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https://www.readbyqxmd.com/read/29547537/toxins-in-drug-discovery-and-pharmacology
#1
EDITORIAL
Steve Peigneur, Jan Tytgat
Venoms from marine and terrestrial animals (cone snails, scorpions, spiders, snakes, centipedes, cnidarian, etc.) can be seen as an untapped cocktail of biologically active compounds, being increasingly recognized as a new emerging source of peptide-based therapeutics.
March 16, 2018: Toxins
https://www.readbyqxmd.com/read/29522462/venomics-accelerated-cone-snail-venom-peptide-discovery
#2
REVIEW
S W A Himaya, Richard J Lewis
Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This "venomic" approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution...
March 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29514313/targeted-sequencing-of-venom-genes-from-cone-snail-genomes-improves-understanding-of-conotoxin-molecular-evolution
#3
Mark A Phuong, Gusti N Mahardika
To expand our capacity to discover venom sequences from the genomes of venomous organisms, we applied targeted sequencing techniques to selectively recover venom gene superfamilies and non-toxin loci from the genomes of 32 cone snail species (family, Conidae), a diverse group of marine gastropods that capture their prey using a cocktail of neurotoxic peptides (conotoxins). We were able to successfully recover conotoxin gene superfamilies across all species with high confidence (> 100X coverage) and used these data to provide new insights into conotoxin evolution...
March 5, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29328093/trajectories-on-the-poincar%C3%A3-sphere-of-polarization-states-of-a-beam-passing-through-a-rotating-linear-retarder
#4
Karol Salazar-Ariza, Rafael Torres
The emerging polarization states from a linearly polarized monochromatic light passing through a rotating linear quarter-wave plate have been characterized as the intersection curve of a cylinder and the Poincaré sphere. But in the cases where the input polarization states are in general elliptical or circular and pass through a rotating linear retarder, the emerging polarization states produce trajectories that do not correspond to the intersection of a sphere with one cylinder. Hence, in this work, we present a full characterization of the trajectories on the Poincaré sphere for monochromatic input beams with an arbitrary polarization state passing through a rotating linear retarder as the intersection curve of the Poincaré sphere with a cone...
January 1, 2018: Journal of the Optical Society of America. A, Optics, Image Science, and Vision
https://www.readbyqxmd.com/read/29321522/accelerated-proteomic-visualization-of-individual-predatory-venoms-of-conus-purpurascens-reveals-separately-evolved-predation-evoked-venom-cabals
#5
S W A Himaya, Frank Marí, Richard J Lewis
Cone snail venoms have separately evolved for predation and defense. Despite remarkable inter- and intra-species variability, defined sets of synergistic venom peptides (cabals) are considered essential for prey capture by cone snails. To better understand the role of predatory cabals in cone snails, we used a high-throughput proteomic data mining and visualisation approach. Using this approach, the relationship between the predatory venom peptides from nine C. purpurascens was systematically analysed. Surprisingly, potentially synergistic levels of κ-PVIIA and δ-PVIA were only identified in five of nine specimens...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29305264/functional-and-phenotypic-distinction-of-the-first-two-trophoblast-subdivisions-and-identification-of-the-border-between-them-during-early-postimplantation-a-prerequisite-for-understanding-early-patterning-during-placentogenesis
#6
Stavros Nikolaou, Xenia Hadjikypri, Giasemia Ioannou, Artemis Elia, Pantelis Georgiades
The early stages of mouse placentogenesis (placenta formation) involve poorly understood patterning events within polar trophectoderm-derived trophoblast, the progenitor of all placental trophoblast cell types. By early postimplantation [embryonic day 5.5 (E5.5)], this patterning causes early trophoblast to become subdivided into extraembryonic ectoderm (ExE) and ectoplacental cone (EPC). A prerequisite to understanding this patterning requires knowing the location of ExE-EPC border and being able to distinguish the entire ExE from EPC at E5...
January 29, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29303983/a-dipteran-s-novel-sucker-punch-evolution-of-arthropod-atypical-venom-with-a-neurotoxic-component-in-robber-flies-asilidae-diptera
#7
Stephan Holger Drukewitz, Nico Fuhrmann, Eivind A B Undheim, Alexander Blanke, Julien Giribaldi, Rosanna Mary, Guillaume Laconde, Sébastien Dutertre, Björn Marcus von Reumont
Predatory robber flies (Diptera, Asilidae) have been suspected to be venomous due to their ability to overpower well-defended prey. However, details of their venom composition and toxin arsenal remained unknown. Here, we provide a detailed characterization of the venom system of robber flies through the application of comparative transcriptomics, proteomics and functional morphology. Our results reveal asilid venoms to be dominated by peptides and non-enzymatic proteins, and that the majority of components in the crude venom is represented by just ten toxin families, which we have named Asilidin1-10...
January 5, 2018: Toxins
https://www.readbyqxmd.com/read/29283511/structural-plasticity-of-mini-m-conotoxins-expression-of-all-mini-m-subtypes-by-conus-regius
#8
Aldo Franco, Sanaz Dovell, Carolina Möller, Meghan Grandal, Evan Clark, Frank Marí
The mini-M conotoxins are peptidic scaffolds found in the venom of cones snails. These scaffolds are tightly folded structures held together by three disulfide bonds with a CC-C-C-CC arrangement (conotoxin framework III) and belong to the M Superfamily of conotoxins. Here, we describe mini-M conotoxins from the venom of Conus regius, a Western Atlantic worm-hunting cone snail species using transcriptomic and peptidomic analyses. These C. regius conotoxins belong to three different subtypes: M1, M2, and M3. The subtypes show little sequence homology, and their loop sizes (intercysteine amino acid chains) vary significantly...
March 2018: FEBS Journal
https://www.readbyqxmd.com/read/29225593/diverse-cone-snail-species-harbor-closely-related-streptomyces-species-with-conserved-chemical-and-genetic-profiles-including-polycyclic-tetramic-acid-macrolactams
#9
Michelle Quezada, Cuauhtemoc Licona-Cassani, Pablo Cruz-Morales, Angela A Salim, Esteban Marcellin, Robert J Capon, Francisco Barona-Gómez
Streptomyces are Gram-positive bacteria that occupy diverse ecological niches including host-associations with animals and plants. Members of this genus are known for their overwhelming repertoire of natural products, which has been exploited for almost a century as a source of medicines and agrochemicals. Notwithstanding intense scientific and commercial interest in Streptomyces natural products, surprisingly little is known of the intra- and/or inter-species ecological roles played by these metabolites. In this report we describe the chemical structures, biological properties, and biosynthetic relationships between natural products produced by Streptomyces isolated from internal tissues of predatory Conus snails, collected from the Great Barrier Reef, Australia...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29215605/cone-snails-a-big-store-of-conotoxins-for-novel-drug-discovery
#10
REVIEW
Bingmiao Gao, Chao Peng, Jiaan Yang, Yunhai Yi, Junqing Zhang, Qiong Shi
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...
December 7, 2017: Toxins
https://www.readbyqxmd.com/read/29207558/three-new-cytotoxic-steroidal-glycosides-isolated-from-conus-pulicarius-collected-in-kosrae-micronesia
#11
Yeon-Ju Lee, Saem Han, Su Hyun Kim, Hyi-Seung Lee, Hee Jae Shin, Jong Seok Lee, Jihoon Lee
Three new sulfated steroidal glycosides ( 3 - 5 ), along with known cholesterol derivatives ( 1 , 2 ), were isolated from the visceral extract of the cone snail Conus pulicarius . The structure of each new compound was elucidated by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The three new compounds exhibited significant in vitro cytotoxicity (GI50 values down to 0.49 μM) against the K562 human leukemia cell line.
December 4, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29199094/%C3%AE-conotoxins-to-explore-the-molecular-physiological-and-pathophysiological-functions-of-neuronal-nicotinic-acetylcholine-receptors
#12
REVIEW
Julien Giribaldi, Sébastien Dutertre
The vast diversity of neuronal nicotinic acetylcholine subunits expressed in the central and peripheral nervous systems, as well as in non-neuronal tissues, constitutes a formidable challenge for researchers and clinicians to decipher the role of particular subtypes, including complex subunit associations, in physiological and pathophysiological functions. Many natural products target the nAChRs, but there is no richer source of nicotinic ligands than the venom of predatory gastropods known as cone snails. Indeed, every single species of cone snail was shown to produce at least one type of such α-conotoxins...
December 2, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29178825/phylogenetic-relationships-of-cone-snails-endemic-to-cabo-verde-based-on-mitochondrial-genomes
#13
Samuel Abalde, Manuel J Tenorio, Carlos M L Afonso, Juan E Uribe, Ana M Echeverry, Rafael Zardoya
BACKGROUND: Due to their great species and ecological diversity as well as their capacity to produce hundreds of different toxins, cone snails are of interest to evolutionary biologists, pharmacologists and amateur naturalists alike. Taxonomic identification of cone snails still relies mostly on the shape, color, and banding patterns of the shell. However, these phenotypic traits are prone to homoplasy. Therefore, the consistent use of genetic data for species delimitation and phylogenetic inference in this apparently hyperdiverse group is largely wanting...
November 25, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/29090697/pharmacology-of-predatory-and-defensive-venom-peptides-in-cone-snails
#14
REVIEW
Jutty Rajan Prashanth, Sebastien Dutertre, Richard James Lewis
Cone snails are predatory gastropods whose neurotoxic venom peptides (conotoxins) have been extensively studied for pharmacological probes, venom evolution mechanisms and potential therapeutics. Conotoxins have a wide range of structural and functional classes that continue to undergo accelerated evolution that underlies the rapid expansion of the genus over their short evolutionary history. A number of pharmacological classes, driven by separately evolved defensive and predatory venoms, have been hypothesised to facilitate shifts in prey that exemplify the adaptability of cone snails...
November 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29027927/conotoxins-as-tools-to-understand-the-physiological-function-of-voltage-gated-calcium-ca-v-channels
#15
REVIEW
David Ramírez, Wendy Gonzalez, Rafael A Fissore, Ingrid Carvacho
Voltage-gated calcium (CaV ) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV 1.1-1.4; CaV 2.1-2.3) and Low-voltage activated (LVA, CaV 3.1-3...
October 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28986377/stenotrophomonas-like-bacteria-are-widespread-symbionts-in-cone-snail-venom-ducts
#16
Joshua P Torres, Maria Diarey Tianero, Jose Miguel D Robes, Jason C Kwan, Jason S Biggs, Gisela P Concepcion, Baldomero M Olivera, Margo G Haygood, Eric W Schmidt
Cone snails are biomedically important sources of peptide drugs, but it is not known whether snail-associated bacteria affect venom chemistry. To begin to answer this question, we performed 16S rRNA gene amplicon sequencing of eight cone snail species, comparing their microbiomes with each other and with those from a variety of other marine invertebrates. We show that the cone snail microbiome is distinct from those in other marine invertebrates and conserved in specimens from around the world, including the Philippines, Guam, California, and Florida...
December 1, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28943883/in-silico-analysis-of-binding-interaction-of-conantokins-with-nmda-receptors-for-potential-therapeutic-use-in-alzheimer-s-disease
#17
Maleeha Waqar, Sidra Batool
BACKGROUND: The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28922871/divergence-of-the-venom-exogene-repertoire-in-two-sister-species-of-turriconus
#18
Qing Li, Neda Barghi, Aiping Lu, Alexander E Fedosov, Pradip K Bandyopadhyay, Arturo O Lluisma, Gisela P Concepcion, Mark Yandell, Baldomero M Olivera, Helena Safavi-Hemami
The genus Conus comprises approximately 700 species of venomous marine cone snails that are highly efficient predators of worms, snails, and fish. In evolutionary terms, cone snails are relatively young with the earliest fossil records occurring in the Lower Eocene, 55 Ma. The rapid radiation of cone snail species has been accompanied by remarkably high rates of toxin diversification. To shed light on the molecular mechanisms that accompany speciation, we investigated the toxin repertoire of two sister species, Conus andremenezi and Conus praecellens, that were until recently considered a single variable species...
September 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28891599/expression-in-escherichia-coli-of-fusion-protein-comprising-%C3%AE-conotoxin-txib-and-preservation-of-selectivity-to-nicotinic-acetylcholine-receptors-in-the-purified-product
#19
EDITORIAL
Jinpeng Yu, Xiaopeng Zhu, Yang Yang, Sulan Luo, Dongting Zhangsun
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels, which are widely distributed in the central and peripheral nervous system. The α6β2* nAChR is an important subtype, which is closely associated with nicotine addiction and movement disorders etc. α-conotoxin TxIB with 16-amino acid residues specifically targets α6β2* nAChR with no obvious effect on other nAChR subtypes. However, chemical synthesis of TxIB is expensive, and the quantity of native TxIB extracted from cone snail is limited...
February 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28856545/oxidative-folding-of-conopeptides-modified-by-conus-protein-disulfide-isomerase
#20
Lei Wang, Xiaomin Wang, Zhenghua Ren, Wei Tang, Qiong Zou, Jinxing Wang, Shangwu Chen, Han Zhang, Anlong Xu
Protein disulfide isomerase is a type of enzyme that catalyses the oxidation, isomerization and reduction of disulfide bonds. Conotoxins that containing disulfide bonds are likely substrates of protein disulfide isomerise. Here, we cloned 12 protein disulfide isomerise genes from 12 different cone snail species that inhabited the sea near Sanya in China. The full-length amino acid sequences of these protein disulfide isomerase genes share a high degree of homology, including the same -CGHC- active site sequence and -RDEL- endoplasmic reticulum retention signal...
October 2017: Protein Journal
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