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Most Cited Toxicon Articles
The most cited articles published since 2011, extracted from Scopus.
Trends in Ostreopsis proliferation along the Northern Mediterranean coastsLuisa Mangialajo | Nicolas Ganzin | Stefano Accoroni | Valentina Asnaghi | Aurélie Blanfuné | Marina Cabrini | Riccardo Cattaneo-Vietti | Fabienne Chavanon | Mariachiara Chiantore | Stéphanie Cohu | Eleonora Costa | Daniela Fornasaro | Hubert Grossel | Françoise Marco-Miralles | Mercedes Masó | Albert Reñé | Anna Maria Rossi | M. Montserrat Sala | Thierry Thibaut | Cecilia Totti | Magda Vila | Rodolphe Lemée
Volume 57, Issue 3, March 2011, Pages 408-420
Harmful benthic microalgae blooms represent an emergent phenomenon in temperate zones, causing health, ecological and economic concern. The main goal of this work was to compile records of Ostreopsis at large temporal and spatial scales, in order to study the relationship between cell abundances, the periodicity and intensity of the blooms and the role of sea water temperature in 14 Spanish, French, Monegasque and Italian sites located along the northern limits of the Mediterranean Sea. General trends were observed in the two considered basins: the north-western Mediterranean Sea, in which higher cell abundances were mostly recorded in mid-summer (end of July), and the northern Adriatic Sea where they occur in early fall (end of September). The sea-water temperature does not seem to be a primary driver, and the maximal abundance periods were site and year specific. Such results represent an important step in the understanding of harmful benthic microalgae blooms in temperate areas, and provide a good base for policy makers and managers in the attempt to monitor and forecast benthic harmful microalgae blooms. © 2010 Elsevier Ltd.
Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseasesVictor Chi | Michael W. Pennington | Raymond S. Norton | Eric J. Tarcha | Luz M. Londono | Brian Sims-Fahey | Sanjeev K. Upadhyay | Jonathan T. Lakey | Shawn Iadonato | Heike Wulff | Christine Beeton | K. George Chandy
Volume 59, Issue 4, March 2012, Pages 529-546
Electrophysiological and pharmacological studies coupled with molecular identification have revealed a unique network of ion channels-Kv1.3, KCa3.1, CRAC (Orai1 + Stim1), TRPM7, Cl swell-in lymphocytes that initiates and maintains the calcium signaling cascade required for activation. The expression pattern of these channels changes during lymphocyte activation and differentiation, allowing the functional network to adapt during an immune response. The Kv1.3 channel is of interest because it plays a critical role in subsets of T and B lymphocytes implicated in autoimmune disorders. The ShK toxin from the sea anemone Stichodactyla helianthus is a potent blocker of Kv1.3. ShK-186, a synthetic analog of ShK, is being developed as a therapeutic for autoimmune diseases, and is scheduled to begin first-in-man phase-1 trials in 2011. This review describes the journey that has led to the development of ShK-186. © 2011 Elsevier Ltd.
World-wide occurrence of the toxic dinoflagellate genus Ostreopsis SchmidtLesley Rhodes
Volume 57, Issue 3, March 2011, Pages 400-407
The dinoflagellate genus, Ostreopsis Schmidt, has an increasingly global distribution. It blooms in temperate to tropical coastal waters, and toxic species are present in all regions in which the genus has been recorded. The distribution has increased markedly in the last decade and associated illnesses have also increased. These trends are likely to continue. © 2010 Elsevier Ltd.
Case definitions for human poisonings postulated to palytoxins exposureA. Tubaro | P. Durando | G. Del Favero | F. Ansaldi | G. Icardi | J. R. Deeds | S. Sosa
Volume 57, Issue 3, March 2011, Pages 478-495
A series of case reports and anecdotal references describe the adverse effects on human health ascribed to the marine toxin palytoxin (PLTX) after different exposure routes. They include poisonings after oral intake of contaminated seafood, but also inhalation and cutaneous/systemic exposures after direct contact with aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing cnidarian zoanthids. The symptoms commonly recorded during PLTX intoxication are general malaise and weakness, associated with myalgia, respiratory effects, impairment of the neuromuscular apparatus and abnormalities in cardiac function. Systemic symptoms are often recorded together with local damages whose intensity varies according to the route and length of exposure. Gastrointestinal malaise or respiratory distress is common for oral and inhalational exposure, respectively. In addition, irritant properties of PLTX probably account for the inflammatory reactions typical of cutaneous and inhalational contact. Unfortunately, the toxin identification and/or quantification are often incomplete or missing and cases of poisoning are indirectly ascribed to PLTXs, according only to symptoms, anamnesis and environmental/epidemiological investigations (i.e. zoanthid handling or ingestion of particular seafood). Based on the available literature, we suggest a " case definition of PLTX poisonings" according to the main exposure routes, and, we propose the main symptoms to be checked, as well as, hemato-clinical analysis to be carried out. We also suggest the performance of specific analyses both on biological specimens of patients, as well as, on the contaminated materials responsible for the poisoning. A standardized protocol for data collection could provide a more rapid and reliable diagnosis of palytoxin-poisoning, but also the collection of necessary data for the risk assessment for this family of toxins. © 2011 Elsevier Ltd.
Haemostatically active proteins in snake venomsTamara Sajevic | Adrijana Leonardi | Igor Križaj
Volume 57, Issue 5, April 2011, Pages 627-645
Snake venom proteins that affect the haemostatic system can cause (a) lowering of blood coagulability, (b) damage to blood vessels, resulting in bleeding, (c) secondary effects of bleeding, e.g. hypovolaemic shock and organ damage, and (d) thrombosis. These proteins may, or may not, be enzymes. We review the data on the most relevant haemostatically active proteinases, phospholipases A 2, l-amino acid oxidases and 5′-nucleotidases from snake venoms. We also survey the non-enzymatic effectors of haemostasis from snake venoms - disintegrins, C-type lectins and three-finger toxins. Medical applications have already been found for some of these snake venom proteins. We describe those that have already been approved as drugs to treat haemostatic disorders or are being used to diagnose such health problems. No clinical applications, however, currently exist for the majority of snake venom proteins acting on haemostasis. We conclude with the most promising potential uses in this respect. © 2011 Elsevier Ltd.
Spider-venom peptides that target voltage-gated sodium channels: Pharmacological tools and potential therapeutic leadsJulie K. Klint | Sebastian Senff | Darshani B. Rupasinghe | Sing Yan Er | Volker Herzig | Graham M. Nicholson | Glenn F. King
Volume 60, Issue 4, September 2012, Pages 478-491
Voltage-gated sodium (Na V) channels play a central role in the propagation of action potentials in excitable cells in both humans and insects. Many venomous animals have therefore evolved toxins that modulate the activity of Na V channels in order to subdue their prey and deter predators. Spider venoms in particular are rich in Na V channel modulators, with one-third of all known ion channel toxins from spider venoms acting on Na V channels. Here we review the landscape of spider-venom peptides that have so far been described to target vertebrate or invertebrate Na V channels. These peptides fall into 12 distinct families based on their primary structure and cysteine scaffold. Some of these peptides have become useful pharmacological tools, while others have potential as therapeutic leads because they target specific Na V channel subtypes that are considered to be important analgesic targets. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides and so far only 0.01% of this diversity been characterised. Thus, it is likely that future research will reveal additional structural classes of spider-venom peptides that target Na V channels. © 2012 Elsevier Ltd.
From snake venom toxins to therapeutics - Cardiovascular examplesCho Yeow Koh | R. Manjunatha Kini
Volume 59, Issue 4, March 2012, Pages 497-506
Snakes have fascinated the imaginations of people since the dawn of civilization. Their deadly venoms cause significant mortality and morbidity worldwide, and strike fear in most of us. Snake venoms contain a huge variety of molecules affecting vital physiological systems, and scientists are turning some of these life-threatening toxins into a source of life-saving therapeutics. Since the approval of captopril - the first drug based on snake venom protein - more than 30 years ago, snake venom toxins have become a valuable natural pharmacopeia of bioactive molecules that provide lead compounds for the development of new drugs. Many toxins are being explored and developed into drugs for the treatment of conditions such as hypertension, thrombosis and cancer. A number of new drugs are constantly emerging from this pipeline. In this review, we briefly highlight the molecular basis of developing therapeutic agents, such as Captopril, Tirofiban, and Eptifibatide, from snake venom proteins. We also discuss the successes and failures as an update to the advances in the field. © 2011 Elsevier Ltd.
Studies on the dissociation of botulinum neurotoxin type A complexesKarl Heinz Eisele | Klaus Fink | Martin Vey | Harold V. Taylor
Volume 57, Issue 4, March 2011, Pages 555-565
The neurotoxins produced by the various strains of the anaerobic bacterium Clostridium botulinum naturally occur associated with complexing proteins which serve to protect the neurotoxins from the harsh environment of the mammalian gastrointestinal tract during bacterial invasion of the host. Three different complex species with the discrete sizes 19S (900 kDa, LL complex), 16S (500 kDa, L complex) and 12S (300 kDa, M complex) may be isolated from C. botulinum type A cultures. However, to affect their target cells these complexes must dissociate releasing the free 150 kDa neurotoxin. This study assesses the stability of these Clostridium botulinum neurotoxin serotype A (BoNT/A) complexes and identifies factors which influence their dissociation. The knowledge gained with purified toxin complexes was subsequently employed to analyze the presence of such complexes in the freeze or spray-dried commercial BoNT/A products Botox and Dysport in comparison to the complexing protein free product Xeomin. Purified 900 kDa and 500 kDa toxin complex preparations show a pH and time dependent release of the 150 kDa neurotoxin with a half-life of less than a minute at pH values >7.0. At pH values of 6.25 or less, the complexes are stable. Furthermore, dilution of concentrated 900 kDa complexes leads to dissociation into 500 kDa, neurotoxin containing complexes. Addition of sodium chloride as contained in isotonic saline leads to further disruption of these complexes resulting in the release of the free 150 kDa neurotoxin. Examination of the commercial botulinum neurotoxin products Botox and Dysport using the same analytical procedures leads to the same conclusion: the dilution, drying and reconstitution processes of these products lead to a complete dissociation of 900 kDa complexes and 85% or more of neurotoxin are present in free form. Conclusion: BoNT A toxin complexes have evolved to quickly respond to specific environmental changes by efficient release of the neurotoxin. During pharmaceutical production and reconstitution of BoNT A products, the same principles effect the quantitative dissociation of 900 kDa complexes and release of free neurotoxin prior to injection into target tissues. © 2011 Elsevier Ltd.
Shiga toxinsJonas Bergan | Anne Berit Dyve Lingelem | Roger Simm | Tore Skotland | Kirsten Sandvig
Volume 60, Issue 6, November 2012, Pages 1085-1107
Shiga toxins are virulence factors produced by the bacteria Shigella dysenteriae and certain strains of Escherichia coli. There is currently no available treatment for disease caused by these toxin-producing bacteria, and understanding the biology of the Shiga toxins might be instrumental in addressing this issue. In target cells, the toxins efficiently inhibit protein synthesis by inactivating ribosomes, and they may induce signaling leading to apoptosis. To reach their cytoplasmic target, Shiga toxins are endocytosed and transported by a retrograde pathway to the endoplasmic reticulum, before the enzymatically active moiety is translocated to the cytosol. The toxins thereby serve as powerful tools to investigate mechanisms of intracellular transport. Although Shiga toxins are a serious threat to human health, the toxins may be exploited for medical purposes such as cancer therapy or imaging. © 2012 Elsevier Ltd.
Occurrence of palytoxin-group toxins in seafood and future strategies to complement the present state of the artKaterina Aligizaki | Panagiota Katikou | Anna Milandri | Jorge Diogène
Volume 57, Issue 3, March 2011, Pages 390-399
Palytoxin (PlTX) and palytoxin-like (PlTX-like) compounds in seafood have been raising scientific concern in the last years. The constant increase in record numbers of the causative dinoflagellates of the genus Ostreopsis together with the large spatial expansion of this genus has led to intensification of research towards optimization of methods for determination of PlTX presence and toxicity. In this context, identification of seafood species which could possibly contain PlTXs constitutes an important issue for public health protection.In the present paper, worldwide occurrence of PlTX-like compounds in seafood is reviewed, while potential future strategies are discussed. PlTX has been reported to be present in several species of fish, crustaceans, molluscs and echinoderms. In one occasion, PlTX has been identified in freshwater puffer fish whereas all other records of PlTXs refer to marine species and have been recorded in latitudes approximately between 43°N and 15°S. PlTX determination in seafood has relied on different methodologies (mainly LC-MS, mouse bioassay and hemolysis neutralization assay) that have evolved over time. Future recommendations include systematic screening of PlTX in those species and areas where PlTX has already been recorded implementing updated methodologies. © 2010 Elsevier Ltd.
LC-MS of palytoxin and its analogues: State of the art and future perspectivesPatrizia Ciminiello | Carmela Dell'Aversano | Emma Dello Iacovo | Ernesto Fattorusso | Martino Forino | Luciana Tartaglione
Volume 57, Issue 3, March 2011, Pages 376-389
The state of the art of LC-MS of palytoxin and its analogues is reported in the present review. MS data for palytoxin, 42-hydroxy-palytoxin, ostreocin-D, mascarenotoxins, and ovatoxins, obtained using different ionization techniques, namely fast-atom bombardment (FAB), matrix assisted laser desorption ionization (MALDI), and electrospray ionization (ESI), are summarized together with the LC-MS methods used for their detection. Application of the developed LC-MS methods to both plankton and seafood analysis is also reported, paying attention to the extraction procedures used and to limits of detection (LOD) and quantitation (LOQ) achieved. In a research setting, LC-MS has shown a good potential in determination of palytoxin and its analogues from various sources, but, in a regulatory setting, routine LC-MS analysis of palytoxins is still at a preliminary stage. The LOQ currently achieved in seafood analysis appears insufficient to detect palytoxins in shellfish extract at levels close to the tolerance limit for palytoxins (30 μg/kg) proposed by the European Food Safety Authority (EFSA, 2009). In addition, lacking of certified reference standard of palytoxins as well as of validation studies for the proposed LC-MS methods represent important issues that should be faced for future perspectives of LC-MS technique. © 2010 Elsevier Ltd.
Evidence-based review and assessment of botulinum neurotoxin for the treatment of movement disordersMark Hallett | Alberto Albanese | Dirk Dressler | Karen R. Segal | David M. Simpson | Daniel Truong | Joseph Jankovic
Volume 67, Issue , June 2013, Pages 94-114
Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions. To assess the efficacy and safety of BoNT injections for the treatment of certain movement disorders, including blepharospasm, hemifacial spasm, oromandibular dystonia, cervical dystonia, focal limb dystonias, laryngeal dystonia, tics, and essential tremor, an expert panel reviewed evidence from the published literature. Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials. Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for movement disorders were also reviewed and updated. The panel evaluated evidence at several levels, supporting BoNT as a class, the serotypes BoNT-A and BoNT-B, as well as the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima). The panel ultimately made recommendations for each therapeutic indication, based upon the strength of clinical evidence and following the AAN classification scale. For the treatment of blepharospasm, the evidence supported a Level A recommendation for BoNT-A, A/Inco, and A/Ona; a Level B recommendation for A/Abo; and a Level U recommendation for B/Rima. For hemifacial spasm, the evidence supported a Level B recommendation for BoNT-A and A/Ona, a Level C recommendation for A/Abo, and a Level U recommendation for A/Inco and B/Rima. For the treatment of oromandibular dystonia, the evidence supported a Level C recommendation for BoNT-A, A/Abo, and A/Ona, and a Level U recommendation for A/Inco and B/Rima. For the treatment of cervical dystonia, the published evidence supported a Level A recommendation for all four BoNT formulations. For limb dystonia, the available evidence supported a Level B recommendation for both A/Abo and A/Ona, but no published studies were identified for A/Inco or B/Rima, resulting in a Level U recommendation for these two formulations. For adductor laryngeal dystonia, evidence supported a Level C recommendation for the use of A/Ona, but a Level U recommendation was warranted for B/Rima, A/Abo, and A/Inco. For the treatment of focal tics, a Level U recommendation was warranted at this time for all four formulations. For the treatment of tremor, the published evidence supported a level B recommendation for A/Ona, but no published studies were identified for A/Abo, A/Inco, or B/Rima, warranting a Level U recommendation for these three formulations. Further research is needed to address evidence gaps and to evaluate BoNT formulations where currently there is insufficient or conflicting clinical data. © 2012 Elsevier Ltd.
Snake venom metalloproteinasesFrancis S. Markland | Stephen Swenson
Volume 62, Issue , February 2013, Pages 3-18
Recent proteomic analyses of snake venoms show that metalloproteinases represent major components in most of the Crotalid and Viperid venoms. In this chapter we discuss the multiple activities of the SVMPs. In addition to hemorrhagic activity, members of the SVMP family also have fibrin(ogen)olytic activity, act as prothrombin activators, activate blood coagulation factor X, possess apoptotic activity, inhibit platelet aggregation, are pro-inflammatory and inactivate blood serine proteinase inhibitors. Clearly the SVMPs have multiple functions in addition to their well-known hemorrhagic activity. The realization that there are structural variations in the SVMPs and the early studies that led to their classification represents an important event in our understanding of the structural forms of the SVMPs. The SVMPs were subdivided into the P-I, P-II and P-III protein classes. The noticeable characteristic that distinguished the different classes was their size (molecular weight) differences and domain structure: Class I (P-I), the small SVMPs, have molecular masses of 20-30 kDa, contain only a pro domain and the proteinase domain; Class II (P-II), the medium size SVMPs, molecular masses of 30-60 kDa, contain the pro domain, proteinase domain and disintegrin domain; Class III (P-III), the large SVMPs, have molecular masses of 60-100 kDa, contain pro, proteinase, disintegrin-like and cysteine-rich domain structure. Another significant advance in the SVMP field was the characterization of the crystal structure of the first P-I class SVMP. The structures of other P-I SVMPs soon followed and the structures of P-III SVMPs have also been determined. The active site of the metalloproteinase domain has a consensus HEXXHXXGXXHD sequence and a Met-turn. The " Met-turn" structure contains a conserved Met residue that forms a hydrophobic basement for the three zinc-binding histidines in the consensus sequence. © 2012 Elsevier Ltd.
A high-throughput venom-gland transcriptome for the Eastern Diamondback Rattlesnake (Crotalus adamanteus) and evidence for pervasive positive selection across toxin classesDarin R. Rokyta | Kenneth P. Wray | Alan R. Lemmon | Emily Moriarty Lemmon | S. Brian Caudle
Volume 57, Issue 5, April 2011, Pages 657-671
Despite causing considerable human mortality and morbidity, animal toxins represent a valuable source of pharmacologically active macromolecules, a unique system for studying molecular adaptation, and a powerful framework for examining structure-function relationships in proteins. Snake venoms are particularly useful in the latter regard as they consist primarily of a moderate number of proteins and peptides that have been found to belong to just a handful of protein families. As these proteins and peptides are produced in dedicated glands, transcriptome sequencing has proven to be an effective approach to identifying the expressed toxin genes. We generated a venom-gland transcriptome for the Eastern Diamondback Rattlesnake (Crotalus adamanteus) using Roche 454 sequencing technology. In the current work, we focus on transcripts encoding toxins. We identified 40 unique toxin transcripts, 30 of which have full-length coding sequences, and 10 have only partial coding sequences. These toxins account for 24% of the total sequencing reads. We found toxins from 11 previously described families of snake-venom toxins and have discovered two putative, previously undescribed toxin classes. The most diverse and highly expressed toxin classes in the C. adamanteus venom-gland transcriptome are the serine proteinases, metalloproteinases, and C-type lectins. The serine proteinases are the most abundant class, accounting for 35% of the toxin sequencing reads. Metalloproteinases are the most diverse; 11 different forms have been identified. Using our sequences and those available in public databases, we detected positive selection in seven of the eight toxin families for which sufficient sequences were available for the analysis. We find that the vast majority of the genes that contribute directly to this vertebrate trait show evidence for a role for positive selection in their evolutionary history. © 2011 Elsevier Ltd.
Antioxidant properties of Thymus vulgaris oil against aflatoxin-induce oxidative stress in male ratsAziza A. El-Nekeety | Sherif R. Mohamed | Amal S. Hathout | Nabila S. Hassan | Soher E. Aly | Mosaad A. Abdel-Wahhab
Volume 57, Issues 7-8, June 2011, Pages 984-991
The leafy parts of thyme and its essential oil have been used in foods for the flavor, aroma and preservation and also in folk medicines. The aim of the current study was to determine the components of Thymus vulgaris L essential oil and to evaluate the protective effects of this oil against aflatoxin-induce oxidative stress in rats. Thirty six mature male Sprague-Dawley were divided into six treatment groups and treated for 2 weeks as follows: control group; the groups treated orally with low and high doses of T. vulgaris oil (5 and 7.5 mg/kg b.w.); the group fed AFs-contaminated diet (2.5 mg/kg diet) and the groups fed AFs-contaminated diet and treated orally with the oil at the two tested doses. Blood and tissue samples were collected at the end of treatment period for biochemical study and histological examination. The results indicated that the oil contains Carvarcrol (45 mg/g), Thymol (24.7 mg/g), β-Phellandrene (9.7 mg/g), Linalool (4.1 mg/g), Humuline (3.1 mg/g), α-Phellandrene (2.3 mg/g) and Myrcene (2.1 mg/g). However, α and β-pinene, Myrcene, α-thyjone, Tricyclene, 1, 8-cineole, and β-sabinene were found in lower concentrations. Treatment with AFs alone disturbs lipid profile in serum, decreases Total antioxidant capacity, increase creatinine, uric acid and nitric oxide in serum and lipid peroxidation in liver and kidney accompanied with a sever histological changes in the liver tissues. The oil alone at the two tested doses did not induce any significant changes in the biochemical parameters or the histological picture. The combined treatment showed significant improvements in all tested parameters and histological pictures in the liver tissues. Moreover, this improvement was more pronounced in the group received the high dose of the oil. It could be concluded that the essential oil of T. vulgaris has a potential antioxidant activity and a protective effect against AFs toxicity and this protection was dose dependent. © 2011 Elsevier Ltd.
Snake venomics: From the inventory of toxins to biologyJuan J. Calvete
Volume 75, Issue , December 2013, Pages 44-62
A deep understanding of the composition of venoms and of the principles governing the evolution of venomous systems is of applied importance for exploring the enormous potential of venoms as sources of chemical and pharmacological novelty but also to fight the dire consequences of snakebite envenomings. This goal is now within the reach of "omic" technologies. A central thesis developed in this essay is the view that making sense of the huge inventory of data gathered through "omic" approaches requires the integration of this information across the biological system. Key to this is the identification of evolutionary and ecological trends; without the evolutionary link, systems venomics is relegated to a set of miscellaneous facts. The interplay between chance and adaptation plays a central role in the evolution of biological systems (Monod, 1970). However, the evolution of venomous species and their venoms do not always follow the same course, and the identification of structural and functional convergences and divergences among venoms is often unpredictable by a phylogenetic hypothesis. Toxins sharing a structural fold present in venoms from phylogenetically distant snakes often share antigenic determinants. The deficit of antivenom supply in certain regions of the world can be mitigated in part through the optimized use of existing antivenoms, and through the design of novel broad-range polyspecific antivenoms. Proteomics-guided identification of evolutionary and immunoreactivity trends among homologous and heterologous venoms may aid in the replacement of the traditional geographic- and phylogenetic-driven hypotheses for antivenom production strategies by a more rationale approach based on a hypothesis-driven systems venomics approach. Selected applications of venomics and antivenomics for exploring the chemical space and immunological profile of venoms will illustrate the author's views on the impact these proteomics tools may have in the field of toxinology. © 2013 Elsevier Ltd.
The tale of a resting gland: Transcriptome of a replete venom gland from the scorpion Hottentotta judaicusDavid Morgenstern | Bettina H. Rohde | Glenn F. King | Tzachy Tal | Daniel Sher | Eliahu Zlotkin
Volume 57, Issue 5, April 2011, Pages 695-703
cDNA libraries are increasingly being used for high-throughput interrogation of animal venomes. Most previous studies have focused on discovery of new venom toxins, whereas the dynamics of toxin transcription and associated cellular processes have received much less attention. Here we provide, for the first time, an analysis of a transcriptome from the venom gland of a scorpion (Hottentotta judaicus) that is not actively engaged in regenerating its venom. We demonstrate a low abundance of toxin-encoding transcripts coupled with a previously unobserved proliferation of protease sequences. Additionally, we identified several low abundance, toxin-like sequences that may represent decommissioned toxins that are unlikely to be translated. These sequences are not evenly distributed across all toxin families, but rather appear more frequently in transcripts related to α-toxins and β-toxins that are known to target voltage-gated sodium channels. The transcriptomic profile of the replete venom gland is very different to that obtained previously from scorpion venom glands actively engaged in venom regeneration, and it highlights our lack of knowledge as to how the dynamics of transcription changes as the gland progresses from venom regeneration to a " resting" state. This study therefore provides an important foundation for future studies into the dynamics of transcription in the venom glands of scorpions and other venomous animals. © 2011 Elsevier Ltd.
Scorpion venom components that affect ion-channels functionV. Quintero-Hernández | J. M. Jiménez-Vargas | G. B. Gurrola | H. H. Valdivia | L. D. Possani
Volume 76, Issue , December 2013, Pages 328-342
The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na+-, K+- and Ca++-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are nowadays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na +-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K+-channels are normally pore blocking agents. The Ryanodine Ca ++-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells. © 2013 Elsevier Ltd. All rights reserved.
Estimate of the burden of snakebites in sub-Saharan Africa: A meta-analytic approachJean Philippe Chippaux
Volume 57, Issue 4, March 2011, Pages 586-599
Snakebites represent an important neglected public health problem in many developing countries. There is a lack of epidemiological data, which would be very useful for the organisation of snakebite management and provision of antivenom. An extensive literature search for the years 1970-2010 was performed. Data were analysed using meta-analysis to take into account the heterogeneity between the studies and their respective weight. Incidence, mortality and population at risk were estimated after stratification according to the environment (urban or rural) and survey methodologies (national, hospital or community studies). The incidence of snakebite was inversely correlated with population density. The number of envenomings was estimated at 314,078 [CI95% = 251,513-377,462], of which 95% occurred in rural areas. The remainder occurred in cities. The annual mortality was estimated at 7,331 [5,148-9,568], of which 97% occurred in a rural environment. The annual number of amputations ranged from 5,908 to 14,614. The population most at risk was young men engaged in agricultural or pastoral labours. Household surveys indicated that actual incidence and mortality were likely 3-5 times higher. The difference maybe explained by treatment seeking behaviour. However, incidences and mortalities reported here reflect the number of patients who attend modern health facilities, giving underestimated figures of the burden of snakebites in sub-Saharan Africa but realistic current requirements for antivenoms. © 2011 Elsevier Ltd.
A review on the effects of environmental conditions on growth and toxin production of Ostreopsis ovataR. Pistocchi | L. Pezzolesi | F. Guerrini | S. Vanucci | C. Dell'Aversano | E. Fattorusso
Volume 57, Issue 3, March 2011, Pages 421-428
Since the end of the 1990s the occurrence of blooms of the benthic dinoflagellates Ostreopsis spp. is spreading in many tropical and temperate regions worldwide, sometimes causing benthonic biocenosis suffering and occasional human distress. Ostreopsis ovata has been found to produce palytoxin-like compounds, a class of highly potent toxins. As general, the highest abundances of Ostreopsis spp. are recorded during warmer periods characterized by high temperature, salinity, and water column stability. Moreover, as these cells are easily resuspended in the water column, the role of hydrodynamism in the blooms development and decline has been highlighted. The environmental conditions appear, therefore, to be one of the main factors determining the proliferation of these species as testified by several field surveys. Laboratory studies on the effect of environmental parameters on growth and toxicity of O. ovata are rather scarce. With regard to the effects of temperature, culture results indicate that different strains blooming along Italian coasts displayed different optima, in accordance to blooming periods, and that higher toxin levels correlated with best growth conditions. Additionally, in relation to an Adriatic strain, cell growth positively correlated with the increase in salinity, while toxicity was lowest at the highest salinity value (i.e. 40). For the same strain, both nitrogen and phosphorus limitation determined a decrease in cell toxicity showing different behaviour with respect to many other toxic dinoflagellates. © 2010 Elsevier Ltd.
High-resolution picture of a venom gland transcriptome: Case study with the marine snail Conus consorsYves Terrat | Daniel Biass | Sébastien Dutertre | Philippe Favreau | Maido Remm | Reto Stöcklin | David Piquemal | Frédéric Ducancel
Volume 59, Issue 1, January 2012, Pages 34-46
Although cone snail venoms have been intensively investigated in the past few decades, little is known about the whole conopeptide and protein content in venom ducts, especially at the transcriptomic level. If most of the previous studies focusing on a limited number of sequences have contributed to a better understanding of conopeptide superfamilies, they did not give access to a complete panorama of a whole venom duct. Additionally, rare transcripts were usually not identified due to sampling effect. This work presents the data and analysis of a large number of sequences obtained from high throughput 454 sequencing technology using venom ducts of Conus consors, an Indo-Pacific living piscivorous cone snail. A total of 213,561 Expressed Sequence Tags (ESTs) with an average read length of 218 base pairs (bp) have been obtained. These reads were assembled into 65,536 contiguous DNA sequences (contigs) then into 5039 clusters. The data revealed 11 conopeptide superfamilies representing a total of 53 new isoforms (full length or nearly full-length sequences). Considerable isoform diversity and major differences in transcription level could be noted between superfamilies. A, O and M superfamilies are the most diverse. The A family isoforms account for more than 70% of the conopeptide cocktail (considering all ESTs before clustering step). In addition to traditional superfamilies and families, minor transcripts including both cysteine free and cysteine-rich peptides could be detected, some of them figuring new clades of conopeptides. Finally, several sets of transcripts corresponding to proteins commonly recruited in venom function could be identified for the first time in cone snail venom duct. This work provides one of the first large-scale EST project for a cone snail venom duct using next-generation sequencing, allowing a detailed overview of the venom duct transcripts. This leads to an expanded definition of the overall cone snail venom duct transcriptomic activity, which goes beyond the cysteine-rich conopeptides. For instance, this study enabled to detect proteins involved in common post-translational maturation and folding, and to reveal compounds classically involved in hemolysis and mechanical penetration of the venom into the prey. Further comparison with proteomic and genomic data will lead to a better understanding of conopeptides diversity and the underlying mechanisms involved in conopeptide evolution. © 2011 Elsevier Ltd.
Phospholipases AJosé María Gutiérrez | Bruno Lomonte
2: Unveiling the secrets of a functionally versatile group of snake venom toxins
Volume 62, Issue , February 2013, Pages 27-39
Phospholipases A2 (PLA2s) are abundant components of snake venoms, where they play toxic and digestive roles. Despite having a similar three-dimensional structure, venom PLA2s exert an amazing variety of toxic and pharmacological effects, which include neurotoxic, myotoxic, hemolytic, edematogenic, hyperalgesic, pro-inflammatory, hypotensive, platelet-aggregation inhibitory, anticoagulant, cytotoxic, and bactericidal activities. Toxinologists have made significant contributions to deciphering the structure, molecular evolution, mechanisms of action, receptors, role of enzymatic activity for toxicity, structural determinants of toxicity and selectivity, and the impact of these enzymes in the overall pathophysiology of snakebite envenoming. The present work highlights some of the most relevant contributions in the study of venom PLA2s, including the personal accounts of the authors of these studies. © 2012 Elsevier Ltd.
The UniProtKB/Swiss-Prot Tox-Prot program: A central hub of integrated venom protein dataFlorence Jungo | Lydie Bougueleret | Ioannis Xenarios | Sylvain Poux
Volume 60, Issue 4, September 2012, Pages 551-557
Animal toxins are of interest to a wide range of scientists, due to their numerous applications in pharmacology, neurology, hematology, medicine, and drug research. This, and to a lesser extent the development of new performing tools in transcriptomics and proteomics, has led to an increase in toxin discovery. In this context, providing publicly available data on animal toxins has become essential. The UniProtKB/Swiss-Prot Tox-Prot program (http://www.uniprot.org/program/Toxins) plays a crucial role by providing such an access to venom protein sequences and functions from all venomous species. This program has up to now curated more than 5000 venom proteins to the high-quality standards of UniProtKB/Swiss-Prot (release 2012_02). Proteins targeted by these toxins are also available in the knowledgebase. This paper describes in details the type of information provided by UniProtKB/Swiss-Prot for toxins, as well as the structured format of the knowledgebase. © 2012 Elsevier Ltd.
On the venom system of centipedes (Chilopoda), a neglected group of venomous animalsEivind A B Undheim | Glenn F. King
Volume 57, Issue 4, March 2011, Pages 512-524
Centipedes are among the oldest extant terrestrial arthropods and are an ecologically important group of soil and leaf litter predators. Despite their abundance and frequent, often painful, encounters with humans, little is known about the venom and venom apparatus of centipedes, although it is apparent that these are both quite different from other venomous lineages. The venom gland can be regarded as an invaginated cuticle and epidermis, consisting of numerous epithelial secretory units each with its own unique valve-like excretory system. The venom contains several different enzymes, but is strikingly different to most other arthropods in that metalloproteases appear to be important. Myotoxic, cardiotoxic, and neurotoxic activities have been described, most of which have been attributed to high molecular weight proteins. Neurotoxic activities are also unusual in that G-protein coupled receptors often seem to be involved, either directly as targets of neurotoxins or indirectly by activating endogenous agonists. These relatively slow responses may be complemented by the rapid effects caused by histamines present in the venom and from endogenous release of histamines induced by venom cytotoxins. The differences probably reflect the ancient and independent evolutionary history of the centipede venom system, although they may also be somewhat exaggerated by the paucity of information available on this largely neglected group. © 2011 Elsevier Ltd.
Toxin profiles of five geographical isolates of Dinophysis spp. from North and South AmericaElie Fux | Juliette L. Smith | Mengmeng Tong | Leonardo Guzmán | Donald M. Anderson
Volume 57, Issue 2, February 2011, Pages 275-287
Marine dinoflagellates of the genus Dinophysis can produce toxins of the okadaic acid (OA) and pectenotoxin (PTX) groups. These lipophilic toxins accumulate in filter-feeding shellfish and cause an illness in consumers called diarrhetic shellfish poisoning (DSP). In 2008, a bloom of Dinophysis led to the closure of shellfish harvesting areas along the Texas coast, one of the first DSP-related closures in the U.S. This event resulted in a broad study of toxin production in isolates of Dinophysis spp. from U.S. waters. In the present study, we compared toxin profiles in geographical isolates of Dinophysis collected in the U.S. (Eel Pond, Woods Hole MA; Martha's Vineyard, MA; and Port Aransas Bay, Texas), and in those from Canada (Blacks Harbour, Bay of Fundy) and Chile (Reloncavi Estuary), when cultured in the laboratory under the same conditions. For each isolate, the mitochondrial cox1 gene was sequenced to assist in species identification. Strains from the northeastern U.S. and Canada were all assigned to Dinophysis acuminata, while those from Chile and Texas were most likely within the D. acuminata complex whereas precise species designation could not be made with this marker. Toxins were detected in all Dinophysis isolates and each isolate had a different profile. Toxin profiles of isolates from Eel Pond, Martha's Vineyard, and Bay of Fundy were most similar, in that they all contained OA, DTX1, and PTX2. The Eel Pond isolate also contained OA-D8 and DTX1-D7, and low levels (unconfirmed structurally) of DTX1-D8 and DTX1-D9. D. acuminata from Martha's Vineyard produced DTX1-D7, along with OA, DTX1, and PTX2, as identified in both the cells and the culture medium. D. acuminata from the Bay of Fundy produced DTX1 and PTX2, as found in both cells and culture medium, while only trace amounts of OA were detected in the medium. The Dinophysis strain from Texas only produced OA, and the one from Chile only PTX2, as confirmed in both cells and culture medium. © 2010.


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Talk:White Tower (Tower of London)
|This article is of interest to the following WikiProjects:
The White Tower has no significance at and is merely a figment of the human imagination, although it may be seen with the naked eye it is just a myth of what actually was and what may or may not be real. — Preceding unsigned comment added by Pudge0426 (talk • contribs) 20:17, 14 February 2011 (UTC)
Richard I[edit]
This text was removed from the article with the comment "rm tangential material riddled with inaccuracies and misunderstandings"
In the 12th century, King Richard the Lionheart enclosed the White Tower with a curtain wall,[1] and had a moat dug around it filled with water from the River Thames. The works were considered inadequate by the reign of Henry III. He left Richard's walls as an enceinte and constructed an new outer ring of curtain walls protected by large bastions and a much deeper moat which replaced the former inadequate one that had failed to flood.[2]
- notes
- ^ Tatton-Brown 1990, p. 1.
- ^ Carpenter 1996, pp. 199,200.
What are the inaccuracies and misunderstandings? -- PBS (talk) 03:10, 29 September 2011 (UTC)
- Richard did not build the stone curtain wall, it was William Longchamp during Richard's reign. Longchamp was disliked and the citizens of London celebrated set backs during building.
- The implication of the first sentence is that before Richard's reign the White Tower was unenclosed. This was of course not the case.
- It was stated that the moat was filled with water from the Thames, but two sentences later it is stated that this early moat had failed to flood. Which is it?
- Enceinte is jargon that most readers will not understand. Some terms are inescapable, and I try to introduce terms such as "ward" into articles in a context which will explain them to the reader as these are terms which they are likely to encounter in other castle-related texts. It is quite possible to explain what happened without using "enceinte", especially when Wikipedia's article is referenced to the Encyclopaedia Britannica.
- This demonstrates the importance of using top-quality sources rather than those which mention the Tower tangentially. Small inaccuracies may be acceptable when the mistake is not the subject of the article, but not here. There is information here which is not directly about the White Tower. By all means, it can provide context by the quality of information is poor. Nev1 (talk) 11:22, 29 September 2011 (UTC)
The wording above was a replacement put in place by me for the previous wording.
In the 12th century, King Richard the Lionheart enclosed the White Tower with a curtain wall and had a moat dug around it filled with water from the River Thames. The moat was not successful until Henry III, in the 13th century, employed a Dutch moat-building technique. Henry refurnished the Chapel and had the exterior of the building whitewashed in 1240, hence its name.
"In the 12th Century during the reign of Richard I" should cover the point. As for the implication that can be fixed by adding the word "new". (Although the sources says "This tower and the contemporary curtain wall running east from it, was originally built along the waterfront of the Thames. It possibly sits on and replaces the late Roman riverside wall, but all the visible masonry, including that uncovered in the magnificent plinth, is clearly late 12th century in date." and does not explicitly say that there was an earlier wall, although I agree it would be very unlikely that there would not have been a ward around the keep enclosed with a perimeter defence). "In the 12th Century during the reign of Richard I the White Tower was enclosed with a new curtain wall". I'm not much fussed about the sentence on the moat. As you can see the contradiction exists because I chose not to remove the previous sentence but added a sourced new sentence to replace the bit about Dutch Engineers (they may well have done it but not in the sources I found). The older moat would have had to go anyway because the new outer walls would have enclosed it/sat on top of it.
So perhaps the first sentence can read:
- "In the 12th Century during the reign of Richard I the White Tower was enclosed with a new curtain wall and ditch (that failed to fill with water from the Thames as intended).
The advantage of links is that if someone does not know what an "enceinte" is they can follow the link, and then they have learnt something. You state it is jargon but so is the word "bastion(s)" so were does one draw the line? It seems to me that if someone is interested in castles then they will be interested in knowing terms like enceinte and bastion, bailey etc. The second and third sentences can then read:
- "The works were considered inadequate by the reign of Henry III. He left Richard's walls as an enceinte and constructed an new outer ring of curtain walls protected by large bastions and a much deeper ditch that was filled with water creating a moat".
--PBS (talk) 23:31, 29 September 2011 (UTC)
- It was shit and no amount of lawyering will change that. Give me a day or two and I'll either redraft the article completely or redirect it to the Tower of London article which deals with the White Tower much more effectively. I contemplated doing that a year ago but had hoped someone would come along and improve this article. Sadly that has not happened. Nev1 (talk) 23:38, 29 September 2011 (UTC)
a tower?[edit]
The White Tower is a central tower, the old keep, at the Tower of London.
A tower? To me it seems a building with four towers. It isn't even claimed that White Tower would be just one of the four towers in the building. 22.214.171.124 (talk) 19:06, 4 March 2014 (UTC)
- See http://books.google.com/books?id=jeeGAAAAQBAJ&pg=PT3633#v=onepage&q&f=false WikiParker (talk) 21:22, 5 March 2014 (UTC)
- Huh? You cite me a quote from "An Etymological Dictionary of the English Language"? That is just what it is, an etymology of a word. And etymology article has this: Etymology is the study of the history of words, their origins, and how their form and meaning have changed over time. By an extension, the term "the etymology of [a word]" means the origin of the particular word. 220.127.116.11 (talk) 23:54, 11 April 2014 (UTC)
Bricked-up window[edit]
The fifth picture shows a bricked-up window. Does anyone have a good source that confirms (or refutes) that it's that specific window which was used by Gruffydd ap Llywelyn Fawr in his escape attempt? I ask in part because our article on that person states that the window was 27m above ground level, but this article states that the Tower was 27m tall. --NellieBly (talk) 18:59, 20 May 2014 (UTC)
- I just double checked what Parnell said about the height of the Tower in his 1993 book for English Heritage and he says it is 27m high "to its battlements". I suspect that means the top of the battlements rather than the bottom, but even if it's the latter there is a gap of several metres between the battlements and the next row of windows. In short, Gruffydd's article has got the length of the drop wrong. I checked for details of Gruffydd's imprisonment in both Parnell and Brown's books but to no avail. They're very strong on structural history, and with a site with such a varied and detailed past some aspects are given less weight. If that's the right window, I don't know, but it's likely that's the level from which Gruffydd made his escape.
- Nearly 150 years earlier Flambard – a portly man – was imprisoned in the White Tower and made his escape by climbing out of a window. Though his rope wasn't long enough and the final drop winded him, he fared better than the Welsh prince. Flambard anchored one end of the rope to the dividing pillar in one of the windows, which would help explain why he exited from the gallery level rather than one floor lower in the hall where he was most likely confined. As a high-status prisoner the prince was treated well and most likely given rooms fitting his status, most likely in the White Tower itself. His ODNB only says "He tried, however, to escape, on the night of 1 March 1244, having made a rope from his linen, and broke his neck in the attempt, as he was a very tall and heavy man." So I wonder if the Wikipedia article has been embellished. There's no indication, for instance, that the window was blocked as a result of Gruffydd's escape attempt. Nev1 (talk) 19:29, 20 May 2014 (UTC)
- While it's very likely the prince was held in the White Tower, the sources available don't seem to state as much. It's not uncommon for this kind of information to be unknown; in cases where contemporary documents record people as being imprisoned at a castle, it's often without clarifying which part. Nev1 (talk) 19:34, 20 May 2014 (UTC)
- Thank you for the reply. If you haven't yet, I'll edit Gryffydd's article right now to add a cn tag and remove the exact height of the drop, and search for a reference. If it is an embellishment, it long predates the article or Wikipedia itself; I first heard the bricking-up story at the Tower itself in the 80s, and the story has made its way into many pre-Wikipedia (and pre-Internet) novels. I suspect that some reliable source somewhere discusses it; I'll do some searching and see what I find. Many thanks again. --18.104.22.168 (talk) 03:38, 21 May 2014 (UTC) Why does it log me out at the most inopportune times? --NellieBly (talk) 03:40, 21 May 2014 (UTC)
- B-Class London-related articles
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subset: commoncrawl


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Mares-Morel, Moreno-De La Mora Double Heads To Texas
By Jhonny Gonzalez
Last week, it was announced that a Showtime televised bantamweight doubleheader would take place in Cancun, Mexico. But, according to sources who spoke to BoxingScene.com, the show is now going to take place in Texas - possibly at the Don Haskins Convention Center in El Paso.
In the main event, unbeaten Mexican Abner Mares (23-0-1, 13KOs) will face Eric Morel (46-2, 23KOs) of Puerto Rico. The co-feature will have Anselmo "Chemito" Moreno (32-1-1, 11KOs) defending his WBA championship against David De la Mora (24-1, 17KOs) of Mexico.
Now even though Showtime shouldn't be showcasing this double header. It looks like I will have to drive to El Paso....ChemitooooooooooooooComment by Roman Moreno on 03-08-2012
[QUOTE=Bushbaby;11863753]Thank you showtime!!:fing02:[/QUOTE] Honestly this double header is not worthy enough to be on Showtime Championship Boxing. These are not the type of fights that Showtime should be buying. But, we all know that the reason Showtime bought this is…Comment by Ringlife on 03-07-2012
It should be a good turn out in Texas.Comment by JoelRa79 on 03-07-2012
good card, wonder if morel can hang in there against mares...Comment by fceeviper on 03-07-2012
Fuk! Why not in Staples Center?!! :(Post a Comment - View More User Comments (7)


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Two Easter eBooks Capture Spring Crafting Fever
Free eBooks from FaveCrafts.com provide creative inspiration for Easter.
March 23, 2010—Northbrook, IL—The upcoming Easter holiday will provide many people with an opportunity for creative crafting. Whether to celebrate the Christian holiday or the coming of spring with eggs and bunnies, crafters are looking for inspiration for Easter. The popular crafting website FaveCrafts.com has published two Easter eBooks with free craft projects, decorating ideas and even recipes. The eBooks are FREE to download at FaveCrafts.com.
Easter is sure to be a popular crafting occasion for all ages. According to a recent report from the Craft & Hobby Association, the craft industry continues to flourish despite a depressed economy in recent years. Between 2008 and 2009, the industry enjoyed an 11% increase in sales. Whether to make homemade gifts or engage in a therapeutic activity, people are crafting more and more.
The first, Hop into Spring: Easter Craft and Recipe eBook, is a 95-page guide to celebrating Easter with 6 craft categories and a bonus section of Easter recipes from RecipeLion.com. Find 8 Easter card crafts like the Glitter Chicks Card (pg. 12), 11 Easter egg decorating projects such as the Needle-felt Easter Eggs (pg. 22), and 8 simple Easter Home Décor ideas like the Colorful Easter Place-card Holders (pg. 57).
The second, Easter Crafts: Blogger Edition 2010 eBook, is a 45-page collection of Easter craft projects from talented craft bloggers. Readers will find 19 craft projects for Easter decorating and gift-giving using inexpensive, household materials. Crafters can make the Braided Easter Eggs (pg. 6) with recycled water bottles or learn how to use vegetables and foliage to dye Easter eggs naturally (pg. 25).
The Easter Crafts eBooks can be downloaded for FREE from the Easter category at FaveCrafts: http://www.favecrafts.com/Easter.
Caley Walsh
Editorial Director
FaveCrafts.com is a property of Prime Publishing LLC
About FaveCrafts.com:
FaveCrafts.com is an exciting resource for all things craft - from expert tips to project ideas for every style and skill level. We also publish Quick & Crafty, a free e-mail newsletter, publish crafting eBooks, and create crafting related product promotions, contests and giveaways.
Prime Publishing LLC was established in 1995 as a traditional niche book publishing company. Today, we are an Internet Media Company that operates web site communities and e-mail newsletters in niche areas such as crafting and cooking. To learn more, visit www.primenewsletters.com.
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- "18 Projects Every Crafter Wants" free eBook
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- Retro Gumball Machine Craft


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Special topics courses (X99), like blanket-numbered courses, may be repeated without limit by students. This is an "automatic" feature for X99 courses. Further, it is implied, but not monitored centrally, that the course content is different each time the student takes the course (unless the student is retaking the course to replace a grade as specified under Academic Regulation 20). Each academic unit monitors the repeatability characteristic of X99 courses to avoid abuse of this feature by repeating the same course over and over again. Inserting a phrase in the course description indicating that the course may be repeated more than once is at the discretion of the academic unit.
Unless there is a specific limit placed on the number of times an X99 course may be taken, special topics courses are encoded with "99" in the credit field of Banner, allowing for indefinite repeatability capacity of that particular topics course.
Special Topics (e.g., X99) courses require a New Course Proposal to become an established course. Please complete the New Course Proposal but do not attach a syllabus or take further action. Please contact the Office of Academic Programs, Assessment, and Accreditation (APAA) for assistance. APAA will submit the proposal on your behalf.
Additional Information: Course Numbering Guidelines


text:
IMS Country Review provides comprehensive qualitative insights into a specific pharmaceutical market as well as showing sales trends over the last 5 years.
Sales performance is analysed in terms of major corporations, therapeutic classes, major products and new product activity.
Key Benefits:
- Targeted national sales analysis by company, product and therapy areas, allowing you to understand the pharmaceutical performance of the country.
- Synopsis of the healthcare system and relevant pharmaceutical issues, based on primary research gathered by the IMS country experts.
- Standardised comparable data against which the industry is measured, stemming from accurate and reliable IMS audited year-end sales data.
Includes useful measures:
- US$ sales
- 5 year growth in US $ and local currency dollar (eliminating inaccuracies due to exchange rate fluctuations)
- Evolution Index
- market share
- Detailed information file allowing a thorough understanding of the data values and definitions, the universe/country abbreviations, and the EphMRA anatomical therapeutic classification
- Cost-effective strategic analysis tool that will provide the essential insights needed to get insights into a country market of interest
IMS Country Review comprises 2 sections:
1. Qualitative country overview, featuring consistent sections on:
- Market Trends
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- Country ranking amongst 40 markets
- Audited Market Trend
- Leading 35 local companies
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- 15 Fastest-Growing Therapeutic Classes
- Leading 15 Therapeutic Class Profiles, including trends for top 10 corporations and top 10 products
- Leading 40 Products
- Leading 40 New Products
- Leading 15 product forms


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How casting ruins a mystery: 'NCIS Los Angeles' edition
While watching a recent CBS's "NCIS: Los Angeles" (don't judge - ladies do love cool James), I witnessed what has to be one of the most egregious offenses on television crime dramas and it's posing a serious threat to my TV viewing (and by extension to anyone watching TV with me).
In an early scene from the aforementioned episode, Kensi Blye (Daniela Ruah) and her partner Marty Deeks (Eric Christian Olsen) are heading down the garden path of a Beverly Hills mansion when they pass a gardener. He gives the agents a passing glance, but that look, that stealthy stare tells me instantly that the gardener is not just pruning the roses, he's the bad guy, the guilty party and the reason for the episode's murder and mayhem. »Read Full Article(1)
Singles Scorecard: Hear new songs from B.o.B., Chris Young and "American Idol" winner Candice Glover
Lori Waxman's "60 wrd/min art critic" comes to Inova
Deborah Solomon, known for her writing on art for the New York Times, offered up a "little prayer for art critics" recently on WNYC radio.
Calling critics bossy and easy to hate, she reported a sorry fact: that there are only 10 full-time art critics left at newspapers and magazines in the U.S. »Read Full Blog Post
Milwaukee band Die Kreuzen gets 2nd chance
Die Kreuzen should have been one of the handful of Milwaukee-area bands like the Violent Femmes and the BoDeans that made it in a big way.
Butch Vig produced some of its albums before finding fame with Nirvana's "Nevermind." Die Kreuzen found fans in seminal rock figures including Steve Albini and Sonic Youth's Thurston Moore. The band was offered a contract with Atlantic Records. »Read Full Article
Festa Italiana adds new acts to schedule
Festa Italiana has announced additions to its festival schedule that include opera, classic Italian and jazz, completing a lineup of nearly 40 acts.
The festival runs July 19 through 21 at Henry W. Maier Festival Park. »Read Full Article
Headliners set for Summer Soulstice Music Festival
The music is set for the annual Summer Soulstice Music Festival. Now bring on the sun.
Kane Place Record Club; Hugh Bob and the Hustle; I'm Not a Pilot; De La Buena; Hayward Williams; and Evan Christian will headline the East Side festival on June 22. »Read Full Article
Milwaukee Symphony Orchestra season ending in style
The Milwaukee Symphony Orchestra will conclude this season's classical concerts with two proverbial last hurrahs.
Music director Edo de Waart will lead the orchestra in a program of Johannes Brahms' first and fourth symphonies Friday through Sunday and then wrap up with Edward Elgar's "The Dream of Gerontius" the following weekend. »Read Full Article
Summer Reading: 4 books from big-name writers
On May 26, we're publishing our Summer Reading preview in the Journal Sentinel's Sunday Cue section and at TapMilwaukee.com, with dozens of suggestions for your enjoyment.
For today's preview of those suggestions, here are four new books by some of the big-name writers we know and love for their skill in transporting us to different worlds: »Read Full Blog Post
Teeny, tiny and fabulous
It's time for a little tiny talk.
I recently perused the tips for making teeny spaces spot-on fabulous at the drool-worthy website Apartment Therapy. »Read Full Blog Post
On Tap for Today: Talk, music, books and baseball
Welcome to the middle -- of your week, that is.
As always, we love to direct your dial to "The Disclaimer" radio show, entertaining talk about Milwaukee doings for sane people. You can listen in live via the WMSE web site at noon or download the show later. »Read Full Blog Post


text:
28 years of experience
Accepting new patients
Video profile
6720 Bertner Ave
Houston, TX 77030 Phone number & directions
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor's specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Rhonda Shannon:
View the full profile to get information on:
- Qualifications
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View full profile
Patient Reviews
The overall average patient rating of Dr. Rhonda Shannon is Excellent.
|Patient Ratings
|Accurate Diagnosis
|Bedside Manner
|Spends Time with Me
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Specialties & Research
Dr. Rhonda Shannon, MD is board certified in Anatomic Pathology & Clinical Pathology.
Education & Awards
Dr. Shannon graduated from The University of Texas at Houston.
Dr. Shannon has 10 hospital affiliations:
- St Luke's Community Medical Ct Woodlands
- St Luke's Episcopal Hospital
- Spanish
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- Additional Information
- Dr. Rhonda Lea Shannon MD is a female Pathologist, has 28 years of experience and practices in Anatomic Pathology & Clinical Pathology and Anatomic Pathology.
- Where does Dr. Rhonda L. Shannon practice?
- Dr. Rhonda Shannon has 1 office location.
Dr. Rhonda Shannon practices Anatomic Pathology & Clinical Pathology and Anatomic Pathology near Houston, TX.
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Top Definition
A word deprived from the great Polo. Its to express great desire for whats upcoming in the future such as ice cream, or sex.
"Dont you just love and want some ice cream"
girl: "you wanna have sex?"
guy: "fersuree"
girl: "you wanna have sex?"
guy: "fersuree"
viết bởi jesuscrackerblack 27 Tháng một, 2011
Trending Now
Can you define these popular missing words?


text:
For some reason when I create aseries of essay questions in a Quiz, the editor tool bar only appears for the answer area for the 1st question. This is quite frustrating for students. Is there a setting I am missing?
Essay - Editor tool bar appears in question 1 only
This only happens if you are running Moodle 1.9 or earlier. You should upgrade.
There was a good, or possibly supid, reason why it worked like this. If you search these forums, you can probably find the sordid details. As far as I am concerned, this is all ancient history.


text:
44 years of experience
44 years of experience
1623 W 23rd St
Little Rock, AR 72206 Phone number & directions
Little Rock, AR 72206 Phone number & directions
License & Identifications
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor's specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Roosevelt Brown:
View the full profile to get information on:
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View full profile
Patient Reviews
Have you visited Dr. Brown? Share your experience.
Write a Review
Write a Review
Education & Awards
Dr. Brown graduated from Howard University , Washington.
Home > Find a Dentist > AR > Little Rock Dentists > Dr. Roosevelt Brown, DDS
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- Additional Information
- Dr. Roosevelt Brown DDS is a male dentist, has 44 years of experience and practices in Family Dentistry.
- Where does Dr. Roosevelt Brown practice?
- Dr. Roosevelt Brown has 1 office location.
Dr. Roosevelt Brown practices Family Dentistry near Little Rock, AR.
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