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https://www.readbyqxmd.com/read/28316260/animal-physiology-and-genetic-aspects-of-ryegrass-staggers-in-grazing-sheep
#1
C A Morris, T T Wheeler, H V Henderson, N R Towers, S H Phua
Ryegrass staggers (RGS) is a metabolic disease of herbivores, caused by the ingestion of perennial ryegrass (Lolium perenne L.) containing a fungal endophyte (Neotyphodium lolii) which produces a tremorgenic toxin, lolitrem B. RGS has a major economic impact for agriculture in New Zealand as well as internationally. Management of RGS in grazing sheep can be problematic, and there is an incomplete knowledge of the interaction between the toxin and the grazing animal. This review is focused on recent advances in understanding the molecular physiology of RGS in the affected animal as well as the influence of animal genetics on the degree of susceptibility to RGS...
March 19, 2017: New Zealand Veterinary Journal
https://www.readbyqxmd.com/read/28301520/the-structure-dynamics-and-selectivity-profile-of-a-nav1-7-potency-optimised-huwentoxin-iv-variant
#2
Sassan Rahnama, Jennifer R Deuis, Fernanda C Cardoso, Venkatraman Ramanujam, Richard J Lewis, Lachlan D Rash, Glenn F King, Irina Vetter, Mehdi Mobli
Venom-derived peptides have attracted much attention as potential lead molecules for pharmaceutical development. A well-known example is Huwentoxin-IV (HwTx-IV), a peptide toxin isolated from the venom of the Chinese bird-eating spider Haplopelma schmitdi. HwTx-IV was identified as a potent blocker of a human voltage-gated sodium channel (hNaV1.7), which is a genetically validated analgesic target. The peptide was promising as it showed high potency at NaV1.7 (IC50 ~26 nM) and selectivity over the cardiac NaV subtype (NaV1...
2017: PloS One
https://www.readbyqxmd.com/read/28300784/the-molecular-basis-of-toxins-interactions-with-intracellular-signaling-via-discrete-portals
#3
REVIEW
Adi Lahiani, Ephraim Yavin, Philip Lazarovici
An understanding of the molecular mechanisms by which microbial, plant or animal-secreted toxins exert their action provides the most important element for assessment of human health risks and opens new insights into therapies addressing a plethora of pathologies, ranging from neurological disorders to cancer, using toxinomimetic agents. Recently, molecular and cellular biology dissecting tools have provided a wealth of information on the action of these diverse toxins, yet, an integrated framework to explain their selective toxicity is still lacking...
March 16, 2017: Toxins
https://www.readbyqxmd.com/read/28300777/functional-contributions-of-positive-charges-in-the-pore-lining-helix-3-of-the-bordetella-pertussis-cyaa-hemolysin-to-hemolytic-activity-and-ion-channel-opening
#4
Chattip Kurehong, Chalermpol Kanchanawarin, Busaba Powthongchin, Panchika Prangkio, Gerd Katzenmeier, Chanan Angsuthanasombat
The Bordetella pertussis CyaA-hemolysin (CyaA-Hly) domain was previously demonstrated to be an important determinant for hemolysis against target erythrocytes and ion-channel formation in planar lipid bilayers (PLBs). Here, net-charge variations in the pore-lining helix of thirteen related RTX cytolysins including CyaA-Hly were revealed by amino acid sequence alignments, reflecting their different degrees of hemolytic activity. To analyze possible functional effects of net-charge alterations on hemolytic activity and channel formation of CyaA-Hly, specific mutations were made at Gln(574) or Glu(581) in its pore-lining α3 of which both residues are highly conserved Lys in the three highly active RTX cytolysins (i...
March 16, 2017: Toxins
https://www.readbyqxmd.com/read/28300672/discovery-of-three-toxin-peptides-with-kv1-3-channel-and-il-2-cytokine-inhibiting-activities-from-non-buthidae-scorpions-chaerilus-tricostatus-and-chaerilus-tryznai
#5
Li Ding, Jing Chen, Jinbo Hao, Jiahui Zhang, Xuejun Huang, Fangfang Hu, Zheng Wu, Yaru Liu, Wenxin Li, Zhijian Cao, Yingliang Wu, Jian Li, Shan Li, Hongyan Liu, Wenlong Wu, Zongyun Chen
Non-Buthidae venomous scorpions are huge natural sources of toxin peptides; however, only a few studies have been done to understand their toxin peptides. Herein, we describe three new potential immunomodulating toxin peptides, Ctri18, Ctry68 and Ctry2908, from two non-Buthidae scorpions, Chaerilus tricostatus and Chaerilus tryznai. Sequence alignment analyses showed that Ctri18, Ctry68 and Ctry2908 are three new members of the scorpion toxin α-KTx15 subfamily. Electrophysiological experiments showed that Ctri18, Ctry68 and Ctry2908 blocked the Kv1...
March 12, 2017: Peptides
https://www.readbyqxmd.com/read/28298531/reply-to-yamini-and-nestorovich-alternate-clamped-states-of-the-anthrax-toxin-protective-antigen-channel
#6
Bryan A Krantz
No abstract text is available yet for this article.
March 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28268294/spatial-characterization-of-innervation-zones-under-electrically-elicited-m-wave
#7
C Zhang, Y Peng, S Li, P Zhou, A Munoz, D Tang, Y Zhang
The three dimensional (3D) innervation zone (IZ) imaging approach (3DIZI) has been developed in our group to localize the IZ of a particular motor unit (MU) from its motor unit action potentials decomposed from high-density surface electromyography (EMG) recordings. In this study, the developed 3DIZI approach was combined with electrical stimulation to investigate global distributions of IZs in muscles from electrically elicited M-wave recordings. Electrical stimulations were applied to the musculocutaneous nerve to activate supramaximal muscle response of the biceps brachii in one healthy subject, and high-density (128 channels) surface EMG signals of the biceps brachii muscles were recorded...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28260386/measurement-of-hanatoxin-induced-membrane-thinning-with-lamellar-x-ray-diffraction
#8
Meng-Hsuan Hsieh, Yu-Shuan Shiau, Horng-Huei Liou, U-Ser Jeng, Ming-Tao Lee, Kuo-Long Lou
Membrane perturbation induced by cysteine-rich peptides is a crucial biological phenomenon but scarcely investigated, in particular with effective biophysical-chemical methodologies. Hanatoxin (HaTx), a 35-residue polypeptide from spider venom, works as an inhibitor of drk1 (Kv2.1) channels, most likely by interacting with the voltage-sensor. However, how this water-soluble peptide modifies the gating remains poorly understood, as the voltage sensor was proposed to be deeply embedded within the bilayer. To see how HaTx interacts with phospholipid bilayers, we observe the toxin-induced perturbation on POPC/DOPG-membranes through measurements of the change in membrane thickness...
March 21, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28260030/bmk-ct-and-125i-bmk-ct-suppress-the-invasion-of-glioma-cells-in%C3%A2-vitro-via-matrix-metalloproteinase-2
#9
Na Sun, Lingzhou Zhao, Wenli Qiao, Yan Xing, Jinhua Zhao
Chlorotoxin (CTX) is an established blocker of small‑conductance Cl‑ channels and has previously been demonstrated to inhibit the invasion of glioma cells. Buthus martensii Karsch chlorotoxin‑like toxin (BmK CT) is the first chlorotoxin-like peptide. The present study aimed to determine the inhibitory effect of BmK CT on the invasive ability of glioma cells, using a Transwell assay. BmK CT was subsequently radiolabeled with radionuclide 125I and its activity was compared with BmK CT. Additionally, the underlying anti‑invasive mechanism of BmK CT and 125I‑BmK CT on glioma cells was investigated by ELISA and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
March 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28247497/centipede-venom-peptide-ssmtx-i-with-two-intramolecular-disulfide-bonds-shows-analgesic-activities-in-animal-models
#10
Ying Wang, Xiaojie Li, Meifeng Yang, Chunyun Wu, Zhirong Zou, Jing Tang, Xinwang Yang
Pain is a major symptom of many diseases and results in enormous pressures on human body or society. Currently, clinically used analgesic drugs, including opioids and nonsteroidal anti-inflammatory drugs, have adverse reactions, and thus, the development of new types of analgesic drug candidates is urgently needed. Animal venom peptides have proven to have potential as new types of analgesic medicine. In this research, we describe the isolation and characterization of an analgesic peptide from the crude venom of centipede, Scolopendra subspinipes mutilans...
March 1, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28245573/acute-oral-toxicity-of-tetrodotoxin-in-mice-determination-of-lethal-dose-50-ld50-and-no-observed-adverse-effect-level-noael
#11
Paula Abal, M Carmen Louzao, Alvaro Antelo, Mercedes Alvarez, Eva Cagide, Natalia Vilariño, Mercedes R Vieytes, Luis M Botana
Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard...
February 24, 2017: Toxins
https://www.readbyqxmd.com/read/28241514/antivenom-evaluation-by-electrophysiological-analysis
#12
Rita Restano-Cassulini, Walter Garcia, Jorge F Paniagua-Solís, Lourival D Possani
Scorpion stings on humans are medically relevant because they may contain toxins that specifically target ion channels. During antivenom production, pharmaceutical companies must use a large number of experimental animals to ensure the antivenom's efficacy according to pharmacopeia methods. Here we present an electrophysiological alternative for the evaluation of horse antivenoms produced against two species of Moroccan scorpions: Buthus mardochei and Androctonus mauretanicus. Human sodium and potassium channels and acetylcholine nicotinic receptors were analyzed by standard patch-clamp techniques...
February 23, 2017: Toxins
https://www.readbyqxmd.com/read/28238803/discovery-and-characterization-of-eiib-a-new-%C3%AE-conotoxin-from-conus-ermineus-venom-by-nachrs-affinity-capture-monitored-by-maldi-tof-tof-mass-spectrometry
#13
Julien Echterbille, Nicolas Gilles, Romulo Araóz, Gilles Mourier, Muriel Amar, Denis Servent, Edwin De Pauw, Loic Quinton
Animal toxins are peptides that often bind with remarkable affinity and selectivity to membrane receptors such as nicotinic acetylcholine receptors (nAChRs). The latter are, for example, targeted by α-conotoxins, a family of peptide toxins produced by venomous cone snails. nAChRs are implicated in numerous physiological processes explaining why the design of new pharmacological tools and the discovery of potential innovative drugs targeting these receptor channels appear so important. This work describes a methodology developed to discover new ligands of nAChRs from complex mixtures of peptides...
February 24, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28238802/phoneutria-nigriventer-spider-toxin-tx2-6-induces-priapism-in-mice-even-after-cavernosal-denervation
#14
Katherine Garcia Ravelli, Adriana de Toledo Ramos, Luana Baracho Gonçalves, Fábio Carlos Magnoli, Lanfranco Ranieri Paolo Troncone
The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin produces a delay in Sodium channel inactivation, generalized vascular congestion and death by respiratory failure. NO-Synthase inhibitors seem to abolish toxin-induced priapism. The understanding of the ultimate molecular mechanism involved in toxin-induced priapism may shed light on aspects of erectile function/dysfunction. This study investigates if cavernosal denervation can abolish the toxin-induced priapism. Surgical cavernosal nerve excision/denervation was performed in mice and confirmed by infertility, histological assessment of fibrosis and immunohistochemical staining for synaptophysin...
February 24, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28226453/spatial-characterization-of-innervation-zones-under-electrically-elicited-m-wave
#15
C Zhang, Y Peng, S Li, P Zhou, A Munoz, D Tang, Y Zhang, C Zhang, Y Peng, S Li, P Zhou, A Munoz, D Tang, Y Zhang, C Zhang, P Zhou, D Tang, Y Zhang, S Li, A Munoz, Y Peng
The three dimensional (3D) innervation zone (IZ) imaging approach (3DIZI) has been developed in our group to localize the IZ of a particular motor unit (MU) from its motor unit action potentials decomposed from high-density surface electromyography (EMG) recordings. In this study, the developed 3DIZI approach was combined with electrical stimulation to investigate global distributions of IZs in muscles from electrically elicited M-wave recordings. Electrical stimulations were applied to the musculocutaneous nerve to activate supramaximal muscle response of the biceps brachii in one healthy subject, and high-density (128 channels) surface EMG signals of the biceps brachii muscles were recorded...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225079/multiple-sodium-channel-isoforms-mediate-the-pathological-effects-of-pacific-ciguatoxin-1
#16
Marco C Inserra, Mathilde R Israel, Ashlee Caldwell, Joel Castro, Jennifer R Deuis, Andrea M Harrington, Angelo Keramidas, Sonia Garcia-Caraballo, Jessica Maddern, Andelain Erickson, Luke Grundy, Grigori Y Rychkov, Katharina Zimmermann, Richard J Lewis, Stuart M Brierley, Irina Vetter
Human intoxication with the seafood poison ciguatoxin, a dinoflagellate polyether that activates voltage-gated sodium channels (NaV), causes ciguatera, a disease characterised by gastrointestinal and neurological disturbances. We assessed the activity of the most potent congener, Pacific ciguatoxin-1 (P-CTX-1), on NaV1.1-1.9 using imaging and electrophysiological approaches. Although P-CTX-1 is essentially a non-selective NaV toxin and shifted the voltage-dependence of activation to more hyperpolarising potentials at all NaV subtypes, an increase in the inactivation time constant was observed only at NaV1...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224710/extended-low-dose-exposure-to-saxitoxin-inhibits-neurite-outgrowth-in-model-neuronal-cells
#17
Katie O'Neill, Ian F Musgrave, Andrew Humpage
The potent neurotoxin saxitoxin (STX) belongs to a group of structurally related analogues produced by both marine and freshwater phytoplankton. The toxins act by blocking voltage-gated sodium channels stopping the inflow of sodium ions and the generation of action potentials. Exposure from marine sources occurs as a result of consuming shellfish which have concentrated the toxins, and freshwater exposure can occur from drinking water although there have been no acute poisonings from the latter source to date...
April 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#18
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223151/testosterone-rapidly-increases-ca-2-activated-k-currents-causing-hyperpolarization-in-human-coronary-artery-endothelial-cells
#19
Katesirin Ruamyod, Wattana B Watanapa, Chairat Shayakul
Testosterone has endothelium-dependent vasodilatory effects on the coronary artery, with some reports suggesting endothelial ion channel involvement. This study employed the whole-cell patch clamp technique to investigate the effect of testosterone on ion channels in human coronary artery endothelial cells (HCAECs) and the mechanisms involved. We found that 0.03-3μM testosterone significantly induced a rapid, concentration-dependent increase in total HCAEC current (EC50, 71.96±1.66nM; maximum increase, 59...
February 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28223047/diversity-in-sequences-post-translational-modifications-and-expected-pharmacological-activities-of-toxins-from-four-conus-species-revealed-by-the-combination-of-cutting-edge-proteomics-transcriptomics-and-bioinformatics
#20
Michel Degueldre, Marion Verdenaud, Garikoitz Legarda, Rebeca Minambres, Sheila Zuniga, Mathieu Leblanc, Nicolas Gilles, Frederic Ducancel, Edwin De Pauw, Loic Quinton
Venomous animals have developed a huge arsenal of reticulated peptides for defense and predation. Based on various scaffolds, they represent a colossal pharmacological diversity, making them top candidates for the development of innovative drugs. Instead of relying on the classical, low-throughput bioassay-guided approach to identify innovative bioactive peptides, this work exploits a recent paradigm to access to venom diversity. This strategy bypasses the classical approach by combining high-throughput transcriptomics, proteomics and bioinformatics cutting-edge technologies to generate reliable peptide sequences...
February 20, 2017: Toxicon: Official Journal of the International Society on Toxinology
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