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Tetrodotoxin

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https://www.readbyqxmd.com/read/28821632/transcriptomic-and-epigenetic-regulation-of-disuse-atrophy-and-the-return-to-activity-in-skeletal-muscle
#1
Andrew G Fisher, Robert A Seaborne, Thomas M Hughes, Alex Gutteridge, Claire Stewart, Judy M Coulson, Adam P Sharples, Jonathan C Jarvis
Physical inactivity and disuse are major contributors to age-related muscle loss. Denervation of skeletal muscle has been previously used as a model with which to investigate muscle atrophy following disuse. Although gene regulatory networks that control skeletal muscle atrophy after denervation have been established, the transcriptome in response to the recovery of muscle after disuse and the associated epigenetic mechanisms that may function to modulate gene expression during skeletal muscle atrophy or recovery have yet to be investigated...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28811506/an-amphibian-chemical-defense-phenotype-is-inducible-across-life-history-stages
#2
Gary M Bucciarelli, H Bradley Shaffer, David B Green, Lee B Kats
Inducible phenotypic responses to environmental variation are ubiquitous across the tree of life, but it remains an open question whether amphibian chemical defense phenotypes are inducible. Tetrodotoxin (TTX) is a key chemical defense trait in North American and Eurasian newts (Salamandridae). We tested if TTX can be induced by exposing populations of adult and larval California newts (Taricha torosa) to sustained stressful conditions while longitudinally quantifying TTX concentrations. Adult newts rapidly increased chemical defenses in response to simulated predator attacks and consistently maintained elevated TTX concentrations relative to wild, non-captive individuals...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28809766/crispr-cas9-editing-of-nf1-gene-identifies-crmp2-as-a-therapeutic-target-in-neurofibromatosis-type-1-nf1-related-pain-that-is-reversed-by-s-lacosamide
#3
Aubin Moutal, Xiaofang Yang, Wennan Li, Kerry B Gilbraith, Shizhen Luo, Song Cai, Liberty François-Moutal, Lindsey A Chew, Seul Ki Yeon, Shreya S Bellampalli, Chaoling Qu, Jennifer Y Xie, Mohab M Ibrahim, May Khanna, Ki Duk Park, Frank Porreca, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. NF1 patients commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by NF1 patients. However, behavioral assessments of Nf1+/- mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats/(CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain...
July 3, 2017: Pain
https://www.readbyqxmd.com/read/28803761/an-in-silico-perspective-on-the-toxicodynamic-of-tetrodotoxin-and-analogues-a-tool-for-supporting-the-hazard-identification
#4
Luca Dellafiora, Gianni Galaverna, Chiara Dall'Asta
Tetrodotoxin (TTX) is a potent neurotoxin naturally found in terrestrial and marine animals targeting the voltage-gated sodium channels. Historically, TTX has raised food safety concerns mainly in the Asian countries due to the consumption of the typical pufferfish-derived delicacy fugu. However, the diffusion of TTX is getting wider today, reasonably threating in a close future a broader number of consumers than before. The understanding of TTX group toxicity is still incomplete as most of the analogues and metabolites found together with TTX are largely understudied...
August 10, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28755852/noxious-newts-and-their-natural-enemies-experimental-effects-of-tetrodotoxin-exposure-on-trematode-parasites-and-aquatic-macroinvertebrates
#5
Dana M Calhoun, Gary M Bucciarelli, Lee B Kats, Richard K Zimmer, Pieter T J Johnson
The dermal glands of many amphibian species secrete toxins or other noxious substances as a defense strategy against natural enemies. Newts in particular possess the potent neurotoxin tetrodotoxin (TTX), for which the highest concentrations are found in species within the genus Taricha. Adult Taricha are hypothesized to use TTX as a chemical defense against vertebrate predators such as garter snakes (Thamnophis spp.). However, less is known about how TTX functions to defend aquatic-developing newt larvae against natural enemies, including trematode parasites and aquatic macroinvertebrates...
July 27, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28752895/development-of-resurgent-and-persistent-sodium-currents-in-mesencephalic-trigeminal-neurons
#6
Akifumi Enomoto, Soju Seki, Susumu Tanaka, Kohji Ishihama, Tadashi Yamanishi, Mikihiko Kogo, Suguru Hamada
Sodium channels play multiple roles in the formation of neural membrane properties in mesencephalic trigeminal (Mes V) neurons and in other neural systems. Mes V neurons exhibit conditional robust high-frequency spike discharges. As previously reported, resurgent and persistent sodium currents (INaR and INaP , respectively) may carry small currents at subthreshold voltages that contribute to generation of spike firing. These currents play an important role in maintaining and allowing high-frequency spike discharge during a burst...
July 28, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28734983/dietary-administration-of-tetrodotoxin-and-its-putative-biosynthetic-intermediates-to-the-captive-reared-non-toxic-japanese-fire-bellied-newt-cynops-pyrrhogaster
#7
Yuta Kudo, Chikafumi Chiba, Keiichi Konoki, Yuko Cho, Mari Yotsu-Yamashita
The origin of tetrodotoxin (TTX) in amphibians has long been disputed. In this study, TTX and its putative biosynthetic intermediates or shunt compounds (4,9-anhydro-10-hemiketal-5-deoxyTTX and Cep-242) were dietary administered to the captive-reared, non-toxic Japanese fire-bellied newt, Cynops pyrrhogaster. After 4 weeks, the ingested compounds were detected mainly in the newt body using liquid chromatography-mass spectrometry (LC-MS), while these compounds were not converted into other TTX analogues in newts...
July 20, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28732557/a-negative-slope-conductance-of-the-persistent-sodium-current-prolongs-subthreshold-depolarizations
#8
Cesar C Ceballos, Antonio C Roque, Ricardo M Leão
Neuronal subthreshold voltage-dependent currents determine membrane properties such as the input resistance (Rin) and the membrane time constant (τm) in the subthreshold range. In contrast with classical cable theory predictions, the persistent sodium current (INaP), a non-inactivating mode of the voltage-dependent sodium current, paradoxically increases Rin and τm when activated. Furthermore, this current amplifies and prolongs synaptic currents in the subthreshold range. Here, using a computational neuronal model, we showed that the creation of a region of negative slope conductance by INaP activation is responsible for these effects and the ability of the negative slope conductance to amplify and prolong Rin and τm relies on the fast activation of INaP...
July 18, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28729685/nucleocytoplasmic-shuttling-of-histone-deacetylase-9-controls-activity-dependent-thalamocortical-axon-branching
#9
Ricardo Alchini, Haruka Sato, Naoyuki Matsumoto, Tomomi Shimogori, Noriyuki Sugo, Nobuhiko Yamamoto
During development, thalamocortical (TC) axons form branches in an activity-dependent fashion. Here we investigated how neuronal activity is converted to molecular signals, focusing on an epigenetic mechanism involving histone deacetylases (HDACs). Immunohistochemistry demonstrated that HDAC9 was translocated from the nucleus to the cytoplasm of thalamic cells during the first postnatal week in rats. In organotypic co-cultures of the thalamus and cortex, fluorescent protein-tagged HDAC9 also exhibited nuclueocytoplasmic translocation in thalamic cells during culturing, which was reversed by tetrodotoxin treatment...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714912/urinary-excretion-of-tetrodotoxin-modeled-in-a-porcine-renal-proximal-tubule-epithelial-cell-line-llc-pk%C3%A2
#10
Takuya Matsumoto, Yui Ishizaki, Keika Mochizuki, Mitsuru Aoyagi, Yoshiharu Mitoma, Shoichiro Ishizaki, Yuji Nagashima
This study examined the urinary excretion of tetrodotoxin (TTX) modeled in a porcine renal proximal tubule epithelial cell line, LLC-PK₁. Time course profiles of TTX excretion and reabsorption across the cell monolayers at 37 °C showed that the amount of TTX transported increased linearly for 60 min. However, at 4 °C, the amount of TTX transported was approximately 20% of the value at 37 °C. These results indicate that TTX transport is both a transcellular and carrier-mediated process. Using a transport inhibition assay in which cell monolayers were incubated with 50 µM TTX and 5 mM of a transport inhibitor at 37 °C for 30 min, urinary excretion was significantly reduced by probenecid, tetraethylammonium (TEA), l-carnitine, and cimetidine, slightly reduced by p-aminohippuric acid (PAH), and unaffected by 1-methyl-4-phenylpyridinium (MPP+), oxaliplatin, and cefalexin...
July 17, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28710688/death-by-food
#11
Roger W Byard
Although death from food is not an uncommon finding in forensic facilities worldwide, the range of underlying lethal mechanisms and associated conditions that should be sought at the time of autopsy is quite disparate. Deaths may occur from i) infectious agents including bacteria, viruses, protozoa, cestodes, nematodes and prions; ii) natural toxins including amanita toxins, tetrodotoxin, ciguatera and scombroid; iii) anaphylaxis; iv) poisoning; v) mechanical issues around airway and gut obstruction and/or perforation; and vi) miscellaneous causes...
July 15, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28695626/mucosal-glucagon-like-peptide-1-glp-1-responses-are-mediated-by-calcitonin-gene-related-peptide-cgrp-in-the-mouse-colon-and-both-peptide-responses-are-area-specific
#12
I R Tough, R Moodaley, H M Cox
BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI) disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL/6J mice...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28679669/a-small-molecule-trkb-ligand-restores-hippocampal-synaptic-plasticity-and-object-location-memory-in-rett-syndrome-mice
#13
Wei Li, Alba Bellot-Saez, Mary L Phillips, Tao Yang, Frank M Longo, Lucas Pozzo-Miller
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein-2 (MECP2), a transcriptional regulator of many genes, including brain-derived neurotrophic factor (BDNF). BDNF levels are reduced in RTT autopsy brains and in multiple brain areas of Mecp2-deficient mice. Furthermore, experimental interventions that increase BDNF levels improve RTT-like phenotypes in Mecp2 mutant mice. Here, we characterized the actions of a small-molecule ligand of the BDNF receptor TrkB in hippocampal function in Mecp2 mutant mice...
July 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28671709/transient-receptor-potential-a1-trpa1-agonists-inhibit-contractions-of-the-isolated-human-ureter
#14
Philipp Weinhold, Martin Hennenberg, Frank Strittmatter, Christian G Stief, Christian Gratzke, Petter Hedlund
AIMS: Mechanoafferent and peristaltic mechanisms of the human ureter involve transient receptor potential V1 (TRPV1)- and purinoceptor-mediated functions. Hydrogen sulphide, an endogenous TRPA1 ligand, is linked to inhibitory neurotransmission of the pig ureter. No information is available on TRPA1 activity in the human ureter. We therefore examined the distribution and function of TRPA1 in the human ureter. METHODS: Expression of TRPA1 in human ureter tissue was studied by Western blot and immunofluorescence...
July 3, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28659731/modulatory-effect-of-intestinal-polyamines-and-trace-amines-on-the-spontaneous-phasic-contractions-of-the-isolated-ileum-and-colon-rings-of-mice
#15
Manuel Sánchez, Lorena Suárez, María Teresa Andrés, Blanca Henar Flórez, Javier Bordallo, Sabino Riestra, Begoña Cantabrana
Background: Gastrointestinal motility modulatory factors include substances of the intestinal content, such as polyamines and trace amines (TAs), the focus of this study. Methods: The amines of food, intestinal content and from faecal bacteria of Swiss mice were determined by HPLC and functionally characterised in isolated distal ileum and medial colon rings. Results: Mouse food and intestinal content contain polyamines (spermidine>putrescine>spermine) and TAs (isoamylamine>cadaverine). Intestinal bacteria mainly produce putrescine and cadaverine...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28651990/a-novel-function-of-vitellogenin-subdomain-vwf-type-d-as-a-toxin-binding-protein-in-the-pufferfish-takifugu-pardalis-ovary
#16
Xianzhe Yin, Aya Kiriake, Akira Ohta, Yoichiro Kitani, Shoichiro Ishizaki, Yuji Nagashima
Marine pufferfish of the Tetraodontidae family contain high levels of tetrodotoxin (TTX) in the liver and ovary. TTX is suggested to transfer from the liver to the ovary in female pufferfish during maturation. TTX in pufferfish eggs may act as a repellent against predators and as a sexual pheromone to attract male pufferfish. The toxification mechanism of the pufferfish ovary is poorly understood. Here we evaluated the chemical form of TTX and its related substances in the ovary of the panther pufferfish Takifugu pardalis by LC-ESI/MS...
June 23, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28638222/corticotropin-releasing-factor-stimulates-colonic-motility-via-muscarinic-receptors-in-the-rat
#17
Kyung-Jo Kim, Ki Bae Kim, Soon Man Yoon, Joung-Ho Han, Hee Bok Chae, Seon Mee Park, Sei Jin Youn
AIM: To measure exogenous corticotropin-releasing factor (CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility. METHODS: The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous CRF was administered in a stepwise manner and the concentration of CRF yielding maximal colonic motility was selected...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28635651/effects-of-tetrodotoxin-in-mouse-models-of-visceral-pain
#18
Rafael González-Cano, Miguel Ángel Tejada, Antonia Artacho-Cordón, Francisco Rafael Nieto, José Manuel Entrena, John N Wood, Cruz Miguel Cendán
Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28634472/antifungal-activity-against-filamentous-fungi-of-ts1-a-multifunctional-toxin-from-tityus-serrulatus-scorpion-venom
#19
Welligton M Santussi, Karla C F Bordon, Ana P N Rodrigues Alves, Camila T Cologna, Suraia Said, Eliane C Arantes
Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28623807/hiv-tat-excites-d1-receptor-like-expressing-neurons-from-rat-nucleus-accumbens
#20
G Cristina Brailoiu, Elena Deliu, Jeffrey L Barr, Linda M Console-Bram, Alexandra M Ciuciu, Mary E Abood, Ellen M Unterwald, Eugen Brailoiu
BACKGROUND: HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. METHODS: We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca(2+) homeostasis of NAcc neurons...
June 8, 2017: Drug and Alcohol Dependence
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