zhao, Wen-Ling Li, Chang-Zheng Dong, Zhe Zhang, Qi-Jun Li
The present study aimed to investigate the effects of neuropeptide Y (NPY) on the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor glutamate receptor 2 (GluR2) subunit in epileptiform discharge hippocampal neurons. Hippocampal neurons were harvested from neonatal Sprague‑Dawley rats aged <24 h and primarily cultured in vitro. At day 12 following culture, hippocampal neurons were divided into the following groups: Control, Mg2+‑free, NPY+Mg2+‑free and BIBP3226+NPY+Mg2+‑free...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28496108/alpha7-nicotinic-acetylcholine-receptor-agonist-promotes-retinal-ganglion-cell-function-via-modulating-gabaergic-presynaptic-activity-in-a-chronic-glaucomatous-model
#14
Xujiao Zhou, Yun Cheng, Rong Zhang, Gang Li, Boqi Yang, Shenghai Zhang, Jihong Wu
Alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonists can prevent glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs). However, the neuroprotective effects and the mechanism of action of PNU-282987, an α7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly understood. We found that elevated intraocular pressure (IOP) downregulated retinal α7-nAChR expression. Electroretinography revealed that the amplitude of the photopic negative response (PhNR) decreased in parallel with the loss of RGCs caused by elevated IOP...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28495885/proteolytic-cleavage-of-the-hydrophobic-domain-in-the-cav%C3%AE-2%C3%AE-1-subunit-improves-assembly-and-activity-of-cardiac-cav1-2-channels
#15
Emilie Segura, Benoîte Bourdin, Marie-Philippe Tétreault, Julie Briot, Bruce G Allen, Gaétan Mayer, Lucie Parent
Voltage-gated L-type CaV1.2 channels in cardiomyocytes exist as heteromeric complexes with the pore-forming CaVα1, CaVβ, and CaVα2δ1 subunits. The full complement of subunits is required to reconstitute the native-like properties of L-type Ca(2+) currents but the molecular determinants responsible for the formation of the heteromeric complex are still being studied. Enzymatic treatment with PI-PLC, a phospholipase C specific for the cleavage of glycosyl-phosphatidylinositol (GPI)-anchored proteins, disrupted plasma membrane localization of the cardiac CaVα2δ1 prompting us to investigate deletions of its hydrophobic transmembrane domain...
May 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28489932/camkii%C3%AE-may-modulate-fentanyl-induced-hyperalgesia-via-a-celc-pag-rvm-spinal-cord-descending-facilitative-pain-pathway-in-rats
#16
Zhen Li, Pingping Yin, Jian Chen, Shenglan Jin, Jieqiong Liu, Fang Luo
Each of the lateral capsular division of central nucleus of amygdala(CeLC), periaqueductal gray (PAG), rostral ventromedial medulla(RVM) and spinal cord has been proved to contribute to the development of opioid-induced hyperalgesia(OIH). Especially, Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) in CeLC and spinal cord seems to play a key role in OIH modulation. However, the pain pathway through which CaMKIIα modulates OIH is not clear. The pathway from CeLC to spinal cord for this modulation was explored in the present study...
2017: PloS One
https://www.readbyqxmd.com/read/28489663/use-dependent-inhibition-of-glycine-activated-chloride-current-in-rat-neurons-by-%C3%AE-amyloid-peptide-pretreated-with-hexafluoroisopropanol
#17
Elena I Solntseva, Julia V Bukanova
Hexafluoroisopropanol (HFIP) is a nonpolar organic solvent that is often used to prepare β-amyloid peptide (Aβ) samples. In this work, we compare the effects of two different species derived from synthetic Aβ1-42 and prepared without HFIP (Aβ) or using HFIP (Aβ/HFIP) on the glycine-activated chloride current (IGly). The experiments were conducted on the pyramidal neurons isolated from CA3 region of rat hippocampus. Transmembrane currents were recorded using a conventional patch-clamp technique in the whole-cell configuration...
May 5, 2017: Neuroreport
https://www.readbyqxmd.com/read/28488367/chemosensitive-phox2b-expressing-neurons-are-crucial-for-hypercapnic-ventilatory-response-in-the-nucleus-tractus-solitarius
#18
Congrui Fu, Jinyu Xue, Ri Wang, Jinting Chen, Lan Ma, Yixian Liu, Xuejiao Wang, Fang Guo, Yi Zhang, Xiangjian Zhang, Sheng Wang
The nucleus tractus solitarius (NTS) neurons have been thought to function as central respiratory chemoreceptors. However, it remains unknown regarding the common molecular marker defined for these neurons. Here we ask whether paired-like homeobox 2b (Phox2b)-expressing NTS neurons are recruited in hypercapnic ventilatory response (HCVR) and whether these neurons exhibit intrinsic chemosensitivity. HCVR was assessed using whole body plethysmography and neuronal chemosensitivity was examined by patch clamp recordings in brainstem slices or dissociated neurons from Phox2b-EGFP transgenic mice...
May 10, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28487470/discrepant-effects-of-heart-failure-on-electrophysiological%C3%A2-property-in-right-ventricular-outflow-tract-and-left-ventricular-outflow-tract-cardiomyocytes
#19
Yen-Yu Lu, Chen-Chuan Cheng, Chin-Feng Tsai, Yung Kuo Lin, Ting-I Lee, Yao-Chang Chen, Shih-Ann Chen, Yi Jen Chen
Ventricular arrhythmias commonly arise from the right and left ventricular outflow tracts (RVOT/LVOT) in patients without structural heart disease. Heart failure (HF) significantly increases the risk of ventricular arrhythmias. The regional differences and how HF affects the electrophysiological characteristics of RVOT and LVOT cardiomyocytes remain unclear. The whole-cell patch clamp technique was used to investigate the action potentials and ionic currents in isolated single RVOT and LVOT cardiomyocytes from control and rapid ventricular pacing-induced HF rabbit...
May 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28483800/xe991-and-linopirdine-are-state-dependent-inhibitors-for-kv7-kcnq-channels-that-favor-activated-single-subunits
#20
Derek L Greene, Seungwoo Kang, Naoto Hoshi
M-channel inhibitors, especially XE991, are increasingly being used in animal experiments. However, insufficient characterization of XE991 at times confounds the interpretation of results when using this compound. Here, we demonstrate that XE991 and linopirdine are state-dependent inhibitors that favor the activated-subunit of neuronal Kv7/KCNQ channels. We performed patch clamp experiments on homomeric Kv7.2 or heteromeric Kv7.2/3 channels expressed in Chinese hamster ovary cells in order to characterize XE991 and linopirdine...
May 8, 2017: Journal of Pharmacology and Experimental Therapeutics
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