Conotoxins: Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Conus Snail: A genus of cone-shaped marine snails in the family Conidae, class GASTROPODA. It comprises more than 600 species, many containing unique venoms (CONUS VENOMS) with which they immobilize their prey.Mollusk Venoms: Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.Snails: Marine, freshwater, or terrestrial mollusks of the class Gastropoda. Most have an enclosing spiral shell, and several genera harbor parasites pathogenic to man.Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Disulfides: Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of CYSTEINE. Two molecules of cysteine are joined together by a disulfide bridge to form cystine.Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Sodium Channel Blockers: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Calcium Channels, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.omega-Conotoxins: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry of calcium into the presynaptic membrane. They selectively inhibit N-, P-, and Q-type calcium channels.Biological Products: Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.omega-Conotoxin GVIA: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.Sodium Channels: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.Pain Perception: The process by which PAIN is recognized and interpreted by the brain.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.).Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.Diabetic Neuropathies: Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.G Protein-Coupled Inwardly-Rectifying Potassium Channels: A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Mexiletine: Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.Cardiac Complexes, Premature: A group of cardiac arrhythmias in which the cardiac contractions are not initiated at the SINOATRIAL NODE. They include both atrial and ventricular premature beats, and are also known as extra or ectopic heartbeats. Their frequency is increased in heart diseases.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.Aminocaproic Acid: An antifibrinolytic agent that acts by inhibiting plasminogen activators which have fibrinolytic properties.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Aminocaproates: Amino derivatives of caproic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the amino caproic acid structure.Electrodes: Electric conductors through which electric currents enter or leave a medium, whether it be an electrolytic solution, solid, molten mass, gas, or vacuum.Electrochemistry: The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes.2,2'-Dipyridyl: A reagent used for the determination of iron.Solar Energy: Energy transmitted from the sun in the form of electromagnetic radiation.Electrochemical Techniques: The utilization of an electrical current to measure, analyze, or alter chemicals or chemical reactions in solution, cells, or tissues.Luminescent Measurements: Techniques used for determining the values of photometric parameters of light resulting from LUMINESCENCE.Ruthenium: A hard, brittle, grayish-white rare earth metal with an atomic symbol Ru, atomic number 44, and atomic weight 101.07. It is used as a catalyst and hardener for PLATINUM and PALLADIUM.OregonPublic Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level.Public Health Administration: Management of public health organizations or agencies.State Health Plans: State plans prepared by the State Health Planning and Development Agencies which are made up from plans submitted by the Health Systems Agencies and subject to review and revision by the Statewide Health Coordinating Council.Public Health Practice: The activities and endeavors of the public health services in a community on any level.Communicable DiseasesCommunicable Disease Control: Programs of surveillance designed to prevent the transmission of disease by any means from person to person or from animal to man.

Ultra-slow inactivation in mu1 Na+ channels is produced by a structural rearrangement of the outer vestibule. (1/410)

While studying the adult rat skeletal muscle Na+ channel outer vestibule, we found that certain mutations of the lysine residue in the domain III P region at amino acid position 1237 of the alpha subunit, which is essential for the Na+ selectivity of the channel, produced substantial changes in the inactivation process. When skeletal muscle alpha subunits (micro1) with K1237 mutated to either serine (K1237S) or glutamic acid (K1237E) were expressed in Xenopus oocytes and depolarized for several minutes, the channels entered a state of inactivation from which recovery was very slow, i.e., the time constants of entry into and exit from this state were in the order of approximately 100 s. We refer to this process as "ultra-slow inactivation". By contrast, wild-type channels and channels with the charge-preserving mutation K1237R largely recovered within approximately 60 s, with only 20-30% of the current showing ultra-slow recovery. Coexpression of the rat brain beta1 subunit along with the K1237E alpha subunit tended to accelerate the faster components of recovery from inactivation, as has been reported previously of native channels, but had no effect on the mutation-induced ultra-slow inactivation. This implied that ultra-slow inactivation was a distinct process different from normal inactivation. Binding to the pore of a partially blocking peptide reduced the number of channels entering the ultra-slow inactivation state, possibly by interference with a structural rearrangement of the outer vestibule. Thus, ultra-slow inactivation, favored by charge-altering mutations at site 1237 in micro1 Na+ channels, may be analogous to C-type inactivation in Shaker K+ channels.  (+info)

NMR spatial structure of alpha-conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors. (2/410)

A 600 MHz NMR study of alpha-conotoxin ImI from Conus imperialis, targeting the alpha7 neuronal nicotinic acetylcholine receptor (nAChR), is presented. ImI backbone spatial structure is well defined basing on the NOEs, spin-spin coupling constants, and amide protons hydrogen-deuterium exchange data: rmsd of the backbone atom coordinates at the 2-12 region is 0.28 A in the 20 best structures. The structure is described as a type I beta-turn (positions 2-5) followed by a distorted helix (positions 5-11). Similar structural patterns can be found in all neuronal-specific alpha-conotoxins. Highly mobile side chains of the Asp-5, Arg-7 and Trp-10 residues form a single site for ImI binding to the alpha7 receptor. When depicted with opposite directions of the polypeptide chains, the ImI helix and the tip of the central loop of long chain snake neurotoxins demonstrate a common scaffold and similar positioning of the functional side chains, both of these structural elements appearing essential for binding to the neuronal nAChRs.  (+info)

A conotoxin from Conus textile with unusual posttranslational modifications reduces presynaptic Ca2+ influx. (3/410)

Cone snails are gastropod mollusks of the genus Conus that live in tropical marine habitats. They are predators that paralyze their prey by injection of venom containing a plethora of small, conformationally constrained peptides (conotoxins). We report the identification, characterization, and structure of a gamma-carboxyglutamic acid-containing peptide, conotoxin epsilon-TxIX, isolated from the venom of the molluscivorous cone snail, Conus textile. The disulfide bonding pattern of the four cysteine residues, an unparalleled degree of posttranslational processing including bromination, hydroxylation, and glycosylation define a family of conotoxins that may target presynaptic Ca2+ channels or act on G protein-coupled presynaptic receptors via another mechanism. This conotoxin selectively reduces neurotransmitter release at an Aplysia cholinergic synapse by reducing the presynaptic influx of Ca2+ in a slow and reversible fashion. The three-dimensional structure, determined by two-dimensional 1H NMR spectroscopy, identifies an electronegative patch created by the side chains of two gamma-carboxyglutamic acid residues that extend outward from a cavernous cleft. The glycosylated threonine and hydroxylated proline enclose a localized hydrophobic region centered on the brominated tryptophan residue within the constrained intercysteine region.  (+info)

Solution structure of alpha-conotoxin ImI determined by two-dimensional NMR spectroscopy. (4/410)

The three-dimensional structure of alpha-conotoxin ImI, a potent antagonist targeting the neuronal alpha7 subtype of nicotinic acetylcholine receptor (nAChR), has been investigated by NMR spectroscopy. On the basis of 181 experimental constraints, a total of 25 converged structures were obtained. The average pairwise atomic root mean square difference is 0.40+/-0.11 A for the backbone atoms. The resulting structure indicates the presence of two successive type I beta-turns and a 310 helix for residues Cys2-Cys8 and Ala9-Arg11, respectively, and shows a significant structural similarity to that of alpha-conotoxin PnIA, which is also selective for the neuronal nAChR.  (+info)

Pairwise interactions between neuronal alpha7 acetylcholine receptors and alpha-conotoxin ImI. (5/410)

The present work uses alpha-conotoxin ImI (CTx ImI) to probe the neurotransmitter binding site of neuronal alpha7 acetylcholine receptors. We identify key residues in alpha7 that contribute to CTx ImI affinity, and use mutant cycles analysis to identify pairs of residues that stabilize the receptor-conotoxin complex. We first mutated key residues in the seven known loops of alpha7 that converge at the subunit interface to form the ligand binding site. The mutant subunits were expressed in 293 HEK cells, and CTx ImI binding was measured by competition against the initial rate of 125I-alpha-bungarotoxin binding. The results reveal a predominant contribution by Tyr-195 in alpha7, accompanied by smaller contributions by Thr-77, Tyr-93, Asn-111, Gln-117, and Trp-149. Based upon our previous identification of bioactive residues in CTx ImI, we measured binding of receptor and toxin mutations and analyzed the results using thermodynamic mutant cycles. The results reveal a single dominant interaction between Arg-7 of CTx ImI and Tyr-195 of alpha7 that anchors the toxin to the binding site. We also find multiple weak interactions between Asp-5 of CTx ImI and Trp-149, Tyr-151, and Gly-153 of alpha7, and between Trp-10 of CTx ImI and Thr-77 and Asn-111 of alpha7. The overall results establish the orientation of CTx ImI as it bridges the subunit interface and demonstrate close approach of residues on opposing faces of the alpha7 binding site.  (+info)

Acetylcholine and epibatidine binding to muscle acetylcholine receptors distinguish between concerted and uncoupled models. (6/410)

The muscle acetylcholine receptor (AChR) has served as a prototype for understanding allosteric mechanisms of neurotransmitter-gated ion channels. The phenomenon of cooperative agonist binding is described by the model of Monod et al. (Monod, J., Wyman, J., and Changeux, J. P. (1965) J. Mol. Biol. 12, 88-118; MWC model), which requires concerted switching of the two binding sites between low and high affinity states. The present study examines binding of acetylcholine (ACh) and epibatidine, agonists with opposite selectivity for the two binding sites of mouse muscle AChRs. We expressed either fetal or adult AChRs in 293 HEK cells and measured agonist binding by competition against the initial rate of 125I-alpha-bungarotoxin binding. We fit predictions of the MWC model to epibatidine and ACh binding data simultaneously, taking as constants previously determined parameters for agonist binding and channel gating steps, and varying the agonist-independent parameters. We find that the MWC model describes the apparent dissociation constants for both agonists but predicts Hill coefficients that are far too steep. An Uncoupled model, which relaxes the requirement of concerted state transitions, accurately describes binding of both ACh and epibatidine and provides parameters for agonist-independent steps consistent with known aspects of AChR function.  (+info)

The block of Shaker K+ channels by kappa-conotoxin PVIIA is state dependent. (7/410)

kappa-conotoxin PVIIA is the first conotoxin known to interact with voltage-gated potassium channels by inhibiting Shaker-mediated currents. We studied the mechanism of inhibition and concluded that PVIIA blocks the ion pore with a 1:1 stoichiometry and that binding to open or closed channels is very different. Open-channel properties are revealed by relaxations of partial block during step depolarizations, whereas double-pulse protocols characterize the slower reequilibration of closed-channel binding. In 2.5 mM-[K+]o, the IC50 rises from a tonic value of approximately 50 to approximately 200 nM during openings at 0 mV, and it increases e-fold for about every 40-mV increase in voltage. The change involves mainly the voltage dependence and a 20-fold increase at 0 mV of the rate of PVIIA dissociation, but also a fivefold increase of the association rate. PVIIA binding to Shaker Delta6-46 channels lacking N-type inactivation or to wild phenotypes appears similar, but inactivation partially protects the latter from open-channel unblock. Raising [K+]o to 115 mM has little effect on open-channel binding, but increases almost 10-fold the tonic IC50 of PVIIA due to a decrease by the same factor of the toxin rate of association to closed channels. In analogy with charybdotoxin block, we attribute the acceleration of PVIIA dissociation from open channels to the voltage-dependent occupancy by K+ ions of a site at the outer end of the conducting pore. We also argue that the occupancy of this site by external cations antagonizes on binding to closed channels, whereas the apparent competition disappears in open channels if the competing cation can move along the pore. It is concluded that PVIIA can also be a valuable tool for probing the state of ion permeation inside the pore.  (+info)

A marine snail neurotoxin shares with scorpion toxins a convergent mechanism of blockade on the pore of voltage-gated K channels. (8/410)

kappa-Conotoxin-PVIIA (kappa-PVIIA) belongs to a family of peptides derived from a hunting marine snail that targets to a wide variety of ion channels and receptors. kappa-PVIIA is a small, structurally constrained, 27-residue peptide that inhibits voltage-gated K channels. Three disulfide bonds shape a characteristic four-loop folding. The spatial localization of positively charged residues in kappa-PVIIA exhibits strong structural mimicry to that of charybdotoxin, a scorpion toxin that occludes the pore of K channels. We studied the mechanism by which this peptide inhibits Shaker K channels expressed in Xenopus oocytes with the N-type inactivation removed. Chronically applied to whole oocytes or outside-out patches, kappa-PVIIA inhibition appears as a voltage-dependent relaxation in response to the depolarizing pulse used to activate the channels. At any applied voltage, the relaxation rate depended linearly on the toxin concentration, indicating a bimolecular stoichiometry. Time constants and voltage dependence of the current relaxation produced by chronic applications agreed with that of rapid applications to open channels. Effective valence of the voltage dependence, zdelta, is approximately 0.55 and resides primarily in the rate of dissociation from the channel, while the association rate is voltage independent with a magnitude of 10(7)-10(8) M-1 s-1, consistent with diffusion-limited binding. Compatible with a purely competitive interaction for a site in the external vestibule, tetraethylammonium, a well-known K-pore blocker, reduced kappa-PVIIA's association rate only. Removal of internal K+ reduced, but did not eliminate, the effective valence of the toxin dissociation rate to a value <0.3. This trans-pore effect suggests that: (a) as in the alpha-KTx, a positively charged side chain, possibly a Lys, interacts electrostatically with ions residing inside the Shaker pore, and (b) a part of the toxin occupies an externally accessible K+ binding site, decreasing the degree of pore occupancy by permeant ions. We conclude that, although evolutionarily distant to scorpion toxins, kappa-PVIIA shares with them a remarkably similar mechanism of inhibition of K channels.  (+info)

Marine drugs have developed rapidly in recent decades. Cone snails, a group of more than 700 species, have always been one of the focuses for new drug discovery. These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or conopeptides. These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and affinity to ion channels, receptors, and transporters in the nervous systems of target prey and humans. Several research groups, including ours, have examined the venom gland of cone snails using a combination of transcriptomic and proteomic sequencing, and revealed the existence of hundreds of conotoxin transcripts and thousands of conopeptides in each Conus species. Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. However, more than 98% of these sequences still lack 3D structural and functional information. With
Highly selective N-type voltage-gated calcium (CaV) channel inhibitors from cone snail venom (the ω-conotoxins) have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Earlier in 2005, Prialt (Elan) or synthetic ω-conotoxin MVIIA, was the first ω-conotoxin to be approved by Food and Drug Administration for human use. This review compares the action of three ω-conotoxins, GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved N-type therapeutics that are more useful in the treatment of chronic pain.
α-Conotoxins Vc1.1 and RgIA are small peptides isolated from the venom of marine cone snails. They have effective anti-nociceptive actions in rat models of neuropathic pain. Pharmacological studies in rodent dorsal root ganglion (DRG) show their analgesic effect is mediated by inhibition of N-type (Cav2.2) calcium channels via a pathway involving γ-aminobutyric acid type B (GABAB) receptor. However, there is no direct demonstration that functional GABAB receptors are needed for inhibition of the Cav2.2 channel by analgesic α-conotoxins. This study examined the effect of the GABAB agonist baclofen and α-conotoxins Vc1.1 and RgIA on calcium channel currents after transient knockdown of the GABAB receptor using RNA interference. Isolated rat DRG neurons were transfected with small interfering RNAs (siRNA) targeting GABAB subunits R1 and R2. Efficient knockdown of GABAB receptor expression at mRNA and protein levels was confirmed by quantitative real time PCR (qRT-PCR) and immunocytochemical analysis,
Designing novel conotoxins with therapeutic potential Conotoxins, with their exquisite specificity and potency have recently created much excitement as drug leads for the treatment of chronic pain. For example, the conotoxin MVIIA (also known as Ziconotide or Prialt) has been approved for use in the U.S. and Europe for the treatment of pain and several other conotoxins have entered clinical trials. In addition, a number of conotoxins have played a critical role in dissecting the molecular mechanisms of ion channel and transporter functions in the nervous system.. There are projects available in the design of novel conotoxins that target specific receptors involved in pain.. ...
1G1P: NMR Solution Structures of delta-Conotoxin EVIA from Conus ermineus That Selectively Acts on Vertebrate Neuronal Na+ Channels.
by Justin A. Varholick Ph.D., University of Florida, Department of Biology and UF Genetics Institute Too often we read about new research using mice, rats, non-human primates, and fish. These few categories of animals teach us a lot about biology and how we may intervene to cure or alleviate a human disease. But, what about…
α-Conotoxins that are thought to act as antagonists of nicotinic acetylcholine receptors (nAChRs) containing α3-subunits are efficacious in several preclinical models of chronic pain. Potent interactions of Vc1.1 with other targets have suggested that the pain-relieving actions of α-conotoxins might be mediated by either α9α10 nAChRs or a novel GABA B receptor-mediated inhibition of N-type calcium channels. Here we establish that three α-conotoxins, Vc1.1, AuIB and MII have distinct selectivity profiles for these three potential targets. Their potencies after intramuscular administration were then determined for reversal of allodynia produced by partial nerve ligation in rats. Vc1.1, which potently inhibits α9α10 nAChRs and GABA B/Ca 2+ channels but weakly blocks α3β2 and α3β4 nAChRs, produced potent, long-lasting reversal of allodynia that were prevented by pre-treatment with the GABA B receptor antagonist, SCH50911. α-Conotoxin AuIB, a weak α3β4 nAChR antagonist, inhibited GABA B/Ca 2+
Disulfide-rich neurotoxins from venomous animals continue to provide compounds with therapeutic potential. Minimizing neurotoxins often results in removal of disulfide bridges or critical amino acids. To address this drug-design challenge, we explored the concept of disulfide-rich scaffolds consisting of isostere polymers and peptidic pharmacophores. Flexible spacers, such as amino-3-oxapentanoic or 6-aminohexanoic acids, were used to replace conformationally constrained parts of a three-disulfide-bridged conotoxin, SIIIA. The peptide-polymer hybrids, polytides, were designed based on cladistic identification of nonconserved loci in related peptides. After oxidative folding, the polytides appeared to be better inhibitors of sodium currents in dorsal root ganglia and sciatic nerves in mice. Moreover, the polytides appeared to be significantly more potent and longer-lasting analgesics in the inflammatory pain model in mice, when compared to SIIIA. The resulting polytides provide a promising ...
2LZ5: Characterization of a novel alpha-conotoxin from conus textile that selectively targets alpha6/alpha3beta2beta3 nicotinic acetylcholine receptors.
CONICET Digital, el repositorio institucional del CONICET, un servicio gratuito para acceder a la producción científico-tecnológica de investigadores, becarios y demás personal del CONICET.
http://onlinelibrary.wiley.com/doi/10.1002/anie.201000620/abstract The Engineering of an Orally Active Conotoxin for the Treatment of Neuropathic Pain...
Voltage-gated Na+ channels are involved in the generation of action potentials in excitable cells. Structural determinants of major physiological characteristics (i.e., ion selectivity, gating, and ligand binding) are localized in the α subunit (Catterall, 2000; Hille, 2001). It is composed of four homologous domains (I-IV) quasi-symmetrically arranged around the central pore (Sato et al., 2001). Each domain contains six transmembrane segments (S1-S6), a pore-forming region (P), and the intracellular N and C ends (Guy and Seetharamulu, 1986; Denac et al., 2000). The P region contains the selectivity filter formed by a circular motif of highly conserved Asp, Glu, Lys, and Ala residues called the DEKA locus (Terlau et al., 1991; Heinemann et al., 1992). The selectivity filter separates the outer pore, which is targeted by tetrodotoxin (TTX), saxotoxin, and conotoxins, from the inner pore, which is targeted by local anesthetics (LAs) and other small cationic drugs (Zhorov and Tikhonov, 2004). Na+ ...
Raffaella G., Sole,C., Llecha,N, Segura, M.F., Moubarak,R., Iglesias-Guimarais,V., Perez-Garcia,M.J., Reix,S., Zhang,J., Badiola,N., Sanchis,D., Rodriguez-Alvarez,J.,Trullas,R., Yuste,V.J., and J.X. Comella ...
Analizar y valorar, en la rata como modelo animal de neurodegeneración, posibles mecanismos inflamatorios involucrados en la toxicidad del péptido Aβ. Así como mecanismos por los que el calcio participa en la activación de astrocitos en fases tempranas (24h - 2 semanas) de la toxicidad inducida por el péptido Aβ1-42. ...
Am vazut emisiunea lui Maruta si sunt impresionata de evolutia voastra, a fratilor Traistariu! Sunteti cu totii niste artisti, fiecare in arta lui. Parintii vostri de acolo de unde sunt, va lumineaza drumul cu dragoste si cu siguranta sunt mandrii ca voi sunteti cu totii si fiecare in parte niste copii atat de minunati. Imi plac tablourile tale Vasile, dar nu imi este clar cum pot sa le cumpar?! Imi plac absolut toate, si imi doresc sa imi impodobesc micuta mea casa cu cateva dintre ele...caci simt energia lor benefica...Astept un semn in acest sens pe adresa mea de email pe care am lasat-o. Dumnezeu sa va ocroteasca sa fiti cu sufletul mereu impreuna...viata asta materiala, vine si pleaca...voi existati prin simtul vostru artistic. Va doresc din tot sufletul sa fiti de sfintele sarbatori de Paste impreuna asa cum imi doresc si pentru familia mea (eu am trei copii minunati si extraordinari ca si voi) si pentru toti cei care pe lumea asta inteleg ca ne-am nascut sa ne iubim neconditionat ...
Marine snails form the dominant component of molluscan faunas throughout the worlds oceans. There are about 600 different species of cone snails found distributed in warm and tropical seas and oceans worldwide, and the greatest diversity is seen in the Western Indo-Pacific Region. Cone snail venoms such as conotoxins and conopeptides show great promise as a source of new and medically important substances. The synthetic version of the conopeptide called ziconotide has been approved as a medication in the United States by the FDA (Food and Drug Administration) and is in current use as an analgesic (pain reliever). Conantokins, which are a family of conopeptides found in cone snail venom, serve as "sleeper peptides," and these peptides work by a mechanism that may be helpful for people with epilepsy ...
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6 ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia. The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik ([email protected]). ...
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6 ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia. The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik ([email protected]). ...
With more than 2600 studies published in the last 20 years, there is much excitement about conotoxins in biomedicine. "Most conotoxins are a succinct ten to forty amino acids in length and are exquisitely selective about their receptor binding sites. This makes them powerful tools for understanding how cells work and a rich source for discovery of new medicines", said Bernstein. Among many discoveries, conotoxins that block key neurological pathways have been effective in the early detection and may also help treat small-cell lung cancer, one of the most devastating human cancers. A compound now in clinical trials has powerful anti-epileptic activity. Experiments suggest that conotoxins could treat muscle spasticity following spinal cord injury. They could prevent cell death when there is inadequate circulation, such as during strokes, head injuries or coronary bypass surgery. They could also be used to treat clinical depression, heart arrhythmias and urinary incontinence ...
Conus geographus�Intro - Slide 1 (Cone shell snail)Ralph Waldo Emerson once stated The most dangerous thing is illusion. Good morning/afternoon ladies and gentlemen, my name is Tobias and today I will speak to you on the dangerous illusion tha...
Cone shells (Conidae) are a group of predatory marine snails. This group has not yet been divided into various genera, so that all of the approximately 300 species are included in the genus Conus.. Cone shells, like their close relatives the Turrids (Turridae), Mitre shells (Mitridae), Cytharidae and Auger shells (Terebridae), have developed an unusual venom apparatus for catching prey. However, only Cone shells are known to have caused envenoming in humans.. The shell of the Conidae is in the form of a rolled cone. There is a slit-like opening on the long side through which the animals evert their foot. The larger species, such as C. geographus, reach a length of up to 15 cm. With their often strikingly beautifully patterned shells, Cone shells are highly prized among shell collectors.. Cone shells live in shallow water, including coastal zones, especially reef areas, where they conceal themselves in crevices or bury themselves in the sand during the day. Only at dusk do they start appearing ...
The GluN2B subunit of the N-methyl-d-aspartate receptor (NMDAr) modulates many physiological processes including learning, memory, and pain. Excessive increase in NMDAr/GluN2B activity has been associated with various disorders such neuropathic pain and neuronal death following hypoxia. Thus there is an interest in identifying NMDAr antagonists that interact specifically with the GluN2B subunit. Recently based on structural analysis between the GluN2B subunit and conantokin-G, a toxin that interacts selectively with the GluN2B subunit, we designed various peptides that are predicted to act as NMDAr antagonists by interacting with the GluN2B subunit. In this study we tested this prediction for two of these peptides EAR16 and EAR18. The effects of EAR16 and EAR18 in NMDA-evoked currents were measured in cultured rat embryonic hippocampal neurons and in HEK-293 cells expressing recombinant NMDAr comprised of GluN1a-GluN2A or GluN1a-GluN2B subunits. In hippocampal neurons, EAR16 and EAR18 reduced the NMDA
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
TY - JOUR. T1 - Identification of residues in the neuronal α7 acetylcholine receptor that confer selectivity for conotoxin ImI. AU - Quiram, Polly A.. AU - Sine, Steven M.. PY - 1998/5/1. Y1 - 1998/5/1. N2 - To identify residues in the neuronal α7 acetylcholine subunit that confer high affinity for the neuronal-specific toxin conotoxin ImI (CTx ImI), we constructed α7-α1 chimeras containing segments of the muscle α1 subunit inserted into equivalent positions of the neuronal α7 subunit. To achieve high expression in 293 human embryonic kidney cells and formation of homo-oligomers, we joined the extracellular domains of each chimera to the M1 junction of the 5-hydroxytryptamine-3 (5HT-3) subunit. Measurements of CTx ImI binding to the chimeric receptors reveal three pairs of residues in equivalent positions of the primary sequence that confer high affinity of CTx ImI for α7/5HT-3 over α1/5HT-3 homo-oligomers. Two of these pairs, α7Trp55/α1Arg55 and α7Ser59/α1Gln59, are within one of ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
The tradition continues with Kalins Lunker Grub. Precise, proven design provides Maximum Action at Ultra-Slow Speed, the hallmark of all Kalin baits.
imi place sa plang. imi face buzele mai mari. am cearcane. asta inseamna ca ele au luat o parte din ochii mei. nori de cenusa. ma destram. dar imi place. imi place sa plang. ceva imi apasa inima. or fi lacrimi? tip: aaaaaaaaaaaaaaaaaaa! pot sa fac asta. sau nu. imi place sa plang.
The Conus genus includes around 500 species of marine mollusks using a peculiar production of venomous peptides referred to as conotoxins (CTX). S1) living generally in the tropical marine areas. About 700 species of Cone snails express hundreds of peptide toxins collectively known as conotoxins (CTX) aimed to self-defense, competition and predation of other marine species by means of stingCstructures that were reported to be fatal for human since from 300 years ago. CTX, however, do not exert only venomous activity but have a lot of pharmacological properties with specific bioactivity in the treatment of neurological disorders and the associated pain belief [1,2,3]. The presence of disulfide bonds is the important characteristic for natural function of CTX that enable to separate CTX into two primary types, the disulfide-rich peptides and no-disulfide-rich types; the foremost is generally composed of no more than 30 proteins and the next contains as much as 80 proteins. CTX are grouped into ...
But beware! Cone Snails have a extremely potent toxin (called Conotoxin), and they have to. They are tiny little guys who dont move very fast. Their toxin needs to paralyze their prey quickly, otherwise itll get away. The toxin in these Snails has the ability to kill a human being, and there is no known antivenom. They attack via a barb that shoots out from their shell, and the type of paralysis is dependent on the species. When their prey is immobilized, they draw it back in to their shell, still attached to the barb. Cone Snails are carnivorous and predatory, and feed off of fish, worms, and other mollusks, depending on the specific species ...
Tiny marine snails known as sea butterflies appear to fly underwater much like winged insects do when taking to the sky - representsing a remarkable example of convergent evolution, where two unrelated species develop features that are used in similar ways.
While considered a delicacy in some parts of the world, snails have found a more intriguing use to scientists and the medical profession offering a plethora of research possibilities.
Research Interests:. Foldamers are unnatural oligomers with a propensity to adopt well-defined conformations. These molecules have seen success in the mimicry of canonical peptide secondary structures such as -helices and -sheets. Current efforts in the field involve the application of foldamer design strategies to mimic higher-order protein structures and novel peptide architectures. Disulfide-rich peptides are notable candidates for foldamer research due to their intricate folding patterns and potent bioactivities. I am interested in establishing foldamer design principles for the synthesis of disulfide-rich peptide analogs with heterogeneous backbone modifications that manifest specific conformations, desired functionality and improved pharmacological properties.. Education:. B.S. in Microbiology, University of Hawaii at Manoa, 2008. M.S. in Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, 2014. ...
The big problems with morphine are addictiveness and the fact that people develop a tolerance to it," says Professor David Adams, director of the RMIT Health Innovations Research Institute. "With the painkillers derived from cone snail venom, we dont have those problems. People dont develop tolerance, and they dont get hooked.. "Also, theres a wide safety margin. With morphine, theres little room for error. If you overdose, youre likely to die. But with the venom peptides, there may be side-effects but you will survive.". David leads research into the cocktail of peptides-fragments of protein-with which the cone snail paralyses its prey. "These peptides have exquisite selectivity for their molecular targets," he says. So his team is geared to developing new treatments for chronic nerve-based pain by discovering and purifying peptides that target particular pain receptors.. Worldwide, there are more than 700 species of cone snails, about two-thirds of which are found in the Great Barrier ...
... ,(2S)-2-Propylpiperidine,cicutine,conicine,Hydrobromide,Coniine Hydrobromide,Hydrochloride,Coniine Hydrochloride,(R)-(-)-Form,(R)-(-)-Coniine,(+/-)-Form,(+/-)-Coniine
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
IMI held its IMI 2 Open Info Day in Brussels on Tuesday 30 September 2014. The event was well-attended, with more than 290 people participating either in person or remotely via the webcast. On top of a review of the new IMI 2 rules and Call procedures, IMIs founding partners presented their perspectives on IMI 2. In the afternoon, there were two topic-related workshops on the IMI 2 Call 1 topics, as well as plenty of networking opportunities throughout the day. During the workshops, participants were invited to make an elevator pitch or short presentation to the other participants about their organisation. The final session gave a preview of whats coming later this year in IMIs second IMI 2 Call, giving participants the chance to ask three of the topic writers directly about the new indicative topics.. The whole days events were recorded and the videos of each session will be viewable on IMIs YouTube channel.. ...
The first Part is atmospheric, dense and more progressive. The second part (my favorite) is also atmospheric, dense with some guttural vocals and painful chants, and the best ultra-slow riffs, sometimes almost Funeral Doom (anybody says Evoken ...
The Merck Index* Online | Coniine | Monograph containing literature references, physical and biological properties and relevant information
This week on Science and the Sea: Lethal Snails By Damond BenningfieldThe geographic cone snail was already known as a quiet killer. Its only a few inches long. And like many other species of cone snail, it lurks at the bottom...
And a handful are already being developed by companies in Australia and the US as non-addictive pain killers up to 10,000 times stronger than morphine.. With up to 50,000 toxins, cone snails may contain the largest and most clinically important pharmacopoeia of any genus in nature, says Professor Chivian. To lose them would be a self-destructive act of unparalleled folly.. Tropical reefs and mangroves where the cone snails live are being degraded by coastal development, overfishing, pollution, disease epidemics, and global climate change, his team says. Capture for the ornamental shell trade is also escalating. Millions of cone snails are now sold annually for as little as a few cents each in shops all over the world. But we could not find any country that monitors this trade, they concluded recently in the journal Science. ...
This National Geographic video shows a cone snail hunting by using its . harpoonlike tooth that can be propelled from an extendable proboscis. The harpoon is loaded with a complex mix of toxins. A cone snail can be seen blasting a fish with its harpoon out in the open. Another cone snail buries itself in the sand and then attacks a fish with its toxic harpoon from below. It then swallows the fish whole. Take a look: ...
So the question is: what is this barbed appendage that the critter used to poke my thumb? It is not well seen in the image, but the tail is hard, barbed and crescent-shaped and not visible unless the animal lashes out. The animal also used it to turn itself into correct position, if I placed it on its back. The whip of the tail was very fast (I always thought that snails are slow!). What is the primary use of the tail? Self-defense? Correcting the animals position? Attack? Also, is the real stinger supposed to be inside that sack-like structure that is located between the eyes? How easily does one get stung? Should one avoid stepping on a cone snail if walking along the ocean floor? (I know that handling the more exotic cone snails can be dangerous, even fatal - but what about these common ones ...
Midbrain slices and electrophysiology. Midbrain slices containing the VTA and SNc were prepared from 15- to 24-d-old Sprague Dawley rats, wild-type C57BL/6J mice, or mutant mice that were anesthetized before decapitation (Xu et al., 1999;Orr-Urtreger et al., 2000). Slices (300-350 μm thick, rats; 200-250 μm, mice) were prepared following previously published procedures (Pidoplichko et al., 1997; Zhou et al., 2001). The cutting solution was either of the following and usually a 50/50% mixture of the two solutions (in mm): 230 sucrose, 1 KCl, 1.25 NaH2PO4, 30 NaHCO3, 1 CaCl2, 7 MgCl2, 25 d-glucose; and 144 NMDG, 1.5 KCl, 1.25 NaH2PO4, 30 NaHCO3, 2 CaCl2, 2 MgCl2, 25 d-glucose, 30 NaHCO3. The slices were then transferred to a holding chamber containing the bath solution (in mm): 125 NaCl, 2.5 KCl, 1.25 NaH2PO4, 21 NaHCO3, 2.5 CaCl2, 1 MgCl2, 25 d-glucose. The experimental chamber (0.5 ml capacity) had a continuously flowing bath solution (∼5 ml/min) at 32-34°C. The external solutions contained ...
Posted by Chris on April 01, 2006 at 10:29:19:. In Reply to: Re: Conus californicus, the California Cone Snail posted by Deb Karimoto on April 01, 2006 at 08:50:01:. ...
Mollusk Venoms: Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.
The underwater version of a tank, this cone snail boasts an armored shell and enough venom to kill a human. Nearby fish dont stand a chance.
Chronic pain is very difficult to treat. Thus, novel analgesics are a critical area of research. Strong pre-clinical evidence supports the analgesic effects of α-conopeptides, Vc1.1 and RgIA, which block α9α10 nicotinic acetylcholine receptors (nAChRs). However, the analgesic mechanism is controversial. Some evidence supports the block of α9α10 nAChRs as an analgesic mechanism, while other evidence supports the inhibition of N-type CaV (CaV2.2) current via activation of GABAB receptors. Here we reassess the effect of Vc1.1 and RgIA on CaV current in rat sensory neurons. Unlike the previous findings, we found highly variable effects among individual sensory neurons, but on average only minimal inhibition induced by Vc1.1, and no significant effect on the current by RgIA. We also investigated the potential involvement of GABAB receptors in the Vc1.1 induced inhibition, and found no correlation between the size of CaV current inhibition induced by baclofen (GABAB agonist) vs. that induced by ...
Nielsen, Katherine J. and Watson, Michael and Adams, David J. and Hammarstrom, Anna K. and Gage, Peter W. and Hill, Justine M. and Craik, David J. and Thomas, Linda and Adams, Denise and Alewood, Paul F. and Lewis, Richard J. (2002) Solution structure of μ-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels. Journal of Biological Chemistry, 277 (30). pp. 27247-27255. ISSN 0021-9258 ...
The rasping organ of the humble marine snail assembles tools from the hardest known biomaterial - fiber-reinforced crystalline magnetite. Fortunately, the marine snail has been slow to file its patents and others have now jumped in to command this newly revealed tool for themselves.. ...
Sephiroth 20140618 :: DESCRIPTION Sephiroth is a disulfide connectivity pattern predictor based on evolutionary information retrieved from Multiple Sequence Alignments (MSAs). ::DEVELOPER (IB)² - Interuniver
What does a marine snails ability to kill prey with two shots of venom have to do with the opioid epidemic ravaging the United States?
From 17 December 2014 to 26 January 2015 IMI held webinars on each topic of the IMI2 3rd and 4th Calls for proposals, as well as its new rules and procedures.. All webinars on the Call topics featured a presentation by the EFPIA topic coordinator, as well as time for questions and answers. The webinars therefore represented an excellent opportunity to learn more about the topics, interact directly with the topic coordinators, and get in touch with potential project partners. The webinar on IMIs new rules and procedures also included presentations of IMIs intellectual property policy and tips on the preparation of proposal submissions.. ...
Rafael D. Mesquita, Alan Brito Carneiro, André Bafica, Felipe Gazos-Lopes, Christina M. Takiya, Thaís Souto-Padron, Danielle P. Vieira, Antônio Ferreira-Pereira, Igor C. Almeida, Rodrigo T. Figueiredo, Bárbara N. Porto, Marcelo T. Bozza, Aurélio V. Graça-Souza, Angela H. C. S. Lopes, Geórgia C. Atella, Mário A. C. Silva-Neto ...
This Histri was built automatically but not manually verified. As a consequence, the Histri can be incomplete or can contain errors ...
Small and speedy. Human insulin is a hormone that is produced in the pancreas and secreted to aid in the bodys uptake of glucose. The insulin molecule consists of an "A" region and a "B" region. Diabetes mellitus disorders arise from impairment of the bodys normal production of insulin. The most effective treatment for diabetes is injection of synthetic insulin.. But a part of the B region causes insulin molecules to stick together and form aggregations of six insulin molecules. Its how insulin is stored in the pancreas. But injected insulin must de-aggregate into individual molecules before doing a person any good - and that process can take up to an hour. The fastest-acting insulin on the market, Humalog, still takes 15-30 minutes to become active. "The ideal scenario would be to take the region off of the B chain" Safavi says. "But then you completely abolish insulin activity.". Chou, Safavi, and colleagues found that insulin produced by the cone snail Conus geographus lacked the segment ...
Conus textile is a species of cone snail known as the "cloth of gold." It lives in the waters of the Indo-Pacific, Australia, the Indian Ocean from eastern Africa to Hawaii, and French Polynesia. Typical length of adults is about 9.0 cm (3.5 in).. It uses a conotoxin to kill its prey. The animal uses microscopic needles to inject the toxin into its prey. The proboscis, the tip which holds the harpoon-like, radular tooth, is capable of being extended to any part of its own shell. The living animal is a risk to any person handling it who has not taken proper care to protect exposed skin. Several human deaths have been attributed to this species.. The female lays several hundred eggs at a time, which hatch after about 16 or 17 days. After hatching, the larvae float around in the current for approximately 16 days. Afterward, they settle at the bottom of the ocean. By this point their length is about 1.5 mm (0.06 in).. ...
I will only name my one favorite Conus species: C. ebraeus, mainly because it is the most successful of all. The criteria for biological success vary with the category. At the genus level, Conus is of course the most successful in the sea, because it has the most species and occupies a correspondingly broad array of habitats and areas. For a species, criteria for success include how widespread it is, how abundant it is, and how many types of environment it can exploit. (This is why our species, Homo sapiens, is so successful on land.) C. ebraeus has the widest geographic range of any Conus species. It occurs throughout the Indo-Pacific region (1/4 of the worlds ocean area), and it has also crossed the East Pacific Barrier to colonize the coast of Costa Rica. It has a planktonic larva that stays afloat feeding and growing for at least several weeks and can thus be transported widely by currents. Tom Duda and Haris Lessios have shown that its populations in widely separated regions have almost ...
These toxins target sodium and calcium channels in the body. At the time of their discovery, little was known about voltage-gated calcium-channels, which are present in excitable cells such as muscle cells and neurons and which initiate a response such as contraction or excitation, respectively, upon the passage of calcium through the channels. One of Oliveras peptides from cone snails, the Ω-conotoxin GVIA, functioned through inhibition of calcium uptake through binding to neuronal calcium channels. News of this discovery caused a boon of research in this field, yielding more than 2,000 studies, which utilized Oliveras synthesized version of the Ω-GVIA peptide, active at concentrations of less than 1E-12M! Research in this field finally resulted in the purification of the neuronal calcium channel, which was subsequently named after Oliveras peptide, "the conotoxin receptor." In addition to the impact this discovery had in the field of neuroscience, a conotoxin peptide has been approved as ...
Cone snails are marine predators that use venoms to immobilize their prey. The venoms of these mollusks contain a cocktail of peptides that mainly target different voltage- and ligand-gated ion channe
Late 1980s and 1990s - description of normal level of conus in infants: Using sonography, Robbin et al. (23) refuted the idea of ascension during childhood and posited that by approximately 19 weeks gestation, the conus should have achieved its adult position. Wilson and Prince (38) concluded that a conus positioned at L2-L3 should be considered normal at any age. DiPietro (4) added to these data, showing that children younger than 2 months of age had a mean conus termination at the lower third of the L1 vertebral body, whereas children between the ages of 1 and 4 years had a mean conus termination at the upper third of the L1 vertebral body, and furthermore that the conus of children between the ages of 4 and 13 years was located at the upper third of the L1 vertebral body. Their study (4) also concluded that criteria for the determination of conus level should be age-dependent. Another sonography study (23) found that the conus was located above the L2 vertebral level in 92.1% of term babies, ...
By Glen F King; C R Ganellin; Salvatore Guccione. The pharmaceutical has turn into more and more drawn to biologics from animal venoms as a possible resource for healing brokers in recent times, with a very emphasis on peptides. thus far six medications derived from venom peptides or proteins were licensed via the FDA, with 9 additional brokers at present being investigated in scientific trials. as well as those medications in authorized or complicated levels of improvement, many extra peptides and proteins are being studied in various levels of preclinical improvement. This particular e-book offers an up-to-the-minute and entire account of the opportunity of peptides and proteins from animal venoms as attainable therapeutics. subject matters lined contain chemistry and structural biology of animal venoms, proteomic and transcriptomic methods to drug discovery, bioassays, high-throughput monitors and aim identity, and reptile, scorpion, spider and cone snail venoms as a platform for drug ...
Pharmacological and molecular studies on the interaction of varenicline with different nicotinic acetylcholine receptor subtypes. Potential mechanism underlying partial agonism at human a4 2 and a3 4 subtypes ...
It is beneficial for males to mate as often as possible, since this is the only way in which they can influence the number of offspring they father. But it is costly for the females to mate often, and this is important for them in surviving during the period they are carrying offspring.". A situation in which individuals of different gender have conflicting interests is known as a "sexual conflict". Such conflicts can arise in various situations, and this is one of few examples of a sexual conflict in which the females attempt to conceal their gender. There are some other examples, including certain species of damselfly in which some of the females conceal their gender, simply by having the same colouring as the males.. ...
Pixdaus.com is an environmental photo-bookmarking and sharing service. All the pictures are uploaded by users and the copyrights belong to the rightholders. You can request a removal using the Copyright flag link below each image if you find an image that shouldnt belong here ...
Conus (Virgiconus) frigidus Reeve, 1848) Puillandre N., Duda T.F., Meyer C., Olivera B.M. & Bouchet P. (2015). One, four or 100 genera? A new classification of the cone snails. Journal of Molluscan Studies. 81: 1-23., available online at https://doi.org/10.1093/mollus/eyu055 [details] Available for editors ...
Researchers are increasingly turning to nature for inspiration for new drugs. One example is Prialt. It's an incredibly powerful painkiller tha
Historical remote sensing phenology (RSP) image data and graphics for the conterminous U.S. are made freely available from the USGS/EROS Center through this website. Five data sets are distributed: CONUS 1 km AVHRR RSP data, C5 Eastern CONUS 250 m eMODIS RSP data, C6 Eastern CONUS 250 m eMODIS RSP data, C5 Western CONUS 250 m eMODIS RSP data, and C6 Western CONUS 250 m eMODIS RSP data.. ...
Historical remote sensing phenology (RSP) image data and graphics for the conterminous U.S. are made freely available from the USGS/EROS Center through this website. Five data sets are distributed: CONUS 1 km AVHRR RSP data, C5 Eastern CONUS 250 m eMODIS RSP data, C6 Eastern CONUS 250 m eMODIS RSP data, C5 Western CONUS 250 m eMODIS RSP data, and C6 Western CONUS 250 m eMODIS RSP data.. ...
This species is restricted to a single bay in Angola. The threats are unknown. Oil prospection has been going on along the Angolan coast, but there is no further development on this at the moment, so this is not considered a current threat; it may be more significant in the future if oil drilling commences (M. J. Tenorio and S. Veldsman pers. comm. 2011 ...
Vagal efferent activation can reduce inflammation and disease activity in various animal models of intestinal inflammation, likely via a mechanism involving activation of a a7nAChR subtype. The current hypothesis for this ...
Vagal efferent activation can reduce inflammation and disease activity in various animal models of intestinal inflammation, likely via a mechanism involving activation of a a7nAChR subtype. The current hypothesis for this ...
Celem niniejszej pracy było przeprowadzenie analizy morfologicznej nerwu mięśniowoskórnego (nervus musculocutaneus) i jego odgałęzień u przedstawicieli następujących rzędów: torbaczy, owadożernych, naczelnych, gryzoni, zajęczaków, szczerbaków, mięsożernych, góralków, nieparzystokopytnych i parzystokopytnych. Opierając się na przeprowadzonych badaniach można stwierdzić, że morfologia i topografia nerwu mięśniowoskórnego u poszczególnych gatunków wykazuje dość znaczne różnice. Dotyczą one zarówno samego pnia tego nerwu jak i jego odgałęzień.
As humans release more and more carbon dioxide into the atmosphere, the gas is dissolving into the ocean, making seawater more acidic. This threatens the growth and survival of animals such as some corals and snails, whose skeletons and shells may become thinner under more acidic conditions.. But ocean acidification can have more subtle consequences, such as affecting animal behavior and the relationships between predators and prey. Researchers in Senior Scientist Jim Barrys lab at MBARI have been studying these effects in the institutes state-of-the-art seawater lab. They recently published a paper showing how ocean acidification makes some snails more susceptible to being eaten by invasive (and predatory) green crabs.. The study, published in early May 2019 in the journal Marine Ecology Progress Series, involved placing green crabs in containers with three different species of marine snails, and exposing the animals to seawater at different temperatures and levels of acidity. The idea was to ...
Synonyms for Epacris purpurascens in Free Thesaurus. Antonyms for Epacris purpurascens. 1 synonym for Epacris purpurascens: Port Jackson heath. What are synonyms for Epacris purpurascens?
Ziconotide (SNX-111; Prialt) is an atypical analgesic agent for the amelioration of severe and chronic pain. Derived from Conus magus (Cone Snail), it is the synthetic form of an ω-conotoxin peptide. In December 2004 the Food and Drug Administration approved ziconotide when delivered as an infusion into the cerebrospinal fluid using an intrathecal pump system.
University of Utah researchers have found that the structure of an insulin molecule produced by predatory cone snails may be an improvement over current fast-acting therapeutic insulin.
Spent about 2 hours at Whiskey Bridge today. I found that theres a decent bit of stuff directly under the bridge, but if you walk upstream, theres a lot of areas that havent really been dug in. Plus, up that way the fossiliferous material is over my height, and you can just walk along it and look at all the layers. Thats interesting, in and of itself. Not just because of the appearance, but because I tend to get to thinking about how old they are, and about how every one of those fossils is somethings entire life, the cumulation of its efforts to survive. Its fascinating to picture- these layers on layers of life. I wouldnt make it as a paleontologist, not with my fatigue issues, but Ill gladly do this hobby-type stuff just for those moments. I found a good handful of shells, including a nice cone snail. I also brought home some shell-rich clods of matrix to work with. Gonna give those a good long soak and see if I can break them open without breaking the shells inside. A lot of these ...
Girit T p Bebek Merkezi bireylere, cinsiyet se imi, yumurta nakli, yumurta donasyonu, sperm nakli ve donasyonu alanlar nda profesyonel destek sunar!
எம்.ஜீயில் தன்பிறப்பொருளெதிரிகள் பெரும்பாலாக நிகோடினிக் அசிடைல்கொலின் ஏற்பிகளுக்கு( என்.ஏ.சி.எச்.ஆர் (nAChR)) எதிராக இயக்கப்படுகின்றன.[5] என்.ஏ.சி.எச்.ஆர் தசை இறுக்கத்தைத் தூண்டும் நரம்பியத்தாண்டுவிப்பியாக அசிடைல்கொலினுக்கான இயக்க முனைத்தட்டுக்கான ஏற்பியாகும். பிறப்பொருளெதிரியின் சில வடிவங்கள் அசிடைல்கொலின் ஏற்பிகளுடன் பிணைவதை பாழாக்குகின்றன. மற்றவை ஏற்பிகள் அழியக் ...
Neuronal nicotinic acetylcholine receptors (nAChRs) are excitatory ligand‐gated ion channels that perform important roles throughout the nervous systems of both vertebrate and invertebrate organisms. Impairments to human nAChRs and cholinergic transmission are thought to underlie the pathophysiologies of several neurological and psychological diseases including schizophrenia, Alzheimers disease, Parkinsons disease and certain forms of epilepsy. They are also the receptors that mediate the effects of tobacco smoking and contribute to the physiological and psychological changes associated with nicotine addiction. The aim of this thesis is to further our understanding of neuronal nAChRs from a pharmacological and molecular viewpoint. Research described in this thesis focuses on numerous aspects of neuronal nAChRs; allosteric modulators, insect nAChRs and chaperone proteins. Allosteric modulators of nAChRs are ligands that alter the receptors responsiveness to agonists via sites that are ...
Cone snails may look harmless but a sting from one can be lethal. Find out how these pretty-looking shells could possibly pose a threat and what to do if you encounter one.
We previously found that the Hookean region of the stress-strain behaviour could be reversibly eliminated from the material behavior with a thermal treatment pointing to the fact that the Hookean region is heat labile and the yield region is not. The present study determined that high concentrations of formic acid as well as buffers with low pH could also mimic aspects of the thermal effect. In sum, the results of these treatments suggest a crosslinked polymer with the ability to maintain long-range elasticity in conditions that might otherwise be destructive to proteins.. There is utility in exploring the conditions necessary for diminishment of the Hookean region. A synthesis of the salient features of alpha-keratin mechanical models suggest that the Hookean region represents coiled-coil structural motifs, and that by applying strain to the material, sufficient energy is applied to begin unraveling these domains at the transition between the Hookean and yield regions. Additional unraveling ...
Neuropeptides are a diverse assemblage of signalling molecules that have key roles in the regulation of behaviour. Understanding the evolutionary relationships and functions of the plethora of neuropeptides has presented a considerable challenge to biologists. Based on presentations and discussions at a Royal Society meeting in 2017, three companion Review articles by Elphick et al., Jékely et al. and DeLaney et al. discuss advances in our knowledge of neuropeptide evolution and function and the techniques that have facilitated progress in this field of research.. ...
But following in the success of zicontide(Prialt(R)), the pain reliever made the venom of the cone snail, researchers started looking at other natural venoms to see if they could be tamed as pain relievers. These new pain relievers is touted as a non-addictive pain reliever 1000 times as powerful as, and possibly a replacement for, morphine. These are various peptides, targeting each a specific nerve channel or receptor. This venom also contains a pain-reducing component, first pacifying the victim, before immobilising and then killing it. Many peptides produced by the cone snails show prospects for being potent pharmaceuticals, such as AVC1, isolated from the Australian cone shell Conus victoriae. This has proved very effective in treating post-surgical and neuropathic pain, even accelerating recovery from nerve injury. Other drugs are in clinical and preclinical trials, such as compounds of the toxin that may be used in the treatment of Alzheimers disease, Parkinsons disease, and epilepsy ...
Christened the state seashell in 1987, the knobbed whelk is a whorled shell, eight inches long at maturity, displaying heavy spines, many knobs, and an orange or red mouth. Minerals in Georgia coastal waters cause ocher striations on the sand-colored, semi-gloss surface. This marine snail shell is found all along Georgias shoreline, out to 30 feet of water.
Após sorteio desta sexta-feira em Nyon, na Suíça, para definir os confrontos da última fase preliminar da Liga Europa, com jogos de ida em 22 de
Available: http://www.calflora.org/ (Accessed: Jan 18, 2018). The information on this page comes from diverse sources. None of the links are sponsored. ...
Ziconotide (SNX-111; Prialt) is an atypical analgesic agent for the amelioration of severe and chronic pain. Derived from Conus magus, a cone snail, it is the synthetic form of an ω-conotoxin peptide. In December 2004 the Food and Drug Administration approved ziconotide when delivered as an infusion into the cerebrospinal fluid using an intrathecal pump system. Ziconotide is derived from the toxin of the cone snail species Conus magus. Scientists have been intrigued by the effects of the thousands of chemicals in marine snail toxins since the initial investigations in the late 1960s by Baldomero Olivera. Olivera, now a professor of biology in the University of Utah, was inspired by accounts of the deadly effects of these toxins from his childhood in the Philippines. Ziconotide was discovered in the early 1980s by University of Utah research scientist Michael McIntosh, when he was barely out of high school and working with Baldomero Olivera. Ziconotide was developed into an artificially ...
The sharp, venomous stinger of the cone snail imparts a paralytic toxin similar to that of the pufferfish and the blue-ringed octopus; poisoning symptoms may include pain, numbness, tingling, muscle paralysis, blurred/double vision, and respiratory paralysis.
Conus badius Kiener, 1845) Kiener, L.C. (1844-1850). Spécies général et iconographie des coquilles vivantes. Vol. 2. Famille des Enroulées. Genre Cone (Conus, Lam.), pp. 1-379, pl. 1-111 [pp. 1-48 (1846); 49-160 (1847); 161-192 (1848); 193-240 (1849); 241-[379](assumed to be 1850); plates 4,6 (1844); 2-3, 5, 7-32, 34-36, 38, 40-50 (1845); 33, 37, 39, 51-52, 54-56, 57-68, 74-77 (1846); 1, 69-73, 78-103 (1847); 104-106 (1848); 107 (1849); 108-111 (1850)]. Paris, Rousseau & J.B. Baillière., available online at http://www.biodiversitylibrary.org/item/88016 ...
IMI delivers fiber admixtures in our concrete. Fibers are integrally mixed in your concrete to provide three dimensional crack controls. Concrete fibers vary in length, thickness and fiber count. Talk to your local IMI sales representative to discuss your particular job and to determine the type and amount of fiber needed.. Contact a sales representative. ...
Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. ...
The extremely potent and selective nicotinic acetylcholine receptor antagonist methyllycaconitine, MLA, and related norditerpene alkaloids are finding increasing use as neurochemical probes and as targets for structure-activity relationship studies. In this work, an assay procedure for MLA which utilises ion suppression reverse-phase HPLC with UV absorbance detection at 270 nm is described. The method detected 280 ng MLA on column.
Molecular and cell biological characterisation of neuronal nicotinic acetylcholine receptors (nAChRs) provides an insight into their functional roles and potential as therapeutic targets for neurological disorders. Nicotinic receptors are oligomeric ligand-gated ion channels, comprising five subunits. Twelve vertebrate neuronal nAChR subunits (2-10 and 2-4) have been cloned to date, with considerable diversity observed in nAChR subunit composition. Heterologous expression of cloned subunits is a powerful method for investigating ion channel receptor pharmacology and subunit composition, but achieving efficient expression of some nAChRs in cultured cell lines has proved difficult. In this study, chimeras containing the N-terminal domain of the nAChR subunits, fused to the C-terminal region of the 5-hydroxtryptamine type 3 receptor subunit, 5HT3A, were constructed to overcome some of the challenges of recombinant nAChR expression. When combinations of wild-type and chimeric subunits were expressed ...
Recently, information derived by correlated mutations in proteins has regained relevance for predicting protein contacts. This is due to new forms of mutual information analysis that have been proven to be more suitable to highlight direct coupling between pairs of residues in protein structures and to the large number of protein chains that are currently available for statistical validation. It was previously discussed that disulfide bond topology in proteins is also constrained by correlated mutations. In this paper we exploit information derived from a corrected mutual information analysis and from the inverse of the covariance matrix to address the problem of the prediction of the topology of disulfide bonds in Eukaryotes. Recently, we have shown that Support Vector Regression (SVR) can improve the prediction for the disulfide connectivity patterns. Here we show that the inclusion of the correlated mutation information increases of 5 percentage points the SVR performance (from 54% to 59%). When this
In the former Bufo marmoreus group of Martin, 1972, in Blair (ed.), Evol. Genus Bufo: 50. See map, description of geographic range and habitat, and conservation status (as Bufo perplexus) in Stuart, Hoffmann, Chanson, Cox, Berridge, Ramani, and Young, 2008, Threatened Amph. World: 190. Mendelson, Mulcahy, Williams, and Sites, 2011, Zootaxa, 3138: 1-34, suggested that Incilius canaliferus is a members in an a monophyletic group referred to as the Pacific Versant group (the name Incilius marmoreus group is available-DRF) that includes Incilius canaliferus, Incilius marmoreus, and Incilius perplexus. Oliver-López, Woolrich-Piña, and Lemos-Espinal, 2009, Fam. Bufonidae Mex.: 88-89, provided an account for Mexico (as Ollotis perplexa) although the range map is substantially out of date ...
Of the 42 patients, 21 had been treated with steroid and immunosuppresion therapy. LRNC quantification may be an effective complementary strategy to stenosis for classifying carotid atherosclerotic disease severity. Intravenous administration of acepromazine increases peripheral blood flow causing an earlier onset of the vascular phase during the three-phase bone scan. Recruitment into lafavre pharmacy viagra online nursing degree courses in the UK is considered in relation to overall recruitment into nursing. Hidden diversity in a hyperdiverse gastropod genus: discovery of previously unidentified members of a Conus species complex. Reduction of bacteria levels can provide additional means of preventing dental caries.. In this study, we show that IQGAP1 is robustly expressed in ECs and binds to the VEGFR2. Furthermore, it was observed that at higher pH, a longer duration of time is required before viagra generic with out a prescription equilibrium is established. Upside-down position to ...
The synthesis, characterization and thermogravimetric study of the adducts ZnCl2.2Imi, ZnBr2.2Imi, CdCl.Imi, CdCl2.2Imi, CdBr2.2Imi, CdBr2.3Imi, CdI2.2.5Imi, HgCl2.2Imi, HgBr2.1.5Imi and HgI2.1.5Imi (Imi = imidazole) is reported. The following sequence of thermal stability is observed for the synthesized adducts: Zn , Hg , Cd. It is also verified that larger cations, as well as larger anions, result in a smaller number of imidazole molecules in the coordination sphere of the considered cation and that hard acids exhibit stronger bonds to imidazole than soft acids, and this fact is reflected in the thermal stability sequence. ZnCl2.2Imi behaves as a non-electrolyte in acetonitrile and ethanol, whereas ZnBr2.2Imi is a non-electrolyte in acetonitrile and a 1:1 electrolyte in ethanol. CdI2.2.5Imi is a non-electrolyte in acetonitrile and a 1:2 electrolyte in ethanol. (C) 2003 Elsevier B.V. All rights reserved ...
... is a volatile fluid alkaloid of hemlock (conium). It is somewhat irritant to the skin and mucous mem branes, and is absorbed from the latter. It acts upon the terminations of the motor nerves...
Conotoxins[edit]. Ziconotide is a voltage-gated calcium channel blocker which may be used in severe cases of ongoing ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
Daly, N. L.; Craik, D. J. (2009). "Structural studies of conotoxins". IUBMB Life. 61 (2): 144-50. doi:10.1002/iub.158. PMID ... Such proteins include C1q, elastins, PrP, Argonaute 2, and conotoxins, among others. As prolyl hydroxylase requires ascorbate ...
Conotoxins represent a category of poisons produced by the marine cone snail, and are capable of inhibiting the activity of a ... One of the unique forms of conotoxins, ω-conotoxin (ω-CgTx) is highly specific for Ca channels and has shown usefulness in ... In many cases, the toxins released by the different types of cone snails include a range of different types of conotoxins, ... doi:10.1016/s0166-2236(96)10074-6. Jacob, Reed B.; McDougal, Owen M. (2010). "The M-superfamily of Conotoxins: a Review". ...
These toxins are known as conotoxins or conopeptides. The toxins are of importance to medical research. A notable feature of ...
Their venom contains conotoxins which have powerful neurotoxic effects. Given that they are capable of "stinging" humans, live ...
Several of the conotoxins contain two to five Gla residues. Vitamin K status can be assessed by: The prothrombin time (PT) test ... These snails produce a venom containing hundreds of neuroactive peptides, or conotoxins, which is sufficiently toxic to kill an ... Buczek, O.; Bulaj, G.; Olivera, BM (Dec 2005). "Conotoxins and the posttranslational modification of secreted gene products". ...
ω-Conotoxins are derived from the venom of cone snails. ω-Conotoxin MVIIC acts within the hippocampal CA1 pyramidal neurons to ...
"Therapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor". Toxicon. 48 (7): 810-29. doi ...
Blockers, like ω-Conotoxins, can interfere with many different therapeutic processes. In addition to the α1 subunit, the ... ω-Conotoxins Cadmium Caroverine Cilnidipine Gabapentin Levetiracetam Lamotrigine Nicardipine NP078585 Pregabalin TROX-1 ... There are many known N-type calcium channel blockers, but the most notable blocker are ω-Conotoxins. ...
The Conus Biodiversity website Cone Shell and Conotoxins website Pain Killer Comes out of its Shell - The Age 25 July 2005 ... "Therapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor". Toxicon. 48 (7): 810-29. doi ...
Some snail poisons, conotoxins, contain hydroxyproline, but lack collagen-like sequences. Hydroxylation of proline has been ...
Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. Mu-conotoxins target the ... whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers. ... The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ( ... Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However, it appears that many of ...
"The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels". The ...
She also contributed to the development of conotoxins as tools for examining the activity of the human brain. For instance, w- ...
These molecules, called conotoxins, led to a breakthrough in the study of ion channels and neuro-muscular synapses. He ... His impressive research on both DNA biophysics and conotoxins has enabled Dr. Olivera to serve as an editorial board member of ...
HWTX-X has selectivity for isoforms of N-type Ca2+ channels, compared with ω-conotoxins GVIA and MVIIA. HWTX-X specifically ... While structurally similar to ω-conotoxins that block the twitch response to electrical nerve stimulation, HWTX-X has no effect ...
The Waglerins and complementary conotoxins are useful tools to discover the contribution of acetylcholine receptor subunits to ... "Definition and Characterization of the Short alphaA-Conotoxins: A Single Residue Determines Dissociation Kinetics from the ...
... s typically lack disulfide bonds, in contrast to most families of conotoxins, which have an unusually high density of ...
Buczek O, Bulaj G, Olivera BM (December 2005). "Conotoxins and the posttranslational modification of secreted gene products". ...
Jacob, Reed B., and Owen M. McDougal (2010) "The M-superfamily of Conotoxins: a Review." Cellular and Molecular Life Sciences, ...
They are relatively homologous to the calcium channel blockers omega-conotoxins from marine cone snails and belong to the four- ...
Jacob, Reed B., and Owen M. McDougal (2010) "The M-superfamily of Conotoxins: a Review." Cellular and Molecular Life Sciences, ...
We tested two alternative oxidation strategies to produce conotoxins α-GI and μ-PIIIA. The peptides were either reversibly ...
The mode of action of several conotoxins has been the subject of investigation, while for many others this remains unknown. ... This review aims to give an overview of the knowledge we have today on the molecular pharmacology of conotoxins specifically ... Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview by Eline K. M. Lebbe. , Steve Peigneur. , Isuru Wijesekara ... The mode of action of several conotoxins has been the subject of investigation, while for many others this remains unknown. ...
Biotinylated derivatives of omega-conotoxins GVIA and MVIID: probes for neuronal calcium channels.. Haack JA1, Kinser P, ... The omega-conotoxins are small, disulfide-rich peptides which inhibit voltage-sensitive calcium channels. Biotinylated omega- ... We describe the preparation and characterization of biotinylated derivatives of two specific omega-conotoxins, GVIA and MVIID, ... conotoxins are potentially useful reagents for characterizing distinct subsets of calcium channels. ...
omega-Conotoxins: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry ... omega-Conotoxins. Subscribe to New Research on omega-Conotoxins A family of structurally related neurotoxic peptides from ... 03/01/2013 - "Omega-conotoxins as experimental tools and therapeutics in pain management.". 11/10/2000 - "omega-Conotoxins ... 02/01/2010 - "Neuronal (N)-type Ca(2+) channel-selective omega-conotoxins have emerged as potential new drugs for the treatment ...
These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and ... These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or ... Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. ... and nine more conotoxins are at various stages of preclinical or clinical evaluation. In short, the genus Conus, the big family ...
This review compares the action of three ω-conotoxins, GVIA, MVIIA and CVID, describing their structure-activity relationships ... the ω-conotoxins) have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Earlier in ... ω-Conotoxins. All ω-conotoxins identified to date have been found in piscivorous cone snails ranging from the small Conus catus ... Structural studies of ω-conotoxins. To date, all structural information available on the ω-conotoxins has been obtained from 1H ...
Although ω-conotoxins demonstrate analgesic efficacy in animal models of neuropathic pain and in human clinical trials, there ... In this review we discuss the growing application of ω-conotoxins, small peptides isolated from Conus species, in the ... The potency and selectivity with which ω-conotoxins inhibit their molecular targets, voltage-gated Ca2+ channels, is ...
Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins ... Halai, R.; Craik, D.J. Conotoxins: Natural product drug leads. Nat. Prod. Rep. 2009, 26, 526-536. [Google Scholar] [CrossRef] [ ... Li, R.A.; Tomaselli, G.F. Using the deadly μ-conotoxins as probes of voltage-gated sodium channels. Toxicon 2004, 44, 117-122 ... Daly, N.L.; Ekberg, J.A.; Thomas, L.; Adams, D.J.; Lewis, R.J.; Craik, D.J. Structures of μO-conotoxins from Conus marmoreus ...
In this case, over 40 conotoxins are characterized based on only two LC-ESI-MS experiments in terms of mass, number of ... Sequencing and mass profiling highly modified conotoxins using global reduction/alkylation followed by mass spectrometry.. ...
... ... ω-conotoxins, such MVIIA and CVID are effective in neuropathic pain models. CVID is reported to have a greater therapeutic ... All ω-conotoxins produced dose-dependent reduction in mechanical allodynia. They also produced side effects on the rotarod test ... Finally, the conotoxins all presynaptically inhibited excitatory synaptic neurotransmission into the dorsal horn and displayed ...
Another family of conotoxins, the α-conotoxins, are competitive antagonists of mammalian nicotinic acetylcholine receptors ( ... Surprisingly, however, α-conotoxins Vc1.1, RgIA and PeIA more potently inhibit N-type VGCC currents via a GABA B GPCR mechanism ... Structurally related ω-conotoxins bind directly to and selectively inhibit neuronal (N)-type voltage-gated calcium channels ( ... A series of newly discovered ω-conotoxins from Conus catus, including CVID-F, are potent and selective antagonists of N-type ...
Here we report the isolation of μ-conotoxins SIIIA and SIIIB by 125I-TIIIA-guided fractionation of milked Conus striatus venom ... in solution comprising a series of turns and anα-helical motif across residues 11-16 that is not found in larger μ-conotoxins. ... "μ-Conotoxins are small peptide inhibitors of muscle and neuronal tetrodotoxin (TTX)-sensitive voltage-gated sodium channels ( ... μ-Conotoxins are small peptide inhibitors of muscle and neuronal tetrodotoxin (TTX)-sensitive voltage-gated sodium channels ( ...
Conotoxins[edit]. Ziconotide is a voltage-gated calcium channel blocker which may be used in severe cases of ongoing ...
Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins ... µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission. Elisabetta Tosti , Raffaele Boni , Alessandra ... Tosti, E.; Boni, R.; Gallo, A. µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic ... Tosti, E.; Boni, R.; Gallo, A. µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic ...
Disulfide bond assignments by mass spectrometry of native natural peptides: cysteine pairing in disulfide bonded conotoxins. ... Disulfide bond assignments by mass spectrometry of native natural peptides: cysteine pairing in disulfide bonded conotoxins. ... Disulfide bond assignments by mass spectrometry of native natural peptides: cysteine pairing in disulfide bonded conotoxins ( ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
Abrin; conotoxins; diacetoxyscirpenol; ricin; saxitoxin; Shiga-like ribosome inactivating proteins; tetrodotoxin Exclusions: ¶ ... 100 mg of conotoxins; 1,000 mg of diacetoxyscirpenol; 100 mg of ricin; 100 mg of saxitoxin; 100 mg of Shiga-like ribosome ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
Conotoxins; Diacetoxyscirpenol; Diphtheria toxin; Grayanotoxin; mushroom toxins such as amanitins, gyromitrin, and orellanine; ...
Conotoxins. *Crimean-Congo hemorrhagic fever. *Diacetoxyscirpenol. *Eastern equine encephalitis virus. *Ebola virus ...
The M-superfamily of conotoxins: a review. Cell Mol Life Sci. 2010;67:17-27.CrossRefPubMedGoogle Scholar ... Structure-activity studies on alpha-conotoxins. Curr Pharm Des. 2011;17:4226-41.CrossRefPubMedGoogle Scholar ... α-Conotoxins (α-CTxs) are small (10-30 residue) peptides derived from the venom of predatory marine cone snails of the genus ...
Asi3a is classified in the M-superfamily, acting generally on NaVs (μ-conotoxins), KVs (κM-conotoxins) and nAChRs (ψ-conotoxins ... κ-conotoxins target KV channels; and μO- or δ-conotoxins influence NaV channels. By performing a Conoserver alignment search on ... Chen, J.S.; Fan, C.X.; Hu, K.P.; Wei, K.H.; Zhong, M.N. Studies on conotoxins of Conus betulinus. J. Nat. Toxins 1999, 8, 341- ... Literature indications for conotoxins as potential antimicrobial compounds are given by Biggs et al. [34], Jiang et al. [35] ...
What are conotoxins?. Venomous sea snails use conotoxins to immobilise and kill their prey. ... Photo: Conotoxins, found in sea snail venom, appear to provide long-lasting pain relief. (Supplied: University of Wollongong) ... But the conotoxins now in development would hopefully be administered orally.. External Link: Killer Cone Snails: National ... "The conotoxins that were working on, we have intellectual property protection on most of them, were looking for commercial ...
  • This review compares the action of three ω-conotoxins, GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved N-type therapeutics that are more useful in the treatment of chronic pain. (mdpi.com)
  • ω-conotoxins, such MVIIA and CVID are effective in neuropathic pain models. (ovid.com)
  • Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. (mdpi.com)
  • About 700 species of Cone snails express hundreds of peptide toxins collectively known as conotoxins (CTX) aimed to self-defense, competition and predation of other marine species by means of sting-structures that were reported to be fatal for human since from 300 years ago. (mdpi.com)
  • Mu-conotoxins as leads in the development of new analgesics. (nih.gov)
  • Certain α-conotoxins have also been mooted as potential analgesics. (sigmaaldrich.com)
  • Additionally, as a Chief Investigator on a NHMRC Program Grant, Professor Christie is leading collaborative research (with researchers at the University of Queensland and at RMIT) on the development and discovery of novel analgesics based on conotoxins. (edu.au)
  • Prof. Dr. Diana Imhof from the Pharmaceutical Institute of the University of Bonn, who is the project's PI, explained, "We are interested in the cone snail's neurotoxins, called conotoxins. (uni-bonn.de)
  • While structurally similar to ω-conotoxins that block the twitch response to electrical nerve stimulation, HWTX-X has no effect on the twitch response of rat vas deferens. (wikipedia.org)
  • Sequencing and mass profiling highly modified conotoxins using global reduction/alkylation followed by mass spectrometry. (nih.gov)
  • Analgesic conotoxins: block and G protein-coupled receptor modulation " by David J. Adams, Brid P. Callaghan et al. (edu.au)
  • But in humans, Craik says some of these conotoxins appear to have analgesic effects. (eurekalert.org)
  • Lebbe EKM, Peigneur S, Wijesekara I, Tytgat J. Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview. (mdpi.com)
  • These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and affinity to ion channels, receptors, and transporters in the nervous systems of target prey and humans. (mdpi.com)
  • Another family of conotoxins, the α-conotoxins, are competitive antagonists of mammalian nicotinic acetylcholine receptors (nAChRs). (edu.au)
  • Conotoxins are also active on human receptors (e.g., ion channels), which is of particular interest as they thus can be used as tools to study pain pathways in humans. (eurekalert.org)
  • Addiction is less of a concern, Craik said, because conotoxins act on different receptors in the brain than morphine and other opiate drugs. (eurekalert.org)
  • According to its different targets acting on the organism, the conotoxins can be divided into three categories : (1) acting on voltage-gated ion channels, (2) acting on the ligand-gated ion channel , and (3) acting on other receptors. (thefreedictionary.com)
  • Each of the five types of conotoxins attacks a different target: α-conotoxin inhibits nicotinic acetylcholine receptors at nerves and muscles. (wikipedia.org)
  • This review aims to give an overview of the knowledge we have today on the molecular pharmacology of conotoxins specifically interacting with nAChRs along with the structure-function relationship data. (mdpi.com)
  • In this case, over 40 conotoxins are characterized based on only two LC-ESI-MS experiments in terms of mass, number of disulfide-linked cysteine residues (and hence, potential toxin superfamilies), relative hydrophobicity, and other posttranslational modifications. (nih.gov)
  • The disulfide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins. (rug.nl)
  • Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. (rug.nl)
  • Results: The unusual cysteine arrangements observed suggests novel class of conotoxins. (iisc.ac.in)
  • These results expand our understanding of the diversity of odd cysteine arrangements in conotoxins. (iisc.ac.in)
  • Targeted re-engineering of native α-conotoxins has resulted in excellent tools for nAChR research as well as potential therapeutics. (frontiersin.org)
  • With the help of conotoxins, researchers can now define the physiological as well as pathological relevance of the different receptor subtypes. (eurekalert.org)
  • The Waglerins and complementary conotoxins are useful tools to discover the contribution of acetylcholine receptor subunits to synaptogenesis. (wikipedia.org)
  • Finally, the conotoxins all presynaptically inhibited excitatory synaptic neurotransmission into the dorsal horn and displayed recovery that was largely dependent upon the magnitude of inhibition and not the conotoxin type. (ovid.com)
  • Conotoxins have revolutionised pain research since their extraordinary potency and selectivity enables us to study the individual subtypes of ion channels, which was not possible before," explains Markus Muttenthaler. (eurekalert.org)
  • 1H NMR studies revealed that SIIIA adopted a single conformation in solution comprising a series of turns and anα-helical motif across residues 11-16 that is not found in larger μ-conotoxins. (edu.au)
  • Entity 1, M-2 Branch Mini-M Conotoxins 15 residues - 1454.814 Da. (wisc.edu)
  • Current research focuses now on conotoxins that could already target nerve endings outside the spinal cord, which would facilitate administration. (eurekalert.org)
  • Biotinylated omega-conotoxins are potentially useful reagents for characterizing distinct subsets of calcium channels. (nih.gov)
  • The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ(kappa)-, μ(mu)-, and ω(omega)- types. (rug.nl)
  • In laboratory rats, a common stand-in for humans in many experiments, a single, small oral dose of a prototype drug based on one of these looped conotoxins appeared to significantly reduce pain, as measured by a standard protocol. (eurekalert.org)