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Sample records for por tityus pusillus

  1. [Scorpionism caused by Tityus pusillus Pocock, 1893 (Scorpiones; Buthidae) in State of Pernambuco].

    PubMed

    Albuquerque, Cleide Maria Ribeiro de; Porto, Tiago Jordão; Amorim, Maria Lucineide Porto; Santana Neto, Pedro de Lima

    2009-01-01

    This paper presents the first reports on scorpion accidents caused by Tityus pusillus (Buthidae). The accidents took place within the home environment, in rural areas located in the municipalities of Paudalho and São Lourenço da Mata, Pernambuco, Brazil. The two cases described (a child and a pregnant woman) were classified as mild and moderate, respectively. The clinical symptoms presented were local disorders (pain and paresthesia) and systemic disorders (chills, dizziness, headache and vomiting). These records make it possible to including Tityus pusillus as a species of medical importance in Brazil. PMID:19448944

  2. Insights into reproductive strategies of Tityus (Archaeotityus) pusillus Pocock, 1893 (Scorpiones, Buthidae).

    PubMed

    de Albuquerque, Cleide Maria Ribeiro; de Araujo Lira, André Felipe

    2016-01-01

    A remarkable diversity of life history strategies has evolved among species for achieving reproductive success, including adaptive growth, protandry, iteroparity, and extra molting. Here, we report on the reproductive strategies of the litter-dwelling scorpion, Tityus (Archaeotityus) pusillus, the most abundant and widespread scorpion species in the Atlantic Forest of northeastern Brazil. We observed both iteroparity and protandry reproductive strategies in this species. Females were competent to produce up to three broods after a single insemination, and no correlation between female size and litter size was observed. Most males reached adulthood 1 month before females following four molts, characterizing protandry. Nevertheless, an extra molt was observed to occur in some males (n=4) and females (n=1). These findings highlight the life history traits of T. (A.) pusillus, which may imply in reproductive success and adaptation to changes in environmental conditions. PMID:27083999

  3. Bilateral ocular anomalies in a South African fur seal (Arctocephalus pusillus pusillus).

    PubMed

    Colitz, Carmen M H; Rudnick, Jens-Christian; Heegaard, Steffen

    2014-07-01

    A female South African fur seal (Arctocephalus pusillus pusillus) began having obvious clinical ophthalmologic problems by 8 weeks of age. The initial clinical sign was diffuse corneal edema, which progressed to bullae formation and ulcers; the underlying cause of corneal edema and bullous keratopathy was not identified antemortem.An ophthalmological evaluation was performed when the fur seal was approximately 6 months of age, but due to the diffuse corneal edema, intraocular structures could not be easily evaluated. An underlying infectious etiology was suspected; therefore,appropriate diagnostics were pursued, but did not identify a cause. Initial improvement was noted, but the fur seal then became blind and eventually became very painful.Due to decreased quality of life and aggressive behavior, the fur seal was euthanized.Histopathological diagnoses were persistent tunica vasculosa lentis and persistent hyperplastic primary vitreous with bilateral hypermature resorbed cataracts and retinal detachments with rosette formation. PMID:24283987

  4. Tityus: a forgotten myth of liver regeneration.

    PubMed

    Tiniakos, Dina G; Kandilis, Apostolos; Geller, Stephen A

    2010-08-01

    The ancient Greek myth of Tityus is related to liver regeneration in the same way as the well known myth of Prometheus is. Depictions of the punishment of Prometheus are frequently used by lecturers on liver regeneration; however, Tityus remains unknown despite the fact that he received the same punishment and his myth could also be used as a paradigm for the organ's extraordinary ability to regenerate. Nevertheless, there is no convincing evidence that ancient Greeks had any specific knowledge about liver regeneration, a concept introduced in the early 19th century. We describe and analyze the myth of Tityus and compare it to the myth of Prometheus. We also explore artistic and literary links and summarize recent scientific data on the mechanisms of liver regeneration. Finally, we highlight links of the legend of Tityus with other sciences. PMID:20472318

  5. Metastatic Liposarcoma in a South African Fur Seal (Arctocephalus pusillus).

    PubMed

    Pervin, M; Izawa, T; Ito, S; Kuwamura, M; Yamate, J

    2016-07-01

    A 14-year-old female South African fur seal (Arctocephalus pusillus) was presented with a large skin mass on the right shoulder. At necropsy examination, multiple white nodules were found in the lungs, liver, spleen and right axillary lymph nodes. Histologically, the skin mass was composed of round to polygonal neoplastic cells with round to oval nuclei and variably sized cytoplasmic vacuoles. Cellular and nuclear atypia were prominent. Immunohistochemically, the neoplastic cells expressed vimentin, but not cytokeratins, S100 protein, adipophilin or desmin. The cytoplasmic lipid droplets stained positively with oil red O. Metastasis was seen in the lungs, liver, spleen and right axillary lymph nodes, with similar morphological features to the skin mass. Based on these findings, a diagnosis of a pleomorphic liposarcoma with systemic metastasis was made. No previous reports of metastatic liposarcomas have been published in marine mammals. PMID:27290645

  6. Toxic peptides and genes encoding toxin gamma of the Brazilian scorpions Tityus bahiensis and Tityus stigmurus.

    PubMed

    Becerril, B; Corona, M; Coronas, F I; Zamudio, F; Calderon-Aranda, E S; Fletcher, P L; Martin, B M; Possani, L D

    1996-02-01

    Seven toxic peptides from the venom of Tityus bahiensis and Tityus stigmurus was isolated and sequenced, five of them to completion. The most abundant peptide from each of these two species of scorpion was 95% identical with that of toxin gamma from the venom of Tityus serrulatus. They were consequently named gamma-b and gamma-st respectively. The genes encoding these new gamma-like peptides were cloned and sequenced by utilizing oligonucleotides synthesized according to known cDNA sequences of toxin gamma, and amplified by PCR on templates of DNA purified from both T. bahiensis and T. stigmurus. They contain an intron of approx. 470 bp. Possible mechanisms of processing and expressing these peptides are discussed, in view of the fact that glycine is the first residue of the N-terminal sequence of T. stigmurus, whereas lysine is the residue at position 1 of toxin gamma from T. serrulatus and T. bahiensis. In addition, chemical characterization of the less abundant toxic peptides showed the presence of at least four distinct families of peptides in all three species of the genus Tityus studied. There is a large degree of similarity among peptides from different venoms of the same family. By using specific horse and rabbit antisera, the venoms of T. bahiensis, T. serrulatus and T. stigmurus were compared. They showed an extended degree of cross-reactivity. Thus these three species of scorpion have similar toxic components, the genes of which are similarly organized, processed and expressed. PMID:8611151

  7. Complete mitochondrial genome of Cryptolestes pusillus (Coleoptera: Laemophloeidae).

    PubMed

    Li, Lei; Liu, Guanghua; Sun, Tanyi; Xin, Tianrong; Li, Meiyun; Zou, Zhiwen; Xia, Bin

    2016-09-01

    In this study, the complete mitochondrial genome of Cryptolestes pusillus (GenBank accession number KT070713) was sequenced by long PCR and primer walking methods. The total length of mitochondrial DNA is 15 502 bp and contains 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a A + T-rich region. The base composition of the genome is A (39.04%), T (37.07%), C (23.4%), and G (14.6%). Except for COI and ATP8 with TCC and ATC as start codon, respectively, the remaining protein-coding genes initiated with the three orthodox start codons. Two complete stop codons (TAA and TAG) and two incomplete stop codons (COIII stop with T and ND5 stop with TA) were used in the protein-coding genes. The A + T-rich region is located between 12s rRNA and tRNA(Ile) with the length of 859 bp. The phylogenetic relationships of Coleoptera species were constructed based on the nucleotide sequences of 13 protein-coding genes of mitogenome using the neighbor-joining method. The molecular-based phylogenetic analysis supported the traditional morphological classification on relationships within Coleoptera species. PMID:26329895

  8. Toxins and genes isolated from scorpions of the genus Tityus.

    PubMed

    Becerril, B; Marangoni, S; Possani, L D

    1997-06-01

    Scorpion venoms contain a variety of low mol. wt peptides toxic to different organisms. These peptides have been intensively studied because they represent excellent models for investigating structure-function relationships and they are also fine probes for studying ionic channel functions. This review deals with the biological and chemical aspects of toxic peptides that affect Na+ or K+ channels and the cloning of the cDNAs and genes encoding the main alpha and beta neurotoxins present in the venom of the three most dangerous species of Brazilian scorpion, Tityus bahiensis, Tityus stigmurus and Tityus serrulatus, and the Venezuelan scorpion Tityus discrepans. At least 16 different peptides specific for Na+ channels and five affecting K+ channels were isolated and characterized from the venom of these scorpions. The isolation of cDNAs and genes encoding four distinct toxins has permitted the elucidation of their nucleotide sequences as well as their genomic organization. Venoms and isolated toxins from scorpions of the genus Tityus were shown to enhance the secretory activity of the pancreas. Antisera obtained against venom of T. serrulatus show cross-reactivity with other species of the Brazilian scorpions. PMID:9241777

  9. Mercury concentrations in the Australian fur seal Arctocephalus pusillus from SE Australian waters

    SciTech Connect

    Bacher, G.J.

    1985-10-01

    Marine carnivores such as seals and sea lions occupy an important position in the upper trophic level of the marine food web and this, together with their longevity, makes these marine mammals useful indicators of mercury accumulation in the marine environment. Little information exists on mercury concentrations in marine mammals from the southern hemisphere. This paper reports total mercury concentrations in the tissues of the Australian Fur Seal Arctocephalus pusillus from southeastern Australian waters.

  10. A comparative study of severe scorpion envenomation in children caused by Tityus bahiensis and Tityus serrulatus.

    PubMed

    Bucaretchi, F; Baracat, E C; Nogueira, R J; Chaves, A; Zambrone, F A; Fonseca, M R; Tourinho, F S

    1995-01-01

    From January 1984 to May 1994, 17 of 239 children under 15 years old stung by Tityus serrulatus (15.1%) or Tityus bahiensis (84.9%) presented severe envenoming. Of these 17 patients (1-11 years old; median = 2 yr) 14 were stung by T. serrulatus and three by T. bahiensis. All of them received scorpion antivenom i.v. at times ranging from 45 min. to 5 h after the accident (median = 2 h). On admission, the main clinical manifestations and laboratory and electrocardiographic changes were: vomiting (17), diaphoresis (15), tachycardia (14), prostration (10), tachypnea (8), arterial hypertension (7), arterial hypotension (5), tremors (5), hypothermia (4), hyperglycemia (17), leukocytosis (16/16), hypokalemia (13/17), increased CK-MB enzyme activity (> 6% of the total CK, 11/12), hyperamylasemia (11/14), sinusal tachycardia (16/17) and a myocardial infarction-like pattern (11/17). Six patients stung by T. serrulatus had depressed left ventricular systolic function assessed by means of echocardiography. Of these, five presented pulmonary edema and four had shock. A child aged two-years old presented severe respiratory failure and died 65 h after being stung by T. serrulatus. Severe envenomations caused by T. serrulatus were 26.2 times more frequent than those caused by T. bahiensis (p < 0.001). PMID:8599062

  11. Tityus serrulatus venom--A lethal cocktail.

    PubMed

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

    2015-12-15

    Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). PMID:26522893

  12. Compatibility Relations Between the Edible Carrot Daucus Carota and D. Pusillus, a Related Wild Species from the Argentinian Pampas

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To establish the feasibility of hybridization between the wild carrot species Daucus pusillus Michx. (2n = 2x = 22; 2n = 2x = 22 and 20), collected in the pampas grasslands of Argentina, and the edible carrot, Daucus carota L. (2n = 2x = 18), controlled pollinations were attempted on the plant. Due ...

  13. Central effects of Tityus serrulatus and Tityus bahiensis scorpion venoms after intraperitoneal injection in rats.

    PubMed

    Nencioni, Ana Leonor A; Lourenço, Geane Antiques; Lebrun, Ivo; Florio, Jorge Camilo; Dorce, Valquiria A C

    2009-10-01

    A great number of studies on scorpion venoms associate their effects to the autonomic nervous system, and few data are available about their action on the central nervous system (CNS). The aim of this work was to evaluate some central effects after intraperitoneal injection of Tityus serrulatus or T. bahiensis scorpion venoms. The hippocampal concentration of some neurotransmitters and their metabolites were determined. Electroencephalographic and behavioral observations were performed, and all brains were removed for histopathological analysis of hippocampal areas. Both venoms induced electrographic and behavioral alterations despite T. bahiensis venom affects less the electrographic activity than T. serrulatus venom. Neurochemical analysis demonstrated no alteration in the extracellular levels of almost all the neurotransmitters evaluated, at least in the hippocampus, and no neuronal loss in this area was observed. Meanwhile, extracellular concentration of HVA increased up to 10 times in approximately 1/3 of the animals of both groups. Scorpion venoms seem to exert a small but important central effect. More studies in this field are necessary because they may be useful in developing new strategies to reduce the damage caused by scorpion stings. PMID:19664683

  14. Coping with Heat: Function of The Natal Coat of Cape Fur Seal (Arctocephalus Pusillus Pusillus) Pups in Maintaining Core Body Temperature

    PubMed Central

    Erdsack, Nicola; Dehnhardt, Guido; Hanke, Wolf

    2013-01-01

    Cape fur seal (Arctocephalus pusillus) pups spend the first weeks of life exclusively or mainly ashore. They are exposed to intense solar radiation and high temperatures for long time periods, which results in temperatures up to at least 80°C on their black natal coat. To test the hypothesis that the natal coat has a crucial function in coping with these extreme conditions, we investigated the insulating properties of the natal coat in six captive newborn Cape fur seals during the first 50 days after birth. The natal fur differs from the adult fur not only in colour, but also in density, structure, and water repellence. We measured temperature on the fur surface and within the fur, as well as skin and rectal temperature under varying environmental conditions, comparable to the species' habitat. Experiments were designed to not influence the spontaneous behaviour of the pups. Rectal temperature was constant as long as the pups stayed dry, even during long-lasting intense solar radiation for up to 3 h. Skin temperature remained close to rectal temperature as long as the fur was dry, while with wet fur, skin temperature was significantly reduced as well. Our results show that the natal coat provides an effective insulation against overheating. The severely reduced insulation of wet natal fur against cold supports the assumption that the natal fur is an adaptation to the pups' terrestrial phase of life. PMID:23951287

  15. Activity Budgets of Captive Cape Fur Seals (Arctocephalus pusillus) Under a Training Regime.

    PubMed

    Wierucka, Kaja; Siemianowska, Sonia; Woźniak, Marta; Jasnosz, Katarzyna; Kieliszczyk, Magdalena; Kozak, Paulina; Sergiel, Agnieszka

    2016-01-01

    Ethograms and time budgets are crucial for the behavioral assessment of nonhuman animals in zoos, and they serve as references for welfare research. This study was conducted to obtain detailed time budgets of trained Cape fur seals (Arctocephalus pusillus) in captivity, to evaluate variations of these patterns, and to determine whether abnormal behaviors had been displayed. Behavioral data for 3 Cape fur seals in the Wroclaw Zoo were collected, and more than 300 observation hours (during a 12-month period) per individual were analyzed. The studied animals exhibited a diversified repertoire of natural behaviors with apparent seasonal and daily patterns, and they did not present stereotypic behaviors. Significant differences of interaction rates between individuals suggest more frequent affiliative interactions among related animals. The absence of stereotypic behaviors, good health of individuals, and the presence of diversified natural behaviors indicated relatively good welfare of Cape fur seals kept in the Wroclaw Zoo. PMID:26709628

  16. Variations in the morphology of Rhizomucor pusillus in granulomatous lesions of a Magellanic penguin (Spheniscus magellanicus).

    PubMed

    Suzuta, Fumiko; Kimura, Kumiko; Urakawa, Ryo; Kusuda, Yukio; Tanaka, Shogo; Hanafusa, Yasuko; Haritani, Makoto

    2015-08-01

    This report presents a new case of mucormycosis encountered in penguin characterized by morphological variation of hyphae and presence of sporangia with numerous sporangiospores. A 4.5-year-old Magellanic penguin (Spheniscus magellanicus) died after exhibiting anorexia, poor nutritional condition and dyspnea. Multiple nodular lesions were observed in the thoracic and abdominal regions. Histopathologically, hyphae of various sizes were seen in the lungs, air sac and nodular lesions. Myriad sporangiospores and several sporangia were observed in/around the bronchi or parabronchi. The very narrow and short hyphae in the nodules were not consistent with the characteristics of Mucorales. However, for most hyphae, including those in the nodules, sporangiospores and sporangia, immunohistochemistry revealed Mucorales-positive reactions. In addition, these fungi were identified as Rhizomucor pusillus by gene analysis. PMID:25892614

  17. Variations in the morphology of Rhizomucor pusillus in granulomatous lesions of a Magellanic penguin (Spheniscus magellanicus)

    PubMed Central

    SUZUTA, Fumiko; KIMURA, Kumiko; URAKAWA, Ryo; KUSUDA, Yukio; TANAKA, Shogo; HANAFUSA, Yasuko; HARITANI, Makoto

    2015-01-01

    This report presents a new case of mucormycosis encountered in penguin characterized by morphological variation of hyphae and presence of sporangia with numerous sporangiospores. A 4.5-year-old Magellanic penguin (Spheniscus magellanicus) died after exhibiting anorexia, poor nutritional condition and dyspnea. Multiple nodular lesions were observed in the thoracic and abdominal regions. Histopathologically, hyphae of various sizes were seen in the lungs, air sac and nodular lesions. Myriad sporangiospores and several sporangia were observed in/around the bronchi or parabronchi. The very narrow and short hyphae in the nodules were not consistent with the characteristics of Mucorales. However, for most hyphae, including those in the nodules, sporangiospores and sporangia, immunohistochemistry revealed Mucorales-positive reactions. In addition, these fungi were identified as Rhizomucor pusillus by gene analysis. PMID:25892614

  18. Antibodies against Tityus discrepans venom do not abolish the effect of Tityus serrulatus venom on the rat sodium and potassium channels.

    PubMed

    Borges, A; Tsushima, R G; Backx, P H

    1999-06-01

    Anti-(Tityus serrulatus + Tityus bahiensis) and anti-Tityus discrepans venom polyclonal antisera were used to investigate whether antigenic differences exist between the venoms of the Brazilian T. serrulatus and the Venezuelan T. discrepans scorpions. Both antisera recognised the toxin-containing electrophoretic fractions of their cognate venoms and also those from Tityus zulianus and Tityus trinitatis venoms on Western blots. The anti-T. discrepans antiserum reacted only weakly with T. serrulatus toxic polypeptides. The effect of T. serrulatus alpha- or beta-toxins on rat skeletal muscle Na+ channels expressed in Xenopus laevis oocytes was abolished by pre-incubating the venom with anti-(T. serrulatus + T. bahiensis) serum but not with anti-T. discrepans serum. Nor did the Brazilian or the Venezuelan sera prevent the reduction in K+ currents by T. serrulatus venom in X. laevis oocytes expressing the rat brain delayed rectifying Shaker K+ channel (Kv1.2). These results indicate that toxins from T. serrulatus and T. discrepans venoms, which primarily target mammalian Na+ channels, are antigenically distinct, although they probably share common epitopes. Our results also suggest that Na+ channel-active toxins are the immunodominant antigens of the T. serrulatus venom. PMID:10340827

  19. Mycobacterium pinnipedii tuberculosis in a free-ranging Australian fur seal (Arctocephalus pusillus doriferus) in South Australia.

    PubMed

    Boardman, Wayne S J; Shephard, Lisa; Bastian, Ivan; Globan, Maria; Fyfe, Janet A M; Cousins, Debby V; Machado, Aaron; Woolford, Lucy

    2014-12-01

    This report describes the first case in South Australia, Australia, of Mycobacterium pinnipedii tuberculosis in a free-ranging Australian fur seal (Arctocephalus pusillus doriferus). Severe pyogranulomatous pleuropneumonia with intrahistocytic acid-fast beaded filamentous bacilli was seen on histology. M. pinnipedii was confirmed by full 24-loci mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing. Spillover concerns for public health and cattle are discussed. PMID:25632695

  20. Proteomic analysis of the venom from the scorpion Tityus stigmurus: biochemical and physiological comparison with other Tityus species.

    PubMed

    Batista, C V F; Román-González, S A; Salas-Castillo, S P; Zamudio, F Z; Gómez-Lagunas, F; Possani, L D

    2007-01-01

    The venom from the Brazilian scorpion Tityus stigmurus was fractionated by high performance liquid chromatography (HPLC) and the corresponding components were used for molecular mass determination using electrospray ion trap mass spectrometry. One hundred distinct components were clearly assigned showing molecular masses from 216.5 to 44,800.0 Da. Fifteen new components were isolated and sequenced, four of them to completion: Tst-3 (similar to Na(+) channel specific scorpion toxins), Tst-17 (a K(+) channel blocking peptide similar to Tc1), Tst beta KTx (a peptide with identical sequence as that of TsTX-K beta toxin earlier described to exist in T. serrulatus venom) and finally a novel proline-rich peptide of unknown function. Among the eleven components partially sequenced were two enzymes: hyaluronidase and lysozyme. The first enzyme has a molecular mass of 44,800.0 Da. This enzyme showed high activity against the substrate hyaluronan in vitro. Amino acid sequence of the second enzyme showed that it is similar to other known lysozymes, with similar molecular mass and sequence to that of bona fide lysozymes reported in public protein data banks. Finally, this communication reports a correlation among HPLC retention times and molecular masses of folded scorpion toxins as well as a comparative structural and physiological analysis of components from the venom of several species of the genus Tityus. PMID:17270501

  1. Olfactory discrimination ability of South African fur seals (Arctocephalus pusillus) for enantiomers.

    PubMed

    Kim, Sunghee; Amundin, Mats; Laska, Matthias

    2013-06-01

    Using a food-rewarded two-choice instrumental conditioning paradigm we assessed the ability of South African fur seals, Arctocephalus pusillus, to discriminate between 12 enantiomeric odor pairs. The results demonstrate that the fur seals as a group were able to discriminate between the optical isomers of carvone, dihydrocarvone, dihydrocarveol, menthol, limonene oxide, α-pinene, fenchone (all p < 0.01), and β-citronellol (p < 0.05), whereas they failed to distinguish between the (+)- and (-)-forms of limonene, isopulegol, rose oxide, and camphor (all p > 0.05). An analysis of odor structure-activity relationships suggests that a combination of molecular structural properties rather than a single molecular feature may be responsible for the discriminability of enantiomeric odor pairs. A comparison between the discrimination performance of the fur seals and that of other species tested previously on the same set of enantiomers (or subsets thereof) suggests that the olfactory discrimination capabilities of this marine mammal are surprisingly well developed and not generally inferior to that of terrestrial mammals such as human subjects and non-human primates. Further, comparisons suggest that neither the relative nor the absolute size of the olfactory bulbs appear to be reliable predictors of between-species differences in olfactory discrimination capabilities. Taken together, the results of the present study support the notion that the sense of smell may play an important and hitherto underestimated role in regulating the behavior of fur seals. PMID:23011284

  2. Foraging-Based Enrichment Promotes More Varied Behaviour in Captive Australian Fur Seals (Arctocephalus pusillus doriferus)

    PubMed Central

    Hocking, David P.; Salverson, Marcia; Evans, Alistair R.

    2015-01-01

    During wild foraging, Australian fur seals (Arctocephalus pusillus doriferus) encounter many different types of prey in a wide range of scenarios, yet in captive environments they are typically provided with a narrower range of opportunities to display their full repertoire of behaviours. This study aimed to quantitatively explore the effect of foraging-based enrichment on the behaviour and activity patterns displayed by two captive Australian fur seals at Melbourne Zoo, Australia. Food was presented as a scatter in open water, in a free-floating ball device, or in a static box device, with each treatment separated by control trials with no enrichment. Both subjects spent more time interacting with the ball and static box devices than the scatter feed. The total time spent pattern swimming was reduced in the enrichment treatments compared to the controls, while the time spent performing random swimming behaviours increased. There was also a significant increase in the total number of bouts of behaviour performed in all three enrichment treatments compared to controls. Each enrichment method also promoted a different suit of foraging behaviours. Hence, rather than choosing one method, the most effective way to increase the diversity of foraging behaviours, while also increasing variation in general activity patterns, is to provide seals with a wide range of foraging scenarios where food is encountered in different ways. PMID:25946412

  3. Characterisation of the mitochondrial genome of Parafilaroides normani (lungworm) of Arctocephalus pusillus doriferus (Australian fur seal).

    PubMed

    Jabbar, Abdul; Mohandas, Namitha; Gasser, Robin B

    2014-08-01

    Parafilaroides normani is a metastrongyloid nematode of clinical relevance in some species of pinnipeds. The taxonomy, biology and epidemiology of this and related species are not well understood. Mitochondrial (mt) DNA can provide markers for studies in these areas, but genetic data are scant. Here, we characterised the mt genome of P. normani. Adults of this nematode were collected from Arctocephalus pusillus doriferus from Phillip Island, Victoria, Australia, and genomic DNA was extracted from individuals. The complete mt genome was amplified from DNA from a single adult male by long-range PCR, as two overlapping amplicons (~5 and ~10 kb), and then sequenced employing 454 technology (Roche). The mt genome was assembled from reads of ~300 bp and annotated using an established bioinformatic pipeline. This circular mt genome is 13,411 bp and contains two ribosomal RNA, 12 protein-coding and 22 transfer RNA genes, consistent with those of other lungworms studied to date. This mt genome is intended to provide a source of genetic markers for future investigations of the biology, epidemiology and systematics of Parafilaroides spp. and related lungworms. PMID:24924434

  4. Age-related differences revealed in Australian fur seal Arctocephalus pusillus doriferus gut microbiota.

    PubMed

    Smith, Stuart C; Chalker, Andrea; Dewar, Meagan L; Arnould, John P Y

    2013-11-01

    The gut microbiota of Australian fur seals (Arctocephalus pusillus doriferus) was examined at different age classes using fluorescent in situ hybridisation (FISH) and 16S rRNA gene pyrosequencing. The FISH results indicated that in the fur seal groups, the predominant phyla are Firmicutes (22.14-67.33%) followed by Bacteroidetes (3.11-15.45%) and then Actinobacteria (1.4-5.9%) consistent with other mammals. Phylum Proteobacteria had an initial abundance of 1.8% in the 2-month-old pups, but < 1% of bacterial numbers for the other fur seal age groups. Significant differences did occur in the abundance of Clostridia, Lactobacilli and Bifidobacteria between 2 months pups and 9 months pups and adult fur seals. Results from the 16S rRNA gene pyrosequencing supported the FISH data and identified significant differences in the composition of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia and Fusobacteria at all ages. Class Clostridia in phylum Firmicutes dominates the microbiota of the 2 months and 9 months seal pups, whilst class Bacilli dominates the 6 months pups. In addition, a high level of dissimilarity was observed between all age classes. This study provides novel insight into the gut microbiota of Australian fur seals at different age classes. PMID:23746080

  5. Tityus serrulatus venom peptidomics: assessing venom peptide diversity.

    PubMed

    Rates, Breno; Ferraz, Karla K F; Borges, Márcia H; Richardson, Michael; De Lima, Maria Elena; Pimenta, Adriano M C

    2008-10-01

    MALDI-TOF-TOF and de novo sequencing were employed to assess the Tityus serrulatus venom peptide diversity. Previous works has shown the cornucopia of molecular masses, ranging from 800 to 3000Da, present in the venom from this and other scorpions species. This work reports the identification/sequencing of several of these peptides. The majority of the peptides found were fragments of larger venom toxins. For instance, 28 peptides could be identified as fragments from Pape proteins, 10 peptides corresponded to N-terminal fragments of the TsK beta (scorpine-like) toxin and fragments of potassium channel toxins (other than the k-beta) were sequenced as well. N-terminal fragments from the T. serrulatus hypotensins-I and II and a novel hypotensin-like peptide could also be found. This work also reports the sequencing of novel peptides without sequence similarities to other known molecules. PMID:18718845

  6. Clinical consequences of Tityus bahiensis and Tityus serrulatus scorpion stings in the region of Campinas, southeastern Brazil.

    PubMed

    Bucaretchi, Fábio; Fernandes, Luciane C R; Fernandes, Carla B; Branco, Maíra M; Prado, Camila C; Vieira, Ronan J; De Capitani, Eduardo M; Hyslop, Stephen

    2014-10-01

    Scorpion stings account for most envenomations by venomous animals in Brazil. A retrospective study (1994-2011) of the clinical consequences of Tityus scorpion stings in 1327 patients treated at a university hospital in Campinas, southeastern Brazil, is reported. The clinical classification, based on outcome, was: dry sting (no envenoming), class I (only local manifestations), class II (systemic manifestations), class III (life-threatening manifestations, such as shock and/or cardiac failure requiring inotropic/vasopressor agents, and/or respiratory failure), and fatal. The median patient age was 27 years (interquartile interval = 15-42 years). Scorpions were brought for identification in 47.2% of cases (Tityus bahiensis 27.7%; Tityus serrulatus 19.5%). Sting severity was classified and each accounted for the following percentage of cases: dry stings - 3.4%, class I - 79.6%, class II - 15.1%, class III - 1.8% and fatal - 0.1%. Pain was the primary local manifestation (95.5%). Systemic manifestations such as vomiting, agitation, sweating, dyspnea, bradycardia, tachycardia, tachypnea, somnolence/lethargy, cutaneous paleness, hypothermia and hypotension were detected in class II or class III + fatal groups, but were significantly more frequent in the latter group. Class III and fatal cases occurred only in children <15 years old, with scorpions being identified in 13/25 cases (T. serrulatus, n = 12; T. bahiensis, n = 1). Laboratory blood abnormalities (hyperglycemia, hypokalemia, leukocytosis, elevations in serum total CK, CK-MB and troponin T, bicarbonate consumption and an increase in base deficit and blood lactate), electrocardiographic changes (ST segment) and echocardiographic alterations (ventricular ejected fraction <54%) were frequently detected in class III patients. Seventeen patients developed pulmonary edema, 16 had cardiac failure and seven had cardiogenic shock. These results indicate that most scorpion stings involved only local manifestations

  7. Mycoplasmas in Australian fur seals (Arctocephalus pusillus doriferus): identification and association with abortion.

    PubMed

    Lynch, Michael; Taylor, Trevor K; Duignan, Pádraig J; Swingler, Jane; Marenda, Marc; Arnould, John P Y; Kirkwood, Roger

    2011-11-01

    Bacteria from the genus Mycoplasma are common inhabitants of the respiratory, gastrointestinal, and genital tracts of mammals. The understanding of the pathological significance of mycoplasmas in seals is poor, as few studies have utilized the specific culture techniques required to isolate these bacteria. The current study surveyed for the Mycoplasma species present in Australian fur seals (Arctocephalus pusillus doriferus) and investigated the association between infection and pathology. Mycoplasmas were found in the nasal cavities of 55/80 (69%) of apparently healthy individuals. Isolates from 18 individuals were investigated through 16S ribosomal RNA sequencing, and 3 species were identified: M. zalophi, M. phocae, and Mycoplasma sp. (GenBank no. EU714238.1), all of which had previously been isolated from Northern Hemisphere pinnipeds. In addition, mycoplasmas were isolated from the lungs of 4 out of 16 juveniles and 1 out of 5 adults sampled at necropsy. Isolates obtained were M. zalophi, Mycoplasma sp. EU714238.1, and M. phocicerebrale, but infection was not associated with lung pathology in these age classes. Inflammatory disease processes of the heart and/or lungs were present in 12 out of 32 (38%) aborted fetuses on microscopic examination. Predominant findings were interstitial pneumonia, pericarditis, and myocarditis. Mycoplasma phocicerebrale was isolated from the thymus of an aborted fetus, and 3 out of 11 (27%) fetuses with inflammatory heart or lung lesions were PCR-positive for Mycoplasma. In conclusion, several species of Mycoplasma are part of the normal flora of the nasal cavity of Australian fur seals, and some mycoplasmas may be associated with abortion in this species of seal. PMID:22362792

  8. Renal effects and vascular reactivity induced by Tityus serrulatus venom.

    PubMed

    de Sousa Alves, Renata; do Nascimento, Nilberto Robson Falcão; Barbosa, Paulo Sérgio Ferreira; Kerntopf, Marta Regina; Lessa, Lucília Maria Abreu; de Sousa, Clauber Mota; Martins, René Duarte; Sousa, Daniel Freire; de Queiroz, Maria Goretti Rodrigues; Toyama, Marcos Hikari; Fonteles, Manassés Claudino; Martins, Alice Maria Costa; Monteiro, Helena Serra Azul

    2005-09-01

    Tityus serrulatus, popularly known as yellow scorpion, is one of the most studied scorpion species in South America and its venom has supplied some highly active molecules. The effects of T. serrulatus venom upon the renal physiology in human showed increased renal parameters, urea and creatinine. However, in perfused rat kidney the effects were not tested until now. Isolated kidneys from Wistar rats, weighing 240-280 g, were perfused with Krebs-Henseleit solution containing 6% (g weight) of previously dialysed bovine serum albumin. The effects of T. serrulatus venom were studied on the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), sodium tubular transport (%TNa+), potassium tubular transport (%TK+) and chloride tubular transport (%TCl-). Tityus serrulatus venom (TsV; 10 microg/mL) was added to the system 30 min after the beginning of each experiment (n=6). This 30 min period was used as an internal control. The mesenteric bed was perfused with Krebs solution kept warm at 37 degrees C by a constant flow (4 mL/min), while the variable perfusion pressure was measured by means of a pressure transducer. The direct vascular effects of TsV (10 microg/mL/min; n=6), infused at a constant rate (0.1 mL/min), were examined and compared to the infusion of the vehicle alone at the same rate. TsV increased PP (PP30'=127.8+/-0.69 vs PP60'=154.2+/-14 mmHg*, *p<0.05) and RVR (RVR30'=6.29+/-0.25 vs RVR60'=8.03+/-0.82 mmHg/mLg(-1)min(-1)*, *p<0.05), decreased GFR (GFR30'=0.58+/-0.02 vs GFR60'=0.46+/-0.01mLg(-1)min(-1)*, *p<0.05) and UF (UF30'=0.135+/-0.001 vs UF60'=0.114+/-0.003mLg(-1)min(-1)*, *p<0.05). Tubular transport was not affected during the whole experimental period (120 min). On the other hand, the infusion of TsV (10 microg/mL/min) increased the basal perfusion pressure of isolated arteriolar mesenteric bed (basal pressure: 74.17+/-3.42 vs TsV 151.8+/-17.82 mmHg*, *p<0.05). TsV affects renal haemodynamics

  9. [A new species of Tityus (Scorpiones: Buthidae) from Turimiquire, Venezuela].

    PubMed

    De Sousa, Leonardo; Manzanilla, Jesús; Parrilla-Alvarez, Pedro

    2006-06-01

    We describe a new species of Buthid scorpion, Tityus quirogae, from the Turimiquire mountains, eastern side of the La Costa range, Monagas and Sucre States, Venezuela. It is morphologically similar to T. nematochirus and T. meridanus. It differs from these species in the distribution of the dorsal femoral trichobothria and in the following combination of characters: (1) I caudal segment with two parallel ventral keels. Caudal segments II to IV with ventral keels that are double in the extremes of the segments and single in the middle, (2) noticeable sexual dimorphism, especially in pedipalp shape; the male chelae are markedly thin and long, (3) number of pectineous teeth (male: 18 in each pecten; female: 18 in the right pecten and 19 in the left one), and (4) number of denticle rows in the movable finger of the right chela (16 in both sexes). T. quirogae is the first species of this genus, in the Northeastern region of Venezuela, with thin and elongated pedipalps. PMID:18494317

  10. Inter- and intrapopulational genetic variability of Tityus serrulatus (Scorpiones, Buthidae).

    PubMed

    Scholte, Ronaldo G Carvalho; Caldeira, Roberta Lima; Simões, Mariana Crivellari Machado; Stutz, William H; Silva, Larissa Lopes; Carvalho, Omar dos Santos; Oliveira, Guilherme

    2009-11-01

    In Brazil, there are near 20 genera and almost 120 species of scorpions of which 95% reproduce sexually. Parthenogenetic reproduction, however, may also take place. To gain insight into useful molecular markers in parthenogenetic scorpion species, we studied DNA polymorphism using two molecular approaches: simple sequence repeat anchored polymerase chain reaction (SSR-PCR) and sequencing of the cytochrome C oxidase subunit I of the mitochondrial genome, mtDNA (COXI), of Tityus serrulatus. Three different groups were used: group 1, composed of 1 female and 14 descendants; group 2 with 1 female and 17 descendants, both from the city of Uberlândia, State of Minas Gerais (MG), Brazil, and the third group that consisted of three adult scorpions from the city of Belo Horizonte, MG. The profiles generated by SSR-PCR were identical for all specimens, while partial sequencing of COXI showed the presence of SNPs. After aligning COXI contigs, one of the groups presented 18 SNPs and the second 8 SNPs. The two groups were differentiated by two diagnostic SNPs. We did not find evidence of mitochondrial recombination. The results are in agreement with the parthenogenetic mode of reproduction of this species and sequencing of the COXI gene enabled the separation of scorpions groups. PMID:19595660

  11. Diversity of long-chain toxins in Tityus zulianus and Tityus discrepans venoms (Scorpiones, Buthidae): molecular, immunological, and mass spectral analyses.

    PubMed

    Borges, Adolfo; García, Carmen C; Lugo, Elizabeth; Alfonzo, Marcelo J; Jowers, Michael J; Op den Camp, Huub J M

    2006-01-01

    In Venezuela, stings by Tityus zulianus scorpions produce cardiorespiratory arrest, whereas envenoming by Tityus discrepans involves gastrointestinal/pancreatic complications, suggesting structural and/or functional differences. We sought to compare their toxin repertoires through immunological, molecular, and mass spectral analyses. First, in vivo tests showed that neutralization of T. zulianus venom toxicity by the anti-T. discrepans antivenom was not complete. To compare T. discrepans and T. zulianus long-chain (sodium channel-active) toxins, their most toxic Sephadex G-50 fractions, TdII and TzII, were subjected to acid-urea PAGE, which showed differences in composition. Amplification of toxin-encoding mRNAs using a leader peptide-based oligonucleotide rendered cDNAs representing twelve T. discrepans and two T. zulianus distinct toxin transcripts, including only one shared component, indicating divergence between T. zulianus and T. discrepans 5' region-encoded, toxin signal peptides. A 3'-UTR polymorphism was also noticed among the transcripts encoding shared components Tz1 and Td4. MALDI-TOF MS profiling of TdII and TzII produced species-specific spectra, with seven of the individual masses matching those predicted by cDNA sequencing. Phylogenetic analysis showed that the unique T. zulianus transcript-encoded sequence, Tz2, is structurally related to Tityus serrulatus and Centruroides toxins. Together with previous reports, this work indicates that T. zulianus and T. discrepans toxin repertoires differ structurally and functionally. PMID:16356783

  12. Reproductive toxic effects of Tityus serrulatus scorpion venom in rats.

    PubMed

    Cruttenden, Karen; Nencioni, Ana Leonor A; Bernardi, Maria Martha; Dorce, Valquiria A C

    2008-08-01

    Tityus serrulatus is the most venomous scorpion in Brazil. Little is known about the effect of maternal exposure to the venom on fetal development. We investigated the effect of low to moderate doses of the venom (0.3 or 1.0 mg/kg s.c. on either day 5 or day 10 of gestation) on pregnant rats and on their offspring. For dams, we observed their body weight gain and reproductive parameters. For the offspring, we observed their body weight and weight of internal organs and the number of live and dead fetuses, and we investigated whether the venom caused external, visceral, skeletal or histopathological alterations in the offspring. The offspring were examined on gestational day 21. Injection of the venom on gestational day 5 did not change the reproductive parameters of the dams, their weight or fetuses' weight. Rats that received the high dose of the venom (1.0 mg/kg) on gestational day 10 had heavier placentas and heavier fetuses with heavier lungs. Injections on day 10 of gestation did not alter the reproductive parameters of the dams nor their weight gain at either dose. The venom did not cause malformations of the fetal skeleton or viscera and did not delay fetal development with either dose. In conclusion, subcutaneous administration of 0.3 or 1.0 mg/kg T. serrulatus venom to pregnant Wistar rats at either day 5 or day 10 of gestation did not cause maternal or clear fetal toxicity. Subtle increases in placental weight and fetal body and lung weights observed following treatment with 1.0 mg/kg on day 10 of gestation were not associated with histopathological findings. Whether these observations represent a reaction to treatment and, if so, the underlying mechanisms and their toxicological impact remain to be examined further in future studies. PMID:18550329

  13. [Poisonous sting by Tityus stigmurus (Scorpiones; Buthidae) in the state of Bahia, Brazil].

    PubMed

    Lira-da-Silva, R M; Amorim, A M; Brazil, T K

    2000-01-01

    The present investigation is a descriptive study regarding the clinical aspects of accidents caused by the scorpion Tityus stigmurus in Bahia, Brazil. We analyzed 237 confirmed cases treated by the Antivenom Information Centre (CIAVE) from 1982 to 1995. Envenomation by T. stigmurus was mainly characterized by local symptoms: pain (94.4%), dormancy (30.0%), edema (17.8%), erythema (17.8), paresthesia (15.6%) and general manifestations such as headache (4.4%), vomiting (4.4%) and sudoresis (3.3%). Most of the envenomation cases were mild (94%) and all were successfully cured. Although T. stigmurus venom is not in the pool of anti-venom serum (SAE), the absence of lethality and benign nature of the cases suggest the efficiency of SAE. With the exception of deaths and systemic complications, envenoming gravity was similar to those of Tityus serrulatus. PMID:10967591

  14. The Scorpion Toxin Tf2 from Tityus fasciolatus Promotes Nav1.3 Opening

    PubMed Central

    Camargos, Thalita S.; Bosmans, Frank; Rego, Solange C.; Mourão, Caroline B. F.; Schwartz, Elisabeth F.

    2015-01-01

    We identified Tf2, the first β-scorpion toxin from the venom of the Brazilian scorpion Tityus fasciolatus. Tf2 is identical to Tb2-II found in Tityus bahiensis. We found that Tf2 selectively activates human (h)Nav1.3, a neuronal voltage-gated sodium (Nav) subtype implicated in epilepsy and nociception. Tf2 shifts hNav1.3 activation voltage to more negative values, thereby opening the channel at resting membrane potentials. Seven other tested mammalian Nav channels (Nav1.1-1.2; Nav1.4-1.8) expressed in Xenopus oocytes are insensitive upon application of 1 μM Tf2. Therefore, the identification of Tf2 represents a unique addition to the repertoire of animal toxins that can be used to investigate Nav channel function. PMID:26083731

  15. Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus ().

    PubMed

    Martin-Eauclaire, Marie-France; Pimenta, Adriano M C; Bougis, Pierre E; De Lima, Maria-Elena

    2016-09-01

    Potassium (K(+)) channels are trans-membrane proteins, which play a key role in cellular excitability and signal transduction pathways. Scorpion toxins blocking the ion-conducting pore from the external side have been invaluable probes to elucidate the structural, functional, and physio-pathological characteristics of these ion channels. This review will focus on the interaction between K(+) channels and their peptide blockers isolated from the venom of the scorpion Tityus serrulatus, which is considered as the most dangerous scorpion in Brazil, in particular in Minas-Gerais State, where many casualties are described each year. The primary mechanisms of action of these K(+) blockers will be discussed in correlation with their structure, very often non-canonical compared to those of other well known K(+) channels blockers purified from other scorpion venoms. Also, special attention will be brought to the most recent data obtained by proteomic and transcriptomic analyses on Tityus serrulatus venoms and venom glands. PMID:27349167

  16. Scorpion envenoming caused by Tityus cf. silvestris evolving with severe muscle spasms in the Brazilian Amazon.

    PubMed

    Monteiro, Wuelton Marcelo; de Oliveira, Sâmella Silva; Pivoto, Guilherme; Alves, Eliane Campos; de Almeida Gonçalves Sachett, Jacqueline; Alexandre, Cleber Nunes; Fé, Nelson Ferreira; Barbosa Guerra, Maria das Graças Vale; da Silva, Iran Mendonça; Tavares, Antonio Magela; Ferreira, Luiz Carlos de Lima; Lacerda, Marcus Vinícius Guimarães

    2016-09-01

    Scorpion stings are a public health problem in the Brazilian Amazon. However, detailed clinical characterization with the proper animal identification is scarce. Here we report a confirmed case of envenoming by Tityus cf. silvestris in the Brazilian Amazon. The case evolved with generalized muscle spasms and was treated with antivenom and supportive therapy, requiring intensive care unit admission. The patient evolved favourably and was discharged after 9 days of hospitalization. PMID:27368713

  17. Scorpionism due to Tityus neoespartanus (Scorpiones, Buthidae) in Margarita Island, northeastern Venezuela.

    PubMed

    De Sousa, Leonardo; Boadas, Jenny; Kiriakos, Demetrio; Borges, Adolfo; Boadas, Jesús; Marcano, Jenny; Turkali, Iván; De Los Ríos, Miguel

    2007-01-01

    The first two cases of scorpion envenoming caused by Tityus neoespartanus (Buthidae) are described. The accidents took place within human environments (one inside a home and the other inside a school), in the village of La Sierra, Margarita Island, State of Nueva Esparta, northeastern Venezuela. Both cases were moderately severe and developed pancreatic involvement and electrocardiographic abnormalities. This report allows inclusion of Margarita Island among the endemic areas of scorpionism in Venezuela. PMID:18200425

  18. Tityus bahiensis scorpion venom injected to dams during pregnancy affects some cytokines of fetuses.

    PubMed

    Dorce, Ana L C; Frare, Eduardo O; Paulo, Maria E F V; Dorce, Valquiria A C; Nencioni, Ana L A

    2015-09-01

    Due to the high incidence of scorpion stings in Brazil, pregnant women are among the possible victims. Cytokines are important during the pregnancy, and scorpion venoms can change their release. We evaluated the levels of some cytokines in the fetuses after the treatment of pregnant rats with the Tityus bahiensis scorpion venom. The concentration of some of them is altered and can be responsible for the effects previously observed on innate reflexes, and the physical and behavioral development of the offspring. PMID:26140840

  19. Profiling the resting venom gland of the scorpion Tityus stigmurus through a transcriptomic survey

    PubMed Central

    2012-01-01

    Background The scorpion Tityus stigmurus is widely distributed in Northeastern Brazil and known to cause severe human envenoming, inducing pain, hyposthesia, edema, erythema, paresthesia, headaches and vomiting. The present study uses a transcriptomic approach to characterize the gene expression profile from the non-stimulated venom gland of Tityus stigmurus scorpion. Results A cDNA library was constructed and 540 clones were sequenced and grouped into 153 clusters, with one or more ESTs (expressed sequence tags). Forty-one percent of ESTs belong to recognized toxin-coding sequences, with transcripts encoding antimicrobial toxins (AMP-like) being the most abundant, followed by alfa KTx- like, beta KTx-like, beta NaTx-like and alfa NaTx-like. Our analysis indicated that 34% of the transcripts encode “other possible venom molecules”, which correspond to anionic peptides, hypothetical secreted peptides, metalloproteinases, cystein-rich peptides and lectins. Fifteen percent of ESTs are similar to cellular transcripts. Sequences without good matches corresponded to 11%. Conclusions This investigation provides the first global view of gene expression of the venom gland from Tityus stigmurus under resting conditions. This approach enables characterization of a large number of venom gland component molecules, which belong either to known or non yet described types of venom peptides and proteins from the Buthidae family. PMID:22853446

  20. Neurotoxic effects of fractions isolated from Tityus bahiensis scorpion venom (Perty, 1834).

    PubMed

    Lourenço, Geane Antiques; Lebrun, Ivo; Dorce, Valquiria A Coronado

    2002-02-01

    Tityus serrulatus and Tityus bahiensis are considered to be the most venomous scorpions in Brazil and are responsible for most of the accidents that occur in our country. The main toxic agents in scorpion venoms are small basic polypeptides that act as neurotoxins. They cause a derangement of ion channels that result in abnormal release of neurotransmitters. In the present study we fractionated the venom of Tityus bahiensis and studied the effects of fractions P2, P3, P4, P5, P6 and P7, on the mammalian central nervous system. Intravenous injection of P5, P6 and P7 in rats induced spontaneous convulsion, intrahippocampal injection caused behavioural seizures, and P5 and P6 induced electrographic seizures. P5 caused neuronal damage in the CA1 area and P6 in the CA1, CA3 areas and hilus of the dentate gyrus (DG) of the hippocampus. Injection of P3 in the hippocampus did not induce convulsions or lesions. However, when injected intravenously in mice, this fraction reduced behavioural activity in an open field test. Unilateral injection of P4 in the hippocampus caused neuronal damage in the contralateral CA3, but not in the ipsilateral hippocampus. These results suggest that scorpion toxins present in the venom are able to act directly on the central nervous system promoting behavioural and histopathological effects. PMID:11689236

  1. Diagnosis and treatment considerations in a case of malignant mesenchymoma in an African fur seal (Arctocephalus pusillus).

    PubMed

    Laricchiuta, Pietro; Campolo, Marco; Martelli, Paolo; Cantore, Angela; Menga, Giuseppe; Tortorella, Giovanni; Grillo, Isidoro G; de Ruvo, Giuseppe; Gelli, Donatella; Lai, Olimpia R

    2013-06-01

    A 20-yr-old African fur seal (Arctocephalus pusillus) presented with a slowly growing mass located on the dorsum at the level of the last thoracic vertebrae. The mass was hard, 10 cm in diameter, and not adherent to the underlying tissues. Multiple biopsies were collected for histopathology and revealed extensive areas of necrosis, small nodules of malignant mesenchymal proliferation with areas of chondroid metaplasia, and atypical cells in vessel walls. The morphologic diagnosis was suggestive of malignant mesenchymal neoplasia originating from the vascular wall. The mass was removed 1 mo later due to ulceration and infection. Histologically, based on the World Health Organization's classification of neoplastic processes in domestic animals, the tumor was consistent with malignant mesenchymoma. The margins of resection revealed the presence of neoplastic cells. Based on these results, the particular species involved, the high local invasiveness, and the high metastatic index of this malignant tumor in domestic mammals and humans, the prognosis was poor. The animal died 6 mo later with metatastic disease. PMID:23805568

  2. Electrophysiological characterization, solubilization and purification of the Tityus gamma toxin receptor associated with the gating component of the Na+ channel from rat brain.

    PubMed

    Barhanin, J; Pauron, D; Lombet, A; Norman, R I; Vijverberg, H P; Giglio, J R; Lazdunski, M

    1983-01-01

    Electrophysiological studies with neuroblastoma cells have shown that toxin gamma from the venom of the scorpion Tityus serrulatus is a new toxin specific for the gating system of the Na+ channel. The procedure which solubilizes the tetrodotoxin receptor from rat brain also solubilizes the Tityus gamma toxin receptor. Binding experiments on the solubilized receptor with a radioiodinated derivative of Tityus gamma toxin have shown: (i) that the TiTx gamma-receptor complex is very stable with a dissociation constant of 8.6 X 10(-12) M and a very slow dissociation (T 1/2 = 15 h); (ii) that the toxin recognizes a class of sites with a 1:1 stoichiometry with those for tetrodotoxin (Bmax = 1.3 pmol/mg protein). The radioiodinated Tityus gamma-receptor complex has been substantially purified by ion-exchange chromatography, lectin affinity chromatography and sucrose gradient sedimentation. A ratio of one Tityus gamma toxin binding site per tetrodotoxin binding site was found throughout the purification. The purified material exhibited a sedimentation coefficient of 10.4S and had an apparent mol. wt. of 270 000 on SDS-gel electrophoresis. No other polypeptide chains were demonstrated to be associated with this large protein in the Tityus gamma receptor. The main conclusion is that the tetrodotoxin binding site associated with the selectivity filter of the Na+ channel and the Tityus gamma toxin binding site associated with the gating component are probably carried by the same polypeptide chain. PMID:6315420

  3. Molecular systematics of the neotropical scorpion genus Tityus (Buthidae): the historical biogeography and venom antigenic diversity of toxic Venezuelan species.

    PubMed

    Borges, Adolfo; Bermingham, Eldredge; Herrera, Nimiadina; Alfonzo, Marcelo J; Sanjur, Oris I

    2010-01-01

    We provide a mitochondrial DNA-based phylogenetic hypothesis for 21 Tityus species collected in Venezuela, Trinidad, Brazil and Panama, including 12 taxa known to be toxic to humans. Our phylogenetic reconstruction is based on 850 nucleotides of the combined cytochrome oxidase subunit I and 16S rRNA genes for most species, and centered on Venezuelan scorpions owing to the detailed taxonomic and biogeographic information available for Tityus in this region. The principal phylogenetic result was the strong support for mtDNA clades representing geographical groupings associated with the Perijá mountain range, the Mérida Andes, or the central and eastern coastal ranges in Venezuela, suggesting that vicariance has been a potent force in the diversification of local scorpions. Venezuelan Tityus species have been organized by González-Sponga into three artificial morphological groups, "androcottoides", "discrepans", and "nematochirus", based on the array of ventral carinae in metasomal segments II-IV. We also incorporated a fourth morphological group ("Tityus clathratus"), recently documented in Venezuela. Our results do not support the clustering of the species in the "androcottoides" and "discrepans" morphological groups, which include the majority of taxa of medical importance, but provided support for the "nematochirus" species group. T. clathratus was found to cluster with the Brazilian T. serrulatus and T. bahiensis. Divergence times of most clades are consistent with major events in the geological history of northern Venezuela and suggest that many Venezuelan Tityus species formed in the late Miocene and the Pliocene. In turn, we used the Tityus mtDNA phylogeny to determine the potential utility of phylogenetic systematics to predict Tityus venom antigenic reactivity by testing the recognition of T. nororientalis, T. discrepans, T. zulianus, T. perijanensis, and T. clathratus venoms by anti-T. discrepans horse antibodies. Cross-reactivity was significantly

  4. Description of the male of Tityus kuryi Lourenço, 1997 and notes about males of Tityus stigmurus (Thorell, 1877) and Tityus serrulatus Lutz & Mello, 1922 (Scorpiones, Buthidae).

    PubMed

    Dos Santos, Maria Dulcinéia Sales; Porto, Tiago Jordão; Lira-da-Silva, Rejâne Maria; Brazil, Tania Kobler

    2014-01-01

    The male of Tityus kuryi Lourenço, 1997 is described for the first time. Despite being very similar to the female, the male presents more robust metasomal segments. Additionally, the distribution of the sexual populations of another two species of the T. stigmurus complex is reported herein: T. serrulatus Lutz & Mello, 1922 and T. stigmurus (Thorell, 1877). Males of T. serrulatus were, until now, restricted to the Minas Gerais State (Southwestern region of Brazil), and with new records reported here, its known distribution now encompasses the Northeastern region of Brazil. Males of T. stigmurus were previously recorded only for two municipalities in the State of Bahia, and here we present eight new records for Bahia State and one for Pernambuco State. We present a key to related species of the T. stigmurus complex based on morphology and coloration pattern. PMID:25152686

  5. Description of the male of Tityus kuryi Lourenço, 1997 and notes about males of Tityus stigmurus (Thorell, 1877) and Tityus serrulatus Lutz & Mello, 1922 (Scorpiones, Buthidae)

    PubMed Central

    dos Santos, Maria Dulcinéia Sales; Porto, Tiago Jordão; Lira-da-Silva, Rejâne Maria; Brazil, Tania Kobler

    2014-01-01

    Abstract The male of Tityus kuryi Lourenço, 1997 is described for the first time. Despite being very similar to the female, the male presents more robust metasomal segments. Additionally, the distribution of the sexual populations of another two species of the T. stigmurus complex is reported herein: T. serrulatus Lutz & Mello, 1922 and T. stigmurus (Thorell, 1877). Males of T. serrulatus were, until now, restricted to the Minas Gerais State (Southwestern region of Brazil), and with new records reported here, its known distribution now encompasses the Northeastern region of Brazil. Males of T. stigmurus were previously recorded only for two municipalities in the State of Bahia, and here we present eight new records for Bahia State and one for Pernambuco State. We present a key to related species of the T. stigmurus complex based on morphology and coloration pattern. PMID:25152686

  6. Identification and characterization of D-xylose reductase involved in pentose catabolism of the zygomycetous fungus Rhizomucor pusillus.

    PubMed

    Komeda, Hidenobu; Yamasaki-Yashiki, Shino; Hoshino, Kazuhiro; Asano, Yasuhisa

    2015-01-01

    Rhizomucor pusillus NBRC 4578 efficiently produces ethanol from lignocellulosic biomass because of its ability to ferment not only d-glucose, but also d-xylose. When the strain was cultivated on d-xylose, ethanol was gradually formed in the culture medium with a decrease in d-xylose and the simultaneous accumulation of xylitol, which suggested that the strain catabolized d-xylose with d-xylose reductase (XR) and xylitol dehydrogenase (XDH). XR (RpXR) was purified to homogeneity from the crude extract prepared from the mycelia of the strain grown on d-xylose. The purified enzyme was found to be NADPH-dependent and prefer pentoses such as d-xylose, d-ribose, and l-arabinose as substrates. Isolation of the genomic DNA and cDNA of the xyl1 gene encoding RpXR revealed that the gene was interrupted by two introns and the exon of the gene encoded a protein composed of 322 amino acids with a Mr of 36,724. Phylogenetic analysis showed that RpXR is more related to 4-dihydromethyltrisporate dehydrogenases from Mucoraseae fungi rather than the previously reported fungal XRs. Quantitative real-time PCR indicated that transcription of the xyl1 gene was marked in the presence of d-xylose and l-arabinose, but was week in the presence of d-glucose. These biochemical and expression analyses suggest that RpXR is involved in the catabolism of l-arabinose as well as d-xylose. This is the first report of the purification, characterization, and gene cloning of XR from zygomycetous fungi. PMID:25041710

  7. Dive characteristics can predict foraging success in Australian fur seals (Arctocephalus pusillus doriferus) as validated by animal-borne video.

    PubMed

    Volpov, Beth L; Rosen, David A S; Hoskins, Andrew J; Lourie, Holly J; Dorville, Nicole; Baylis, Alastair M M; Wheatley, Kathryn E; Marshall, Greg; Abernathy, Kyler; Semmens, Jayson; Hindell, Mark A; Arnould, John P Y

    2016-01-01

    Dive characteristics and dive shape are often used to infer foraging success in pinnipeds. However, these inferences have not been directly validated in the field with video, and it remains unclear if this method can be applied to benthic foraging animals. This study assessed the ability of dive characteristics from time-depth recorders (TDR) to predict attempted prey capture events (APC) that were directly observed on animal-borne video in Australian fur seals (Arctocephalus pusillus doriferus, n=11). The most parsimonious model predicting the probability of a dive with ≥1 APC on video included only descent rate as a predictor variable. The majority (94%) of the 389 total APC were successful, and the majority of the dives (68%) contained at least one successful APC. The best model predicting these successful dives included descent rate as a predictor. Comparisons of the TDR model predictions to video yielded a maximum accuracy of 77.5% in classifying dives as either APC or non-APC or 77.1% in classifying dives as successful verses unsuccessful. Foraging intensity, measured as either total APC per dive or total successful APC per dive, was best predicted by bottom duration and ascent rate. The accuracy in predicting total APC per dive varied based on the number of APC per dive with maximum accuracy occurring at 1 APC for both total (54%) and only successful APC (52%). Results from this study linking verified foraging dives to dive characteristics potentially opens the door to decades of historical TDR datasets across several otariid species. PMID:26873950

  8. Australian Fur Seals (Arctocephalus pusillus doriferus) Use Raptorial Biting and Suction Feeding When Targeting Prey in Different Foraging Scenarios

    PubMed Central

    Hocking, David P.; Salverson, Marcia; Fitzgerald, Erich M. G.; Evans, Alistair R.

    2014-01-01

    Foraging behaviours used by two female Australian fur seals (Arctocephalus pusillus doriferus) were documented during controlled feeding trials. During these trials the seals were presented with prey either free-floating in open water or concealed within a mobile ball or a static box feeding device. When targeting free-floating prey both subjects primarily used raptorial biting in combination with suction, which was used to draw prey to within range of the teeth. When targeting prey concealed within either the mobile or static feeding device, the seals were able to use suction to draw out prey items that could not be reached by biting. Suction was followed by lateral water expulsion, where water drawn into the mouth along with the prey item was purged via the sides of the mouth. Vibrissae were used to explore the surface of the feeding devices, especially when locating the openings in which the prey items had been hidden. The mobile ball device was also manipulated by pushing it with the muzzle to knock out concealed prey, which was not possible when using the static feeding device. To knock prey out of this static device one seal used targeted bubble blowing, where a focused stream of bubbles was blown out of the nose into the openings in the device. Once captured in the jaws, prey items were manipulated and re-oriented using further mouth movements or chews so that they could be swallowed head first. While most items were swallowed whole underwater, some were instead taken to the surface and held in the teeth, while being vigorously shaken to break them into smaller pieces before swallowing. The behavioural flexibility displayed by Australian fur seals likely assists in capturing and consuming the extremely wide range of prey types that are targeted in the wild, during both benthic and epipelagic foraging. PMID:25390347

  9. Australian fur seals (Arctocephalus pusillus doriferus) use raptorial biting and suction feeding when targeting prey in different foraging scenarios.

    PubMed

    Hocking, David P; Salverson, Marcia; Fitzgerald, Erich M G; Evans, Alistair R

    2014-01-01

    Foraging behaviours used by two female Australian fur seals (Arctocephalus pusillus doriferus) were documented during controlled feeding trials. During these trials the seals were presented with prey either free-floating in open water or concealed within a mobile ball or a static box feeding device. When targeting free-floating prey both subjects primarily used raptorial biting in combination with suction, which was used to draw prey to within range of the teeth. When targeting prey concealed within either the mobile or static feeding device, the seals were able to use suction to draw out prey items that could not be reached by biting. Suction was followed by lateral water expulsion, where water drawn into the mouth along with the prey item was purged via the sides of the mouth. Vibrissae were used to explore the surface of the feeding devices, especially when locating the openings in which the prey items had been hidden. The mobile ball device was also manipulated by pushing it with the muzzle to knock out concealed prey, which was not possible when using the static feeding device. To knock prey out of this static device one seal used targeted bubble blowing, where a focused stream of bubbles was blown out of the nose into the openings in the device. Once captured in the jaws, prey items were manipulated and re-oriented using further mouth movements or chews so that they could be swallowed head first. While most items were swallowed whole underwater, some were instead taken to the surface and held in the teeth, while being vigorously shaken to break them into smaller pieces before swallowing. The behavioural flexibility displayed by Australian fur seals likely assists in capturing and consuming the extremely wide range of prey types that are targeted in the wild, during both benthic and epipelagic foraging. PMID:25390347

  10. Dive characteristics can predict foraging success in Australian fur seals (Arctocephalus pusillus doriferus) as validated by animal-borne video

    PubMed Central

    Volpov, Beth L.; Rosen, David A. S.; Hoskins, Andrew J.; Lourie, Holly J.; Dorville, Nicole; Baylis, Alastair M. M.; Wheatley, Kathryn E.; Marshall, Greg; Abernathy, Kyler; Semmens, Jayson; Hindell, Mark A.; Arnould, John P. Y.

    2016-01-01

    ABSTRACT Dive characteristics and dive shape are often used to infer foraging success in pinnipeds. However, these inferences have not been directly validated in the field with video, and it remains unclear if this method can be applied to benthic foraging animals. This study assessed the ability of dive characteristics from time-depth recorders (TDR) to predict attempted prey capture events (APC) that were directly observed on animal-borne video in Australian fur seals (Arctocephalus pusillus doriferus, n=11). The most parsimonious model predicting the probability of a dive with ≥1 APC on video included only descent rate as a predictor variable. The majority (94%) of the 389 total APC were successful, and the majority of the dives (68%) contained at least one successful APC. The best model predicting these successful dives included descent rate as a predictor. Comparisons of the TDR model predictions to video yielded a maximum accuracy of 77.5% in classifying dives as either APC or non-APC or 77.1% in classifying dives as successful verses unsuccessful. Foraging intensity, measured as either total APC per dive or total successful APC per dive, was best predicted by bottom duration and ascent rate. The accuracy in predicting total APC per dive varied based on the number of APC per dive with maximum accuracy occurring at 1 APC for both total (54%) and only successful APC (52%). Results from this study linking verified foraging dives to dive characteristics potentially opens the door to decades of historical TDR datasets across several otariid species. PMID:26873950

  11. Peptide T, a novel bradykinin potentiator isolated from Tityus serrulatus scorpion venom.

    PubMed

    Ferreira, L A; Alves, E W; Henriques, O B

    1993-08-01

    A bradykinin-potentiating peptide was isolated and characterized from venom of the scorpion Tityus serrulatus by chromatographic techniques followed by biological assays. The complete amino acid sequence (13 residues) of peptide is presented. The peptide potentiated the contractile activity of bradykinin on the isolated guinea-pig ileum, and inhibited the hydrolysis of bradykinin by angiotensin-converting enzyme from B. jararaca plasma and the conversion of angiotensin I to angiotensin II by kininase II from guinea-pig ileum tissue. The peptide also increased the depressor effect of bradykinin on arterial blood pressure in the anaesthetized rat. PMID:8212046

  12. Neutralizing effects of Mimosa tenuiflora extracts against inflammation caused by Tityus serrulatus scorpion venom.

    PubMed

    Bitencourt, Mariana Angélica Oliveira; de Souza Lima, Maira Conceição Jerônimo; Torres-Rêgo, Manoela; Fernandes, Júlia Morais; da Silva-Júnior, Arnóbio Antônio; Tambourgi, Denise Vilarinho; Zucolotto, Silvana Maria; de Freitas Fernandes-Pedrosa, Matheus

    2014-01-01

    Scorpion bite represents a significant and serious public health problem in certain regions of Brazil, as well as in other parts of the world. Inflammatory mediators are thought to be involved in the systemic and local immune response induced by Tityus serrulatus scorpion envenomation. The aim of this study was to evaluate the effect of extracts of Mimosa tenuiflora on model envenomation. In mice, the envenomation model is induced by Tityus serrulatus venom. Previous treatment of mice with fractions from M. tenuiflora was able to suppress the cell migration to the peritoneal cavity. The treatment of mice with M. tenuiflora extracts also decreased the levels of IL-6, IL-12, and IL-1β. We concluded that the administration of the extract and fractions resulted in a reduction in cell migration and showed a reduction in the level of proinflammatory cytokines. This study demonstrates, for the first time, the anti-inflammatory effect of aqueous extract from the Mimosa tenuiflora plant on T. serrulatus venom. PMID:25013776

  13. Serum production against Tityus serrulatus scorpion venom using cross-linked chitosan nanoparticles as immunoadjuvant.

    PubMed

    Rocha Soares, Karla S; Cardozo Fonseca, José L; Oliveira Bitencourt, Mariana A; Santos, Kátia S C R; Silva, Arnóbio A; Fernandes-Pedrosa, Matheus F

    2012-12-15

    Several species of scorpions are known to cause accidents which can lead to death, most of them belonging to the genus Tityus. Tityus serrulatus is considered the most dangerous scorpion in South America. In Brazil, T. serrulatus is responsible for serious accidents, including deaths, which occur mainly with children and elderly people. Anti-scorpion sera are routinely produced by various institutions, and suitable technologies have been investigated for encapsulation and release recombinant or native proteins capable of inducing antibody production. In this context, biocompatible and biodegradable polymers, such as chitosan, have been employed for this purpose. This study aimed to obtain a protein release system for the peptides or proteins from T. serrulatus, based on cross-linked chitosan nanoparticles (CN) in order to generate a new model of immunization in animals, and consequently a potentially novel polyclonal serum, namely an anti-T. serrulatus venom. CN were successfully obtained by ionic gelation using the polyanion tripolyphosphate (TPP), which demonstrated a suitable particle size of about 200 nm, with maximum encapsulation efficiency (100%) and enhanced antigen-specific antibody titers of 72%. The serum production data revealed that CN were equipotent to aluminum hydroxide, the traditional adjuvant for immunization. This study demonstrates that chitosan nanoparticles are a promising and safe system for peptide/protein delivery for T. serrulatus scorpion. PMID:23006936

  14. Positive inotropic effects of Tityus cambridgei and T. serrulatus scorpion venoms on skeletal muscle.

    PubMed

    Borja-Oliveira, C R; Pertinhez, T A; Rodrigues-Simioni, L; Spisni, A

    2009-04-01

    Toxins that block voltage-dependent K+ channels and those that modify Na+ channel gating exhibit positive inotropic effect on skeletal muscle. We compared the effect of the venom of Tityus cambridgei (Tc) and Tityus serrulatus (Ts) scorpions on mouse diaphragm force, in vitro. In indirect and direct (using D-tubocurarine 7.3 microM) stimulation, Tc, 10microg/mL, increased the contractile force, an effect prevented by tetrodotoxin (TTX) while Ts, 0.5 microg/mL, potentiated only indirectly stimulated diaphragm, thus indicating its activity is mainly mediated through acetylcholine release from nerve terminal. This effect is prevented by TTX and attenuated by the K+ channel opener cromakalim. In conclusion, our data show that while the positive inotropic effect of both venoms appears associated to the activity of Na+ and K+ channels, only Tc venom acts also directly on skeletal muscle. This finding call for further studies on Tc venom to identify the toxin responsible for its direct inotropic activity as it may have clinical applications. PMID:18926933

  15. Neutralizing Effects of Mimosa tenuiflora Extracts against Inflammation Caused by Tityus serrulatus Scorpion Venom

    PubMed Central

    Bitencourt, Mariana Angélica Oliveira; Lima, Maira Conceição Jerônimo de Souza; Torres-Rêgo, Manoela; da Silva-Júnior, Arnóbio Antônio; Tambourgi, Denise Vilarinho; Zucolotto, Silvana Maria

    2014-01-01

    Scorpion bite represents a significant and serious public health problem in certain regions of Brazil, as well as in other parts of the world. Inflammatory mediators are thought to be involved in the systemic and local immune response induced by Tityus serrulatus scorpion envenomation. The aim of this study was to evaluate the effect of extracts of Mimosa tenuiflora on model envenomation. In mice, the envenomation model is induced by Tityus serrulatus venom. Previous treatment of mice with fractions from M. tenuiflora was able to suppress the cell migration to the peritoneal cavity. The treatment of mice with M. tenuiflora extracts also decreased the levels of IL-6, IL-12, and IL-1β. We concluded that the administration of the extract and fractions resulted in a reduction in cell migration and showed a reduction in the level of proinflammatory cytokines. This study demonstrates, for the first time, the anti-inflammatory effect of aqueous extract from the Mimosa tenuiflora plant on T. serrulatus venom. PMID:25013776

  16. Novel structural class of four disulfide-bridged peptides from Tityus serrulatus venom.

    PubMed

    Pimenta, Adriano M C; Legros, Christian; Almeida, Flávia de Marco; Mansuelle, Pascal; De Lima, Maria Elena; Bougis, Pierre E; Martin-Eauclaire, Marie France

    2003-02-21

    A new structural class of short peptides folded by four disulfide-bridges was found in the venom of the Brazilian scorpion Tityus serrulatus. Peptides were put on evidence independently by means of two different approaches of structurally guided prospection. First, a cDNA sequence was obtained using a degenerate primer constructed according to the C-terminal sequence of kaliotoxin (KTx2), from the Androctonus australis venom. Second, MALDI-TOF mass spectrometry analyses of toxic fraction FIII from T. serrulatus venom revealed a family of molecules ranging approximately from 2900 to 3000 Da. Three new peptides were isolated and named TsPep1, TsPep2, and TsPep3. Biochemical characterization showed that they are 29 amino acids long, constrained by a new pattern of four disulfide-bridges. These results enable us to classify these new molecules as part of a novel structural class of short peptides from scorpion venoms. PMID:12589824

  17. Apoptogenic peptides from Tityus discrepans scorpion venom acting against the SKBR3 breast cancer cell line.

    PubMed

    D'Suze, Gina; Rosales, Arnaldo; Salazar, Víctor; Sevcik, Carlos

    2010-12-01

    Two novel peptides named neopladine 1 and neopladine 2 were purified from Tityus discrepans scorpion venom and found to be active on human breast carcinoma SKBR3 cells. Mass spectrometry molecular masses of neopladine 1 and 2 were 29918 and 30388 Da, respectively. Their N-terminal sequences were determined by Edman degradation. The peptides induced apoptosis of SKBR3 cells but had a negligible effect on non-malignant MA104 monkey kidney cells. Neopladine 1 and 2 induced 6.3 and 4.1% of SKBR3 apoptosis, respectively, in 5 h of exposure; the effect was larger with more prolonged exposures. Inmunohistochemistry showed that neopladines bind to SKBR3 cell surface inducing FasL and BcL-2 expression. PMID:20888852

  18. Scorpion toxins from Centruroides noxius and Tityus serrulatus. Primary structures and sequence comparison by metric analysis.

    PubMed Central

    Possani, L D; Martin, B M; Svendsen, I; Rode, G S; Erickson, B W

    1985-01-01

    The complete primary structures of toxin II-14 from the Mexican scorpion Centruroides noxius Hoffmann and toxin gamma from the Brazilian scorpion Tityus serrulatus Lutz and Mello have been determined. Cleavage of toxin gamma after Met-6 with CNBr produced the 55-residue peptide 7-61, which maintained the four disulphide bonds but was not toxic to mice at a dose 3 times the lethal dose of native toxin gamma. Pairwise comparison by metric analysis of segment 1-50 of toxin gamma and the corresponding segments from two other South American scorpion toxins, five North American scorpion toxins, nine North African scorpion toxins and one Central Asian scorpion toxin showed that the three Brazilian toxins are intermediate between the North American and North African toxins. This result is consistent with the hypothesis that the South American and African continents were joined by a land connection in the distant past. Images Fig. 1. PMID:4052021

  19. Many unique characteristics revealed by the complete mitochondrial genome of the scorpion Tityus serrulatus (Lutz e Mello 1922) (Chelicerata; Arachnida).

    PubMed

    Martins, Ana Paula Vimieiro; Carmo, Anderson Oliveira do; Mesquita, Flavia Oliveira; Pimenta, Ricardo José Gonzaga; Chagas, Aline Torres de Azevedo; Kalapothakis, Evanguedes

    2016-09-01

    This is the first complete mitochondrial genome of a Tityus species, although it is the most medically important genus in South America. Tityus serrulatus (Brazilian yellow scorpion) mtDNA revealed the same gene arrangement of three out of four other mitogenomes published by now for the same family (Centruroides limpidus, Mesobuthus gibbosus, M. martensii and Buthus occitanus). However, it presented many unique characteristics such as possession of Cox1 gene, different from all other protein-coding genes of scorpion mtDNA, starts with an atypical start codon (CTG). Moreover, no tRNA gene have complete typical secondary structure and the Tytius genome presented three non-coding regions longer than 100bp. Also, it contains the smallest scorpion 16S gene reported by now. Phylogenetic analysis using concatenated homologous genes confirmed Buthidae as a monophyletic clade and supports a monophyletic group including T. serrulatus and the other American species, C. limpidus. PMID:26370626

  20. In vivo protection against Tityus serrulatus scorpion venom by antibodies raised against a discontinuous synthetic epitope.

    PubMed

    Duarte, Clara Guerra; Alvarenga, Larissa Magalhães; Dias-Lopes, Camila; Machado-de-Avila, Ricardo Andrés; Nguyen, Christophe; Molina, Frank; Granier, Claude; Chávez-Olórtegui, Carlos

    2010-02-01

    Scorpion stings cause human fatalities in numerous countries. Serotherapy is the only specific means to try to circumvent the noxious effects of venom toxins. TsNTxP is a natural anatoxin from the venom of the scorpion Tityus serrulatus that may be useful to raise therapeutic anti-venom sera. Linear epitopes recognized by anti-TsNTxP antibodies have previously been mapped. Here, we attempted to identify discontinuous epitopes in TsNTxP since neutralizing epitopes are often associated with such complex entities. One hundred and fifty-three octadecapeptides with the general formula (P1)-(Gly-Gly)-(P2) were synthesized by the Spot method on cellulose membranes. P1 and P2 were octapeptides from the TsNTxP N-terminal and C-terminal sections, respectively. Each sequence of eight amino acids was frameshifted in turn by three residues, in order to cover TsNTxP entire sequence. Binding of neutralizing anti-TsNTxP rabbit antibodies to spotted peptides revealed GREGYPADGGGLPDSVKI as the more reactive peptide sequence. This epitope was made from the first eight residues of the protein (GREGYPAD) and from residues 47 to 54 (GLPDSVKI) of the C-terminal part of TsNTxP. BALB/c mice were immunized with synthetic GREGYPADGGGLPDSVKI peptide conjugated to ovalbumin. One week after the last immunization, in vivo protection assays showed that immunized mice could resist a challenge by an amount of T.serrulatus whole venom equivalent to 1.75 LD(100), a dose that killed all control non-immune mice. Based on molecular models of TsNTxP and related Tityus toxins, we found that the above peptide matches with a discontinuous epitope, well exposed at the toxin molecular surface which contains residues known to be important for the bioactivity of toxins. PMID:19948263

  1. Effects of prenatal exposure to Tityus bahiensis scorpion venom on rat offspring development.

    PubMed

    Dorce, Ana Leticia Coronado; Bellot, Rogério Gentil; Dorce, Valquiria Abrão Coronado; Nencioni, Ana Leonor Abrahão

    2009-11-01

    Scorpion envenoming is a public health problem. In Brazil, the scorpion Tityus serrulatus is considered the most dangerous, but a large number of exposures also occur with Tityus bahiensis. There are quite a few studies in literature about the toxic effects of this venom but it is not known if the venom causes malformations or behavioral defects to the offspring of mothers exposed to the venom during pregnancy. The objective of this work was to determine, in rats, the possible toxic effects of T. bahiensis venom on offspring when injected into rats during different periods of fetal development. Rats were assigned to one of three groups: one control group and two experimental groups that were subcutaneously injected with venom (2.5mg/kg) on the 10th (GD10) or on 16th day (GD16) of gestation. Pups were evaluated for changes in physical and behavioral development. GD10 treatment group offspring showed an increase in body weight gain, earlier ear unfolding, incisor tooth eruption and vaginal opening. A decrease in the time of palmar grasp and surface-righting reflexes was observed only for males. In GD16 treatment group, earlier ear unfolding, incisor tooth eruption, and delay in eye opening were observed in the offspring. In female pups a decrease in weight gain and in time for palmar grasp reflex, and an increase in time for negative geotaxis were observed. In male pups a delay in the testis descent, decrease in the time of palmar grasp, increase in the time of negative geotaxis reflex and in the general and locomotor activities could be noticed. Therefore, we concluded that a moderate dose of scorpion venom administered to pregnant rats was able to elicit alterations in physical and behavioral development in the offspring during the postnatal period. PMID:19383539

  2. Effects of Tityus stigmurus (Thorell 1876) (Scorpiones: Buthidae) venom in isolated perfused rat kidneys.

    PubMed

    Silva, Nathalia A; Albuquerque, Cleide M R; Marinho, Aline D; Jorge, Roberta J B; Silva, Antonio G; Monteiro, Helena S A; Silva, Túlio D; Silva, Márcia V; Correia, Maria Tereza S; Pereira, Ticiana P; Martins, Alice M C; Menezes, Dalgimar B; Ximenes, Rafael M; Martins, René D

    2016-01-01

    Scorpions belonging to the Tityus genus are of medical interest in Brazil. Among them, Tityus stigmurus is the main scorpion responsible for stings in the Northeast region. After a sting, the scorpion venom distributes rapidly to the organs, reaching the kidneys quickly. However, there are few studies concerning the renal pathophysiology of scorpion poisoning. In this study, we evaluated the effects of T. stigmurus venom (TsV) on renal parameters in isolated rat kidneys. Wistar rats (n = 6), weighing 250-300 g, were perfused with Krebs-Henseleit solution containing 6 g/100 mL bovine serum albumin. TsV at 0.3 and 1.0 μg/mL was tested, and the effects on perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and electrolyte excretion were analyzed. Effects were observed only at TsV concentration of 1.0 μg/mL, which increased PP (controlPP40' = 92.7 ± 1.95; TsVPP40' = 182.0 ± 4.70* mmHg, *p < 0.05), RVR (controlRVR40' = 3.28 ± 0.23 mmHg; TstRVR40' = 6.76 ± 0.45* mmHg, *p < 0.05), UF (controlUF50' = 0.16 ± 0.04; TstUF50' = 0.60 ± 0.10* mL/g/min,*p < 0.05), GFR and electrolyte excretion, with histological changes that indicate renal tubular injury. In conclusion, T. stigmurus venom induces a transient increase in PP with tubular injury, both of which lead to an augmented electrolyte excretion. PMID:27142547

  3. [des-Arg(1)]-Proctolin: A novel NEP-like enzyme inhibitor identified in Tityus serrulatus venom.

    PubMed

    Duzzi, Bruno; Cajado-Carvalho, Daniela; Kuniyoshi, Alexandre Kazuo; Kodama, Roberto Tadashi; Gozzo, Fabio Cesar; Fioramonte, Mariana; Tambourgi, Denise Vilarinho; Portaro, Fernanda Vieira; Rioli, Vanessa

    2016-06-01

    The scorpion Tityus serrulatus venom comprises a complex mixture of molecules that paralyzes and kills preys, especially insects. However, venom components also interact with molecules in humans, causing clinic envenomation. This cross-interaction may result from homologous molecular targets in mammalians and insects, such as (NEP)-like enzymes. In face of these similarities, we searched for peptides in Tityus serrulatus venom using human NEP as a screening tool. We found a NEP-inhibiting peptide with the primary sequence YLPT, which is very similar to that of the insect neuropeptide proctolin (RYLPT). Thus, we named the new peptide [des-Arg(1)]-proctolin. Comparative NEP activity assays using natural substrates demonstrated that [des-Arg(1)]-proctolin has high specificity for NEP and better inhibitory activity than proctolin. To test the initial hypothesis that molecular homologies allow Tityus serrulatus venom to act on both mammal and insect targets, we investigated the presence of a NEP-like in cockroaches, the main scorpion prey, that could be likewise inhibited by [des-Arg(1)]-proctolin. Indeed, we detected a possible NEP-like in a homogenate of cockroach heads whose activity was blocked by thiorphan and also by [des-Arg(1)]-proctolin. Western blot analysis using a human NEP monoclonal antibody suggested a NEP-like enzyme in the homogenate of cockroach heads. Our study describes for the first time a proctolin-like peptide, named [des-Arg(1)]-proctolin, isolated from Tityus serrulatus venom. The tetrapeptide inhibits human NEP activity and a NEP-like activity in a cockroach head homogenate, thus it may play a role in human envenomation as well as in the paralysis and death of scorpion preys. PMID:26056922

  4. Human bronchial epithelial cells injury and cytokine production induced by Tityus serrulatus scorpion venom: An in vitro study.

    PubMed

    Rigoni, Vera Lucia Silva; Kwasniewski, Fabio H; Vieira, Rodolfo Paula; Linhares, Ingrid Sestrem; da Silva, Joelmir Lucena Veiga; Nogueira-Pedro, Amanda; Zamuner, Stella Regina

    2016-09-15

    Tityus serrulatus is the scorpion specie responsible for the majority of scorpion sting accidents in Brazil. Symptoms of envenomation by Tityus serrulatus range from local pain to severe systemic reactions such as cardiac dysfunction and pulmonary edema. Thus, this study has evaluated the participation of bronchial epithelial cells in the pulmonary effects of Tityus serrulatus scorpion venom (Tsv). Human bronchial epithelial cell line BEAS-2B were utilized as a model target and were incubated with Tsv (10 or 50 μg/mL) for 1, 3, 6 and 24 h. Effects on cellular response of venom-induce cytotoxicity were examined including cell viability, cell integrity, cell morphology, apoptosis/necrosis as well as cell activation through the release of pro-inflammatory cytokines IL-1β, IL-6 and IL-8. Tsv caused a decrease in cell viability at 10 and 50 μg/mL, which was confirmed by lactate dehydrogenase (LDH) measurement. Flow cytometry analyses revealed necrosis as the main cell death pathway caused by Tsv. Furthermore, Tsv induced the release of IL-1β, IL-6 and IL-8. Altogether, these results demonstrate that Tsv induces cytotoxic effects on bronchial epithelial cells, involving necrosis and release of pro-inflammatory cytokines, suggesting that bronchial epithelial cells may play a role in the pulmonary injury caused by Tsv. PMID:27452928

  5. Serum levels of cytokines in patients envenomed by Tityus serrulatus scorpion sting.

    PubMed

    Magalhães, M M; Pereira, M E; Amaral, C F; Rezende, N A; Campolina, D; Bucaretchi, F; Gazzinelli, R T; Cunha-Melo, J R

    1999-08-01

    Seventeen patients stung by Tityus serrulatus scorpion were classified as mild (pain at the site of the sting, n = 6), moderate (local pain and one of the following manifestations: vomiting, psychomotor agitation, prostration, sweating, tachypnea, tachycardia and mild arterial hypertension, n = 10) and severe cases (equal moderate cases plus cardiac failure, pulmonary edema and shock, n = 1). Venous blood was sampled for biochemical and hematological analysis and for IL-1alpha, IL-6, IL-10, TNF-alpha, IFN-gamma and GM-CSF ELISAs at the time of hospital admission, 6 h (moderate and severe cases), and 12, 18, 36 and 72 h (severe case) later. Ten age-matched healthy volunteers were used as control. Increased serum levels of IL-1alpha was noticed in all patients, high levels of IL-6, IFN-gamma and GM-CSF were observed only in a patient with severe envenomation. Our data suggest that a systemic inflammatory response-like syndrome is triggered during severe envenomation caused by T. serrulatus sting and that release of cytokines may be involved in this response. PMID:10400299

  6. Biochemical profile of dogs experimentally envenomed with Tityus serrulatus scorpion venom.

    PubMed

    Ribeiro, E L; Pinto, M C L; Labarrère, C R; Paes, P R O; Paes-Leme, F O; Chávez-Olórtegui, C; Melo, M M

    2010-06-01

    The aim of this study was to evaluate the canine blood and urinary profiles after envenomation by Tityus serrulatus venom. Twelve dogs were randomly distributed into two equal groups. Control group animals received 0.5 mL phosphate buffered saline (PBS) injected subcutaneously into the internal portion of the left thigh, whilst dogs in the envenomed group were injected with scorpion venom (250 microg/kg in 0.5 mL PBS). No significant alterations were detected in the urine of envenomed dogs. Levels of plasma glucose and serum urea, creatinine, total protein, potassium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), and amylase were determined. Semi-quantitative analysis of serum cardiac troponin I (cTnI) was performed using an immunochromatographic test. The concentrations of cortisol and insulin were determined using commercial radioimmunoassay kits. Increases in serum cortisol levels in experimental group animals coincided with hyperglycaemia and was probably a response to pain. Increased insulin levels were observed during the hyperglycaemic peaks. Envenomed dogs presented discreet increases in ALT, AST and CK, but no alterations in LDH, amylase, cTnI, urea, creatinine and potassium levels were observed. It was concluded that the venom of T. serrulatus induces blood and urinary biochemical changes in dogs. PMID:20060404

  7. Effects of Tityus serrulatus scorpion venom on lung mechanics and inflammation in mice.

    PubMed

    Paneque Peres, Ana Claudia; Nonaka, Paula Naomi; de Carvalho, Paulo de Tarso Camillo; Toyama, Marcos Hikari; Silva, Cesar Augusto Melo e; Vieira, Rodolfo de Paula; Dolhnikoff, Marisa; Zamuner, Stella Regina; de Oliveira, Luis Vicente Franco

    2009-06-01

    The present study evaluated the effects of an intramuscular injection of Tityus serrulatus venom (TsV) (0.67 miocrog/g) on lung mechanics and lung inflammation at 15, 30, 60 and 180 min after inoculation. TsV inoculation resulted in increased lung elastance when compared with the control group (p < 0.001); these values were significantly higher at 60 min than at 15 and 180 min (p < 0.05). Resistive pressure (DeltaP1) values decreased significantly at 30, 60 and 180 min after TsV injection (p < 0.001). TsV inoculation resulted in increased lung inflammation, characterised by an increased density of mononuclear cells at 15, 30, 60 and 180 min after TsV injection when compared with the control group (p < 0.001). TsV inoculation also resulted in an increased pulmonary density of polymorphonuclear cells at 15, 30 and 60 min following injection when compared to the control group (p < 0.001). In conclusion, T. serrulatus venom leads to acute lung injury, characterised by altered lung mechanics and increased pulmonary inflammation. PMID:19470319

  8. Molecular and functional characterization of metalloserrulases, new metalloproteases from the Tityus serrulatus venom gland.

    PubMed

    Carmo, A O; Oliveira-Mendes, B B R; Horta, C C R; Magalhães, B F; Dantas, A E; Chaves, L M; Chávez-Olórtegui, C; Kalapothakis, E

    2014-11-01

    Tityus serrulatus is a Brazilian scorpion species with great medical significance. While the effects of neurotoxins have been extensively studied, little is known about the proteases expressed in the venom gland of this arthropod. In this study, clones from a T. serrulatus (Ts) venom gland cDNA library were selected according to homology to proteases. The sequences were aligned in the database and classified by homology. Similarity and identity analyses of the sequences were carried out, and a phylogenetic tree was constructed with the sequences of other proteases. These cDNA sequences correspond to ten different metalloproteases, named metalloserrulases (TsMS). TsMS 1-9 belong to the metzincin family, which has three domains: signal peptide, propeptide, and metalloprotease domain; while TsMS 10 belongs to the gluzincin family. The proteolytic activity of the venom was inferred from the cleavage of fibrinogen, and the residues recognized by the proteases were determined by cleavage of a tripeptide library using a fluorescence resonance energy transfer assay. The Ts venom showed proteolytic activity on fibrinogen and preferential cleavage close to the basic residues K and R. Its activity could be inhibited by EDTA, indicating that the venom from this scorpion predominantly consists of metalloproteases. PMID:25091350

  9. Pharmacological investigation of the nociceptive response and edema induced by venom of the scorpion Tityus serrulatus.

    PubMed

    Nascimento, Elias B; Costa, Karina A; Bertollo, Caryne M; Oliveira, Antônio Carlos P; Rocha, Leonardo T S; Souza, Adriano L S; Glória, Maria Beatriz A; Moraes-Santos, Tasso; Coelho, Márcio M

    2005-04-01

    In this study we characterized the nociceptive response and edema induced by the venom of the scorpion Tityus serrulatus in rats and mice and carried out a preliminary pharmacological investigation of the mechanisms involved in these responses. Intraplantar injection of the venom (1 or 10mug) induced edema and a marked ipsilateral nociceptive response, characterized by thermal and mechanical allodynia and paw licking behaviour. The nociceptive response was inhibited by previous intraperitoneal administration of indomethacin (4mg/kg), dipyrone (200mg/kg), cyproheptadine (10mg/kg) or morphine (5 or 10mg/kg), but not by dexamethasone (1 or 4mg/kg) or promethazine (1 or 5mg/kg). The edema was inhibited by previous treatment with promethazine (5 or 10mg/kg) or cyproheptadine (5 or 10mg/kg), but not by indomethacin (2 or 4mg/kg), dexamethasone (1 or 4mg/kg) or cromolyn (40 or 80mg/kg). Some bioactive amines, including histamine and 5-hydroxytryptamine, were found in the venom in low concentrations. In conclusion, the nociceptive response and edema induced by the venom of T. serrulatus may result from the action of multiple mediators including eicosanoids, histamine and 5-hydroxytryptamine. These results may lead to a better understanding of the host response to potent animal toxins and also give insights into a more rational pharmacological approach to alleviate the intense pain associated with the scorpion envenomation. PMID:15777954

  10. Evidence for a direct action of Tityus serrulatus scorpion venom on the cardiac muscle.

    PubMed

    Teixeira, A L; Fontoura, B F; Freire-Maia, L; Machado, C R; Camargos, E R; Teixeira, M M

    2001-05-01

    The ability of toxins to activate the cardiovascular system plays an important role in the morbidity and lethality of the Tityus serrulatus scorpion envenoming. Most of the actions of the scorpion toxins are indirect and due to the release of adrenergic and cholinergic neurotransmitters. Accordingly, treatment following envenoming is targeted towards inhibition of adrenergic and cholinergic receptors. Here, we have sought evidence for a direct action of T. serrulatus venom on the isolated rat heart (Langendorff's method). We show that the bradycardia induced by T. serrulatus venom was completely blocked by atropine, a muscarinic receptor antagonist. Similarly, the increase in heart rate that follows the venom-induced bradycardia was totally inhibited by a beta(1)-adrenoceptor antagonist or by chemical sympathetic denervation with 6-hydroxydopamine. In contrast to these findings, the venom-induced increase in contractile force was not modified by beta(1)-adrenoceptor blockade or by chemical sympathetic denervation. The results clearly demonstrate that the chronotropic effects of T. serrulatus are dependent on neurotransmitter release, but the inotropic effects are not. The neurotransmitter-independent increase in contractility seems to be a direct action of the venom on cardiomyocytes. We suggest that this direct effect on cardiac fibers may play a role in the development of cardiac arrhythmias and contractility defects following envenoming with T. serrulatus scorpion. PMID:11072050

  11. Effective Tityus serrulatus anti-venom produced using the Ts1 component.

    PubMed

    Mendes, T M; Dias, F; Horta, C C R; Pena, I F; Arantes, E C; Kalapothakis, E

    2008-12-01

    Scorpion stings are a public health problem in Brazil, with most incidents involving the species Tityus serrulatus. Some T. serrulatus toxins may act as immunogens for the production of a specific anti-venom, but many of the component toxins remain poorly characterized. Here, we describe the immunological characteristics of the toxin Ts1 (also known as TsVII and Ts-gamma) and evaluate production of neutralizing antibodies against the crude venom of T. serrulatus. Recombinant Ts1 with one copy (Ts1(1)) or two copies in tandem (Ts1(2)) was expressed in BL21 (DE3) cells. Rabbits and mice were immunized with the recombinant proteins (inclusion bodies) and then tested for production of neutralizing antibodies. Neutralization assays showed that anti-Ts1(1) and anti-Ts1(2) protected animals challenged with T. serrulatus crude venom and native Ts1. Thus, Ts1 could be used in a mixed "cocktail" of immunogens for T. serrulatus anti-venom production. PMID:18775739

  12. Efficacy of antivenom therapy for neutralizing circulating venom antigens in patients stung by Tityus serrulatus scorpions.

    PubMed

    De Rezende, N A; Dias, M B; Campolina, D; Chavez-Olortegui, C; Diniz, C R; Amaral, C F

    1995-03-01

    Enzyme-linked immunosorbent assays for detection of Tityus serrulatus venom antigen and of horse anti-T. serrulatus venom antibodies were carried out before antivenom treatment and at 1, 6, 12, and 24 hr after antivenom therapy in 18 patients with systemic manifestations following T. serrulatus scorpion sting. Increased levels of circulating venom antigens were detected in the patients before antivenom treatment, but were no longer detected 1 hr after specific antivenom therapy. High titers of antivenom persisted for at least 24 hr after treatment with antivenom. The evolution of clinical and laboratory manifestations of envenoming showed that vomiting and local pain decreased within 1 hr and hyperglycemia was no longer detected 12 hr after antivenom therapy. The cardiorespiratory manifestations disappeared 6-24 hr after the administration of antivenom and all patients recovered completely. This study demonstrates the efficacy of antivenom therapy in neutralizing circulating venom antigens and supports the prompt administration of a potent antivenom to patients with systemic manifestations of envenoming. PMID:7694971

  13. A hyaluronidase from Tityus serrulatus scorpion venom: isolation, characterization and inhibition by flavonoids.

    PubMed

    Pessini, A C; Takao, T T; Cavalheiro, E C; Vichnewski, W; Sampaio, S V; Giglio, J R; Arantes, E C

    2001-10-01

    The purification procedure of a hyaluronidase from Tityus serrulatus scorpion venom is described. It involves basically an ion-exchange chromatography on CM-cellulose at pH 7.8 followed by a rechromatography of the active fraction on the same column at pH 4.7. The optima pH and temperature for maximum activity of the isolated enzyme was 6.0 and 40 degrees C, respectively. Its K(M) was 69.7 microg/ml at 37 degrees C and its specific activity was 19,900+/-1,730 turbidity reducing units (TRU)/mg against 845+/-88TRU/mg for the whole desiccated venom, representing a 23- to 24-fold purification range. The hyaluronidase activity of the purified protein (51kDa) was inhibited by some flavonoid compounds. This article also showed that T. serrulatus hyaluronidase affected on the activity of the venom's major toxin, tityustoxin-I (TsTX-I or Ts1), as reflected by alterations in the serum levels of creatine kinase (CK), lactate dehydrogenase (LD) and aspartate aminotransferase (AST) following injection of TsTX-I, in the presence or absence of hyaluronidase. PMID:11478957

  14. Effects of in utero exposure to Tityus bahiensis scorpion venom in adult rats.

    PubMed

    Dorce, Ana Leticia Coronado; Dorce, Valquiria Abrão Coronado; Nencioni, Ana Leonor Abrahão

    2010-01-01

    The toxicity of Tityus bahiensis scorpion venom is well known, but there are little data about the damage in offspring of dams that were exposed to the venom during pregnancy. The objective of this work was to determine the toxic effects of venom in adult offspring of Wistar rats exposed to venom in utero. Dams were divided into a control group, subcutaneously injected with saline solution on the 10th (GD10) and 16th (GD16) days, and two experimental groups, subcutaneously injected with venom (2.5mg/kg) on GD10 or GD16, respectively. Adult offspring were evaluated according to behavioral development and neuronal integrity in the hippocampus. Tests performed in the activity box and in the enriched environment demonstrated that males from GD10 had motor decrease. Females from GD10 showed a depressive-like state and were more anxious, as demonstrated by the forced swimming test and social interaction. The plus-maze discriminative avoidance task demonstrated that GD16 males had lower levels of anxiety. The number of neuronal cells was decreased in CA1, CA3 and CA4 hippocampal areas of males and females from GD10 group and in CA1 of females and CA4 of males from GD16 group. Thus, we conclude that venom exposure in pregnant dams causes subtle alteration in the behavioral and neuronal development of offspring in adult life in a gender-dependent manner. PMID:19945531

  15. Effect of scorpion toxin from Tityus serrulatus on the contraction of the isolated rat uterus.

    PubMed

    Mendonça, M; Da Luz, M M; Freire-Maia, L; Cunha-Melo, J R

    1995-03-01

    Scorpion toxin T1 from Tityus serrulatus was tested for its effects on the isolated rat uterus preparation. T1 (5 micrograms/ml) caused a contraction of the uterus, which was potentiated by neostigmine (1.64 x 10(-6) M) and abolished by atropine (1.4 x 10(-7) M). After addition of neostigmine to the bath, we noted a higher amplitude of the toxin-induced contractions, and the appearance of repetitive rhythmic contractions. The scorpion toxin-induced contraction was not prevented by previous addition to the bath of hexamethonium or bradykinin, 5-HT and angiotensin II antagonists. The uterine contraction was prevented by previous addition to the bath of either tetrodotoxin (5 x 10(-8) M) or lidocaine (4.2 x 10(-5) M). These data seem to indicate that scorpion toxin-induced rat uterus contractions are due to actions on post-ganglionic autonomic nerve endings, with acetylcholine release and stimulation of muscarinic receptors. PMID:7638874

  16. Differences in venom toxicity and antigenicity between females and males Tityus nororientalis (Buthidae) scorpions

    PubMed Central

    De Sousa, Leonardo; Borges, Adolfo; Vásquez-Suárez, Aleikar; Op den Camp, Huub JM; Chadee-Burgos, Rosa I; Romero-Bellorín, Mirna; Espinoza, Jorge; De Sousa-Insana, Leonardo; Pino-García, Oscar

    2010-01-01

    Venom from male and female specimens of the medically important Venezuelan scorpion Tityus nororientalis have been compared. Males showed a significantly higher venom yield (2.39mg/individual) compared to female scorpions (0.98mg/individual). Female venom was significantly more toxic than that of males, with a median lethal dose (LD50) in C57BL/6 mice of 9.46 μg venom protein/gm body weight [95% confidence interval (8.91-9.94)] whereas LD50 for males was 13.36(12.58-14.03) μg/gm. Mass spectral analyses by MALDI-TOF revealed differences in venom composition between males and females. From a clinical standpoint, the time course of toxicity course indicated a tendency, in the case of the female venom, to elicit the earlier occurrence of severe signs such as sialorrhea, dyspnea (bradypnea/apnea) and exophthalmus particularly in the late toxicity phase. Female venom was significantly less efficient than male venom to inhibit the binding of anti-T. discrepans antibodies to immobilized T. discrepans venom in ELISA assays, suggesting sex-related differences in the bioactive surfaces of T. nororientalis toxins. These results indicate that males and females of T. nororientalis produce venoms with different composition and activity which may have epidemiological implications. PMID:21544184

  17. Effect of maternal exposure to Tityus bahiensis scorpion venom during lactation on the offspring of rats.

    PubMed

    Martins, Adriana do Nascimento; Nencioni, Ana Leonor Abrahão; Dorce, Ana Leticia Coronado; Paulo, Maria Eliza F V; Frare, Eduardo Osório; Dorce, Valquíria Abrão Coronado

    2016-01-01

    Scorpion stings are a public health problem in Brazil and lactating women may be affected. We aimed to study the effects of Tityus bahiensis venom in the offspring of rats treated during lactation. Mothers received a subcutaneous injection of saline (1.0ml/kg) or venom (2.5mg/kg) or an intraperitoneal injection of LPS (lipopolysaccharide) (100μg/kg) on postnatal (PN) days 2 (PN2), 10 (PN10) or 16 (PN16). The offspring were evaluated during the childhood and adulthood. Pups showed a delay in physical and reflexological development, and a decrease in motor activity. Adults displayed low anxiety. There was an increase in the number of viable neuronal cells in hippocampal areas CA1 and CA4. The levels of IFN-γ (interferon-gamma) increased in the experimental groups. Several of the parameters analyzed showed important differences between the sexes. Thus, the scorpion venom affects the development in the offspring of mothers envenomed during the lactation. PMID:26746106

  18. Identification of Prey Captures in Australian Fur Seals (Arctocephalus pusillus doriferus) Using Head-Mounted Accelerometers: Field Validation with Animal-Borne Video Cameras

    PubMed Central

    Volpov, Beth L.; Hoskins, Andrew J.; Battaile, Brian C.; Viviant, Morgane; Wheatley, Kathryn E.; Marshall, Greg; Abernathy, Kyler; Arnould, John P. Y.

    2015-01-01

    This study investigated prey captures in free-ranging adult female Australian fur seals (Arctocephalus pusillus doriferus) using head-mounted 3-axis accelerometers and animal-borne video cameras. Acceleration data was used to identify individual attempted prey captures (APC), and video data were used to independently verify APC and prey types. Results demonstrated that head-mounted accelerometers could detect individual APC but were unable to distinguish among prey types (fish, cephalopod, stingray) or between successful captures and unsuccessful capture attempts. Mean detection rate (true positive rate) on individual animals in the testing subset ranged from 67-100%, and mean detection on the testing subset averaged across 4 animals ranged from 82-97%. Mean False positive (FP) rate ranged from 15-67% individually in the testing subset, and 26-59% averaged across 4 animals. Surge and sway had significantly greater detection rates, but also conversely greater FP rates compared to heave. Video data also indicated that some head movements recorded by the accelerometers were unrelated to APC and that a peak in acceleration variance did not always equate to an individual prey item. The results of the present study indicate that head-mounted accelerometers provide a complementary tool for investigating foraging behaviour in pinnipeds, but that detection and FP correction factors need to be applied for reliable field application. PMID:26107647

  19. Tityus gamma toxin, a high affinity effector of the Na+ channel in muscle, with a selectivity for channels in the surface membrane.

    PubMed

    Barhanin, J; Ildefonse, M; Rougier, O; Sampaio, S V; Giglio, J R; Lazdunski, M

    1984-01-01

    Toxin gamma from the venom of Tityus serrulatus scorpion produces a partial block of the surface Na+ channel in frog muscle. This block occurs with no change in the voltage-dependence or in the kinetics of the remaining surface Na+ current. The partial blockade of Na+ channel activity occurs with no change in tubular Na+ currents nor in twitch tension. The maximum effect of the toxin is attained at concentrations as low as 3 X 10(-10) M. Hyperpolarization to potentials more negative than the resting potential (E = -90 mV) reduces or abolishes the effect of the toxin. Radioiodinated toxin gamma binds to frog muscle membranes with a very high affinity corresponding to a dissociation constant of about 1 X 10(-11) M. Data obtained with both rabbit and frog muscle indicate that toxin gamma is specific for Na+ channels in surface membranes. Toxin gamma does not seem to bind to Na+ channels in T-tubule membranes. The biochemical data are in good agreement with electrophysiological studies and data on contraction. There is one Tityus gamma toxin binding site per tetrodotoxin binding site in surface membranes. Competition experiments have confirmed that Tityus gamma toxin binds to a new toxin receptor site on the Na+ channel structure. This site is the same that the toxin II from Centruroides suffusus binding site, but this toxin has 100 times less affinity for the Na+ channel than Tityus gamma toxin. PMID:6324066

  20. High performance liquid chromatography purification and amino acid sequence of toxins from the muscarinic fraction of Tityus discrepans scorpion venom.

    PubMed

    D'Suze, G; Corona, F; Possani, L D; Sevcik, C

    1996-05-01

    Tityus discrepans venom was fractionated by gel filtration on Sephadex G-50 column. The peptides in fraction II from Sephadex were further purified by high performance liquid chromatography, through a C4 reverse-phase column. Lethality of purified peptides was determined by injection into mice and crabs, and their effects were verified electrophysiologically on frog (Hyla crepitans) sartorius neuromuscular junction. Toxins having retention times between 39.6 and 40.7 min depolarized the muscle membrane and caused acetylcholine release at the endplate. The toxin eluted at 42.67 min increased the frequency of miniature endplate potentials without depolarizing muscle fibres. The four most active toxins were reduced, carboxymethylated and sequenced by automatic Edman degradation and named TdII-1 to II-4. Toxin gamma from Tityus serrulatus venom and the toxins from T. discrepans venom were found to be structurally distinct. TdII-1 to II-4 lack the pancreatic effects of T. serrulatus' toxin gamma; yet, the five toxins act on Na+ channels. PMID:8783453

  1. Isolation, molecular cloning and functional characterization of a novel beta-toxin from the Venezuelan scorpion, Tityus zulianus.

    PubMed

    Borges, Adolfo; Alfonzo, Marcelo J; García, Carmen C; Winand, Nena J; Leipold, Enrico; Heinemann, Stefan H

    2004-05-01

    Sting in children by Tityus zulianus scorpions (western Venezuela) often produces cardiorespiratory arrest and death by pulmonary oedema. To assess its toxicity, lethality in mice of T. zulianus soluble venom was determined. Toxin composition was studied by fractionating the crude venom through reversed-phase HPLC. The most abundant peptide, Tz1, was purified further and its N-terminal sequence, amino acid composition and molecular mass (by electron-spray ionization mass spectrometry) determined. In the presence of Tz1, activation of recombinant rat skeletal muscle sodium channels (Na(V)1.4) was shifted about 35 mV in the hyperpolarizing direction in a prepulse-dependent manner. This typical beta-toxin effect had an apparent EC50 of 3.5 microM A cDNA sequence encoding Tz1 was isolated from T. zulianus venom gland RNA using a combination of 5'- and 3'-RACE PCR. Analysis of the encoded sequence indicated that Tz1 is the processed product of a precursor containing: (i) a 20-residue long leader peptide; (ii) the amino acid sequence of the mature toxin (64 residues); and (iii) an extra Gly-Lys tail at the C-terminus, probably removed post-translationally. A comparison of Tz1 with Tityus serrulatus beta-toxin Ts1 revealed that some of the non-conservative replacements in Tz1 lie in regions potentially involved in receptor recognition. PMID:15109888

  2. Scorpionism in Ecuador: First report of severe and fatal envenoming cases from northern Manabí by Tityus asthenes Pocock.

    PubMed

    Borges, Adolfo; Morales, Melva; Loor, Wilmer; Delgado, Miguel

    2015-10-01

    The presence in rural areas of western Ecuador of scorpions in the genus Tityus capable of producing pediatric mortality is hereby evidenced. The medical significance of scorpions in Ecuador has been underestimated partly because of the clinically unimportant stings delivered by Centruroides margaritatus and Teuthraustes atramentarius, which have venom with low toxicity to vertebrates. Five intra-domiciliary cases of scorpion envenoming in victims aged between 1.9 and 16 years old, including one fatality, are reported from rural settings in forest areas of Chone (n = 2) and Flavio Alfaro (n = 3) counties, northern Manabí province, western Ecuador. Three cases were graded as Class II (moderate) and two in Class III (severe) envenoming. Manifestations showed characteristic autonomic nervous system hyper-stimulation and the fatality (a 1.9-year-old boy from Flavio Alfaro) was due to cardio-respiratory failure. Marked leukocytosis in four of the cases (21,800-31,800 cells/mm(3)), with notable neutrophilia (58-82%), suggests induction of a venom-mediated systemic inflammatory response-like syndrome. Specimens responsible for cases in Flavio Alfaro County, including the fatality, were classified as Tityus asthenes Pocock, accountable for severe scorpionism in Colombia. These findings demand implementation of control and therapeutic measures in affected areas in Ecuador, including evaluation of available scorpion antivenoms. PMID:26344916

  3. General characterization of Tityus fasciolatus scorpion venom. Molecular identification of toxins and localization of linear B-cell epitopes.

    PubMed

    Mendes, T M; Guimarães-Okamoto, P T C; Machado-de-Avila, R A; Oliveira, D; Melo, M M; Lobato, Z I; Kalapothakis, E; Chávez-Olórtegui, C

    2015-06-01

    This communication describes the general characteristics of the venom from the Brazilian scorpion Tityus fasciolatus, which is an endemic species found in the central Brazil (States of Goiás and Minas Gerais), being responsible for sting accidents in this area. The soluble venom obtained from this scorpion is toxic to mice being the LD50 is 2.984 mg/kg (subcutaneally). SDS-PAGE of the soluble venom resulted in 10 fractions ranged in size from 6 to 10-80 kDa. Sheep were employed for anti-T. fasciolatus venom serum production. Western blotting analysis showed that most of these venom proteins are immunogenic. T. fasciolatus anti-venom revealed consistent cross-reactivity with venom antigens from Tityus serrulatus. Using known primers for T. serrulatus toxins, we have identified three toxins sequences from T. fasciolatus venom. Linear epitopes of these toxins were localized and fifty-five overlapping pentadecapeptides covering complete amino acid sequence of the three toxins were synthesized in cellulose membrane (spot-synthesis technique). The epitopes were located on the 3D structures and some important residues for structure/function were identified. PMID:25817000

  4. PPAR-γ activation by Tityus serrulatus venom regulates lipid body formation and lipid mediator production.

    PubMed

    Zoccal, Karina Furlani; Paula-Silva, Francisco Wanderley Garcia; Bitencourt, Claudia da Silva; Sorgi, Carlos Artério; Bordon, Karla de Castro Figueiredo; Arantes, Eliane Candiani; Faccioli, Lúcia Helena

    2015-01-01

    Tityus serrulatus venom (TsV) consists of numerous peptides with different physiological and pharmacological activities. Studies have shown that scorpion venom increases pro-inflammatory cytokine production, contributing to immunological imbalance, multiple organ dysfunction, and patient death. We have previously demonstrated that TsV is a venom-associated molecular pattern (VAMP) recognized by TLRs inducing intense inflammatory reaction through the production of pro-inflammatory cytokines and arachidonic acid-derived lipid mediators prostaglandin (PG)E2 and leukotriene (LT)B4. Lipid bodies (LBs) are potential sites for eicosanoid production by inflammatory cells. Moreover, recent studies have shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) is implicated in LB formation and acts as an important modulator of lipid metabolism during inflammation. In this study, we used murine macrophages to evaluate whether the LB formation induced by TsV after TLR recognition correlates with lipid mediator generation by macrophages and if it occurs through PPAR-γ activation. We demonstrate that TsV acts through TLR2 and TLR4 stimulation and PPAR-γ activation to induce LB formation and generation of PGE2 and LTB4. Our data also show that PPAR-γ negatively regulates the pro-inflammatory NF-κB transcription factor. Based on these results, we suggest that during envenomation, LBs constitute functional organelles for lipid mediator production through signaling pathways that depend on cell surface and nuclear receptors. These findings point to the inflammatory mechanisms that might also be triggered during human envenomation by TsV. PMID:25450800

  5. Characterization of Tityus scorpion venoms using synaptosome binding assays and reactivity towards Venezuelan and Brazilian antivenoms.

    PubMed

    Borges, Adolfo; De Sousa, Leonardo; Espinoza, Jorge; Melo, Marilia Martins; Santos, Raquel G; Kalapothakis, Evanguedes; Valadares, Diogo; Chávez-Olórtegui, Carlos

    2008-01-01

    Venoms from Tityus species inhabiting five endemic regions of scorpionism in Venezuela (Andean, Perijá range, north-central, northeastern, and Guayana) and also southeast Brazil (T. serrulatus and T. bahiensis) were characterized immunologically in ELISA experiments using mouse- and rabbit-derived antibodies to evaluate their cross-reactivity and also functionally, utilizing synaptosome binding assays. While Brazilian and Venezuelan antivenoms cross-reacted poorly, T. discrepans (north-central Venezuela) and T. zulianus (Andean) venoms shared a greater immunological relatedness than with T. perijanensis (Perijá range). Anti-T. breweri (Guayana) antibodies fully cross-reacted with T. discrepans. Native PAGE indicated species-specific fingerprints for all venoms and revealed differences between two populations (Anzoátegui and Monagas States) of T. nororientalis (northeastern Venezuela). Components antigenically related to T. serrulatus beta-toxin TsVII were also detected in T. breweri, T. nororientalis (Anzoátegui) and T. funestus (Andean). Antibodies against T. serrulatus anatoxin TsNTxP did not cross-react significantly with any Venezuelan venoms indicating lack of TsNTxP homologues. The results suggest that the extent of antigenic reactivity depends on the studied species rather than the geographical distance between their habitats. All venoms, with T. discrepans to a lesser extent, were able to significantly displace [(125)I]-TsVII from its binding site in rat brain synaptosomes. Our data indicate that beta-toxins functionally related to TsVII but differing significantly in their antigenic regions exist in Venezuelan venoms from different endemic regions. Identification of shared epitopes with TsVII, at least for some species, may lead to the design of antibodies based on common epitopes for treating scorpion envenoming in Venezuela and Brazil. PMID:17920649

  6. Isolation and characterization of toxic proteins from the venom of the Brazilian scorpion Tityus serrulatus.

    PubMed

    Sampaio, S V; Laure, C J; Giglio, J R

    1983-01-01

    Through gel filtration on Sephadex G-25 and chromatography on CM-cellulose-52 five toxic proteins, electrophoretically pure, were isolated from the venom of the Brazilian scorpion Tityus serrulatus and partially characterized, as follows: 1. Toxin T1 VIII, with 61 amino acid residues, mol. wt 6675 and amino terminal sequence Lys-Glx-Gly-Tyr-Leu-Met-Asx-His-Glx-Gly-Cys-Lys-; 2. Toxin T1VI with amino acid residues, mol. wt. 7549 and amino terminal sequence Gly-His-Phe-Gly-Lys; 3. Toxin T2III(I), with 63 amino acid residues, mol. wt. 7216 and amino terminal sequence Lys-Lys-Asx-Gly-Tyr-Pro-Val-Cys-Cys-Ser-; 4. Toxin T2IV, which is apparently identical to toxin T1VIII above, since it showed the same elution volume in chromatography on CM-cellulose-52, the same N-terminal Lys and the same electrophoretic mobility as T1VIII; 5. Toxin T1IV, a not previously described toxin from the venom of T. serrulatus, with 45 amino acid residues, mol. wt. 5188 and amino terminal sequence Lys-Glx-Gly-Tyr-Leu-, identical to the first five residues of T1VIII, although with a lower molecular weight. The pharmacological study of T1VIII in guinea pig vas deferens showed a pre-junctional sensitizing action, evidenced by a decrease of the dose-response curves to adrenaline and acetylcholine, with no increase of the maximum. This effect may be due to the liberation of noradrenaline. PMID:6857710

  7. Serrumab: a human monoclonal antibody that counters the biochemical and immunological effects of Tityus serrulatus venom.

    PubMed

    Pucca, Manuela Berto; Zoccal, Karina Furlan; Roncolato, Eduardo Crosara; Bertolini, Thaís Barboza; Campos, Lucas Benício; Cologna, Camila Takeno; Faccioli, Lúcia Helena; Arantes, Eliane Candiani; Barbosa, José Elpidio

    2012-01-01

    In Brazil, the species Tityus serrulatus is responsible for the most severe cases of scorpion envenomation. There is currently a need for new scorpion anti-venoms that are more effective and less harmful. This study attempted to produce human monoclonal antibodies capable of inhibiting the activity of T. serrulatus venom (TsV), using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Four rounds of phage antibody selection were performed, and the round with the highest phage antibody titer was chosen for the production of monoclonal phage antibodies and for further analysis. The scFv 2A, designated serrumab, was selected for the production and purification of soluble antibody fragments. In a murine peritoneal macrophage cell line (J774.1), in vitro assays of the cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 were performed. In male BALB/c mice, in vivo assays of plasma urea, creatinine, aspartate transaminase, and glucose were performed, as well as of neutrophil recruitment and leukocyte counts. It was found that serrumab inhibited the TsV-induced increases in the production of IL-6, TNFα, and IL-10 in J774.1 cells. The in vivo inhibition assay showed that serrumab also prevented TsV-induced increases in the plasma levels of urea, creatinine, aspartate transaminase, and glucose, as well as preventing the TsV-induced increase in neutrophil recruitment. The results indicate that the human monoclonal antibody serrumab is a candidate for inclusion in a mixture of specific antibodies to the various toxins present in TsV. Therefore, serrumab shows promise for use in the production of new anti-venom. PMID:22424317

  8. Neuropeptide Y family-degrading metallopeptidases in the Tityus serrulatus venom partially blocked by commercial antivenoms.

    PubMed

    Cajado Carvalho, Daniela; Kuniyoshi, Alexandre K; Kodama, Roberto T; Oliveira, Ana K; Serrano, Solange M T; Tambourgi, Denise V; Portaro, Fernanda V

    2014-12-01

    Accidents caused by scorpions represent a relevant public health issue in Brazil, being more recurring than incidents with snakes and spiders. The main species responsible for this situation is the yellow scorpion, Tityus serrulatus, due especially to the great frequency with which accidents occur and the potential of its venom to induce severe clinical manifestations, even death, mainly among children. Although neurotoxins are well characterized, little information is known about other components of scorpion venoms, such as peptidases, and their effect on envenomation. Previous results from our group showed that the metallopeptidases present in this venom are capable of hydrolyzing the neuropeptide dynorphin 1-13 in vitro, releasing Leu-enkephalin, which may interact with ion channels and promote indirect neurotoxicity. Thus, this study aims to get more information about the effect of toxic peptidase activity present in the venom on biologically active peptides, and to evaluate the in vitro neutralizing potential of commercial antivenoms produced by the Butantan Institute. A set of human bioactive peptides were studied as substrates for the peptidases, and the members of the neuropeptide Y family were found to be the most susceptible ones. All new substrate hydrolyses were totally inhibited by ethylenediaminetetracetic and not blocked by phenylmethanesulfonylfluoride, indicating that metallopeptidases were responsible for the peptidase activity. Also, peptidase activities were only partially inhibited by therapeutic Brazilian scorpion antivenom (SAV) and arachnid antivenom (AAV). The dose-response inhibition by both antivenoms indicates that AAV neutralizes better than SAV at the used doses. These characterizations, unpublished until now, can contribute to the improvement of our knowledge about the venom and envenomation processes by T. serrulatus. PMID:25239630

  9. Mild reproductive effects of the Tityus bahiensis scorpion venom in rats

    PubMed Central

    2014-01-01

    Background Scorpion envenoming is a public health problem in Brazil, where Tityus serrulatus and T. bahiensis are considered the most dangerous scorpions. They are well adapted to urbanized environments, and there is an increasing probability of human exposure to these venoms, including during pregnancy. Not much is known about the effects of prenatal exposure to the venom, and no information is available to aid in the rational treatment of victims stung during pregnancy. Thus, this study aimed to investigate whether venom from the scorpion T. bahiensis administered once to pregnant female rats at a dose that causes a moderate envenomation may lead to deleterious effects on the reproductive performance of the dams and on the development of their offspring. This is the first work demonstrating that T. bahiensis venom, when administered experimentally to rats, alters maternal reproductive performance and the morphological development of fetuses. The venom was given to dams on the 5th (GD5) or on the 10th (GD10) gestational day. After laparotomy, on GD21, fetuses and placentas were counted, weighed and externally analyzed. The corpora lutea were counted. The sex and vitality of fetuses were evaluated, and each litter was then randomly divided for visceral or skeletal analyses. Data were analyzed by ANOVA followed by the Tukey-Kramer test and Fisher’s exact test. The significance level for all tests was set at p < 0.05. Results GD5 group presented an increased number of pre-implantation losses. Weight gains in fetuses and placentas were observed in the GD5 and GD10 groups. Weights of the heart and lungs were elevated in GD5 and GD10 and liver weight in GD10. Conclusions Moderate envenomation by T. bahiensis scorpion venom alters maternal reproductive performance and fetal development. However, these are preliminary results whose causes should be investigated more carefully in future studies. PMID:24521392

  10. A new venomous scorpion responsible for severe envenomation in Argentina: Tityus confluens.

    PubMed

    de Roodt, Adolfo R; Lago, Néstor R; Salomón, Oscar D; Laskowicz, Rodrigo D; Neder de Román, Lilia E; López, Raúl A; Montero, Teresa E; Vega, Valeria Del V

    2009-01-01

    In Argentina the scorpions of medical importance belong to the genus Tityus (T.), particularly the species T. trivittatus, the only scorpion whose sting is recognized to be associated with severe human envenoming and death. This genus is distributed from the north of the Patagonian region to the center and some provinces in the north of the country. During the period 2003-2006 four children died following scorpion stings, of which one was certainly and three were probably by T. confluens. In 2006, in the province of Tucumán, a girl died by scorpion envenoming and the scorpion responsible for the death, found in her shoe, was T. confluens. We thus studied the toxicity of venom gland homogenates from T. confluens from the provinces of Jujuy and Catamarca, and of crude venom from specimens from Catamarca and the province of La Rioja. The lethal potencies of the telson homogenates were 7.0 and 18.6microg/g for Jujuy and Catamarca, respectively, while the lethal potency of the crude venom was 0.7microg/g. Injected mice showed generalized congestion and hepatic lesions. Pancreatic damage was observed in some animals. Lungs showed congestion and foci of hemorrhage and mild edema. The heart showed injury in the muscular fibers. The venom showed high reactivity against anti-T. trivittatus antivenom and against two anti-T. serrulatus antivenoms. The anti-T. trivittatus antivenom neutralized the lethal activity of T. confluens venom. In addition, the venom reacted very slightly against an anti-Centruroides antivenom. Therefore, the stings of this scorpion must be considered of risk for humans to the same degree as the stings of T. trivittatus. PMID:18983868

  11. Developmental effects of Tityus serrulatus scorpion venom on the rat offspring.

    PubMed

    Barão, Aline Aparecida Saltão; Bellot, Rogerio Gentil; Dorce, Valquiria Abrão Coronado

    2008-07-30

    Scorpion envenomation is a public health problem. Extensive research has been conducted to describe the systemic effects of scorpion venoms and their toxins, however, few reports are available about their effects on pre- and post-natal periods. Whole venom of the Tityus serrulatus scorpion was administered to rats on the 10th and 16th days of pregnancy to determine the effect on physical, reflexive and behavioral development of offspring. Thirty female Wistar rats were mated and distributed into three groups with one control group (C) and two experimental groups that were injected with venom (1mg/kg) on the 10th (GD10) or the 16th day (GD16) of pregnancy. After birth, the litter was standardized (eight pups for dam) and the rat pups were submitted to physical and behavioral analysis. A greater weight gain was observed on the 20th day of life (PN20) in the female and male pups of the two experimental groups compared to controls. In the GD16 group, a delay in ear opening and acceleration in ear unfolding were observed. In relation to reflexive development, an increased time for palmar grasp reflex was observed on PN8 in GD16. For this group, there was a decrease in the time of righting reflex on PN4 and PN6, and of negative geotaxis on PN6, PN8 and PN10. In conclusion, scorpion venom administered to pregnant rats on specific gestational days and at a dose that simulates a small accident, results in alterations in some reflex and physical parameters in their offspring. PMID:18534258

  12. General biochemical and immunological characterization of the venom from the scorpion Tityus trivittatus of Argentina.

    PubMed

    de Roodt, Adolfo R; Coronas, Fredy I V; Lago, Nestor; González, María E; Laskowicz, Rodrigo D; Beltramino, Juan C; Saavedra, Silvina; López, Raúl A; Reati, Gustavo J; Vucharchuk, Miriam G; Bazán, Eduardo; Varni, Liliana; Salomón, Oscar D; Possani, Lourival D

    2010-01-01

    Tityus trivittatus is the Argentinean scorpion reported to cause the majority of human fatalities in the country, however no systematic studies have been conducted with the venom of this species. This communication describes a general biochemical and immunological characterization of the venom obtained from T. trivittatus scorpions collected in the city of Buenos Aires and various provinces of Argentina: Catamarca, Cordoba, Entre Rios, La Rioja, Santa Fe and Santiago del Estero. These are places where human accidents were reported to occur due to this scorpion. For comparative purposes two types of samples were assayed: whole soluble venom obtained by electrical stimulation and supernatant from homogenized venomous glands. Two strains of mice (NIH and CF-1) were used for LD(50) determinations by two distinct routes of administration (intravenously and intraperitoneally). Important variations were found that goes from 0.5 to 12 mg/kg mouse body weight. Samples of soluble venom were always more potent than Telson homogenates. More complex pattern was observed in homogenates compared to soluble venom, as expected. This was supported by gel electrophoretic analysis and high performance liquid chromatographic (HPLC) separations. Additionally, the HPLC profile was enriched in proteins resolved at similar elution times as other known toxins from scorpion venoms studied. Immune enzymatic assays were also conducted comparatively, using four different anti-venoms commercially available for treatment of scorpion stings (Argentinean antidote from INPB, two anti-venoms from Butantan Institute of Brazil and Alacramyn from the Mexican Bioclon Institute). Cross-reactivities were observed and are reported among the various venoms and anti-venoms used. Lung, heart, liver and pancreas pathological modifications were observed on tissues of intoxicated mice. It seems that there are important variations on the venom compositions of the various samples studied and reported here

  13. Thoracic auscultation in captive bottlenose dolphins (Tursiops truncatus), California sea lions (Zalophus californianus), and South African fur seals (Arctocephalus pusillus) with an electronic stethoscope.

    PubMed

    Scharpegge, Julia; Hartmann, Manuel García; Eulenberger, Klaus

    2012-06-01

    Thoracic auscultation is an important diagnostic method used in cases of suspected pulmonary disease in many species, as respiratory sounds contain significant information on the physiology and pathology of the lungs and upper airways. Respiratory diseases are frequent in marine mammals and are often listed as one of their main causes of death. The aim of this study was to investigate and report baseline parameters for the electronic-mediated thoracic auscultation of one cetacean species and two pinniped species in captivity. Respiratory sounds from 20 captive bottlenose dolphins (Tursiops truncatus), 6 California sea lions (Zalophus californianus), and 5 South African fur seals (Arctocephalus pusillus) were recorded with an electronic stethoscope. The sounds were analyzed for duration of the respiratory cycle, adventitious sounds, and peak frequencies of recorded sounds during expiration and inspiration as well as for sound intensity as reflected by waveform amplitude during the respiratory cycle. In respiratory cycles of the bottlenose dolphins' expiring "on command," the duration of the expiration was significantly shorter than the duration of the inspiration. In the examined pinnipeds of this study, there was no clear pattern concerning the duration of one breathing phase: Adventitious sounds were detected most often in bottlenose dolphins that were expiring on command and could be compared with "forced expiratory wheezes" in humans. This is the first report of forced expiratory wheezes in bottlenose dolphins; they can easily be misinterpreted as pathologic respiratory sounds. The peak frequencies of the respiratory sounds reached over 2,000 Hz in bottlenose dolphins and over 1,000 Hz in California sea lions and South African fur seals, but the variation of the frequency spectra was very high in all animals. To the authors' knowledge, this is the first systematic analysis of respiratory sounds of bottlenose dolphins and two species of pinnipeds. PMID:22779229

  14. Toxin gamma from Tityus serrulatus scorpion venom plays an essential role in immunomodulation of macrophages.

    PubMed

    Petricevich, Vera L; Hernández Cruz, Anselmo; Coronas, Fredy I V; Possani, Lourival D

    2007-10-01

    Fraction number II obtained from Sephadex G-50 gel filtration of the soluble venom from the Brazilian scorpion Tityus serrulatus (TSV) stimulates macrophage function in vitro. The aim of this study was to identify which one of the several components of this fraction was responsible for the main stimulatory activity on macrophages. This component was identified as sub-fraction II-11, also known by the name of gamma toxin or simply abbreviated Ts1, which stands for toxin 1 of T. serrulatus venom. The effect of Ts1 was analyzed by detection of inflammatory mediators. Several functional bioassays were performed: TNF activity was assayed by measuring its cytotoxicity on L929 cells, whereas IL-1, IL-6, IFN-gamma and IL-10 were assayed by enzyme-linked immunosorbent assay. The levels of NO were evaluated by Griess colorimetric reactions in supernatants of macrophages in culture exposed to Ts1 and compared with FII. Macrophages exposed to Ts1 increase the production of mediators. With respect to the pro-inflammatory cytokines, an increment of IL-1alpha, IL-1beta was observed after 12 h; the maximum levels of IL-6 and TNF were observed after 24 h; the highest levels of IFN-gamma and NO were observed after 72 h. In contrast, the highest levels of anti-inflammatory cytokines such as IL-10 were observed after 120 h. With respect to the balance of pro- and anti-inflammatory cytokines, IL-1alpha/IL-10 and IL-6/IL-10 ratios appear incremented between 12 and 48 h in macrophages exposed to Ts1. IL-1beta/IL-10 and TNF/IL-10 ratios were increased in macrophages exposed to Ts1 for 12 h. IFN-gamma/IL-10 ratios increased up to 48 h, decaying thereafter. Elevated IL-6/TNF ratios were observed up to 24 h. These ratios may possibly reflect the inflammatory status during exposition to the venom. In conclusion, these data indicate that Ts1 has an important immunomodulatory effect on macrophages, and add important knowledge for understanding scorpion envenomation. It also opens the field for

  15. Structural characterization of a novel peptide with antimicrobial activity from the venom gland of the scorpion Tityus stigmurus: Stigmurin.

    PubMed

    de Melo, Edinara Targino; Estrela, Andréia Bergamo; Santos, Elizabeth Cristina Gomes; Machado, Paula Renata Lima; Farias, Kleber Juvenal Silva; Torres, Taffarel Melo; Carvalho, Enéas; Lima, João Paulo Matos Santos; Silva-Júnior, Arnóbio Antonio; Barbosa, Euzébio Guimarães; Fernandes-Pedrosa, Matheus de Freitas

    2015-06-01

    A new antimicrobial peptide, herein named Stigmurin, was selected based on a transcriptomic analysis of the Brazilian yellow scorpion Tityus stigmurus venom gland, an underexplored source for toxic peptides with possible biotechnological applications. Stigmurin was investigated in silico, by circular dichroism (CD) spectroscopy, and in vitro. The CD spectra suggested that this peptide interacts with membranes, changing its conformation in the presence of an amphipathic environment, with predominance of random coil and beta-sheet structures. Stigmurin exhibited antibacterial and antifungal activity, with minimal inhibitory concentrations ranging from 8.7 to 69.5μM. It was also showed that Stigmurin is toxic against SiHa and Vero E6 cell lines. The results suggest that Stigmurin can be considered a potential anti-infective drug. PMID:25805002

  16. Tityus bahiensis toxin IV-5b selectively affects Na channel inactivation in chick dorsal root ganglion neurons.

    PubMed

    Trequattrini, C; Zamudio, F Z; Petris, A; Prestipino, G; Possani, L D; Franciolini, F

    1995-09-01

    A novel toxin was isolated from the venom of the Brazilian scorpion Tityus (T.) bahiensis. The N-terminal amino acid sequence of this toxin was shown to be 80% identical to the corresponding segment of T. serrulatus toxin IV-5. The new toxin was thus named toxin IV-5b. Toxin IV-5b was found to markedly slow inactivation of Na channel in dorsal root ganglion neurons from chick embryo. By contrast, Na channel activation was only negligibly delayed, and deactivation completely unaffected. Similarly unaffected by the toxin were K and Ca currents. The slowing effect of the toxin starts to appear at concentrations of c. 80 nM, and shows a KD of 143 nM. With a toxin concentration of 2.4 microM, the Na channel inactivation time constant was increased c. 3-fold with respect to the control. The slowing of inactivation was voltage dependent, and increased with depolarization. PMID:7553331

  17. ELISA for the detection of toxic antigens in experimental and clinical envenoming by Tityus serrulatus scorpion venom.

    PubMed

    Chávez-Olórtegui, C; Fonseca, S C; Campolina, D; Amaral, C F; Diniz, C R

    1994-12-01

    An ELISA was developed for identification of circulating toxic antigens from Tityus serrulatus scorpion venom. The toxic fraction from the scorpion venom was purified by Sephadex G-50 chromatography and immunoaffinity techniques were used for identifying antibodies that reacted with this fraction. These antibodies were used to develop a sandwich-type ELISA. The specificity of the assay was demonstrated by its capacity for identifying mice that were experimentally inoculated with T. serrulatus venom from those inoculated with Phoneutria nigriventer spider venom, Apis mellifera bee venom and Bothrops atrox, Crotalus durissus terrificus, Lachesis muta muta and Micrurus frontalis snake venoms. Measurable absorbance signals were obtained with 0.1 ng of venom per assay. The ELISA also detected antigens in the sera of patients systemically envenomed by T. serrulatus. Therefore, this ELISA could be a valuable tool for clinicians and epidemiologists, owing to its sensitivity and specificity. PMID:7725332

  18. Isolation of toxin TsTX-VI from Tityus serrulatus scorpion venom. Effects on the release of neurotransmitters from synaptosomes.

    PubMed

    Sampaio, S V; Coutinho-Netto, J; Arantes, E C; Marangoni, S; Oliveira, B; Giglio, J R

    1996-07-01

    A detailed procedure for the purification of Tityustoxin-VI, TsTX-VI, from Tityus serrulatus scorpion venom is described. For comparative purposes, a second toxin, CM-VI, obtained from the same fractionation procedure, was analyzed in parallel. Typical biochemical parameters, such as electrophoretic migration, mol.weight, amino acid composition and N-terminal sequence (first 42 amino acid residues out of a total of approx. 60) were determined for both. Our data showed that CM-VI is identical or extremely homologous to gamma-toxin (TsTX-I), the highly toxic major toxin from T. serrulatus venom. TsTX-VI was less toxic, although still effective at inducing an allergic reaction, lacrymation and contraction of the hind legs of mice. Both toxins produced a dose dependent release of the neurotransmitters glutamic acid and gamma aminobutyric acid from rat brain synaptosomes, this effect being blocked by tetrodotoxin. PMID:8843341

  19. Tityus perijanensis González-Sponga (Scorpiones, Buthidae): molecular assessment of its geographical distribution and venom lethality of Venezuelan populations.

    PubMed

    Borges, Adolfo; Rojas-Runjaic, Fernando J M

    2007-12-01

    An extensive field survey allowed us to expand the geographical distribution of the scorpion Tityus perijanensis in the Perijá range, western Zulia State, Venezuela, including areas where adult cases of severe scorpionism have been reported. 16S ribosomal RNA (rRNA) gene sequencing, DL(50) determination, and native PAGE suggest low genetic and venom proteomic divergence across the distribution range. The results also indicate phylogenetic divergence between T. perijanensis and T. discrepans, the species prevalent in northcentral Venezuela. T. perijanensis venom lethality (0.91-0.94 mg/kg) is comparable to that of the Brazilian T. serrulatus and ranks highest among toxic Venezuelan Tityus studied so far. The data indicate that the Perijá range should be included amongst the endemic areas of scorpionism of Venezuela and Colombia. PMID:17868753

  20. Morphometric and molecular characterization of the species of Uncinaria Frölich, 1789 (Nematoda) parasitic in the Australian fur seal Arctocephalus pusillus doriferus (Schreber), with notes on hookworms in three other pinniped hosts.

    PubMed

    Ramos, Paul; Lynch, Michael; Hu, Min; Arnould, John P Y; Norman, Richard; Beveridge, Ian

    2013-05-01

    This study presents morphological and molecular data on hookworms from the Australian fur seal Arctocephalus pusillus doriferus (Schreber) currently identified in Australian waters as Uncinaria hamiltoni Baylis, 1933. Additional specimens from the Australian sea lion Neophoca cinerea (Péron) and the New Zealand fur seal Arctocephalus forsteri (Lesson) from Australia, and the Southern elephant seal Mirounga leonina (Linnaeus) from Antarctica, were included. Using the internal transcribed spacer (ITS), hookworms from A. p. doriferus, N. cinerea and A. forsteri were found to be genetically similar but distinct from Uncinaria spp. found in M. leonina from Antarctica, as well as from Zalophus californianus (Lesson) and Callorhinus ursinus (Linnaeus) from California. Few morphological differences were detected between these taxa. PMID:23595493

  1. Comments on Environmental and Sanitary Aspects of the Scorpionism by Tityus trivittatus in Buenos Aires City, Argentina

    PubMed Central

    de Roodt, Adolfo Rafael

    2014-01-01

    Deaths by venomous animals are medical emergencies that can lead to death and thus constitute sanitary problems in some regions of the world. In the South of America, the accidents by these animals are a common sanitary problem especially in warm, tropical or subtropical regions, related with rural work in several countries. Argentina is located in the extreme South of South America and a minor part of the continental surface is in tropical or subtropical regions, where most of the accidents by venomous animals happen. However, in the big cities in the center and South of the country, with no relation to rural work, scorpionism, mostly due to the synanthropic and facultative parthenogenetic scorpion Tityus trivittatus, has become a sanitary problem in the last few decades. This scorpion is present in the biggest cities of Argentina and in the last decades has killed over 20 children in provinces of the center and north of the country, mostly in big cities. In addition, it seems that this species is growing and spreading in new regions of the cities. In this revision, some characteristics of this scorpion regarding its habitat, spreading in Buenos Aires city, combat measures and available treatments are discussed. PMID:24759176

  2. Vesicle-associated Membrane Protein (VAMP) Cleavage by a New Metalloprotease from the Brazilian Scorpion Tityus serrulatus*

    PubMed Central

    Fletcher, Paul L.; Fletcher, Maryann D.; Weninger, Keith; Anderson, Trevor E.; Martin, Brian M.

    2010-01-01

    We present evidence that venom from the Brazilian scorpion Tityus serrulatus and a purified fraction selectively cleave essential SNARE proteins within exocrine pancreatic tissue. Western blotting for vesicle-associated membrane protein type v-SNARE proteins (or synaptobrevins) reveals characteristic alterations to venom-treated excised pancreatic lobules in vitro. Immunocytochemistry by electron microscopy confirms both the SNARE identity as VAMP2 and the proteolysis of VAMP2 as a marked decrease in secondary antibody-conjugated colloidal gold particles that are predominantly associated with mature zymogen granules. Studies with recombinant SNARE proteins were used to determine the specific cleavage site in VAMP2 and the susceptibility of VAMP8 (endobrevin). The VAMP2 cleavage site is between the transmembrane anchor and the SNARE motif that assembles into the ternary SNARE complex. Inclusion of divalent chelating agents (EDTA) with fraction ν, an otherwise active purified component from venom, eliminates SNARE proteolysis, suggesting the active protein is a metalloprotease. The unique cleavages of VAMP2 and VAMP8 may be linked to pancreatitis that develops following scorpion envenomation as both of these v-SNARE proteins are associated with zymogen granule membranes in pancreatic acinar cells. We have isolated antarease, a metalloprotease from fraction ν that cleaves VAMP2, and report its amino acid sequence. PMID:20026600

  3. Electrophysiological Characterization of Ts6 and Ts7, K+ Channel Toxins Isolated through an Improved Tityus serrulatus Venom Purification Procedure

    PubMed Central

    Cerni, Felipe A.; Pucca, Manuela B.; Peigneur, Steve; Cremonez, Caroline M.; Bordon, Karla C. F.; Tytgat, Jan; Arantes, Eliane C.

    2014-01-01

    In Brazil, Tityus serrulatus (Ts) is the species responsible for most of the scorpion related accidents. Among the Ts toxins, the neurotoxins with action on potassium channels (α-KTx) present high interest, due to their effect in the envenoming process and the ion channel specificity they display. The α-KTx toxins family is the most relevant because its toxins can be used as therapeutic tools for specific target cells. The improved isolation method provided toxins with high resolution, obtaining pure Ts6 and Ts7 in two chromatographic steps. The effects of Ts6 and Ts7 toxins were evaluated in 14 different types of potassium channels using the voltage-clamp technique with two-microelectrodes. Ts6 toxin shows high affinity for Kv1.2, Kv1.3 and Shaker IR, blocking these channels in low concentrations. Moreover, Ts6 blocks the Kv1.3 channel in picomolar concentrations with an IC50 of 0.55 nM and therefore could be of valuable assistance to further designing immunosuppressive therapeutics. Ts7 toxin blocks multiple subtypes channels, showing low selectivity among the channels analyzed. This work also stands out in its attempt to elucidate the residues important for interacting with each channel and, in the near future, to model a desired drug. PMID:24590385

  4. Time course of acute-phase response induced by Tityus serrulatus venom and TsTX-I in mice.

    PubMed

    Pessini, Andréa C; de Souza, Ana M; Faccioli, Lúcia H; Gregório, Zita M O; Arantes, Eliane C

    2003-05-01

    Animal venom can induce systemic alterations similar to those observed in acute-phase inflammatory response. In the present study, we report the systemic (circulatory) and local (peritoneal cavity) effects induced by Tityus serrulatus venom and its major toxin TsTX-I (Ts1) in mice over various time periods. Both the venom and TsTX-I elicited quite similar responses in most assays. Responses included reduction of albumin, increased C-reactive protein, IL-6, IL-1alpha and TNF-alpha. Local and systemic leucocytosis, with a predominance of polymorphonuclear cells, was also observed. These effects show that a systemic inflammation-like syndrome is triggered during the severe envenomation caused by the T. serrulatus sting. The initial increases of albumin and total protein were probably consequences of the dehydration that occurs at the beginning of envenomation. Time-course analysis of these effects shows that responses are most pronounced on the first day after poisoning. However, leucocytosis and changes in acute-phase protein concentrations can be observed up to 7 days after envenomation. PMID:12757745

  5. Evidence for a role of mast cells in the lung edema induced by Tityus serrulatus venom in rats.

    PubMed

    De-Matos, I M; Talvani, A; Rocha, O O; Freire-Maia, L; Teixeira, M M

    2001-06-01

    In the most severe cases of human poisoning by Tityus serrulatus, pulmonary edema is a frequent finding and can be the cause of death. Mast cells can release a range of mediators known to be involved in the development of lung edema following T. serrulatus venom injection. The present work was designed to investigate whether mast cells participated in the acute lung injury induced by T. serrulatus scorpion venom and could, thus, be an intermediate between neuropeptide release and activation of the inflammatory cascade. To this end, mast cells were depleted using compound 48/80. Pulmonary edema, as assessed by the levels of extravasation of Evans blue dye in the bronchoalveolar lavage and in the left lung, was completely inhibited in compound 48/80-treated animals. Moreover, the number of animals surviving 60min after injection of venom rose from 20 to 60%. Our results demonstrate an important role for mast cells in the development of lung injury and lethality following the intravenous administration of T. serrulatus venom. PMID:11137547

  6. Carbamazepine is effective in the treatment of 21-day-old Wistar rats injected with Tityus serrulatus crude venom.

    PubMed

    Guidine, Patrícia Alves Maia; Moraes-Santos, Tasso; Massensini, André Ricardo; Moraes, Márcio Flávio Dutra

    2008-11-01

    The scorpion-envenoming syndrome has an incidence of approximately 8000 accidents/year in Brazil; with most severe cases occurring during childhood and elderly. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. Our group has shown that the pre-treatment with carbamazepine (CBZ) is able to increase the latency-to-death in developing animals inoculated with tityustoxin, a toxic fraction of the Tityus serrulatus crude venom. Nevertheless, in order to perceive CBZ as potentially useful in clinical practice, the efficiency of CBZ against crude venom inoculation and the pharmacological treatment introduced after envenomation must be addressed. Thus, the objective of this work was to evaluate CBZ therapeutic efficiency against scorpion envenomation in developing rats. Animals were treated with i.p. injections of either vehicle or CBZ (50 mg/kg or 100 mg/kg) 10 min after injected with a s.c. fixed volume of either saline or crude T. serrulatus venom extract (48 mg/kg). The dose chosen for venom inoculation was 16 times its DL50 for 21-day-old Wistar rats, invariably inducing death within 2 h. Although CBZ did not significantly reduce the pulmonary edema, it was effective in increasing survival rate by approximately 75% in treated rats. In conclusion, CBZ was effective in the treatment of T. serrulatus envenomation even though not blocking the pulmonary edema. PMID:18760265

  7. In vivo protection against Tityus serrulatus scorpion toxins by immunization of mice with a non-toxic protein.

    PubMed

    Moreira-Ferreira, A M; Kalapothakis, E; Diniz, C R; Chávez-Olórtegui, C

    1998-02-01

    The possibility of inducing a humoral immune response able to produce neutralizing antibodies against the lethal effects of scorpion toxins was evaluated in the mouse model. A non-toxic protein (TsNTxP) was purified from the venom of the Brazilian scorpion Tityus serrulatus by combining gel filtration, ion exchange and reverse phase HPLC chromatographic steps. After four injections of TsNTxP the mice developed an IgG response. The anti-TsNTxP antibodies had a comparable high cross-reactivity for the crude venom, toxic fraction (toxic fraction of venom that represents most of the toxicity of the crude venom -- TsTFG50) and TsIV, a representative alpha-type toxin of T. serrulatus, and moderate binding capacity for TsVII, a representative beta-type toxin. In vitro neutralization assays indicated that preincubation of a lethal dose of the toxic fraction with immune serum strongly reduced its toxicity. In vivo protection assays showed that mice immunized with TsNTxP resisted a challenge of 10 LD50 (s.c.) of the toxic fraction of T. serrulatus venom. PMID:9620580

  8. Neutralizing capacity of antibodies elicited by a non-toxic protein purified from the venom of the scorpion Tityus serrulatus.

    PubMed

    Chávez-Olórtegui, C; Kalapothakis, E; Ferreira, A M; Ferreira, A P; Diniz, C R

    1997-02-01

    Polyclonal rabbit antibodies raised against a non-toxic protein (TsNTxP) purified from the toxic fraction of the crude venom of Tityus serrulatus can neutralize the effects of the venom. The antigenic specificities of anti-TsNTxP were compared by an indirect enzyme-linked immunosorbent assay using TsNTxP, TstFG50 (toxic fraction of venom that represents most of the toxicity of the crude venom), and crude venoms from T. serrulatus, T. bahiensis, T. cambridgei, T. stigmurus, Androctonus australis Hector and Centruroides sculpturatus to coat microtitration plates. The anti-TsNTxP antibodies had a comparable high cross-reactivity with the toxic fraction and crude venom of T. serrulatus, moderate binding capacity for T. bahiensis, T. cambridgei, T. stigmurus and were unable to recognize the venoms of A. australis Hector and C. sculpturatus. Quantities of venom equivalent to 20 LD50 were effectively neutralized by 1 ml of the anti-TsNTxP serum. This result shows that this protein may be of interest in the production of antivenoms for clinical use. PMID:9080578

  9. Children with adrenergic manifestations of envenomation after Tityus serrulatus scorpion sting are protected from early anaphylactic antivenom reactions.

    PubMed

    Amaral, C F; Dias, M B; Campolina, D; Proietti, F A; de Rezende, N A

    1994-02-01

    The incidence of early anaphylactic reactions to scorpion antivenom given i.v. after Tityus serrulatus scorpion sting was evaluated in 103 children aged up to 15 years in Belo Horizonte, Brazil. Patients without adrenergic manifestations (Group 1, n = 28) were compared with those who presented systemic involvement that included adrenergic manifestations (Group 2, n = 75). Data were recorded on a proforma and the presence or absence of early anaphylactic reaction was cross-tabulated according to clinical features, sex, age and volume of antivenom used in the treatment. Unpaired Student's t-test was used to calculate significance of differences in age and volume of antivenom used. Multivariate logistic regression was used to determine the effects of clinical features and volume of antivenom as predictors of early anaphylactic reaction to antivenom treatment. Twelve (42.9%) of 28 children included in Group 1 presented early anaphylactic reactions compared with 6 (8%) of 75 children of Group 2 (OR = 8.63; 95% CI: 2.88, 25.7). The reactions were more severe in Group 1. There were no significant differences with respect to age and sex. After adjusting for clinical form, volume of antivenom was not significantly associated with presence of reactions (OR = 1.11; 95% CI: 0.70, 2.80 for each 5.0 ml of antivenom administered). The results show that children with adrenergic manifestations after T. serrulatus scorpion sting had significantly lower anaphylactic reactions to antivenom than those without these manifestations. PMID:8153960

  10. Tityus serrulatus scorpion venom improves survival and lung inflammation in lethal sepsis induced by CLP in mice.

    PubMed

    Maciel, Márcia C G; Fialho, Eder M S; Guerra, Rosane N M; Borges, Valéria M; Kwasniewski, Fábio H; Nascimento, Flávia R F

    2014-10-01

    Tityus serrulatus venom (Tsv) modifies the behavior of immune cells and induces the production of inflammatory and anti-inflammatory cytokines; such action may interfere with physiological or pathological states. Because sepsis is characterized as an inflammatory disorder, the aim of present study was to investigate the effect of a non-lethal dose of Tsv in mice submitted to a polymicrobial infection by cecal ligation and puncture (CLP) model. The parameters evaluated were survival index, cellularity on lymphoid organs, peritoneal cavity and brochoalveolar space, production of IL-10, IL-12, IL-6, TNF-α, IFN-γ and MCP-1, pulmonary inflammation and oxidative burst. The results demonstrated that in sharp contrast to CLP group in which sepsis was lethal in a 24 h period all mice pretreated with Tsv survived even 60 h after CLP. Lung inflammation, another hallmark of CLP group, was also dramatically down regulated in Tsv/CLP group. Despite pretreatment with Tsv did not reduce the inflammatory serum cytokines when compared to CLP group; there was an increase in IL-10. In conclusion, subcutaneous Tsv administration 6 h before CLP was able to control the harmful effects of sepsis (lethality and lung inflammation). We suggest that both systemic IL-10 and oxidative burst are involved in this effect. PMID:24976596

  11. Comments on Environmental and Sanitary Aspects of the Scorpionism by Tityus trivittatus in Buenos Aires City, Argentina.

    PubMed

    de Roodt, Adolfo Rafael

    2014-04-01

    Deaths by venomous animals are medical emergencies that can lead to death and thus constitute sanitary problems in some regions of the world. In the South of America, the accidents by these animals are a common sanitary problem especially in warm, tropical or subtropical regions, related with rural work in several countries. Argentina is located in the extreme South of South America and a minor part of the continental surface is in tropical or subtropical regions, where most of the accidents by venomous animals happen. However, in the big cities in the center and South of the country, with no relation to rural work, scorpionism, mostly due to the synanthropic and facultative parthenogenetic scorpion Tityus trivittatus, has become a sanitary problem in the last few decades. This scorpion is present in the biggest cities of Argentina and in the last decades has killed over 20 children in provinces of the center and north of the country, mostly in big cities. In addition, it seems that this species is growing and spreading in new regions of the cities. In this revision, some characteristics of this scorpion regarding its habitat, spreading in Buenos Aires city, combat measures and available treatments are discussed. PMID:24759176

  12. A study on the experimental envenomation in mice with the venom of Tityus trivitattus Kraepelin 1898 (Scorpiones, Buthidae) captured in Argentina.

    PubMed

    de Roodt, A R; Gimeno, E; Portiansky, E; Varni, L; Dolab, J A; Segre, L; Litwin, S; Vidal, J C

    2001-05-01

    Although Tityus trivitattus is the only scorpion species reported to cause severe human envenomation in Argentina, no previous studies on its venom have been done. Telson homogenates from T. trivitattus specimens collected in Santiago del Estero, Cordoba, and Buenos Aires were employed to study their protein composition and toxicity to mice. Regardless of the site of collection, electrophoretic analysis showed bands at 205, 150, 100, 40, 32, and 13 kDa or smaller. FPLC gel filtration showed three major peaks and 6-8 minor peaks with similar elution volumes. One of the minor peaks from FPLC containing a component of approximately 8 kDa was lethal to mice. Mice injected intravenously with different doses of homogenates presented severe autonomic signs like tachypnea, tachycardia, sialorrhea, lacrimation, profuse sweating, diarrhea, dyspnea, and death. Pathology studies of lungs showed severe congestion of alveolar capillaries, pulmonary edema, and hemorrhagic areas. The kidneys showed glomerular as well as tubular lesions and exocrine glands showed areas of necrosis. The calculated LD50 was 0.38 +/- 0.08 telsons per 20 g mouse, which suggests a lethal potency similar to that of T. serrulatus venom. The lethal potency of 5.0 LD50 of T. trivitattus telson homogenate was neutralized by both an anti-T. trivitattus and a heterologous anti Tityus with ED50 values of 41 +/- 19 and 170 +/- 42 microl, respectively. PMID:11405281

  13. Karyotype conservation in 2 populations of the parthenogenetic scorpion Tityus serrulatus (Buthidae): rDNA and its associated heterochromatin are concentrated on only one chromosome.

    PubMed

    Schneider, Marielle C; Cella, Doralice M

    2010-01-01

    Within the order Scorpiones, the parthenogenetic mode of reproduction has been described for 11 species, 6 of which belong to the genus Tityus. In this work, an investigation of the chromosome characteristics of 2 populations of Tityus serrulatus, the first scorpion species known to be thelytokously parthenogenetic, is described. An analysis of 40 individuals revealed holocentric chromosomes of large, medium, and small sizes and an invariable diploid number of 2n = 12. In addition to the conserved macrokaryotype structure, specific chromosome regions also appeared unchanged within and between the samples studied; that is, each sample displayed only one chromosome carrier of the active nucleolar organizer region containing ribosomal genes (5.8S, 18S, and 28S) and AT-rich heterochromatin associated with the ribosomal DNA. The high conservation of the chromosomal features observed in T. serrulatus differed from that verified in certain species of other groups of animals that possess both holocentric chromosomes and parthenogenetic reproduction. Moreover, the cytogenetic results obtained herein permit us to suggest how the eggs of T. serrulatus develop, whether by apomixis or automixis. PMID:20231264

  14. Isolation and characterization of Ts19 Fragment II, a new long-chain potassium channel toxin from Tityus serrulatus venom.

    PubMed

    Cerni, Felipe Augusto; Pucca, Manuela Berto; Amorim, Fernanda Gobbi; de Castro Figueiredo Bordon, Karla; Echterbille, Julien; Quinton, Loïc; De Pauw, Edwin; Peigneur, Steve; Tytgat, Jan; Arantes, Eliane Candiani

    2016-06-01

    Ts19 Fragment II (Ts19 Frag-II) was first isolated from the venom of the scorpion Tityus serrulatus (Ts). It is a protein presenting 49 amino acid residues, three disulfide bridges, Mr 5534Da and was classified as a new member of class (subfamily) 2 of the β-KTxs, the second one described for Ts scorpion. The β-KTx family is composed by two-domain peptides: N-terminal helical domain (NHD), with cytolytic activity, and a C-terminal CSαβ domain (CCD), with Kv blocking activity. The extensive electrophysiological screening (16 Kv channels and 5 Nav channels) showed that Ts19 Frag-II presents a specific and significant blocking effect on Kv1.2 (IC50 value of 544±32nM). However, no cytolytic activity was observed with this toxin. We conclude that the absence of 9 amino acid residues from the N-terminal sequence (compared to Ts19 Frag-I) is responsible for the absence of cytolytic activity. In order to prove this hypothesis, we synthesized the peptide with these 9 amino acid residues, called Ts19 Frag-III. As expected, Ts19 Frag-III showed to be cytolytic and did not block the Kv1.2 channel. The post-translational modifications of Ts19 and its fragments (I-III) are also discussed here. A mechanism of post-translational processing (post-splitting) is suggested to explain Ts19 fragments production. In addition to the discovery of this new toxin, this report provides further evidence for the existence of several compounds in the scorpion venom contributing to the diversity of the venom arsenal. PMID:26116782

  15. Molecular, Immunological, and Biological Characterization of Tityus serrulatus Venom Hyaluronidase: New Insights into Its Role in Envenomation

    PubMed Central

    Oliveira-Mendes, Bárbara Bruna Ribeiro; do Carmo, Anderson Oliveira; Duarte, Clara Guerra; Felicori, Liza Figueiredo; Machado-de-Ávila, Ricardo Andrez; Chávez-Olórtegui, Carlos; Kalapothakis, Evanguedes

    2014-01-01

    Background Scorpionism is a public health problem in Brazil, and Tityus serrulatus (Ts) is primarily responsible for severe accidents. The main toxic components of Ts venom are low-molecular-weight neurotoxins; however, the venom also contains poorly characterized high-molecular-weight enzymes. Hyaluronidase is one such enzyme that has been poorly characterized. Methods and principal findings We examined clones from a cDNA library of the Ts venom gland and described two novel isoforms of hyaluronidase, TsHyal-1 and TsHyal-2. The isoforms are 83% identical, and alignment of their predicted amino acid sequences with other hyaluronidases showed conserved residues between evolutionarily distant organisms. We performed gel filtration followed by reversed-phase chromatography to purify native hyaluronidase from Ts venom. Purified native Ts hyaluronidase was used to produce anti-hyaluronidase serum in rabbits. As little as 0.94 µl of anti-hyaluronidase serum neutralized 1 LD50 (13.2 µg) of Ts venom hyaluronidase activity in vitro. In vivo neutralization assays showed that 121.6 µl of anti-hyaluronidase serum inhibited mouse death 100%, whereas 60.8 µl and 15.2 µl of serum delayed mouse death. Inhibition of death was also achieved by using the hyaluronidase pharmacological inhibitor aristolochic acid. Addition of native Ts hyaluronidase (0.418 µg) to pre-neutralized Ts venom (13.2 µg venom+0.94 µl anti-hyaluronidase serum) reversed mouse survival. We used the SPOT method to map TsHyal-1 and TsHyal-2 epitopes. More peptides were recognized by anti-hyaluronidase serum in TsHyal-1 than in TsHyal-2. Epitopes common to both isoforms included active site residues. Conclusions Hyaluronidase inhibition and immunoneutralization reduced the toxic effects of Ts venom. Our results have implications in scorpionism therapy and challenge the notion that only neurotoxins are important to the envenoming process. PMID:24551256

  16. Investigation of the relationship between the structure and function of Ts2, a neurotoxin from Tityus serrulatus venom.

    PubMed

    Cologna, Camila T; Peigneur, Steve; Rustiguel, Joane K; Nonato, M Cristina; Tytgat, Jan; Arantes, Eliane C

    2012-04-01

    Scorpion toxins targeting voltage-gated sodium (Na(V)) channels are peptides that comprise 60-76 amino acid residues cross-linked by four disulfide bridges. These toxins can be divided in two groups (α and β toxins), according to their binding properties and mode of action. The scorpion α-toxin Ts2, previously described as a β-toxin, was purified from the venom of Tityus serrulatus, the most dangerous Brazilian scorpion. In this study, seven mammalian Na(V) channel isoforms (rNa(V)1.2, rNa(V)1.3, rNa(V)1.4, hNa(V)1.5, mNa(V)1.6, rNa(V)1.7 and rNa(V)1.8) and one insect Na(V) channel isoform (DmNa(V)1) were used to investigate the subtype specificity and selectivity of Ts2. The electrophysiology assays showed that Ts2 inhibits rapid inactivation of Na(V)1.2, Na(V)1.3, Na(V)1.5, Na(V)1.6 and Na(V)1.7, but does not affect Na(V)1.4, Na(V)1.8 or DmNa(V)1. Interestingly, Ts2 significantly shifts the voltage dependence of activation of Na(V)1.3 channels. The 3D structure of this toxin was modeled based on the high sequence identity (72%) shared with Ts1, another T. serrulatus toxin. The overall fold of the Ts2 model consists of three β-strands and one α-helix, and is arranged in a triangular shape forming a cysteine-stabilized α-helix/β-sheet (CSαβ) motif. PMID:22356164

  17. Induction of neutralizing antibodies against Tityus serrulatus scorpion toxins by immunization with a mixture of defined synthetic epitopes.

    PubMed

    Alvarenga, L M; Diniz, C R; Granier, C; Chávez-Olórtegui, C

    2002-01-01

    We have used the Spot method of multiple peptide synthesis to prepare sets of immobilized overlapping peptides of uniform size (15 mer), covering the complete amino acid sequences of TsNTxP a non-toxic and immunogenic protein and TsIV, an alpha-type toxin that is the major lethal component of the venom of scorpion Tityus serrulatus. Anti-TsNTxP antibodies binding to peptides, revealed three antigenic regions, one in the N-terminal, the second in the central part and the other in the C-terminal part of TsNTxP. One peptide epitope in the C-terminal part of TsIV was identified with anti-TsIV neutralizing rabbit antibodies. Anti-peptide antibodies were raised against these four peptides all together covalently coupled to keyhole limpet hemocyanin (KLH) and found to neutralize in vitro the toxic effects of the T. serrulatus venom. Quantities of venom equivalent to 13.5 LD(50) were effectively neutralized by 1ml of the anti-peptide serum. The antigenic specificities of the anti-peptides were compared by an indirect enzyme-linked immunosorbent assay (ELISA) using synthetic peptides and crude venoms from T. serrulatus, T. bahiensis, T. cambridgei, T. stigmurus, Androctonus autralis Hector and Centruroides sculpturatus to coat the microtitration plates. The anti-peptide antibodies had a comparable high reactivity with the crude venom of T. serrulatus, moderate binding to T. bahiensis, T. cambridgei, T. stigmurus and Centruroides sculpturatus venoms but were unable to recognize the venom of Androctonus autralis Hector. These results show that by using peptides derived from the sequence of scorpion toxins, the generation of anti-peptide antibodies able to neutralize the cognate venom appears to be an alternative strategy for the easy preparation of antivenoms. PMID:11602284

  18. Ts6 and Ts2 from Tityus serrulatus venom induce inflammation by mechanisms dependent on lipid mediators and cytokine production.

    PubMed

    Zoccal, Karina Furlani; Bitencourt, Claudia da Silva; Sorgi, Carlos Artério; Bordon, Karla de Castro Figueiredo; Sampaio, Suely Vilela; Arantes, Eliane Candiani; Faccioli, Lúcia Helena

    2013-01-01

    Inflammatory mediators are thought to be involved in the systemic and local immune response induced by the Tityus serrulatus scorpion envenomation. New functional aspects of lipid mediators have recently been described. Here, we examine the unreported role of lipid mediators in cell recruitment to the peritoneal cavity after an injection with Ts2 or Ts6 toxins isolated from the T. serrulatus scorpion venom. In this report, we demonstrate that following a single intraperitoneal (i.p.) injection of Ts2 or Ts6 (250 μg/kg) in mice, there was an induction of leukocytosis with a predominance of neutrophils observed at 4, 24, 48 and 96 h. Moreover, total protein, leukotriene (LT)B(4), prostaglandin (PG)E(2) and pro-inflammatory cytokine levels were increased. We also observed an increase of regulatory cytokines, including interleukin (IL)-10, after the Ts2 injection. Finally, we observed that Ts2 or Ts6 injection in 5-lipoxygenase (LO) deficient mice and in wild type (WT) 129sv mice pre-treated with LTs and PGs inhibitors (MK-886 and celecoxib, respectively) a reduction the influx of leukocytes occurs in comparison to WT. The recruitment of these cells demonstrated a phenotype characteristic of neutrophils, macrophages, CD4 and CD8 lymphocytes expressing GR1+, F4/80+, CD3+/CD4+ and CD3+/CD8+, respectively. In conclusion, our data demonstrate that Ts2 and Ts6 induce inflammation by mechanisms dependent on lipid mediators and cytokine production. Ts2 may play a regulatory role whereas Ts6 exhibits pro-inflammatory activity exclusively. PMID:23085190

  19. Characterization of TistH, a multifunctional peptide from the scorpion Tityus stigmurus: Structure, cytotoxicity and antimicrobial activity.

    PubMed

    Machado, Richele J A; Estrela, Andréia B; Nascimento, Ana K L; Melo, Menilla M A; Torres-Rêgo, Manoela; Lima, Edeltrurdes O; Rocha, Hugo A O; Carvalho, Eneas; Silva-Junior, Arnóbio A; Fernandes-Pedrosa, Matheus F

    2016-09-01

    The presence of bioactive peptides in animal venoms has been targeted in scientific research for assessing biological activities, as well as mechanisms of action. A recent study by our group observed hypotensive action of TistH (Tityus stigmurus Hypotensin), a peptide deduced from the transcriptome of T. stigmurus venom gland. The present study aims to analyze TistH structure properties and to evaluate its toxicity on normal and tumor cells, its in vitro antimicrobial activity, as well as its inflammatory effect. Circular dichroism analyses of TistH showed a general predominance of α-helix conformation in TFE (20-70%) and structural stability to pH variations. TistH was not cytotoxic to normal cell lines (3T3, RAW and HEK), and also not to cancer cell lines (HeLa, B16, 786-0, SiHa and HepG2). The peptide did not present inflammatory activity up to 6 h after administered subcutaneously to Swiss mice. It was observed that concentrations of 4-1024 μg/mL of TistH produced no inhibition against the bacteria Staphylococcus aureus, Staphylococcus epidermidis e Pseudomonas aeruginosa. The results of antifungal assays showed a moderate activity of TistH against Candida albicans strain LM-108 and the filamentous fungus Trichophyton rubrum LM-640, with growth inhibition at a concentration of 1024 μg/mL. In contrast, the peptide presented a greater activity (MIC 128 μg/mL) against C. albicans LM-106, Candida tropicalis ATCC 13308 and Aspergillus flavus strains LM-247 and LM-26, fungi that cause oral and vaginal infections, candidiasis and respiratory allergies, respectively. The present data contribute to a better understanding of TistH and its possible use as a bioactive compound. This multifunctional peptide is capable of acting as anti-hypertensive, as well as to inhibit the growth of fungal strains, having low toxicity, which suggests its safety for using as a pharmacological agent. PMID:27267248

  20. Moving pieces in a proteomic puzzle: mass fingerprinting of toxic fractions from the venom of Tityus serrulatus (Scorpiones, Buthidae).

    PubMed

    Pimenta, A M; Stöcklin, R; Favreau, P; Bougis, P E; Martin-Eauclaire, M F

    2001-01-01

    Scorpion venoms are very complex mixtures of molecules, most of which are peptides that display different kinds of biological activity. These venoms have been studied in the light of their pharmacological targets and their constituents are able to bind specifically to a variety of ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins that modulate Na(+), K(+), Ca(++) and Cl(-) currents have been described in scorpion venoms. Mass spectrometry was employed to analyze toxic fractions from the venom of the Brazilian scorpion Tityus serrulatus in order to shed light on the molecular composition of this venom and to facilitate the search for novel pharmacologically active compounds. T. serrulatus venom was first subjected to gel filtration to separate its constituents according to their molecular size. The resultant fractions II and III, which account for 90 and 10% respectively of the whole venom toxic effect, were further analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), on-line liquid chromatography/electrospray mass spectrometry (LC/ESMS) and off-line LC/MALDI-TOFMS in order to establish their mass fingerprints. The molecular masses in fraction II were predominantly between 6500 and 7500 Da. This corresponds to long-chain toxins that mainly act on voltage-gated Na(+) channels. Fraction III is more complex and predominantly contained molecules with masses between 2500 and 5000 Da. This corresponds to the short-chain toxin family, most of which act on K(+) channels, and other unknown peptides. Finally, we were able to measure the molecular masses of 380 different compounds present in the two fractions investigated. To our knowledge, this is the largest number of components ever detected in the venom of a single animal species. Some of the toxins described previously from T. serrulatus venom could be detected by virtue of their molecular masses. The interpretation of this large set of data

  1. Effects of Tityus serrulatus scorpion venom and its toxin TsTX-V on neurotransmitter uptake in vitro

    SciTech Connect

    Cecchini, Alessandra L.; Vasconcelos, Flavio; Giglio, Jose Roberto; Arantes, Eliane Candiani . E-mail: ecabraga@fcfrp.usp.br

    2006-12-01

    Scorpion neurotoxins targeting the Na{sub v} channel can be classified into two classes: {alpha}- and {beta}-neurotoxins and are reported as highly active in mammalian brain. In this work, we evaluate the effects of Tityus serrulatus venom (Ts venom) and its {alpha}-neurotoxin TsTX-V on {gamma}-aminobutyric acid (GABA), dopamine (DA) and glutamate (Glu) uptake in isolated rat brain synaptosomes. TsTX-V was isolated from Ts venom by ion exchange chromatography followed by reverse-phase (C18) high-performance liquid chromatography. Neither Ts venom nor TsTX-V was able to affect {sup 3}H-Glu uptake. On the other hand, Ts venom (0.13 {mu}g/mg) significantly inhibited both {sup 3}H-GABA and {sup 3}H-DA uptake ({approx} 50%). TsTX-V showed IC{sub 5} values of 9.37 {mu}M and 22.2 {mu}M for the inhibition of {sup 3}H-GABA and {sup 3}H-DA uptake, respectively. These effects were abolished by pre-treatment with tetrodotoxin (TTX, 1 {mu}M), indicating the involvement of voltage-gated Na{sup +} channels in this process. In the absence of Ca{sup 2+}, and at low Ts venom concentrations, the reduction of {sup 3}H-GABA uptake was not as marked as in the presence of Ca{sup 2+}. TsTX-V did not reduce {sup 3}H-GABA uptake in COS-7 cells expressing the GABA transporters GAT-1 and GAT-3, suggesting that this toxin indirectly reduces the transport. The reduced {sup 3}H-GABA uptake by synaptosomes might be due to rapid cell depolarization as revealed by confocal microscopy of C6 glioma cells. Thus, TsTX-V causes a reduction of {sup 3}H-GABA and {sup 3}H-DA uptake in a Ca{sup 2+}-dependent manner, not directly affecting GABA transporters, but, in consequence of depolarization, involving voltage-gated Na{sup +} channels.

  2. Purification and primary structure determination of Tf4, the first bioactive peptide isolated from the venom of the Brazilian scorpion Tityus fasciolatus.

    PubMed

    Wagner, Simone; Castro, Mariana S; Barbosa, João Alexandre R G; Fontes, Wagner; Schwartz, Elisabeth N F; Sebben, Antonio; Rodrigues Pires, Osmindo; Sousa, Marcelo V; Schwartz, Carlos Alberto

    2003-06-01

    In the present study Tityus fasciolatus crude venom toxicity was evaluated and we also report the purification and characterization of a 6.6 kDa neurotoxin isolated from T. fasciolatus venom. This new toxin, named Tf4, has a molecular mass of 6614Da and its primary structure is homologous to TbIT-I from T. bahiensis and TsTX-VI and TsNTxP from T. serrulatus. Tf4 delays frog sodium channel inactivation reversibly, but it is non-toxic to mammals or crustaceans. An attempt to identify the residues responsible for the partial loss of toxicity in Tf4 was carried out based on homology modeling and sequence comparison. PMID:12782073

  3. Clinical aspects of envenomation caused by Tityus obscurus (Gervais, 1843) in two distinct regions of Pará state, Brazilian Amazon basin: a prospective case series

    PubMed Central

    2014-01-01

    Background Scorpion envenomations are a major public health problem in Brazil, whose most dangerous cases are attributable to the genus Tityus. This study was designed to compare the clinical and demographic features of envenomations by Tityus obscurus in two areas of the state of Pará located in the Amazon basin. Were compared demographic findings, local and systemic signs and symptoms of human envenomations caused by T. obscurus that occurred in western and eastern areas of the state. Results Forty-eight patients with confirmed envenomation by T. obscurus were evaluated from January 2008 to July 2011. Most of them came from the eastern region, where male and female patients were present in similar numbers, while males predominated in the west. Median age groups were also similar in both areas. Most scorpion stings took place during the day and occurred significantly more frequently on the upper limbs. The time between the sting and admission to the health center was less than three hours in both areas. Most eastern patients had local manifestations while in the west, systemic manifestations predominated. Local symptoms were similar in both areas, but systemic signs and symptoms were more common in the west. Symptoms frequently observed at the sting site were local and radiating pain, paresthesia, edema, erythema, sweating, piloerection and burning. The systemic manifestations were significantly higher in patients from the west. Futhermore, neurological symptoms such as general paresthesia, ataxia, dysarthria, myoclonus, dysmetria, and electric shock-like sensations throughout the body were reported only by patients from the west. Conclusion The present study shows that two regions of Para state differ in the clinical manifestations and severity of confirmed envenomation by T. obscurus which suggests a toxicity variation resulting from the diversity of T. obscurus venom in different areas of the Brazilian Amazon basin, and that T. serrulatus antivenom can be

  4. Biochemical, Transcriptomic and Proteomic Analyses of Digestion in the Scorpion Tityus serrulatus: Insights into Function and Evolution of Digestion in an Ancient Arthropod

    PubMed Central

    Fuzita, Felipe J.; Pinkse, Martijn W. H.; Patane, José S. L.; Juliano, Maria A.; Verhaert, Peter D. E. M.; Lopes, Adriana R.

    2015-01-01

    Scorpions are among the oldest terrestrial arthropods and they have passed through small morphological changes during their evolutionary history on land. They are efficient predators capable of capturing and consuming large preys and due to envenomation these animals can become a human health challenge. Understanding the physiology of scorpions can not only lead to evolutionary insights but also is a crucial step in the development of control strategies. However, the digestive process in scorpions has been scarcely studied. In this work, we describe the combinatory use of next generation sequencing, proteomic analysis and biochemical assays in order to investigate the digestive process in the yellow scorpion Tityus serrulatus, mainly focusing in the initial protein digestion. The transcriptome generated database allowed the quantitative identification by mass spectrometry of different enzymes and proteins involved in digestion. All the results suggested that cysteine cathepsins play an important role in protein digestion. Two digestive cysteine cathepsins were isolated and characterized presenting acidic characteristics (pH optima and stability), zymogen conversion to the mature form after acidic activation and a cross-class inhibition by pepstatin. A more elucidative picture of the molecular mechanism of digestion in a scorpion was proposed based on our results from Tityus serrulatus. The midgut and midgut glands (MMG) are composed by secretory and digestive cells. In fasting animals, the secretory granules are ready for the next predation event, containing enzymes needed for alkaline extra-oral digestion which will compose the digestive fluid, such as trypsins, astacins and chitinase. The digestive vacuoles are filled with an acidic proteolytic cocktail to the intracellular digestion composed by cathepsins L, B, F, D and legumain. Other proteins as lipases, carbohydrases, ctenitoxins and a chitolectin with a perithrophin domain were also detected. Evolutionarily

  5. Biochemical, transcriptomic and proteomic analyses of digestion in the scorpion Tityus serrulatus: insights into function and evolution of digestion in an ancient arthropod.

    PubMed

    Fuzita, Felipe J; Pinkse, Martijn W H; Patane, José S L; Juliano, Maria A; Verhaert, Peter D E M; Lopes, Adriana R

    2015-01-01

    Scorpions are among the oldest terrestrial arthropods and they have passed through small morphological changes during their evolutionary history on land. They are efficient predators capable of capturing and consuming large preys and due to envenomation these animals can become a human health challenge. Understanding the physiology of scorpions can not only lead to evolutionary insights but also is a crucial step in the development of control strategies. However, the digestive process in scorpions has been scarcely studied. In this work, we describe the combinatory use of next generation sequencing, proteomic analysis and biochemical assays in order to investigate the digestive process in the yellow scorpion Tityus serrulatus, mainly focusing in the initial protein digestion. The transcriptome generated database allowed the quantitative identification by mass spectrometry of different enzymes and proteins involved in digestion. All the results suggested that cysteine cathepsins play an important role in protein digestion. Two digestive cysteine cathepsins were isolated and characterized presenting acidic characteristics (pH optima and stability), zymogen conversion to the mature form after acidic activation and a cross-class inhibition by pepstatin. A more elucidative picture of the molecular mechanism of digestion in a scorpion was proposed based on our results from Tityus serrulatus. The midgut and midgut glands (MMG) are composed by secretory and digestive cells. In fasting animals, the secretory granules are ready for the next predation event, containing enzymes needed for alkaline extra-oral digestion which will compose the digestive fluid, such as trypsins, astacins and chitinase. The digestive vacuoles are filled with an acidic proteolytic cocktail to the intracellular digestion composed by cathepsins L, B, F, D and legumain. Other proteins as lipases, carbohydrases, ctenitoxins and a chitolectin with a perithrophin domain were also detected. Evolutionarily

  6. Acute cerebellar dysfunction with neuromuscular manifestations after scorpionism presumably caused by Tityus obscurus in Santarém, Pará / Brazil.

    PubMed

    Torrez, Pasesa P Q; Quiroga, Mariana M M; Abati, Paulo A M; Mascheretti, Melissa; Costa, Walter Silva; Campos, Luciana P; França, Francisco O S

    2015-03-01

    Scorpionism is a public health problem in many tropical countries, especially in North Africa, South India, Latin America and the Middle East. In Brazil, patients with severe scorpion envenoming have mainly cardiovascular events, including acute heart failure, acute respiratory distress syndrome and shock, death is rare. We described 58 accidents presumably caused by Tityus obscurus in Brazilian Amazonia. Patients reported a sensation of "electric shocks" which could last hours. The vast majority of patients presented a clinical picture compatible with acute cerebellar dysfunction, beginning minutes and lasting up to 2 days after the accident. They presented cerebellar ataxia, dysdiadochokinesia, dysmetry, dysarthria, dyslalia, nausea and vomiting. Besides, some patients presented myoclonus and fasciculation which can also be attributed to cerebellar dysfunction or maybe the result of direct action on skeletal muscle. Two patients had evidence of intense rhabdomyolysis and acute kidney injury. The clinical picture in this scorpion envenoming is mainly characterized by an acute dysfunction of cerebellar activities and abnormal neuromuscular manifestations and in some cases muscle injury which are not described in any other region of the world. This work presents clinical, epidemiologic, laboratory and treatment aspects of this unmatched scorpion envenoming in the state of Pará, northern Brazil. PMID:25549940

  7. Cytogenetic analysis on geographically distant parthenogenetic populations of Tityus trivittatus Kraepelin, 1898 (Scorpiones, Buthidae): karyotype, constitutive heterochromatin and rDNA localization

    PubMed Central

    Adilardi, Renzo Sebastián; Affilastro, Andrés Alejandro Ojanguren; Martí, Dardo Andrea; Mola, Liliana María

    2014-01-01

    Abstract Tityus trivittatus Kraepelin, 1898 is the most medically important scorpion species of Argentina, and parthenogenetic populations are present in the major cities of this country. We performed a detailed cytogenetic analysis of specimens of three synanthropic parthenogenetic populations, all distant about 900 km from each other, using Ag-NOR, C-banding, DAPI/CMA3 staining and FISH with autologous 28S rDNA probes. The karyotype of females and embryos from the three populations showed 2n=6, with two large and four middle-sized holokinetic chromosomes. Constitutive heterochromatin was found in terminal and interstitial location and its pattern allowed the identification of three chromosome pairs. NORs were found on the terminal heterochromatic region of one pair of middle-sized chromosomes. The use of fluorochromes to characterize heterochromatin showed the absence of GC-rich heterochromatin and a low and variable number of AT-rich heterochromatic regions. We propose that a possible explanation for the lack of karyotypic variation between these geographically distant populations could be a recent colonization of urban areas by human means of synanthropic specimens from a single lineage of northeastern Argentina. PMID:25147621

  8. Revealing the Function and the Structural Model of Ts4: Insights into the "Non-Toxic" Toxin from Tityus serrulatus Venom.

    PubMed

    Pucca, Manuela B; Cerni, Felipe A; Peigneur, Steve; Bordon, Karla C F; Tytgat, Jan; Arantes, Eliane C

    2015-07-01

    The toxin, previously described as a "non-toxic" toxin, was isolated from the scorpion venom of Tityus serrulatus (Ts), responsible for the most severe and the highest number of accidents in Brazil. In this study, the subtype specificity and selectivity of Ts4 was investigated using six mammalian Nav channels (Nav1.2→Nav1.6 and Nav1.8) and two insect Nav channels (DmNav1 and BgNav). The electrophysiological assays showed that Ts4 specifically inhibited the fast inactivation of Nav1.6 channels, the most abundant sodium channel expressed in the adult central nervous system, and can no longer be classified as a "non-toxic peptide". Based on the results, we could classify the Ts4 as a classical α-toxin. The Ts4 3D-structural model was built based on the solved X-ray Ts1 3D-structure, the major toxin from Ts venom with which it shares high sequence identity (65.57%). The Ts4 model revealed a flattened triangular shape constituted by three-stranded antiparallel β-sheet and one α-helix stabilized by four disulfide bonds. The absence of a Lys in the first amino acid residue of the N-terminal of Ts4 is probably the main responsible for its low toxicity. Other key amino acid residues important to the toxicity of α- and β-toxins are discussed here. PMID:26153865

  9. Electrophysiological characterization of the first Tityus serrulatus alpha-like toxin, Ts5: Evidence of a pro-inflammatory toxin on macrophages.

    PubMed

    Pucca, Manuela B; Peigneur, Steve; Cologna, Camila T; Cerni, Felipe A; Zoccal, Karina F; Bordon, Karla de C F; Faccioli, Lucia H; Tytgat, Jan; Arantes, Eliane C

    2015-08-01

    Tityus serrulatus (Ts) venom is composed of mainly neurotoxins specific for voltage-gated K(+) and Na(+) channels, which are expressed in many cells such as macrophages. Macrophages are the first line of defense invasion and they participate in the inflammatory response of Ts envenoming. However, little is known about the effect of Ts toxins on macrophage activation. This study investigated the effect of Ts5 toxin on different sodium channels as well as its role on the macrophage immunomodulation. The electrophysiological assays showed that Ts5 inhibits the rapid inactivation of the mammalian sodium channels Nav1.2, Nav1.3, Nav1.4, Nav1.5, Nav1.6 and Nav1.7. Interestingly, Ts5 also inhibits the inactivation of the insect Drosophila melanogaster sodium channel (DmNav1), and it is therefore classified as the first Ts α-like toxin. The immunological experiments on macrophages reveal that Ts5 is a pro-inflammatory toxin inducing the cytokine production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. On the basis of recent literature, our study also stresses a possible mechanism responsible for venom-associated molecular patterns (VAMPs) internalization and macrophage activation and moreover we suggest two main pathways of VAMPs signaling: direct and indirect. This work provides useful insights for a better understanding of the involvement of VAMPs in macrophage modulation. PMID:25906692

  10. Influence of post-starvation extraction time and prey-specific diet in Tityus serrulatus scorpion venom composition and hyaluronidase activity.

    PubMed

    Pucca, Manuela Berto; Amorim, Fernanda Gobbi; Cerni, Felipe Augusto; Bordon, Karla de Castro Figueiredo; Cardoso, Iara Aimê; Anjolette, Fernando Antonio Pino; Arantes, Eliane Candiani

    2014-11-01

    The role of diet in venom composition has been a topic of intense research interest. This work presents evidence that the variation in the venom composition from the scorpion Tityus serrulatus (Ts) is closely associated with post-starvation extraction time and prey-specific diet. The scorpions were fed with cockroach, cricket, peanut beetle or giant Tenebrio. The venoms demonstrated a pronounced difference in the total protein and toxins composition, which was evaluated by electrophoresis, reversed-phase chromatography, densitometry, hyaluronidase activity and N-terminal sequencing. Indeed, many toxins and peptides, such as Ts1, Ts2, Ts4, Ts5, Ts6, Ts15, Ts19 frag. II, hypotensins 1 and 3, PAPE peptide and peptide 9797 (first described in Ts venom), were all identified in different proportions in the analyzed Ts venoms. This study is pioneer on assessing the influence of the starvation time and the prey diet on hyaluronidase activity as well as to describe a modification of Tricine-gel-electrophoresis to evaluate this enzyme activity. Altogether, this study reveal a large contribution of the extraction time and diet on Ts venom variability as well as present a background to recommend the cockroach diet to obtain higher protein content and the cricket diet to obtain higher hyaluronidase specific activity. PMID:25199494

  11. TLR2, TLR4 and CD14 Recognize Venom-Associated Molecular Patterns from Tityus serrulatus to Induce Macrophage-Derived Inflammatory Mediators

    PubMed Central

    Zoccal, Karina Furlani; Bitencourt, Claudia da Silva; Paula-Silva, Francisco Wanderley Garcia; Sorgi, Carlos Artério; de Castro Figueiredo Bordon, Karla; Arantes, Eliane Candiani; Faccioli, Lúcia Helena

    2014-01-01

    Scorpion sting-induced human envenomation provokes an intense inflammatory reaction. However, the mechanisms behind the recognition of scorpion venom and the induction of mediator release in mammalian cells are unknown. We demonstrated that TLR2, TLR4 and CD14 receptors sense Tityus serrulatus venom (TsV) and its major component, toxin 1 (Ts1), to mediate cytokine and lipid mediator production. Additionally, we demonstrated that TsV induces TLR2- and TLR4/MyD88-dependent NF-κB activation and TLR4-dependent and TLR2/MyD88-independent c-Jun activation. Similar to TsV, Ts1 induces MyD88-dependent NF-κB phosphorylation via TLR2 and TLR4 receptors, while c-Jun activation is dependent on neither TLR2 nor TLR4/MyD88. Therefore, we propose the term venom-associated molecular pattern (VAMP) to refer to molecules that are introduced into the host by stings and are recognized by PRRs, resulting in inflammation. PMID:24516606

  12. Role of IgG(T) and IgGa isotypes obtained from arachnidic antivenom to neutralize toxic activities of Loxosceles gaucho, Phoneutria nigriventer and Tityus serrulatus venoms.

    PubMed

    Toro, Ana Flávia; Malta, Marília Brinati; Soares, Sabrina Lucio; Da Rocha, Guilherme Casoni; da Silva Lira, Marcela; De Oliveira, Thais Abbate; Takehara, Harumi Ando; Lopes-Ferreira, Mônica; Santoro, Marcelo Larami; Guidolin, Rosalvo; Gondo Higashi, Hisako; Fernandes, Irene; Barbaro, Katia Cristina

    2006-11-01

    The ability of IgG(T) and IgGa subclasses--isolated by liquid chromatography from equine arachnidic antivenom (AAV)-to neutralize toxic activities of Loxosceles gaucho, Phoneutria nigriventer and Tityus serrulatus venoms as well as to remove venom toxins from circulation was investigated. These subclasses showed similar antibody titers against L. gaucho, P. nigriventer and T. serrulatus venoms, and by immunoblotting few differences were observed in the recognition pattern of venom antigens. IgG(T) and IgGa neutralized 100% lethality induced by L. gaucho and 50% of P. nigriventer venom, but IgGa failed to neutralize T. serrulatus venom, in contrast to IgG(T). Both subclasses neutralized local reactions and dermonecrosis induced by L. gaucho venom in rabbits. In mice, IgG(T) and IgGa partially neutralized the edematogenic activity induced by P. nigriventer and T. serrulatus venoms, but only IgG(T) neutralized (ca. 81%) the nociceptive activity induced by T. serrulatus venom. Both subclasses failed to neutralize nociceptive activity induced by P. nigriventer venom. IgG(T) reduced the serum venom levels of animals injected with L. gaucho, P. nigriventer or T. serrulatus venoms, while IgGa solely reduced L. gaucho and P. nigriventer venoms levels. Our results demostrate that IgG(T) and IgGa subclasses neutralize toxic activities induced by P. nigriventer, T. serrulatus and L. gaucho venoms with different efficacies, as well as depurate these venoms from circulation. PMID:16979205

  13. Biochemical and physiological characterization of a new Na(+)-channel specific peptide from the venom of the Argentinean scorpion Tityus trivittatus.

    PubMed

    Coronas, Fredy I V; Diego-García, Elia; Restano-Cassulini, Rita; de Roodt, Adolfo R; Possani, Lourival D

    2015-06-01

    A new peptide with 61 amino acids cross-linked by 4 disulfide bridges, with molecular weight of 6938.12Da, and an amidated C-terminal amino acid residue was purified and characterized. The primary structure was obtained by direct Edman degradation and sequencing its gene. The peptide is lethal to mammals and was shown to be similar (95% identity) to toxin Ts1 (gamma toxin) from the Brazilian scorpion Tityus serrulatus; it was named Tt1g (from T. trivittatus toxin 1 gamma-like). Tt1g was assayed on several sub-types of Na(+)-channels showing displacement of the currents to more negative voltages, being the hNav1.3 the most affected channel. This toxin displays characteristics typical to the β-type sodium scorpion toxins. Lethality tests and physiological assays indicate that this peptide is probably the most important toxic component of this species of scorpion, known for causing human fatalities in the South American continent. PMID:24862827

  14. Individual variability in Tityus serrulatus (Scorpiones, Buthidae) venom elicited by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

    PubMed

    Pimenta, Adriano M C; De Marco Almeida, Flavia; de Lima, Maria Elena; Martin-Eauclaire, Marie France; Bougis, Pierre E

    2003-01-01

    Venom variability in specimens of Tityus serrulatus scorpion was assessed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) analyses. An expanded time lag venom extraction protocol was carried out using ten scorpions to study individual variations that might occur due to different rates in protein expression and/or processing. The first extraction of venom was made from the animals after 20 days of starvation, which allowed the venom gland to be filled up. The second extraction event was carried out 24 hours after the first one. The third was 8 days after the first extraction. By means of MALDI-TOF analyses, important variations were observed in venoms of a single specimen extracted at different times, especially in latter extraction events. These variations are most probably related to dynamics in cell gland production. Since T. serrulatus is a parthenogenetic species, sexual variations are naturally excluded and we did not expect intra-specific variations, which was confirmed. Knowledge of individual venom variability is extremely important to avoid misunderstandings in the use of venom proteomic analysis as a taxonomic tool. PMID:12590389

  15. Standardization of an enzyme linked immunosorbent assay (ELISA) for detecting circulating toxic venom antigens in patients stung by the scorpion Tityus serrulatus.

    PubMed

    de Rezende, N A; Dias, M B; Campolina, D; Chavéz-Olortegui, C; Amaral, C F

    1995-01-01

    The sensitivity and specificity of an enzyme-linked immunosorbent assay (ELISA) for the detection of circulating antigens from toxic components of Tityus serrulatus scorpion venom was determined in patients stung by T. serrulatus before antivenom administration. Thirty-seven patients were classified as mild cases and 19 as moderate or severe cases. The control absorbance in the venom assay was provided by serum samples from 100 individuals of same socioeconomic group and geographical area who had never been stung by scorpions or treated with horse antisera. The negative cutoff value (mean + 2 SD) corresponded to a venom concentration of 4.8 ng/ml. Three out of the 100 normal sera were positive, resulting in a specificity of 97%. The sensitivity of the ELISA when all cases of scorpion sting were included was 39.3%. When mild cases were excluded, the sensitivity increased to 94.7%. This study showed that this ELISA can be used for the detection of circulating venom toxic antigens in patients with systemic manifestations following. T. serrulatus sting but cannot be used for clinical studies in mild cases of envenoming since the test does not discriminate mild cases from control patients. PMID:7569644

  16. Evidence for a role of capsaicin-sensitive sensory nerves in the lung oedema induced by Tityus serrulatus venom in rats.

    PubMed

    Andrade, Marcus V M; Souza, Danielle G; de A Castro, Maria Salete; Cunha-Melo, José R; Teixeira, Mauro M

    2002-03-01

    In the most severe cases of human envenoming by Tityus serrulatus, pulmonary oedema is a frequent finding and can be the cause of death. We have previously demonstrated a role for neuropeptides acting on tachykinin NK(1) receptors in the development of lung oedema following i.v. injection of T. serrulatus venom (TsV) in experimental animals. The present work was designed to investigate whether capsaicin-sensitive primary afferent neurons were a potential source of NK(1)-acting neuropeptides. To this end, sensory nerves were depleted of neuropeptides by neonatal treatment of rats with capsaicin. The effectiveness of this strategy at depleting sensory nerves was demonstrated by the inhibition of the neuropeptide-dependent response to intraplantar injection of formalin. Pulmonary oedema, as assessed by the levels of extravasation of Evans blue dye in the bronchoalveolar lavage and in the left lung, was markedly inhibited in capsaicin-treated animals. In contrast, capsaicin treatment failed to alter the increase in arterial blood pressure or the lethality following i.v. injection of TsV. Our results demonstrate an important role for capsaicin-sensitive sensory nerves in the cascade of events leading to lung injury following the i.v. administration of TsV. PMID:11711125

  17. Revealing the Function and the Structural Model of Ts4: Insights into the “Non-Toxic” Toxin from Tityus serrulatus Venom

    PubMed Central

    Pucca, Manuela B.; Cerni, Felipe A.; Peigneur, Steve; Bordon, Karla C. F.; Tytgat, Jan; Arantes, Eliane C.

    2015-01-01

    The toxin, previously described as a “non-toxic” toxin, was isolated from the scorpion venom of Tityus serrulatus (Ts), responsible for the most severe and the highest number of accidents in Brazil. In this study, the subtype specificity and selectivity of Ts4 was investigated using six mammalian Nav channels (Nav1.2→Nav1.6 and Nav1.8) and two insect Nav channels (DmNav1 and BgNav). The electrophysiological assays showed that Ts4 specifically inhibited the fast inactivation of Nav1.6 channels, the most abundant sodium channel expressed in the adult central nervous system, and can no longer be classified as a “non-toxic peptide”. Based on the results, we could classify the Ts4 as a classical α-toxin. The Ts4 3D-structural model was built based on the solved X-ray Ts1 3D-structure, the major toxin from Ts venom with which it shares high sequence identity (65.57%). The Ts4 model revealed a flattened triangular shape constituted by three-stranded antiparallel β-sheet and one α-helix stabilized by four disulfide bonds. The absence of a Lys in the first amino acid residue of the N-terminal of Ts4 is probably the main responsible for its low toxicity. Other key amino acid residues important to the toxicity of α- and β-toxins are discussed here. PMID:26153865

  18. Molecular basis for the cross-reactivity of antibodies elicited by a natural anatoxin with alpha- and beta-toxins from the venom of Tityus serrulatus scorpion.

    PubMed

    Chavez-Olortegui, Carlos; Molina, Franck; Granier, Claude

    2002-03-01

    A non-toxic protein (TsNTxP) isolated from the venom of the noxious scorpion Tityus serrulatus (Ts) induces polyclonal antibodies cross-reactive with several toxins from the venom, in sharp contrast to anti-toxin antibodies which are toxin specific. To try to uncover the molecular basis for these unusual properties, peptide scanning experiments were performed and indicated that the N- and C-terminal parts of TsNTxP enclose continuous epitopes (residues 1-15 and 47-61). Antibodies raised against peptides corresponding to these two regions were found to have neutralizing properties against a mixture of all toxic proteins from the T. serrulatus venom, indicating that residues 1-15 and 47-61 correspond to neutralizing epitopes. The identification of key antigenic residues within these two epitopes revealed that several of them are well conserved in the amino-acid sequences of the three main toxins (Ts II, Ts IV and Ts VII) from the venom: Glu 3, Tyr 5, Asp 8, Asp 50, Trp 55 and Lys 61. A single key-residue (Glu 58) is unique to TsNTxP. By using homology modeling, a model of the three-dimensional structure of TsNTxP was obtained. The antigenically important residues from TsNTxP were found to be surface exposed, with five of them clustered on the facet of the protein reported to enclose the active site of toxins. Residues equivalent to the seven key-residues of the anatoxin were also found to be exposed in the active toxins from T. serrulatus venom. These results show that antibodies elicited by the non-toxic protein TsNTxP recognized, within the N- and C-terminal parts of toxins of T. serrulatus, conserved and surface exposed residues which might also be involved in the toxic action of the proteins. PMID:11922945

  19. Isolation, homology modeling and renal effects of a C-type natriuretic peptide from the venom of the Brazilian yellow scorpion (Tityus serrulatus).

    PubMed

    Alves, Renata S; Ximenes, Rafael M; Jorge, Antonio R C; Nascimento, Nilberto R F; Martins, René D; Rabello, Marcelo M; Hernandes, Marcelo Z; Toyama, Daniela O; Toyama, Marcos H; Martins, Alice M C; Havt, Alexandre; Monteiro, Helena S A

    2013-11-01

    Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated. Fractionation of Tityus serrulatus venom using chromatographic techniques yielded a peptide with a molecular mass of 2190.64 Da, which exhibited the pattern of disulfide bridges that is characteristic of a C-type NP (TsNP, T. serrulatus Natriuretic Peptide). In the isolated perfused rat kidney assay, treatment with two concentrations of TsNP (0.03 and 0.1 μg/mL) increased the perfusion pressure, glomerular filtration rate and urinary flow. After 60 min of treatment at both concentrations, the percentages of sodium, potassium and chloride transport were decreased, and the urinary cGMP concentration was elevated. Natriuretic peptide receptor-A (NPR-A) mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP, whereas NPR-B, NPR-C and CG-C mRNAs were up regulated at the 0.1 μg/mL concentration. In conclusion, this work describes the isolation and modeling of the first natriuretic peptide isolated from scorpion venom. In addition, examinations of the renal actions of TsNP indicate that its effects may be related to the activation of NPR-B, NPR-C and GC-C. PMID:23911732

  20. Another record of significant regional variation in toxicity of Tityus serrulatus venom in Brazil: a step towards understanding the possible role of sodium channel modulators.

    PubMed

    Oliveira, Fagner Neves; Mortari, Márcia Renata; Carneiro, Fabiana Pirani; Guerrero-Vargas, Jimmy Alexander; Santos, Daniel M; Pimenta, Adriano M C; Schwartz, Elisabeth F

    2013-10-01

    The scorpion Tityus serrulatus is responsible for the most severe accidents that have been registered in Brazil, mainly in the state of Minas Gerais (MG), being the lung edema (LE), the main cause of death in these accidents. Although an increased in the number of accidents caused to this species in Federal District (Distrito Federal - DF), it seems that this particular species is not responsible for severe scorpionism cases in this region. Given this observation, we tested the toxicity in mice and compared the ability of T. serrulatus venom from DF (Ts-DF) and Minas Gerais State (Ts-MG) to induce LE in rats. The LD50 of Ts-DF venom was 51.6 μg/mouse, almost twice (1.98) higher than that obtained for Ts-MG venom. The ability of venom (0.5 mg/kg) to induce LE in rats was determined by the wet weight differences between treated and untreated lungs, by pulmonary morphological analyses and by pulmonary vascular permeability (PVP) using the Evans blue protocol. Significant differences in the wet weight of lungs and changes in PVP were found in Ts-MG venom treated rats when compared to rats treated with Ts-DF venom or untreated rats (p < 0.001), but no differences occurred when comparing rats treated with Ts-DF venom and untreated rats (p < 0.05). These results were confirmed by evaluation of pulmonary morphology. Comparison of chromatographic profiles obtained from these venoms (Ts-DF and Ts-MG) using the fractal dimension (D) analysis and the molecular mass fingerprint of the chromatographic fractions showed a higher number of components between 35 and 40% acetonitrile in Ts-MG venom than in Ts-DF venom, indicating a higher diversity of sodium channel modulators in that venom. PMID:23851224

  1. Immunosuppressive evidence of Tityus serrulatus toxins Ts6 and Ts15: insights of a novel K(+) channel pattern in T cells.

    PubMed

    Pucca, Manuela B; Bertolini, Thaís B; Cerni, Felipe A; Bordon, Karla C F; Peigneur, Steve; Tytgat, Jan; Bonato, Vânia L; Arantes, Eliane C

    2016-02-01

    The voltage-gated potassium channel Kv1.3 is a novel target for immunomodulation of autoreactive effector memory T cells, which play a major role in the pathogenesis of autoimmune diseases. In this study, the Ts6 and Ts15 toxins isolated from Tityus serrulatus (Ts) were investigated for their immunosuppressant roles on CD4(+) cell subsets: naive, effector (TEF ), central memory (TCM) and effector memory (TEM). The electrophysiological assays confirmed that both toxins were able to block Kv1.3 channels. Interestingly, an extended Kv channel screening shows that Ts15 blocks Kv2.1 channels. Ts6 and Ts15 significantly inhibit the proliferation of TEM cells and interferon-γ production; however, Ts15 also inhibits other CD4(+) cell subsets (naive, TEF and TCM). Based on the Ts15 inhibitory effect of proliferation of all CD4(+) cell subsets, and based on its blocking effect on Kv2.1, we investigated the Kv2.1 expression in T cells. The assays showed that CD4(+) and CD8(+) cells express the Kv2.1 channels mainly extracellularly with TCM cells expressing the highest number of Kv2.1 channels. We also provide in vivo experimental evidence to the protective effect of Ts6 and Ts15 on delayed-type hypersensitivity reaction. Altogether, this study presents the immunosuppressive behaviour of Ts6 and Ts15 toxins, indicating that these toxins could be promising candidates for autoimmune disease therapy. Moreover, this is the first report illustrating the involvement of a novel K(+) channel subtype, Kv2.1, and its distribution in T-cell subsets. PMID:26595158

  2. Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities.

    PubMed

    Guo, Xiaoxiao; Ma, Chengbang; Du, Qiang; Wei, Ran; Wang, Lei; Zhou, Mei; Chen, Tianbao; Shaw, Chris

    2013-09-01

    Here we report two novel 17-mer amidated linear peptides (TsAP-1 and TsAP-2) whose structures were deduced from cDNAs cloned from a venom-derived cDNA library of the Brazilian yellow scorpion, Tityus serrulatus. Both mature peptides were structurally-characterised following their location in chromatographic fractions of venom and synthetic replicates of each were subjected to a range of biological assays. The peptides were each active against model test micro-organisms but with different potencies. TsAP-1 was of low potency against all three test organisms (MICs 120-160 μM), whereas TsAP-2 was of high potency against the Gram-positive bacterium, Staphylococcus aureus (MIC 5 μM) and the yeast, Candida albicans (10 μM). Haemolytic activity of TsAP-1 was low (4% at 160 μM) and in contrast, that of TsAP-2 was considerably higher (18% at 20 μM). Substitution of four neutral amino acid residues with Lys residues in each peptide had dramatic effects on their antimicrobial potencies and haemolytic activities, particularly those of TsAP-1. The MICs of the enhanced cationic analogue (TsAP-S1) were 2.5 μM for S. aureus/C. albicans and 5 μM for E. coli but with an associated large increase in haemolytic activity (30% at 5 μM). The same Lys residue substitutions in TsAP-2 produced a dramatic effect on its MIC for E. coli lowering this from >320 μM to 5 μM. TsAP-1 was ineffective against three of the five human cancer cell lines tested while TsAP-2 inhibited the growth of all five. Lys residue substitution of both peptides enhanced their potency against all five cell lines with TsAp-S2 being the most potent with IC50 values ranging between 0.83 and 2.0 μM. TsAP-1 and TsAP-2 are novel scorpion venom peptides with broad spectrum antimicrobial and anticancer cell activities the potencies of which can be significantly enhanced by increasing their cationicity. PMID:23770440

  3. Portable exhausters POR-004 SKID B, POR-005 SKID C, POR-006 SKID D storage plan

    SciTech Connect

    Nelson, O.D.

    1997-09-04

    This document provides a storage plan for portable exhausters POR-004 SKID B, POR-005 SKID C, AND POR-006 SKID D. The exhausters will be stored until they are needed by the TWRS (Tank Waste Remediation Systems) Saltwell Pumping Program. The storage plan provides criteria for portable exhauster storage, periodic inspections during storage, and retrieval from storage.

  4. Estimation of age from stained sections of canine teeth in the Cape fur seal (Arctocephalus pusillus pusillus).

    PubMed

    Oosthuizen, W H; Greyling, F J; Bester, M N

    1998-02-01

    Methods of cutting and staining thin sections of Cape fur seal canines are described. The accuracy of age determination from the histology of the prepared sections and the suitability of the sectioning method is assessed. Known-age canines were used to validate age determination. Longitudinal sections along the midline enable growth layer groups (GLGs) in the dentine to be counted along the length of the canine root. GLGs in the cementum were either absent, or returned estimates of age that were too low. Only GLGs in the dentine of female upper canines could be used to determine age reliably, and only for the < 10 year age-classes. PMID:9722409

  5. Evolution of NADPH-cytochrome P450 oxidoreductases (POR) in Apiales - POR 1 is missing.

    PubMed

    Andersen, Trine Bundgaard; Hansen, Niels Bjørn; Laursen, Tomas; Weitzel, Corinna; Simonsen, Henrik Toft

    2016-05-01

    The NADPH-dependent cytochrome P450 oxidoreductase (POR) is the obligate electron donor to eukaryotic microsomal cytochromes P450 enzymes. The number of PORs within plant species is limited to one to four isoforms, with the most common being two PORs per plant. These enzymes provide electrons to a huge number of different cytochromes P450s (from 50 to several hundred within one plant). Within the eudicotyledons, PORs can be divided into two major clades, POR 1 and POR 2. Based on our own sequencing analysis and publicly available data, we have identified 45 PORs from the angiosperm order Apiales. These were subjected to a phylogenetic analysis along with 237 other publicly available (NCBI and oneKP) POR sequences found within the clade Asterids. Here, we show that the order Apiales only harbor members of the POR 2 clade, which are further divided into two distinct subclades. This is in contrast to most other eudicotyledon orders that have both POR 1 and POR 2. This suggests that through gene duplications and one gene deletion, Apiales only contain members of the POR 2 clade. Three POR 2 isoforms from Thapsia garganica L., Apiaceae, were all full-length in an Illumina root transcriptome dataset (available from the SRA at NCBI). All three genes were shown to be functional upon reconstitution into nanodiscs, confirming that none of the isoforms are pseudogenes. PMID:26854662

  6. Portable exhauster POR-007/Skid E and POR-008/Skid F storage plan

    SciTech Connect

    Nelson, O.D.

    1998-07-25

    This document provides storage requirements for 1,000 CFM portable exhausters POR-O07/Skid E and POR-008/Skid F. These requirements are presented in three parts: preparation for storage, storage maintenance and testing, and retrieval from storage. The exhauster component identification numbers listed in this document contain the prefix POR-007 or POR-008 depending on which exhauster is being used.

  7. Consequences of POR mutations and polymorphisms.

    PubMed

    Miller, Walter L; Agrawal, Vishal; Sandee, Duanpen; Tee, Meng Kian; Huang, Ningwu; Choi, Ji Ha; Morrissey, Kari; Giacomini, Kathleen M

    2011-04-10

    P450 oxidoreductase (POR) transports electrons from NADPH to all microsomal cytochrome P450 enzymes, including steroidogenic P450c17, P450c21 and P450aro. Severe POR mutations A287P (in Europeans) and R457H (in Japanese) cause the Antley-Bixler skeletal malformation syndrome (ABS) plus impaired steroidogenesis (causing genital anomalies), but the basis of ABS is unclear. We have characterized the activities of ∼40 POR variants, showing that assays based on P450c17 activities, but not cytochrome c assays, correlate with the clinical phenotype. The human POR gene is highly polymorphic: the A503V sequence variant, which decreases P450c17 activities to ∼60%, is found on ∼28% of human alleles. A promoter polymorphism (∼8% of Asians and ∼13% of Caucasians) at -152 reduces transcriptional activity by half. Screening of 35 POR variants showed that most mutants lacking activity with P450c17 or cytochrome c also lacked activity to support CYP1A2 and CYP2C19 metabolism of EOMCC (a fluorogenic non-drug substrate), although there were some remarkable differences: Q153R causes ABS and has ∼30% of wild-type activity with P450c17 but had 144% of WT activity with CYP1A2 and 284% with CYP2C19. The effects of POR variants on CYP3A4, which metabolizes nearly 50% of clinically used drugs, was examined with multiple, clinically relevant drug substrates, showing that A287P and R457H dramatically reduce drug metabolism, and that A503V variably impairs drug metabolism. The degree of activity can vary with the drug substrate assayed, as the drugs can influence the conformation of the P450. POR is probably an important contributor to genetic variation in both steroidogenesis and drug metabolism. PMID:21070833

  8. Consequences of POR mutations and polymorphisms

    PubMed Central

    Miller, Walter L.; Agrawal, Vishal; Sandee, Duanpen; Tee, Meng Kian; Huang, Ningwu; Choi, Ji Ha; Morrissey, Kari; Giacomini, Kathleen M.

    2015-01-01

    P450 oxidoreductase (POR) transports electrons from NADPH to all microsomal cytochrome P450 enzymes, including steroidogenic P450c17, P450c21 and P450aro. Severe POR mutations A287P (in Europeans) and R457H (in Japanese) cause the Antley-Bixler skeletal malformation syndrome (ABS) plus impaired steroidogenesis (causing genital anomalies), but the basis of ABS is unclear. We have characterized the activities of ~40 POR variants, showing that assays based on P450c17 activities, but not cytochrome c assays, correlate with the clinical phenotype. The human POR gene is highly polymorphic: the A503V sequence variant, which decreases P450c17 activities to ~60%, is found on ~28% of human alleles. A promoter polymorphism (~8% of Asians and ~13% of Caucasians) at −152 reduces transcriptional activity by half. Screening of 35 POR variants showed that most mutants lacking activity with P450c17 or cytochrome c also lacked activity to support CYP1A2 and CYP2C19 metabolism of EOMCC (a fluorogenic non-drug substrate), although there were some remarkable differences: Q153R causes ABS and has ~30% of wild-type activity with P450c17 but had 144% of WT activity with CYP1A2 and 284% with CYP2C19. The effects of POR variants on CYP3A4, which metabolizes nearly 50% of clinically used drugs, was examined with multiple, clinically-relevant drug substrates, showing that A287P and R457H dramatically reduce drug metabolism, and that A503V variably impairs drug metabolism. The degree of activity can vary with the drug substrate assayed, as the drugs can influence the conformation of the P450. POR is probably an important contributor to genetic variation in both steroidogenesis and drug metabolism. PMID:21070833

  9. Desigualdades por cáncer

    Cancer.gov

    Información básica de las desigualdades en salud por cáncer en EE. UU., factores que contribuyen a la carga desproporcionada del cáncer en algunos grupos y ejemplos de desigualdades en incidencia y mortalidad entre ciertos grupos de la población.

  10. Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System

    PubMed Central

    Gorasia, Dhana G.; Veith, Paul D.; Hanssen, Eric G.; Glew, Michelle D.; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C.

    2016-01-01

    The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32–36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component. PMID:27509186

  11. Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System.

    PubMed

    Gorasia, Dhana G; Veith, Paul D; Hanssen, Eric G; Glew, Michelle D; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C

    2016-08-01

    The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32-36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component. PMID:27509186

  12. Gross and microscopic visceral anatomy of the male Cape fur seal, Arctocephalus pusillus pusillus (Pinnipedia: Otariidae), with reference to organ size and growth

    PubMed Central

    STEWARDSON, CAROLYN L.; HEMSLEY, SUSAN; MEYER, MIKE A.; CANFIELD, PAUL J.; MAINDONALD, JOHN H.

    1999-01-01

    The gross and microscopic anatomy of the Cape fur seal heart, lung, liver, spleen, stomach, intestine and kidneys (n = 31 seals) is described. Absolute and relative size of organs from 30 male seals are presented, with histological examination conducted on 7 animals. The relationship between log body weight, log organ weight and age was investigated using linear regression. Twenty five animals were of known age, while 6 were aged from counts of incremental lines observed in the dentine of tooth sections. For the range of ages represented in this study, body weight changes were accurately described by the exponential growth equation, weight = wort, with body weight increasing by 23% per annum until at least 9–10 y of age. Organ weight increased at a rate of between 25% and 33% per annum until at least 9–10 y of age, with the exception of the intestines, where exponential increase appeared to have ceased by about 7 y. The relationship between body weight and organ weight was investigated using logarithmic transformations of the allometric equation, y = axb, where the exponent b is 1 if organ weight is proportional to body weight. Most organs increased in proportion to the body. However, the heart, liver and spleen had exponents b > 1, suggesting that these organs increased at a faster rate than the body. The basic anatomical features of the viscera were similar to those of other pinnipeds, with some exceptions, including the arrangement of the multilobed lung and liver. Apart from the large liver and kidneys, relative size of the organs did not differ greatly from similar sized terrestrial carnivores. The histological features of the organs were generally consistent with those previously described for this species and other otariids. The heart, as in other pinnipeds, was unlike that of cetacea in not having unusually thick endocardium or prominent Purkinje cells. Notable histological features of the lungs included prominent fibrous septa, prominent smooth muscle bundles, cartilage extending to the level of the alveolar sacs and ample lymphoid tissue. The spleen had a thick capsule, well developed trabeculae and plentiful plasma cells. Abundant parietal cells were present in the fundic glands and lymphoid follicles were present in the gastric lamina propria, particularly in the pyloric region. Small intestinal villi were very long but this could have resulted from underlying chronic inflammation. Lymphoid follicles were prominent in the colon. The kidney reniculi each had a complete cortex, medulla and calyx, but a sportaperi medullaris musculosa was not identified. PMID:10529060

  13. The PorX Response Regulator of the Porphyromonas gingivalis PorXY Two-Component System Does Not Directly Regulate the Type IX Secretion Genes but Binds the PorL Subunit

    PubMed Central

    Vincent, Maxence S.; Durand, Eric; Cascales, Eric

    2016-01-01

    The Type IX secretion system (T9SS) is a versatile multi-protein complex restricted to bacteria of the Bacteriodetes phylum and responsible for the secretion or cell surface exposition of diverse proteins that participate to S-layer formation, gliding motility or pathogenesis. The T9SS is poorly characterized but a number of proteins involved in the assembly of the secretion apparatus in the oral pathogen Porphyromonas gingivalis have been identified based on genome substractive analyses. Among these proteins, PorY, and PorX encode typical two-component system (TCS) sensor and CheY-like response regulator respectively. Although the porX and porY genes do not localize at the same genetic locus, it has been proposed that PorXY form a bona fide TCS. Deletion of porX in P. gingivalis causes a slight decrease of the expression of a number of other T9SS genes, including sov, porT, porP, porK, porL, porM, porN, and porY. Here, we show that PorX and the soluble cytoplasmic domain of PorY interact. Using electrophoretic mobility shift, DNA-protein co-purification and heterologous host expression assays, we demonstrate that PorX does not bind T9SS gene promoters and does not directly regulate expression of the T9SS genes. Finally, we show that PorX interacts with the cytoplasmic domain of PorL, a component of the T9SS membrane core complex and propose that the CheY-like PorX protein might be involved in the dynamics of the T9SS.

  14. Temporal Allocation of Foraging Effort in Female Australian Fur Seals (Arctocephalus pusillus doriferus)

    PubMed Central

    Hoskins, Andrew J.; Arnould, John P. Y.

    2013-01-01

    Across an individual's life, foraging decisions will be affected by multiple intrinsic and extrinsic drivers that act at differing timescales. This study aimed to assess how female Australian fur seals allocated foraging effort and the behavioural changes used to achieve this at three temporal scales: within a day, across a foraging trip and across the final six months of the lactation period. Foraging effort peaked during daylight hours (57% of time diving) with lulls in activity just prior to and after daylight. Dive duration reduced across the day (196 s to 168 s) but this was compensated for by an increase in the vertical travel rate (1500–1600 m·h−1) and a reduction in postdive duration (111–90 s). This suggests physiological constraints (digestive costs) or prey availability may be limiting mean dive durations as a day progresses. During short trips (<2.9 d), effort remained steady at 55% of time diving, whereas, on long trips (>2.9 d) effort increased up to 2–3 d and then decreased. Dive duration decreased at the same rate in short and long trips, respectively, before stabilising (long trips) between 4–5 d. Suggesting that the same processes (digestive costs or prey availability) working at the daily scale may also be present across a trip. Across the lactation period, foraging effort, dive duration and vertical travel rate increased until August, before beginning to decrease. This suggests that as the nutritional demands of the suckling pup and developing foetus increase, female effort increases to accommodate this, providing insight into the potential constraints of maternal investment in this species. PMID:24244511

  15. Polychlorinated biphenyls and organochlorine pesticides in the Australian fur seal, Arctocephalus pusillus doriferus

    SciTech Connect

    Smillie, R.H.; Waid, J.S.

    1987-08-01

    Seals occupy a high trophic level in the marine ecosystem and have large reserves of subcutaneous fats. It is, therefore, not surprising that they accumulate high concentration of lipophilic substances such as organochlorine pesticides. Seal tissue concentration of pesticides are considered by some workers to be a good indication of local environmental loads. The Australian fur seals at Seal Rocks occupy a breading colony from which they can range into Bass Strait, Westernport Bay and Port Phillip Bay. It is, therefore, reasonable that results obtained for local seals should provide an indication of pesticides and PCBs in local squid and schooling fish. Previous results indicate that biota in Port Phillip Bay and Bass Strait, adjacent to the colony are exposed to elevated concentrations of PCBs. The authors have determined PCB and pesticide levels in local seals.

  16. Characteristics of marine debris that entangle Australian fur seals (Arctocephalus pusillus doriferus) in southern Australia.

    PubMed

    Lawson, T J; Wilcox, Chris; Johns, Karen; Dann, P; Hardesty, Britta Denise

    2015-09-15

    Marine debris is a global issue that can have devastating impacts on marine mammals. To understand the types of materials that result in entanglement and thus the potential impact of entangling items on marine wildlife, we analysed data collected from items in which Australian fur seals had been entangled in southern Victoria, Australia over a 15year period. From 1997 to 2012, 138 entangling items were removed from seals. The majority of these entanglements were plastic twine or rope, and seals were entangled in green items more than in any other colour. In general, younger seals were more likely to be entangled than adults. Understanding the effects of marine debris entanglement on the Australian fur seal population can lead to more effective management of the sources of debris and the wildlife that interact with it. PMID:26165938

  17. Production, Purification, and Characterization of Polygalacturonase from Rhizomucor pusillus Isolated from Decomposting Orange Peels

    PubMed Central

    Siddiqui, Mohd. Asif; Pande, Veena; Arif, Mohammad

    2012-01-01

    A thermophilic fungal strain producing polygalacturonase was isolated after primary screening of 40 different isolates. The fungus was identified as Rhizomucor pusilis by Microbial Type Culture Collection (MTCC), Chandigarh, India. An extracellular polygalacturonase (PGase) from R. pusilis was purified to homogeneity by two chromatographic steps using Sephadex G-200 and Sephacryl S-100. The purified enzyme was a monomer with a molecular weight of 32 kDa. The PGase was optimally active at 55°C and at pH 5.0. It was stable up to 50°C for 120 min of incubation and pH condition between 4.0 and 5.0. The stability of PGase decreases rapidly above 60°C and above pH 5.0. The apparent Km and Vmax values were 0.22 mg/mL and 4.34 U/mL, respectively. It was the first time that a polygalacturonase enzyme was purified in this species. It would be worthwhile to exploit this strain for polygalacturonase production. Polygalacturonase from this strain can be recommended for the commercial production because of its constitutive and less catabolically repressive nature, thermostability, wide range of pH, and lower Km properties. However, scale-up studies are needed for the better output for commercial production. PMID:23125919

  18. Identification of Porphyromonas gingivalis proteins secreted by the Por secretion system.

    PubMed

    Sato, Keiko; Yukitake, Hideharu; Narita, Yuka; Shoji, Mikio; Naito, Mariko; Nakayama, Koji

    2013-01-01

    The Gram-negative bacterium Porphyromonas gingivalis possesses a number of potential virulence factors for periodontopathogenicity. In particular, cysteine proteinases named gingipains are of interest given their abilities to degrade host proteins and process other virulence factors such as fimbriae. Gingipains are translocated on the cell surface or into the extracellular milieu by the Por secretion system (PorSS), which consists of a number of membrane or periplasmic proteins including PorK, PorL, PorM, PorN, PorO, PorP, PorQ, PorT, PorU, PorV (PG27, LptO), PorW and Sov. To identify proteins other than gingipains secreted by the PorSS, we compared the proteomes of P. gingivalis strains kgp rgpA rgpB (PorSS-proficient strain) and kgp rgpA rgpB porK (PorSS-deficient strain) using two-dimensional gel electrophoresis and peptide-mass fingerprinting. Sixteen spots representing 10 different proteins were present in the particle-free culture supernatant of the PorSS-proficient strain but were absent or faint in that of the PorSS-deficient strain. These identified proteins possessed the C-terminal domains (CTDs), which had been suggested to form the CTD protein family. These results indicate that the PorSS is used for secretion of a number of proteins other than gingipains and that the CTDs of the proteins are associated with the PorSS-dependent secretion. PMID:23075153

  19. System design description for portable 1,000 CFM exhauster Skids POR-007/Skid E and POR-008/Skid F

    SciTech Connect

    Nelson, O.D.

    1998-07-25

    The primary purpose of the two 1,000 CFM Exhauster Skids, POR-007-SKID E and POR-008-SKID F, is to provide backup to the waste tank primary ventilation systems for tanks 241-C-106 and 241-AY-102, and the AY-102 annulus in the event of a failure during the sluicing of tank 241-C-106 and subsequent transfer of sluiced waste to 241-AY-102. This redundancy is required since both of the tank ventilation systems have been declared as Safety Class systems.

  20. Disminuyen en los Estados Unidos las infecciones por VPH.

    Cancer.gov

    La infección por los tipos del virus del papiloma humano (VPH) en el blanco de la vacuna cuadrivalente se redujo en casi dos tercios en las adolescentes desde que se recomendó la vacunación en los Estados Unidos.

  1. Centros oncológicos designados por el NCI

    Cancer.gov

    El programa de centros oncológicos designados por el Instituto Nacional del Cáncer (NCI) reconoce a los centros de todo el país que cumplen con rigurosos criterios para participar en proyectos avanzados de primer nivel para la investigación multidisciplinaria del cáncer.

  2. Se evitaron casi 800 000 muertes por descenso del tabaquismo

    Cancer.gov

    Programas y estrategias de control del tabaco del siglo XX fueron responsables de la prevención de más de 795 000 muertes por cáncer de pulmón en Estados Unidos de 1975 al 2000. Si todo el tabaquismo en este país hubiera cesado después de la publicación d

  3. Neisseria meningitidis Lacking the Major Porins PorA and PorB Is Viable and Modulates Apoptosis and the Oxidative Burst of Neutrophils.

    PubMed

    Peak, Ian R; Chen, Adrienne; Jen, Freda E-C; Jennings, Courtney; Schulz, Benjamin L; Saunders, Nigel J; Khan, Arshad; Seifert, H Steven; Jennings, Michael P

    2016-08-01

    The bacterial pathogen Neisseria meningitidis expresses two major outer-membrane porins. PorA expression is subject to phase-variation (high frequency, random, on-off switching), and both PorA and PorB are antigenically variable between strains. PorA expression is variable and not correlated with meningococcal colonisation or invasive disease, whereas all naturally-occurring strains express PorB suggesting strong selection for expression. We have generated N. meningitidis strains lacking expression of both major porins, demonstrating that they are dispensable for bacterial growth in vitro. The porAB mutant strain has an exponential growth rate similar to the parental strain, as do the single porA or porB mutants, but the porAB mutant strain does not reach the same cell density in stationary phase. Proteomic analysis suggests that the double mutant strain exhibits compensatory expression changes in proteins associated with cellular redox state, energy/nutrient metabolism, and membrane stability. On solid media, there is obvious growth impairment that is rescued by addition of blood or serum from mammalian species, particularly heme. These porin mutants are not impaired in their capacity to inhibit both staurosporine-induced apoptosis and a phorbol 12-myristate 13-acetate-induced oxidative burst in human neutrophils suggesting that the porins are not the only bacterial factors that can modulate these processes in host cells. PMID:26562068

  4. Compton imaging with the PorGamRays spectrometer

    NASA Astrophysics Data System (ADS)

    Judson, D. S.; Boston, A. J.; Coleman-Smith, P. J.; Cullen, D. M.; Hardie, A.; Harkness, L. J.; Jones, L. L.; Jones, M.; Lazarus, I.; Nolan, P. J.; Pucknell, V.; Rigby, S. V.; Seller, P.; Scraggs, D. P.; Simpson, J.; Slee, M.; Sweeney, A.; PorGamRays Collaboration

    2011-10-01

    The PorGamRays project aims to develop a portable gamma-ray detection system with both spectroscopic and imaging capabilities. The system is designed around a stack of thin Cadmium Zinc Telluride (CZT) detectors. The imaging capability utilises the Compton camera principle. Each detector is segmented into 100 pixels which are read out through custom designed Application Specific Integrated Circuits (ASICs). This device has potential applications in the security, decommissioning and medical fields. This work focuses on the near-field imaging performance of a lab-based demonstrator consisting of two pixelated CZT detectors, each of which is bonded to a NUCAM II ASIC. Measurements have been made with point 133Ba and 57Co sources located ˜35 mm from the surface of the scattering detector. Position resolution of ˜20 mm FWHM in the x and y planes is demonstrated.

  5. Acceptance test report for portable exhauster POR-007/Skid E

    SciTech Connect

    Kriskovich, J.R.

    1998-07-24

    This document describes Acceptance Testing performed on Portable Exhauster POR-007/Skid E. It includes measurements of bearing vibration levels, pressure decay testing, programmable logic controller interlocks, high vacuum, flow and pressure control functional testing. The purpose of Acceptance testing documented by this report was to demonstrate compliance of the exhausters with the performance criteria established within HNF-0490, Rev. 1 following a repair and upgrade effort at Hanford. In addition, data obtained during this testing is required for the resolution of outstanding Non-conformance Reports (NCR), and finally, to demonstrate the functionality of the associated software for the pressure control and high vacuum exhauster operating modes provided for by W-320. Additional testing not required by the ATP was also performed to assist in the disposition and close out of receiving inspection report and for application design information (system curve). Results of this testing are also captured within this document.

  6. Typing and surface charges of the variable loop regions of PorB from Neisseria meningitidis.

    PubMed

    Stefanelli, Paola; Neri, Arianna; Tanabe, Mikio; Fazio, Cecilia; Massari, Paola

    2016-06-01

    PorB is a pan-Neisserial major outer membrane protein with a trimeric β-barrel structure. Each monomer presents eight periplasmic turns and eight surface exposed loop regions with sequence variability. PorB induces activation of host cell responses via a TLR2-dependent mechanism likely mediated by electrostatic interactions between TLR2 and PorB surface exposed loops. Variability in the loop amino acid sequence is known to influence cell responses to PorB in vitro, particularly for the residues in L5 and L7. In this work, the sequence of the porB gene and the electrostatic surface charges of PorB from 35 invasive meningococcal isolates belonging to the main clonal complexes identified in Italy and from five carriage genomes available on the website http://pubmlst.org/neisseria/ were examined. Analysis of the porB encoding regions from the invasive meningococci has identified four new alleles and a potential association between porB alleles, serogroup, and clonal complexes. Through computer-based modeling and analysis of the electrostatic surface charges of PorB from these strains, loop charge segregation between PorB from invasive serogroups B and C was observed. Specifically, loops 1, 4, and 7 were negatively charged and L2 and L8 were mostly neutral in serogroup B isolates, while an overall homogeneous positive surface charge was present in PorB from invasive serogroup C strains. A higher PorB sequence variability was observed among carriage genomes, and a general prevalence of negative loop surface charges. The surface charge differences in PorB from serogroups B and C invasive and carriage strains may, in part, influence the outcomes of Neisseriae interactions with host cells. © 2016 IUBMB Life, 68(6):488-495, 2016. PMID:27156582

  7. Acceptance test report for portable exhauster POR-008/Skid F

    SciTech Connect

    Kriskovich, J.R.

    1998-07-24

    Portable Exhauster POR-008 was procured via HNF-0490, Specification for a Portable Exhausted System for Waste Tank Ventilation. Prior to taking ownership, acceptance testing was performed at the vendors. However at the conclusion of testing a number of issues remained that required resolution before the exhausters could be used by Project W-320. The purpose of acceptance testing documented by this report was to demonstrate compliance of the exhausters with the performance criteria established within HNF-O49O, Rev. 1 following a repair and upgrade effort at Hanford. In addition, data obtained during this testing is required for the resolution of outstanding Non-conformance Reports (NCR), and finally, to demonstrate the functionality of the associated software for the pressure control and high vacuum exhauster operating modes provided for by W-320. Additional testing not required by the ATP was also performed to assist in the disposition and close out of receiving inspection report and for application design information (system curve). Results of this testing are also captured within this document.

  8. VDAC and the bacterial porin PorB of Neisseria gonorrhoeae share mitochondrial import pathways.

    PubMed

    Müller, Anne; Rassow, Joachim; Grimm, Jan; Machuy, Nikolaus; Meyer, Thomas F; Rudel, Thomas

    2002-04-15

    The human pathogen Neisseria gonorrhoeae induces host cell apoptosis during infection by delivering the outer membrane protein PorB to the host cell's mitochondria. PorB is a pore-forming beta-barrel protein sharing several features with the mitochondrial voltage-dependent anion channel (VDAC), which is involved in the regulation of apoptosis. Here we show that PorB of pathogenic Neisseria species produced by host cells is efficiently targeted to mitochondria. Imported PorB resides in the mitochondrial outer membrane and forms multimers with similar sizes as in the outer bacterial membrane. The mitochondria completely lose their membrane potential, a characteristic previously observed in cells infected with gonococci or treated with purified PorB. Closely related bacterial porins of non-pathogenic Neisseria mucosa or Escherichia coli remain in the cytosol. Import of PorB into mitochondria in vivo is independent of a linear signal sequence. Insertion of PorB into the mitochondrial outer membrane in vitro depends on the activity of Tom5, Tom20 and Tom40, but is independent of Tom70. Our data show that human VDAC and bacterial PorB are imported into mitochondria by a similar mechanism. PMID:11953311

  9. Successful Mnemonics for "por"/"para" and Affirmative Commands with Pronouns.

    ERIC Educational Resources Information Center

    Mason, Keith

    1992-01-01

    Two mnemonic devices, "4A Rule" and "PERFECT," are described to simplify the learning of two grammar points: the placement of object pronouns with respect to commands and the distinction between "por" and "para." (five references) (LB)

  10. Genome Sequences of Pseudomonas oryzihabitans Phage POR1 and Pseudomonas aeruginosa Phage PAE1.

    PubMed

    Dyson, Zoe A; Seviour, Robert J; Tucci, Joseph; Petrovski, Steve

    2016-01-01

    We report the genome sequences of two double-stranded DNA siphoviruses, POR1 infective for Pseudomonas oryzihabitans and PAE1 infective for Pseudomonas aeruginosa The phage POR1 genome showed no nucleotide sequence homology to any other DNA phage sequence in the GenBank database, while phage PAE1 displayed synteny to P. aeruginosa phages M6, MP1412, and YuA. PMID:27313312

  11. Genome Sequences of Pseudomonas oryzihabitans Phage POR1 and Pseudomonas aeruginosa Phage PAE1

    PubMed Central

    Dyson, Zoe A.; Seviour, Robert J.; Tucci, Joseph

    2016-01-01

    We report the genome sequences of two double-stranded DNA siphoviruses, POR1 infective for Pseudomonas oryzihabitans and PAE1 infective for Pseudomonas aeruginosa. The phage POR1 genome showed no nucleotide sequence homology to any other DNA phage sequence in the GenBank database, while phage PAE1 displayed synteny to P. aeruginosa phages M6, MP1412, and YuA. PMID:27313312

  12. Crystallographic analysis of Neisseria meningitidis PorB extracellular loops potentially implicated in TLR2 recognition.

    PubMed

    Kattner, Christof; Toussi, Deana N; Zaucha, Jan; Wetzler, Lee M; Rüppel, Nadine; Zachariae, Ulrich; Massari, Paola; Tanabe, Mikio

    2014-03-01

    Among all Neisseriae species, Neisseria meningitidis and Neisseria gonorrhoeae are the only human pathogens, causative agents of bacterial meningitis and gonorrhoea, respectively. PorB, a pan-Neisseriae trimeric porin that mediates diffusive transport of essential molecules across the bacterial outer membrane, is also known to activate host innate immunity via Toll-like receptor 2 (TLR2)-mediated signaling. The molecular mechanism of PorB binding to TLR2 is not known, but it has been hypothesized that electrostatic interactions contribute to ligand/receptor binding. Strain-specific sequence variability in the surface-exposed loops of PorB which are potentially implicated in TLR2 binding, may explain the difference in TLR2-mediated cell activation in vitro by PorB homologs from the commensal Neisseriae lactamica and the pathogen N. meningitidis. Here, we report a comparative structural analysis of PorB from N. meningitidis serogroup B strain 8765 (63% sequence homology with PorB from N. meningitidis serogroup W135) and a mutant in which amino acid substitutions in the extracellular loop 7 lead to significantly reduced TLR2-dependent activity in vitro. We observe that this mutation both alters the loop conformation and causes dramatic changes of electrostatic surface charge, both of which may affect TLR2 recognition and signaling. PMID:24361688

  13. Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB

    SciTech Connect

    Tanabe, Mikio; Nimigean, Crina M.; Iverson, T.M.

    2010-06-25

    PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 {angstrom} resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP-PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction.

  14. Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB

    PubMed Central

    Tanabe, Mikio; Nimigean, Crina M.; Iverson, T. M.

    2010-01-01

    PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 Å resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP–PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction. PMID:20351243

  15. An investigation of exploitation versus exploration in GBEA optimization of PORS 15 and 16 Problems

    SciTech Connect

    Koch, Kaelynn

    2012-01-01

    It was hypothesized that the variations in time to solution are driven by the competing mechanisms of exploration and exploitation.This thesis explores this hypothesis by examining two contrasting problems that embody the hypothesized tradeoff between exploration and exploitation. Plus one recall store (PORS) is an optimization problem based on the idea of a simple calculator with four buttons: plus, one, store, and recall. Integer addition and store are classified as operations, and one and memory recall are classified as terminals. The goal is to arrange a fixed number of keystrokes in a way that maximizes the numerical result. PORS 15 (15 keystrokes) represents the subset of difficult PORS problems and PORS 16 (16 keystrokes) represents the subset of PORS problems that are easiest to optimize. The goal of this work is to examine the tradeoff between exploitation and exploration in graph based evolutionary algorithm (GBEA) optimization. To do this, computational experiments are used to examine how solutions evolve in PORS 15 and 16 problems when solved using GBEAs. The experiment is comprised of three components; the graphs and the population, the evolutionary algorithm rule set, and the example problems. The complete, hypercube, and cycle graphs were used for this experiment. A fixed population size was used.

  16. Molecular characterisation of Porcine rubulavirus (PorPV) isolates from different outbreaks in Mexico.

    PubMed

    Cuevas-Romero, S; Rivera-Benítez, J F; Blomström, A-L; Ramliden, M; Hernández-Baumgarten, E; Hernández-Jáuregui, P; Ramírez-Mendoza, H; Berg, M

    2016-02-01

    Since the report of the initial outbreak of Porcine rubulavirus (PorPV) infection in pigs, only one full-length genome from 1984 (PorPV-LPMV/1984) has been characterised. To investigate the overall genetic variation, full-length gene nucleotide sequences of current PorPV isolates were obtained from different clinical cases of infected swine. Genome organisation and sequence analysis of the encoded proteins (NP, P, F, M, HN and L) revealed high sequence conservation of the NP protein and the expression of the P and V proteins in all PorPV isolates. The V protein of one isolate displayed a mutation that has been implicated to antagonise the antiviral immune responses of the host. The M protein indicated a variation in a short region that could affect the electrostatic charge and the interaction with the membrane. One PorPV isolate recovered from the lungs showed a mutation at the cleavage site (HRKKR) of the F protein that could represent an important factor to determine the tissue tropism and pathogenicity of this virus. The HN protein showed high sequence identity through the years (up to 2013). Additionally, a number of sequence motifs of very high amino acid conservation among the PorPV isolates important for polymerase activity of the L protein have been identified. In summary, genetic comparisons and phylogenetic analyses indicated that three different genetic variants of PorPV are currently spreading within the swine population, and a new generation of circulating virus with different characteristics has begun to emerge. PMID:26728078

  17. Por Secretion System-Dependent Secretion and Glycosylation of Porphyromonas gingivalis Hemin-Binding Protein 35

    PubMed Central

    Shoji, Mikio; Sato, Keiko; Yukitake, Hideharu; Kondo, Yoshio; Narita, Yuka; Kadowaki, Tomoko; Naito, Mariko; Nakayama, Koji

    2011-01-01

    The anaerobic Gram-negative bacterium Porphyromonas gingivalis is a major pathogen in severe forms of periodontal disease and refractory periapical perodontitis. We have recently found that P. gingivalis has a novel secretion system named the Por secretion system (PorSS), which is responsible for secretion of major extracellular proteinases, Arg-gingipains (Rgps) and Lys-gingipain. These proteinases contain conserved C-terminal domains (CTDs) in their C-termini. Hemin-binding protein 35 (HBP35), which is one of the outer membrane proteins of P. gingivalis and contributes to its haem utilization, also contains a CTD, suggesting that HBP35 is translocated to the cell surface via the PorSS. In this study, immunoblot analysis of P. gingivalis mutants deficient in the PorSS or in the biosynthesis of anionic polysaccharide-lipopolysaccharide (A-LPS) revealed that HBP35 is translocated to the cell surface via the PorSS and is glycosylated with A-LPS. From deletion analysis with a GFP-CTD[HBP35] green fluorescent protein fusion, the C-terminal 22 amino acid residues of CTD[HBP35] were found to be required for cell surface translocation and glycosylation. The GFP-CTD fusion study also revealed that the CTDs of CPG70, peptidylarginine deiminase, P27 and RgpB play roles in PorSS-dependent translocation and glycosylation. However, CTD-region peptides were not found in samples of glycosylated HBP35 protein by peptide map fingerprinting analysis, and antibodies against CTD-regions peptides did not react with glycosylated HBP35 protein. These results suggest both that the CTD region functions as a recognition signal for the PorSS and that glycosylation of CTD proteins occurs after removal of the CTD region. Rabbits were used for making antisera against bacterial proteins in this study. PMID:21731719

  18. Gliding Motility and Por Secretion System Genes Are Widespread among Members of the Phylum Bacteroidetes

    PubMed Central

    Zhu, Yongtao

    2013-01-01

    The phylum Bacteroidetes is large and diverse, with rapid gliding motility and the ability to digest macromolecules associated with many genera and species. Recently, a novel protein secretion system, the Por secretion system (PorSS), was identified in two members of the phylum, the gliding bacterium Flavobacterium johnsoniae and the nonmotile oral pathogen Porphyromonas gingivalis. The components of the PorSS are not similar in sequence to those of other well-studied bacterial secretion systems. The F. johnsoniae PorSS genes are a subset of the gliding motility genes, suggesting a role for the secretion system in motility. The F. johnsoniae PorSS is needed for assembly of the gliding motility apparatus and for secretion of a chitinase, and the P. gingivalis PorSS is involved in secretion of gingipain protease virulence factors. Comparative analysis of 37 genomes of members of the phylum Bacteroidetes revealed the widespread occurrence of gliding motility genes and PorSS genes. Genes associated with other bacterial protein secretion systems were less common. The results suggest that gliding motility is more common than previously reported. Microscopic observations confirmed that organisms previously described as nonmotile, including Croceibacter atlanticus, “Gramella forsetii,” Paludibacter propionicigenes, Riemerella anatipestifer, and Robiginitalea biformata, exhibit gliding motility. Three genes (gldA, gldF, and gldG) that encode an apparent ATP-binding cassette transporter required for F. johnsoniae gliding were absent from two related gliding bacteria, suggesting that the transporter may not be central to gliding motility. PMID:23123910

  19. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant.

    PubMed

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant. PMID:25750999

  20. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant

    PubMed Central

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant. PMID:25750999

  1. An Analysis of Interlanguage Development Over Time: Part 1, "por" and "para".

    ERIC Educational Resources Information Center

    Guntermann, Gail

    1992-01-01

    The first part of a larger planned investigation, this study examines the use of "por" and "para" by nine Peace Corps volunteers in oral interviews at the end of training and roughly one year later, to trace their acquisition over time, in two learning contexts. (24 references) (LB)

  2. The Acquisition of Lexical Meaning in a Study Abroad Context: The Spanish Prepositions "por" and "para."

    ERIC Educational Resources Information Center

    Lafford, Barbara A.; Ryan, John M.

    1995-01-01

    Examination of the development of form/function relations of the prepositions "por" and "para" at different levels of proficiency in the interlanguage of study-abroad students in Granada, Spain, revealed "noncanonical" as well as "canonical" uses of these prepositions. The most common noncanonical uses were as substitutions for other prepositions…

  3. The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation.

    PubMed

    Suker, J; Feavers, I M; Achtman, M; Morelli, G; Wang, J F; Maiden, M C

    1994-04-01

    Molecular analyses were applied to the genes encoding variants of the serosubtyping antigen, the class 1 outer membrane protein (PorA), from 55 serogroup A Neisseria meningitidis strains. These genes were evolutionarily stable and exhibited a limited range of genetic variation, primarily generated by recombination. Translation of the gene sequences revealed a total of 19 distinct amino acid sequences in the variable regions of the protein, 6 of which were not recognized by currently available serosubtyping monoclonal antibodies. Knowledge of these amino acid sequences permitted a rational re-assignment of serosubtype names. Comparison of the complete genes with porA gene sequences from serogroup B and C meningococci showed that serogroup A possessed a limited number of the possible porA genes from a globally distributed gene pool. Each serogroup A subgroup was characterized by one of four porA gene types, probably acquired upon subgroup divergence, which was stable over periods of decades and during epidemiological spread. Comparison with other variable genes (pil and iga) indicated that the three alleles were independently assorted within the subgroup, suggesting that their gene types were older than the subgroups in which they occurred. PMID:8057850

  4. Informe a la Nación de mortalidad por cáncer sigue bajando

    Cancer.gov

    El Informe Anual a la Nación sobre el Estado del Cáncer, de 1975 a 2009, indica que los índices generales de mortalidad por cáncer siguen bajando en los Estados Unidos en hombres y mujeres, entre todos los grupos raciales y étnicos principales y para todo

  5. Detección y estudio mediante Fluorescencia Inducida por Láser de radicales libres formados por Disociación Multifotónica Infrarroja

    NASA Astrophysics Data System (ADS)

    Santos, M.; Díaz, L.; Torresano, J. A.; Rubio, L.; Samoudi, B.

    Una de las principales aplicaciones actuales de los procesos de disociación multifotónica inducidos por radiación láser infrarroja (DMI) es la producción de radiales libres, con el fin de estudiar sus propiedades cinéticas y espectroscópicas. La disociación de moléculas poliatómicas en el IR con láseres de CO2 tiene lugar desde la superficie de energía molecular mas baja y conduce generalmente a la formación de fragmentos en el estado electrónico fundamental, con diversos grados de excitación vibracional. En el Grupo de Procesos Multifotónicos del Instituto de Estructura de la Materia del C.S.I.C. hemos puesto a punto la técnica de Fluorescencia Inducida por Láser (LIF) para la detección y análisis en tiempo real de los fragmentos producidos en la DMI inducida mediante uno o dos campos láseres de diferentes longitudes de onda. Objetivos de nuestro trabajo han sido el estudio de los canales de disociación mayoritarios y de las especies transitoria producidas, así como de la distribución de energía interna con que éstas son generadas. En particular hemos detectado mediante LIF las especies: C2, CF, CH, SiH2, CF2, CH2, SiHCl, y CF3 a partir de la disociación de, entre otras, las siguientes moléculas: C2H3Br, C3F6, C4H8Si, C2H5ClSi y CH5ClSi. En este trabajo presentamos algunos de los resultados obtenidos mediante el estudio por LIF de estos radicales: estudio temporal de la señal LIF obtenida con determinación de tiempos de vida, espectros de excitación y fluorescencia, temperaturas vibracionales de formación, variación de la intensidad LIF con el tiempo de retraso entre los láseres de disociación y prueba, etc.

  6. Spatio-temporal microhabitat use by two co-occurring species of scorpions in Atlantic rainforest in Brazil.

    PubMed

    Lira, André F A; Souza, Adriano M; Silva Filho, Arthur A C; Albuquerque, Cleide M R

    2013-06-01

    With the increasing devastation of the tropical rain forest, there is a critical need to understand how animal forest communities are structured and how habitat degradation will affect these communities. We conducted a field survey to investigate the microhabitat preferences of two co-occurring species of scorpions (Tityus pusillus and Ananteris mauryi) in a fragment of Atlantic rainforest, as well as their abundance and their ecological niche, during both the dry and rainy seasons. Behavioural aspects related to the use of the environment and the proportions of juveniles and adults are also described. The occurrence of intra- and interspecific coexistence was assessed by active search. In addition, pitfall catches were used to assess the structure of the population in the dry and rainy seasons. The differential patterns of spatial distribution in the litter layers provided evidence of partial niche partitioning between the two coexisting scorpion species depending on age and climatic conditions. Abundance, foraging behaviour and age structure (juveniles and adults) were seasonally influenced. We conclude that the diverse and subtle behaviours involved in interaction and habitat use may facilitate species coexistence. Resource partitioning and refuge sharing on a temporal and/or spatial scale, as well as predation pressure, may drive the dynamics and spatial distribution of scorpion species in the rain forest environment. PMID:23664851

  7. ATP for the portable 500 CFM exhauster POR-005 skid C

    SciTech Connect

    Keller, C.M.

    1997-06-27

    This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-005 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

  8. ATP for the portable 500 CFM exhauster POR-006 skid D

    SciTech Connect

    Keller, C.M.

    1997-07-29

    This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-006 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

  9. ATP for the portable 500 CFM exhauster POR-004 skid B

    SciTech Connect

    Keller, C.M.

    1997-05-06

    This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-004 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

  10. Correlation between Serological and Sequencing Analyses of the PorB Outer Membrane Protein in the Neisseria meningitidis Serotyping System

    PubMed Central

    Sacchi, Claudio T.; Lemos, Ana P. S.; Whitney, Anne M.; Solari, Claude A.; Brandt, Mary E.; Melles, Carmo E. A.; Frasch, Carl E.; Mayer, Leonard W.

    1998-01-01

    The current serological typing scheme for Neisseria meningitidis is not comprehensive; a proportion of isolates are not serotypeable. DNA sequence analysis and predicted amino acid sequences were used to characterize the structures of variable-region (VR) epitopes on N. meningitidis PorB proteins (PorB VR typing). Twenty-six porB gene sequences were obtained from GenBank and aligned with 41 new sequences. Primary amino acid structures predicted from those genes were grouped into 30 VR families of related variants that displayed at least 60% similarity. We correlated VR families with monoclonal antibody (MAb) reactivities, establishing a relationship between VR families and epitope locations for 15 serotype-defining MAbs. The current panel of serotype-defining MAbs underestimates by at least 50% the PorB VR variability because reagents for several major VR families are lacking or because a number of VR variants within some families are not recognized by serotype-defining MAbs. These difficulties, also reported for serosubtyping based on the PorA protein, are shown as inconsistent results between serological and sequence analyses, leading to inaccurate strain identification and incomplete epidemiological data. The information from this study enabled the expansion of the panel of MAbs currently available for serotyping, by including MAbs of previously undetermined specificities. Use of the expanded serotype panel enabled us to improve the sensitivity of serotyping by resolving a number of formerly nonserotypeable strains. In most cases, this information can be used to predict the VR family placement of unknown PorB proteins without sequencing the entire porB gene. PorB VR typing complements serotyping, and a combination of both techniques may be used for full characterization of meningococcal strains. The present work represents the most complete and integrated data set of PorB VR sequences and MAb reactivities of serogroup B and C meningococci produced to date. PMID

  11. Behavioural and electroencephalographic effects of Tityus serrulatus scorpion venom in rats.

    PubMed

    Sandoval, M R; Dorce, V A

    1993-02-01

    This study was designed to investigate the convulsant effects of T. serrulatus scorpion venom in rats. Pretreatment of rats with venom increased the minimum convulsant dose of picrotoxin, impaired convulsion generalization and displaced to the left the dose-response curve for picrotoxin. It also decreased the intensity but prolonged the duration of seizures caused by pentylenetetrazol injection. Microinjection of the venom into the dorsal hippocampus induced behavioural alterations and epileptiform waves in the EEG. Venom also altered the threshold for, and intensity of, convulsions induced in different experimental models of epilepsy. Different fractions of the venom may be responsible for these different effects. Therefore, purification of venom toxins is necessary for the complete understanding of the present results. PMID:8456448

  12. Effects of Tityus serrulatus crude venom on the GABAergic and dopaminergic systems of the rat brain.

    PubMed

    Dorce, V A; Sandoval, M R

    1994-12-01

    This study was designed to investigate the effect of T. serrulatus scorpion venom on dopamine (DA) and gamma amino butyric acid (GABA) concentrations in different regions of the brain. The ratio of homovanillic acid (HVA) to DA, and the glutamic acid decarboxylase (GAD) activity were determined following intravenous or intracerebral venom injections. The increase in the HVA/DA ratio in the striatum after i.v. or intrastriatal injection could indicate an increase in DA turnover. One hour after i.v. injection of the venom GAD activity was shown to be decreased in the striatum and hypothalamus. After 24 hr GAD activity increased in the striatum and decreased in the hypothalamus and brain stem. These results could indicate different effects of the venom on the GABA system in different areas of the brain. After intrastriatal injection of the scorpion venom, the animals showed stereotyped behavior and rotation activity. Following intrahippocampal injection, myoclonus and orofacial automatisms, which constitute pro-convulsive signals, were observed. These behavioral alterations could be, at least in part, related to the GABA and dopamine alterations caused by the venom, since stereotypy, circling behavior and convulsions are dependent on dopamine and/or GABA. PMID:7725331

  13. Zinc Finger Nuclease Knock-out of NADPH:Cytochrome P450 Oxidoreductase (POR) in Human Tumor Cell Lines Demonstrates That Hypoxia-activated Prodrugs Differ in POR Dependence*

    PubMed Central

    Su, Jiechuang; Gu, Yongchuan; Pruijn, Frederik B.; Smaill, Jeff B.; Patterson, Adam V.; Guise, Christopher P.; Wilson, William R.

    2013-01-01

    Hypoxia, a ubiquitous feature of tumors, can be exploited by hypoxia-activated prodrugs (HAP) that are substrates for one-electron reduction in the absence of oxygen. NADPH:cytochrome P450 oxidoreductase (POR) is considered one of the major enzymes responsible, based on studies using purified enzyme or forced overexpression in cell lines. To examine the role of POR in HAP activation at endogenous levels of expression, POR knock-outs were generated in HCT116 and SiHa cells by targeted mutation of exon 8 using zinc finger nucleases. Absolute quantitation by proteotypic peptide mass spectrometry of DNA sequence-confirmed multiallelic mutants demonstrated expression of proteins with residual one-electron reductase activity in some clones and identified two (Hko2 from HCT116 and S2ko1 from SiHa) that were functionally null by multiple criteria. Sensitivities of the clones to 11 HAP (six nitroaromatics, three benzotriazine N-oxides, and two quinones) were compared with wild-type and POR-overexpressing cells. All except the quinones were potentiated by POR overexpression. Knocking out POR had a marked effect on antiproliferative activity of the 5-nitroquinoline SN24349 in both genetic backgrounds after anoxic exposure but little or no effect on activity of most other HAP, including the clinical stage 2-nitroimidazole mustard TH-302, dinitrobenzamide mustard PR-104A, and benzotriazine N-oxide SN30000. Clonogenic cell killing and reductive metabolism of PR-104A and SN30000 under anoxia also showed little change in the POR knock-outs. Thus, although POR expression is a potential biomarker of sensitivity to some HAP, identification of other one-electron reductases responsible for HAP activation is needed for their rational clinical development. PMID:24196959

  14. Characterization of Plasmid pOR1 from Ornithobacterium rhinotracheale and Construction of a Shuttle Plasmid

    PubMed Central

    Jansen, Ruud; Chansiripornchai, Niwat; Gaastra, Wim; van Putten, Jos P. M.

    2004-01-01

    The bacterium Ornithobacterium rhinotracheale has been recognized as an emerging pathogen in poultry since about 10 years ago. Knowledge of this bacterium and its mechanisms of virulence is still very limited. Here we report the development of a transformation system that enables genetic modification of O. rhinotracheale. The system is based on a cryptic plasmid, pOR1, that was derived from an O. rhinotracheale strain of serotype K. Sequencing indicated that the plasmid consisted of 14,787 nucleotides. Sequence analysis revealed one replication origin and several rep genes that control plasmid replication and copy number, respectively. In addition, pOR1 contains genes with similarity to a heavy-metal-transporting ATPase, a TonB-linked siderophore receptor, and a laccase. Reverse transcription-PCR demonstrated that these genes were transcribed. Other putative open reading frames exhibited similarities with a virulence-associated protein in Actinobacillus actinomycetemcomitans and a number of genes coding for proteins with unknown function. An Escherichia coli-O. rhinotracheale shuttle plasmid (pOREC1) was constructed by cloning the replication origin and rep genes from pOR1 and the cfxA gene from Bacteroides vulgatus, which codes for resistance to the antibiotic cefoxitin, into plasmid pGEM7 by using E. coli as a host. pOREC1 was electroporated into O. rhinotracheale and yielded cefoxitin-resistant transformants. The pOREC1 isolated from these transformants was reintroduced into E. coli, demonstrating that pOREC1 acts as an independent replicon in both E. coli and O. rhinotracheale, fulfilling the criteria for a shuttle plasmid that can be used for transformation, targeted mutagenesis, and the construction of defined attenuated vaccine strains. PMID:15466524

  15. Expression, purification and preliminary X-ray analysis of the Neisseria meningitidis outer membrane protein PorB

    SciTech Connect

    Tanabe, Mikio; Iverson, Tina M.

    2010-01-28

    The Neisseria meningitidis outer membrane protein PorB was expressed in Escherichia coli and purified from inclusion bodies by denaturation in urea followed by refolding in buffered LDAO on a size-exclusion column. PorB has been crystallized in three different crystal forms: C222, R32 and P6{sub 3}. The C222 crystal form may contain either one or two PorB monomers in the asymmetric unit, while both the R32 and P6{sub 3} crystal forms contained one PorB monomer in the asymmetric unit. Of the three, the P6{sub 3} crystal form had the best diffraction quality, yielding data extending to 2.3 {angstrom} resolution.

  16. Application of POR-Tveks to the radiochemical recovery of yttrium-90

    SciTech Connect

    Maksimova, A.M.; Kvasnitskii, I.B.

    1988-01-01

    The authors describe a method for the radiochemical analysis of fish bones for the accumulation of strontium 90 and yttrium 90 from power plant contamination of surface waters which involves labelling the sample with isotopes and subsequent adsorption of the yttrium component with the use of POR-Tveks, an adsorbent based on a copolymer of styrene and divinylbenzene with heteroradical phosphine oxide. The yield of yttrium is determined from the mass of the oxide and from the half-life of the yttrium isotope.

  17. Antigenic topology of chlamydial PorB protein and identification of targets for immune neutralization of infectivity.

    PubMed

    Kawa, Diane E; Stephens, Richard S

    2002-05-15

    The outer membrane protein PorB is a conserved chlamydial protein that functions as a porin and is capable of eliciting neutralizing Abs. A topological antigenic map was developed using overlapping synthetic peptides representing the Chlamydia trachomatis PorB sequence and polyclonal immune sera. To identify which antigenic determinants were surface accessible, monospecific antisera were raised to the PorB peptides and were used in dot-blot and ELISA-based absorption studies with viable chlamydial elementary bodies (EBs). The ability of the surface-accessible antigenic determinants to direct neutralizing Ab responses was investigated using standardized in vitro neutralization assays. Four major antigenic clusters corresponding to Phe(34)-Leu(59) (B1-2 and B1-3), Asp(112) -Glu(145) (B2-3 and B2-4), Gly(179)-Ala(225) (B3-2 to B3-4), and Val(261)-Asn(305) (B4-4 to B5-2) were identified. Collectively, the EB absorption and dot-blot assays established that the immunoreactive PorB Ags were exposed on the surface of chlamydial EBs. Peptide-specific antisera raised to the surface-accessible Ags neutralized chlamydial infectivity and demonstrated cross-reactivity to synthetic peptides representing analogous C. pneumoniae PorB sequences. Furthermore, neutralization of chlamydial infectivity by C. trachomatis PorB antisera was inhibited by synthetic peptides representing the surface-exposed PorB antigenic determinants. These findings demonstrate that PorB Ags may be useful for development of chlamydial vaccines. PMID:11994474

  18. Multiple active site residues are important for photochemical efficiency in the light-activated enzyme protochlorophyllide oxidoreductase (POR).

    PubMed

    Menon, Binuraj R K; Hardman, Samantha J O; Scrutton, Nigel S; Heyes, Derren J

    2016-08-01

    Protochlorophyllide oxidoreductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide), an essential, regulatory step in chlorophyll biosynthesis. The unique requirement of the enzyme for light has provided the opportunity to investigate how light energy can be harnessed to power biological catalysis and enzyme dynamics. Excited state interactions between the Pchlide molecule and the protein are known to drive the subsequent reaction chemistry. However, the structural features of POR and active site residues that are important for photochemistry and catalysis are currently unknown, because there is no crystal structure for POR. Here, we have used static and time-resolved spectroscopic measurements of a number of active site variants to study the role of a number of residues, which are located in the proposed NADPH/Pchlide binding site based on previous homology models, in the reaction mechanism of POR. Our findings, which are interpreted in the context of a new improved structural model, have identified several residues that are predicted to interact with the coenzyme or substrate. Several of the POR variants have a profound effect on the photochemistry, suggesting that multiple residues are important in stabilizing the excited state required for catalysis. Our work offers insight into how the POR active site geometry is finely tuned by multiple active site residues to support enzyme-mediated photochemistry and reduction of Pchlide, both of which are crucial to the existence of life on Earth. PMID:27285815

  19. Diagnóstico diferencial en la encefalitis por anticuerpos contra el receptor NMDA

    PubMed Central

    González-Valcárcel, J.; Rosenfeld, M.R.; Dalmau, J.

    2011-01-01

    Resumen Introducción La encefalitis por anticuerpos contra el receptor de NMDA (NMDAR) suele desarrollarse como un síndrome característico de evolución multifásica y diagnóstico diferencial amplio. Pacientes Presentamos a 2 pacientes diagnosticadas de encefalitis por anticuerpos NMDAR con un cuadro clínico típico, pero que inicialmente señaló otras etiologías. Discusión La afectación frecuente de pacientes jóvenes con manifestaciones psiquiátricas prominentes indica frecuentemente otras consideraciones diagnósticas; las más frecuentes son las encefalitis virales, los procesos psiquiátricos y el síndrome neuroléptico maligno. Varios síndromes previamente definidos de manera parcial o descriptiva en adultos y pacientes pediátricos probablemente eran casos de encefalitis anti-NMDAR. Conclusiones La encefalitis anti-NMDAR debe considerarse en pacientes jóvenes con manifestaciones psiquiátricas subagudas, movimientos anormales y alteraciones autonómicas. La caracterización clínica e inmunológica de esta enfermedad ha llevado a la identificación de nuevos anticuerpos que afectan a procesos de memoria, aprendizaje, conducta y psicosis. PMID:20964986

  20. Effect of SPM-based cleaning POR on EUV mask performance

    NASA Astrophysics Data System (ADS)

    Choi, Jaehyuck; Lee, Han-shin; Yoon, Jinsang; Shimomura, Takeya; Friz, Alex; Montgomery, Cecilia; Ma, Andy; Goodwin, Frank; Kang, Daehyuk; Chung, Paul; Shin, Inkyun; Cho, H.

    2011-11-01

    EUV masks include many different layers of various materials rarely used in optical masks, and each layer of material has a particular role in enhancing the performance of EUV lithography. Therefore, it is crucial to understand how the mask quality and patterning performance can change during mask fabrication, EUV exposure, maintenance cleaning, shipping, or storage. The fact that a pellicle is not used to protect the mask surface in EUV lithography suggests that EUV masks may have to undergo more cleaning cycles during their lifetime. More frequent cleaning, combined with the adoption of new materials for EUV masks, necessitates that mask manufacturers closely examine the performance change of EUV masks during cleaning process. We have investigated EUV mask quality and patterning performance during 30 cycles of Samsung's EUV mask SPM-based cleaning and 20 cycles of SEMATECH ADT exposure. We have observed that the quality and patterning performance of EUV masks does not significantly change during these processes except mask pattern CD change. To resolve this issue, we have developed an acid-free cleaning POR and substantially improved EUV mask film loss compared to the SPM-based cleaning POR.

  1. Methodology for obtaining stakeholder assessments of obesity policy options in the PorGrow project.

    PubMed

    Stirling, A; Lobstein, T; Millstone, E

    2007-05-01

    The Policy Options for Responding to the Growing Challenge of Obesity Research Project (PorGrow) study provided a unique opportunity to develop a large-scale application of a semi-quantitative technique for exploring interviewees' views on options to tackle obesity, using multi-criteria mapping. This 'heuristic' approach utilizes the advantages of a structured interviews framework by predefining a set of options for appraisal, while leaving interviewees free to select their own criteria for making their judgements. Additional information can be gleaned from the interview transcripts and related materials to set the appraisals in their policy context, and allowing interviewees to express their views on the options presented and their own appraisals. The PorGrow study team agreed a predefined set of 20 options for appraisal, and interviewed sets of stakeholders representing more than 20 aspects of policy development in each of the nine participating countries. The details of the methodology adopted are set out in this paper. PMID:17371304

  2. Effects of heme precursors on CYP1A2 and POR expression in the baculovirus/Spodoptera frugiperda system☆

    PubMed Central

    Lu, Huiyuan; Ma, Jun; Liu, Nian; Wang, Shoulin

    2010-01-01

    Objective CYP1A2 and NADPH-CYP450 oxidoreductase (POR) were expressed in the baculovirus/Spodoptera frugiperda (sf9) system. The aim of this study was to investigate the effects of heme precursors on the expression of CYP1A2 and POR. Methods The heme precursors [δ-Aminolaevulinic Acid (5-ALA), Fe3+ and hemin] were introduced into the system to evaluate their effects on the expression of CYP1A2, POR and their co-expression. All the proteins were identified using immunoblotting, CO-difference spectroscopy, or cytochrome c assay. Results In the present study, functional CYP1A2 and POR were successfully expressed in the baculovirus/sf9 system, and both of them showed high activities. Co-addition of 5-ALA and Fe3+ significantly improved expression of CYP1A2 by about 50% compared with the addition of 5-ALA, Fe3+ or hemin alone. Either co-addition of 5-ALA and Fe3+ or addition of 5-ALA or Fe3+ alone improved the POR expression level 2 fold and its activity 7-10 fold compared with control (no addition). However, unlike CYP1A2, there was no difference between the co-addition and addition of these heme precursors alone. Different ratios of BvCYP1A2 to BvPOR also affected the co-expression of CYP1A2 and POR, with a 3:1 ratio of BvCYP1A2 / BvPOR significantly increasing their co-expression. Surprisingly, the addition of 0.1 mM 5-ALA or Fe3+ alone, but not their co-addition, could significantly improve the CYP1A2 and POR co-expression (P < 0.05). Conclusion 5-ALA and Fe3+ increased the expression of CYP1A2 and POR in a baculovirus/sf9 system, but the pattern of their expression was different between their expression alone and co-expression. PMID:23554636

  3. Geometry sensing through POR1 regulates Rac1 activity controlling early osteoblast differentiation in response to nanofiber diameter.

    PubMed

    Higgins, A M; Banik, B L; Brown, J L

    2015-02-01

    Bone grafting procedures in the United States rely heavily upon autografts and allografts, which are donor-dependent, cause donor site pain, and can transmit disease. Synthetic bone grafts can reduce these risks; however, synthetics lack the bone differentiating (osteoinductive) abilities of auto- and allografts. Achieving innate osteoinductive properties of synthetics through surface modifications is currently under investigation. This study focuses on nanofibers, with emphasis on how fiber diameter and the potential curvature sensor POR1 affect the activation of the signaling molecules Rac1 and Arf1, and leading to expression of alkaline phosphatase (ALP), an osteoinductive marker. Diameters of 0.1, 0.3, and 1.0 μm were compared against a flat control. The highest level of Rac1 activation was achieved on the smallest fibers (0.1 μm), a trend that was lost in POR1 knockdowns. This supports the hypothesis that on small nanofibers, POR1 favorably binds to highly curved cell membranes, which allows Rac1 to subsequently dissociate and activate. When the curvature is insufficient to bind POR1, POR1 binds to inactive Rac1 and competitively inhibits its activation. Arf1 activation followed an opposite trend, with the largest nanofibers exhibiting the highest activity. This trend reinforces the known interaction between Rac1 and Arf1 through the GIT-PIX complex, an Arf1 GAP and Rac1 GEF, respectively. Large, (1.0 μm), nanofibers demonstrated the highest ALP activity, indicating that ALP expression is inversely dependent on Rac1 activation. Knockdown of POR1 resulted in increased ALP activity across the substrates but without regard to the curvature sensing trend seen previously. Thus, POR1 senses curvature and increases Rac1 activity, which negatively regulates bone differentiation. PMID:25539497

  4. Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase (POR)

    PubMed Central

    Agrawal, Vishal; Choi, Ji Ha; Giacomini, Kathleen M.; Miller, Walter L.

    2010-01-01

    Objectives CYP3A4 receives electrons from P450 oxidoreductase (POR) to metabolize about 50% of clinically used drugs. There is substantial inter-individual variation in CYP3A4 catalytic activity that is not explained by CYP3A4 genetic variants. CYP3A4 is flexible and distensible, permitting it to accommodate substrates varying in shape and size. To elucidate mechanisms of variability in CYP3A4 catalysis, we examined the effects of genetic variants of POR, and explored the possibility that substrate-induced conformational changes in CYP3A4 differentially affect the ability of POR variants to support catalysis. Methods We expressed human CYP3A4 and four POR variants (Q153R, A287P, R457H, A503V) in bacteria, reconstituted them in vitro and measured the Michaelis constant and maximum velocity with testosterone, midazolam, quinidine and erythromycin as substrates. Results POR A287P and R457H had low activity with all substrates; Q153R had 76–94% of wild type (WT) activity with midazolam and erythromycin, but 129–150% activity with testosterone and quinidine. The A503V polymorphism reduced CYP3A4 activity to 61–77% of wild type with testosterone and midazolam, but had nearly wild type activity with quinidine and erythromycin. Conclusion POR variants affect CYP3A4 activities. The impact of a POR variant on catalysis by CYP3A4 is substrate-specific, probably due to substrate-induced conformational changes in CYP3A4. PMID:20697309

  5. Intermitência alfvênica gerada por caos na atmosfera solar e no vento solar

    NASA Astrophysics Data System (ADS)

    Rempel, E. L.; Chian, A. C.-L.; Macau, E. E. N.; Rosa, R. R.

    2003-08-01

    Dados medidos no vento solar rápido proveniente dos buracos coronais revelam que os plasmas no meio interplanetário são dominados por flutuações Alfvênicas, caracterizadas por uma alta correlação entre as variações do campo magnético e da velocidade do plasma. As flutuações exibem muitas características esperadas em turbulência magneto-hidrodinâmica totalmente desenvolvida, tais como intermitência e espectros contínuos. Contudo, os mecanismos responsáveis pela evolução de turbulência Alfvênica intermitente não são completamente compreendidos. Neste trabalho a teoria de caos é usada para explicar como sistemas Alfvênicos, modelados pela equação Schrödinger não-linear derivativa e pela equação Kuramoto-Sivashinsky, podem se tornar fortemente caóticos à medida em que parâmetros do plasma são variados. Pequenas perturbações no parâmetro de dissipação podem fazer com que o sistema mude bruscamente de um regime periódico, ou fracamente caótico, para um regime fortemente caótico. As séries temporais das flutuações do campo magnético nos regimes fortemente caóticos exibem comportamento intermitente, em que fases laminares ou fracamente caóticas são interrompidas por fortes estouros caóticos. É mostrado que o regime fortemente caótico é atingido quando as soluções periódicas ou fracamente caóticas globalmente estáveis interagem com soluções do sistema que são fortemente caóticas, mas globalmente instáveis. Estas soluções globalmente instáveis são conjuntos caóticos não-atrativos conhecidos como selas caóticas, e são responsáveis pelos fortes estouros nos regimes intermitentes. Selas caóticas têm sido detectadas experimentalmente em uma grande variedade de sistemas, sendo provável que elas desempenhem um papel importante na turbulência intermitente observada em plasmas espaciais.

  6. Fabrication of por-Si/SnO{sub x} nanocomposite layers for gas microsensors and nanosensors

    SciTech Connect

    Bolotov, V. V. Korusenko, P. M.; Nesov, S. N.; Povoroznyuk, S. N.; Roslikov, V. E.; Kurdyukova, E. A.; Sten'kin, Yu. A.; Shelyagin, R. V.; Knyazev, E. V.; Kan, V. E.; Ponomareva, I. V.

    2011-05-15

    Two-phase nanocomposite layers based on porous silicon and nonstoichiometric tin oxide were fabricated by various methods. The structure, as well as elemental and phase composition, of the obtained nanocomposites were studied using transmission and scanning electron microscopy, Raman spectroscopy, Auger electron spectroscopy, and X-ray photoelectron spectroscopy. The results obtained confirm the formation of nanocomposite layers with a thickness as large as 2 {mu}m thick and SnO{sub x} stoichiometry coefficients x = 1.0-2.0. Significant tin diffusion into the porous silicon matrix with D{sub eff} Almost-Equal-To 10{sup -14} cm{sup 2} s{sup -1} was observed upon annealing at 770 K. Test sensor structures based on por-Si/SnO{sub x} nanocomposite layers grown by magnetron deposition showed fairly high stability of properties and sensitivity to NO{sub 2}.

  7. Recovery of naphthalene during evaporative concentration. [Tenax; XAD-2; POR-Q, XE-340

    SciTech Connect

    Higgins, C.E.; Guerin, M.R.

    1980-10-01

    The analysis of trace organics usually requires concentrating organic extracts to small volumes prior to instrumental analysis. The use of a concentration apparatus employing a nitrogen blanket and reduced pressure is desirable because the inert atmosphere and low temperature help to ensure stable composition. Unfortunately, diaromatic compounds such as the naphthalenes and biphenyls are frequently almost completely lost during the concentration step. Even under carefully controlled conditions only 26 +- 11% of the naphthalene is recovered. By placing a sorbent either in or downstream of the evaporation concentration flask, recovery of diaromatic compounds can be improved significantly. In this investigation, the following sorbents, Tenax, XAD-2, POR-Q, and XE-340 were tested. Recoveries with and without the use of sorbents, effects of solute concentration, purge time after solvent removal, and type of solvent used are reported here.

  8. Using the PORS Problems to Examine Evolutionary Optimization of Multiscale Systems

    SciTech Connect

    Reinhart, Zachary; Molian, Vaelan; Bryden, Kenneth

    2013-01-01

    Nearly all systems of practical interest are composed of parts assembled across multiple scales. For example, an agrodynamic system is composed of flora and fauna on one scale; soil types, slope, and water runoff on another scale; and management practice and yield on another scale. Or consider an advanced coal-fired power plant: combustion and pollutant formation occurs on one scale, the plant components on another scale, and the overall performance of the power system is measured on another. In spite of this, there are few practical tools for the optimization of multiscale systems. This paper examines multiscale optimization of systems composed of discrete elements using the plus-one-recall-store (PORS) problem as a test case or study problem for multiscale systems. From this study, it is found that by recognizing the constraints and patterns present in discrete multiscale systems, the solution time can be significantly reduced and much more complex problems can be optimized.

  9. Display of a PorA peptide from Neisseria meningitidis on the bacteriophage T4 capsid surface.

    PubMed Central

    Jiang, J; Abu-Shilbayeh, L; Rao, V B

    1997-01-01

    The exterior of bacteriophage T4 capsid is coated with two outer capsid proteins, Hoc (highly antigenic outer capsid protein; molecular mass, 40 kDa) and Soc (small outer capsid protein; molecular mass, 9 kDa), at symmetrical positions on the icosahedron (160 copies of Hoc and 960 copies of Soc per capsid particle). Both these proteins are nonessential for phage infectivity and viability and assemble onto the capsid surface after completion of capsid assembly. We developed a phage display system which allowed in-frame fusions of foreign DNA at a unique cloning site in the 5' end of hoc or soc. A DNA fragment corresponding to the 36-amino-acid PorA peptide from Neisseria meningitidis was cloned into the display vectors to generate fusions at the N terminus of Hoc or Soc. The PorA-Hoc and PorA-Soc fusion proteins retained the ability to bind to the capsid surface, and the bound peptide was displayed in an accessible form as shown by its reactivity with specific monoclonal antibodies in an enzyme-linked immunosorbent assay. By employing T4 genetic strategies, we show that more than one subtype-specific PorA peptide can be displayed on the capsid surface and that the peptide can also be displayed on a DNA-free empty capsid. Both the PorA-Hoc and PorA-Soc recombinant phages are highly immunogenic in mice and elicit strong antipeptide antibody titers even with a weak adjuvant such as Alhydrogel or no adjuvant at all. The data suggest that the phage T4 hoc-soc system is an attractive system for display of peptides on an icosahedral capsid surface and may emerge as a powerful system for construction of the next generation multicomponent vaccines. PMID:9353063

  10. Rescue of cytochrome P450 oxidoreductase (Por) mouse mutants reveals functions in vasculogenesis, brain and limb patterning linked to retinoic acid homeostasis.

    PubMed

    Ribes, Vanessa; Otto, Diana M E; Dickmann, Leslie; Schmidt, Katy; Schuhbaur, Brigitte; Henderson, Colin; Blomhoff, Rune; Wolf, C Roland; Tickle, Cheryll; Dollé, Pascal

    2007-03-01

    Cytochrome P450 oxidoreductase (POR) acts as an electron donor for all cytochrome P450 enzymes. Knockout mouse Por(-/-) mutants, which are early embryonic (E9.5) lethal, have been found to have overall elevated retinoic acid (RA) levels, leading to the idea that POR early developmental function is mainly linked to the activity of the CYP26 RA-metabolizing enzymes (Otto et al., Mol. Cell. Biol. 23, 6103-6116). By crossing Por mutants with a RA-reporter lacZ transgene, we show that Por(-/-) embryos exhibit both elevated and ectopic RA signaling activity e.g. in cephalic and caudal tissues. Two strategies were used to functionally demonstrate that decreasing retinoid levels can reverse Por(-/-) phenotypic defects, (i) by culturing Por(-/-) embryos in defined serum-free medium, and (ii) by generating compound mutants defective in RA synthesis due to haploinsufficiency of the retinaldehyde dehydrogenase 2 (Raldh2) gene. Both approaches clearly improved the Por(-/-) early phenotype, the latter allowing mutants to be recovered up until E13.5. Abnormal brain patterning, with posteriorization of hindbrain cell fates and defective mid- and forebrain development and vascular defects were rescued in E9.5 Por(-/-) embryos. E13.5 Por(-/-); Raldh2(+/-) embryos exhibited abdominal/caudal and limb defects that strikingly phenocopy those of Cyp26a1(-/-) and Cyp26b1(-/-) mutants, respectively. Por(-/-); Raldh2(+/-) limb buds were truncated and proximalized and the anterior-posterior patterning system was not established. Thus, POR function is indispensable for the proper regulation of RA levels and tissue distribution not only during early embryonic development but also in later morphogenesis and molecular patterning of the brain, abdominal/caudal region and limbs. PMID:17126317

  11. Global Microlending in Education Reform: Enseñá Por Argentina and the Neoliberalization of the Grassroots

    ERIC Educational Resources Information Center

    Friedrich, Daniel S.

    2010-01-01

    This article examines the workings and underlying assumptions behind Enseñá por Argentina (Teach for Argentina), one specific program that takes part in the larger and expanding network of Teach for All, by thinking about the ways in which a global push for redefining teaching and teacher education encounters local characteristics and histories,…

  12. [Professor Frantisek Por MD and Professor Robert Klopstock MD, students at Budapest and Prague Faculties of Medicine].

    PubMed

    Mydlík, M; Derzsiová, K

    2010-11-01

    Professor Frantisek Por MD and Professor Robert Klopstock MD were contemporaries, both born in 1899, one in Zvolen, the other in Dombovar, at the time of Austro-Hungarian Monarchy. Prof. Por attended the Faculty of Medicine in Budapest from 1918 to 1920, and Prof. Klopstock studied at the same place between 1917 and 1919. From 1920 until graduation on 6th February 1926, Prof. Por continued his studies at the German Faculty of Medicine, Charles University in Prague. Prof. Klopstock had to interrupt his studies in Budapest due to pulmonary tuberculosis; he received treatment at Tatranske Matliare where he befriended Franz Kafka. Later, upon Kafka's encouragement, he changed institutions and continued his studies at the German Faculty of Medicine, Charles University in Prague, where he graduated the first great go. It is very likely that, during their studies in Budapest and Prague, both professors met repeatedly, even though their life paths later separated. Following his graduation, Prof. Por practiced as an internist in Prague, later in Slovakia, and from 1945 in Kosice. In 1961, he was awarded the title of university professor of internal medicine at the Faculty of Medicine, Pavol Jozef Safarik University in Kosice, where he practiced until his death in 1980. Prof. Klopstock continued his studies in Kiel and Berlin. After his graduation in 1933, he practiced in Berlin as a surgeon and in 1938 left for USA. In 1962, he was awarded the title of university professor of pulmonary surgery in NewYork, where he died in 1972. PMID:21250499

  13. Functional POR A503V is associated with the risk of bladder cancer in a Chinese population

    PubMed Central

    Xiao, Xue; Ma, Gaoxiang; Li, Shushu; Wang, Meilin; Liu, Nian; Ma, Lan; Zhang, Zhan; Chu, Haiyan; Zhang, Zhengdong; Wang, Shou-Lin

    2015-01-01

    Human cytochrome P450 oxidoreductase (POR) plays important roles in the metabolism of exogenous carcinogens and endogenous sterol hormones. However, few studies have explored the association between POR variants and the risk of bladder cancer. In this study, we first sequenced all 16 POR exons among 50 randomly selected controls, and found three variants, rs1135612, rs1057868 (A503V) and rs2228104, which were then assessed the relation to risk of bladder cancer in a case-control study of 1,050 bladder cancer cases and 1,404 cancer-free controls in a Chinese population. People with A503V TT genotype have a decreased risk of bladder cancer in a recessive model (TT vs. CC/CT, OR = 0.73, 95% CI = 0.57–0.93), which was more pronounced among elderly male, non-smoking, subjects. Especially, A503V TT genotype showed a protective effect in the invasive tumor stage. Functional analysis revealed that A503V activity decreased in cytochrome c reduction (50.5 units/mg vs. 135.4 units/mg), mitomycin C clearance (38.3% vs. 96.8%), and mitomycin C-induced colony formation (78.0 vs 34.3 colonies per dish). The results suggested that POR A503V might decrease the risk of bladder cancer by reducing its metabolic activity, and should be a potential biomarker for predicting the susceptibility to human bladder cancer. PMID:26123203

  14. Inversor Resonante de Tres Elementos L-LC con Caracteristica Cortocircuitable para Aplicaciones de Calentamiento por Induccion

    NASA Astrophysics Data System (ADS)

    Espi Huerta, Jose Miguel

    Los generadores de calentamiento por induccion son puentes inversores con carga resonante, cuya mision es basicamente crear una corriente sinusoidal de gran amplitud sobre la "bobina de caldeo", que forma parte del tanque resonante. En el interior de esta bobina se introduce la pieza que se desea calentar. EI campo magnetico creado induce corrientes superficiales (corrientes de Foucault) sobre la pieza, que producen su calentamiento. Los tanques resonantes (tambien llamados osciladores) utilizados en la actualidad son el resonante serie y el resonante paralelo. Aunque ya desde hace algun tiempo se vienen construyendo generadores de alta potencia basados en estos dos osciladores, el exito nunca ha. sido completo en ninguno de los dos casos. Tal y como se explica en la introduccion de esta memoria, los puentes inversores utilizados deben operar sobre una carga inductiva (corriente retrasada) para evitar el fenomeno de la recuperacion inversa de sus diodos y la consiguiente ruptura de los transistores. De la restriccion topologica anterior se deduce que el generador paralelo debe conmutar a frecuencias inferiores a la resonancia, y el serie a frecuencias superiores. A esta restriccion topologica hay que unir otra que es exclusiva del calentamiento por induccion: La corriente por la bobina de caldeo debe ser sinusoidal. De no ser asi, resultaria imposible disponer toda la potencia de calentamiento sobre la pieza en el espesor requerido por la aplicacion. Como consecuencia, los inversores no pueden operar por debajo de la frecuencia de resonancia del oscilador, pues en ese caso se amplifican los armonicos de orden superior de la tension/corriente de entrada situados sobre la resonancia, con la consiguiente distorsion de la corriente de salida. La conjuncion de las dos restricciones anteriores obligan al inversor paralelo a funcionar a la frecuencia de resonancia del oscilador. Esto imposibilita un control por variacion de frecuencia, regulandose la potencia desde la

  15. Encefalitis por anticuerpos contra el receptor de NMDA: experiencia con seis pacientes pediátricos. Potencial eficacia del metotrexato

    PubMed Central

    Bravo-Oro, Antonio; Abud-Mendoza, Carlos; Quezada-Corona, Arturo; Dalmau, Josep; Campos-Guevara, Verónica

    2016-01-01

    Introducción La encefalitis por anticuerpos contra el receptor de N-metil-D-aspartato (NMDA) es una entidad cada vez más diagnosticada en edad pediátrica. A diferencia de los adultos, en muchos casos no se asocia a tumores y las manifestaciones iniciales en niños más frecuentes son crisis convulsivas y trastornos del movimiento, mientras que en los adultos predominan las alteraciones psiquiátricas. Casos clínicos Presentamos seis casos pediátricos confirmados con anticuerpos contra la subunidad NR1 del receptor de NMDA en suero y líquido cefalorraquídeo. Cinco de los casos comenzaron con crisis convulsivas como manifestación clínica inicial antes de desarrollar el cuadro clásico de esta entidad. En todos los casos se utilizaron esteroides como primera línea de tratamiento, con los que sólo se observó control de las manifestaciones en uno, por lo que el resto de los pacientes requirió inmunomoduladores de segunda línea. Todos los pacientes recibieron metotrexato como tratamiento inmunomodulador para evitar recaídas y la evolución fue a la mejoría en todos ellos. Conclusiones En nuestra serie de pacientes con encefalitis por anticuerpos contra el receptor de NMDA, ninguno se asoció a tumores. Todos los casos recibieron metotrexato por lo menos durante un año, no observamos eventos adversos clínicos ni por laboratorio, ni hubo secuelas neurológicas ni recaídas durante el tratamiento. Aunque es una serie pequeña y es deseable incrementar el número y tiempo de evolución, consideramos el metotrexato una excelente alternativa como tratamiento inmunomodulador para esta patología. PMID:24150952

  16. Prevalencia y tamizaje del Trastorno por Déficit de Atención con Hiperactividad en Costa Rica

    PubMed Central

    Weiss, Nicholas T.; Schuler, Jovita; Monge, Silvia; McGough, James J.; Chavira, Denise; Bagnarello, Monica; Herrera, Luis Diego; Mathews, Carol A.

    2015-01-01

    Resumen La investigación tuvo como propósito estimar la prevalencia del Trastorno por Déficit de Atención con Hiperactividad (TDAH) en Costa Rica y determinar si la versión en español del cuestionario Swanson Nolan and Pelham Scale IV (SNAP-IV) es un instrumento de tamizaje útil en una población de niños y niñas escolares costarricenses. El instrumento fue entregado a padres y maestros de 425 niños entre 5 y 13 años de edad (promedio = 8.8). Todos fueron evaluados con el instrumento Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP). Su diagnóstico fue confirmado con una entrevista clínica. La sensibilidad y la especificidad del SNAP-IV fueron evaluadas como predictores de criterios de diagnóstico según el DSM-IV. La prevalencia puntual en la muestra del TDAH fue del 5%. El tamizaje más preciso lo hizo el SNAP-IV completado por el maestro en un corte de 20%, con una sensibilidad de 96% y una especificidad de un 82%. La sensibilidad de los instrumentos completados por los padres fue más baja que aquella de los maestros. El SNAP-IV completado por las maestras con un corte aislando el 20% de los mayores puntajes categorizó correctamente a un 87% de los sujetos. PMID:22432094

  17. Targeting of Neisserial PorB to the mitochondrial outer membrane: an insight on the evolution of β-barrel protein assembly machines.

    PubMed

    Jiang, Jhih-Hang; Davies, John K; Lithgow, Trevor; Strugnell, Richard A; Gabriel, Kipros

    2011-11-01

    Mitochondria originated from Gram-negative bacteria through endosymbiosis. In modern day mitochondria, the Sorting and Assembly Machinery (SAM) is responsible for eukaryotic β-barrel protein assembly in the mitochondrial outer membrane. The SAM is the functional equivalent of the β-barrel assembly machinery found in the outer membrane of Gram-negative bacteria. In this study we examined the import pathway of a pathogenic bacterial protein, PorB, which is targeted from pathogenic Neisseria to the host mitochondria. We have developed a new method for measurement of PorB assembly into mitochondria that relies on the mobility shift exhibited by bacterial β-barrel proteins once folded and separated under semi-native electrophoretic conditions. We show that PorB is targeted to the outer mitochondrial membrane with a dependence on the intermembrane space shuttling chaperones and the core component of the SAM, Sam50, which is a functional homologue of BamA that is required for PorB assembly in bacteria. The peripheral subunits of the SAM, Sam35 and Sam37, which are essential for eukaryotic β-barrel protein assembly but do not have distinguishable functional homologues in bacteria, are not required for PorB assembly in eukaryotes. This shows that PorB uses an evolutionary conserved 'bacterial like' mechanism to infiltrate the host mitochondrial outer membrane. PMID:22032638

  18. Epitope specificity of murine and human bactericidal antibodies against PorA P1.7,16 induced with experimental meningococcal group B vaccines.

    PubMed

    Rouppe van der Voort, E M; Kuipers, B; Brugghe, H F; van Unen, L M; Timmermans, H A; Hoogerhout, P; Poolman, J T

    1997-03-01

    Synthetic peptides derived from the predicted loops 1 and 4 of meningococcal PorA, sero-subtype P1.7,16, were used to study the epitope specificity of murine and human PorA P1.7,16 bactericidal antibodies. The predicted loops 1 and 4 are surface exposed and carry in their apices the sero-subtype epitopes P1.7 (loop 1) or P1.16 (loop 4), respectively. Peptides were synthesized as mono- and multimeric peptides. Murine monoclonal and polyclonal antibodies were induced with meningococcal whole cell preparations. Polyclonal antibodies were evoked in volunteers after one immunization with 50 micrograms or 100 micrograms protein of a hexavalent meningococcal PorA vesicle vaccine. The induction of PorA antibodies was determined in ELISA using purified PorA P1.7,16. The epitope specificity of anti-PorA antibodies for both murine and human antibodies could be demonstrated by direct peptide ELISA using overlapping multimeric peptides almost spanning the entire loops 1 or 4 of the protein. The capacity of peptides to inhibit the bactericidal activity of murine and human antibodies was investigated using meningococcal strain H44/76 (B:15:P1.7,16) as a target strain. Bactericidal activities could be inhibited with both monomeric and multimeric peptides derived from epitopes P1.7 and P1.16. PMID:9093834

  19. Effect of acid secretion blockade on acute gastric mucosal lesions induced by Tityus serrulatus scorpion toxin in anaesthetized rats.

    PubMed

    Melo, Júnio Rios; de Araújo, Gnana Keith Marques; da Luz, Magda Maria Profeta; da Conceição, Sérgio Alexandre; Lisboa, Felipe Assis; Moraes-Santos, Tasso; Cunha-Melo, José Renan

    2006-10-01

    Scorpion venom (TX) promotes gastric acid and pepsin secretion leading to acute gastric mucosal lesions (AGML), when injected in animals. The goal of the present study was to observe the effects of acid gastric secretion blockers over the incidence of TX-induced AGML in vivo. To verify this model, we used male albino rats, fasted 18-20 h (n=122) and anaesthetized with urethane (1.4 g/kg, i.p.). Their trachea and left femoral vein were both cannulated; the first to avoid airway obstructions during scorpion intoxication and the second for administration of saline, TX and acid blockers. Following the surgical procedure, the animals were divided in 10 groups of at least 10 animals each. Control groups were injected with NaCl 0.9% 1 ml/kg (n=10) or TX 375 microg/kg (n=32). Test groups (n=10, each) received atropine 5 mg/kg, cimetidine 10mg/kg, ranitidine 2.5mg/kg, ranitidine 5mg/kg, omeprazol 1 mg/kg, omeprazol 4 mg/kg, octreotide 80 and octreotide 100 microg/kg 10 min before the TX was injected. After 1h of intoxication, the stomach was resected for macroscopic study and the gastric secretion was collected for volume, pH and acid output assessment. We observed that all blockers were able to completely or partially prevent the TX-induced acid secretion as well as the AGML (p<0.05). Our data suggest the TX-induced AGML can be prevented by different class of acid blockers injected before the intoxication. PMID:16926041

  20. Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors.

    PubMed

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro-Junior, Ernesto Lopes; Zoccal, Karina Furlani; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Peigneur, Steve; Vriens, Kim; Thevissen, Karin; Cammue, Bruno Philippe Angelo; Júnior, Ronaldo Bragança Martins; Arruda, Eurico; Faccioli, Lúcia Helena; Tytgat, Jan; Arantes, Eliane Candiani

    2016-08-01

    The present study purifies two T. serrulatus non-disulfide-bridged peptides (NDBPs), named venom peptides 7.2 (RLRSKG) and 8 (KIWRS) and details their synthesis and biological activity, comparing to the synthetic venom peptide 7.1 (RLRSKGKK), previously identified. The synthetic replicate peptides were subjected to a range of biological assays: hemolytic, antifungal, antiviral, electrophysiological, immunological and angiotensin-converting enzyme (ACE) inhibition activities. All venom peptides neither showed to be cytolytic nor demonstrated significant antifungal or antiviral activities. Interestingly, peptides were able to modulate macrophages' responses, increasing IL-6 production. The three venom peptides also demonstrated potential to inhibit ACE in the following order: 7.2>7.1>8. The ACE inhibition activity was unexpected, since peptides that display this function are usually proline-rich peptides. In attempt to understand the origin of such small peptides, we discovered that the isolated peptides 7.2 and 8 are fragments of the same molecule, named Pape peptide precursor. Furthermore, the study discusses that Pape fragments could be originated from a post-splitting mechanism resulting from metalloserrulases and other proteinases cleavage, which can be seen as a clever mechanism used by the scorpion to enlarge its repertoire of venom components. Scorpion venom remains as an interesting source of bioactive proteins and this study advances our knowledge about three NDBPs and their biological activities. PMID:27221550

  1. Characterizing Tityus discrepans scorpion venom from a fractal perspective: Venom complexity, effects of captivity, sexual dimorphism, differences among species.

    PubMed

    D'Suze, Gina; Sandoval, Moisés; Sevcik, Carlos

    2015-12-15

    A characteristic of venom elution patterns, shared with many other complex systems, is that many their features cannot be properly described with statistical or euclidean concepts. The understanding of such systems became possible with Mandelbrot's fractal analysis. Venom elution patterns were produced using the reversed phase high performance liquid chromatography (HPLC) with 1 mg of venom. One reason for the lack of quantitative analyses of the sources of venom variability is parametrizing the venom chromatograms' complexity. We quantize this complexity by means of an algorithm which estimates the contortedness (Q) of a waveform. Fractal analysis was used to compare venoms and to measure inter- and intra-specific venom variability. We studied variations in venom complexity derived from gender, seasonal and environmental factors, duration of captivity in the laboratory, technique used to milk venom. PMID:26415902

  2. Análise dos Conceitos Astronômicos Apresentados por Professores de Algumas Escolas Estaduais Brasileiras

    NASA Astrophysics Data System (ADS)

    Voelzke, Marcos Rincon; Gonzaga, Edson Pereira

    2011-12-01

    A razão para o desenvolvimento deste trabalho baseia-se no fato de que muitos professores da Educação Básica (EB) não lidam com conceitos relacionados à astronomia, e quando o fazem eles simplesmente seguem livros didáticos que podem conter erros conceituais. Como é de conhecimento geral a astronomia é um dos conteúdos a serem ensinados na EB fazendo parte dos Parâmetros Curriculares Nacionais e das Propostas Curriculares do Estado de São Paulo, mas é um fato, que vários pesquisadores apontam, a existência de muitos problemas no ensino da astronomia. Com o propósito de minimizar algumas dessas deficiências foi realizado um trabalho de pesquisa com a utilização de questionários pré e pós pesquisa, para tanto foi desenvolvido um Curso de Extensão Universitária para professores da Diretoria de Ensino Regional (DE) que abrange Mauá, Ribeirão Pires e Rio Grande da Serra (no Estado de São Paulo) com os seguintes objetivos: levantar concepções alternativas; subsidiar os professores por meio de palestras, debates e workshops, e verificar o sucesso da aprendizagem após o curso, adotando-se como referência, para a análise dos resultados, os dicionários de Língua Portuguesa (FERREIRA, 2004) e Enciclopédico de Astronomia e Astronáutica (MOURĀO, 1995). Portanto, dezesseis questões foram aplicadas antes e após o curso, assim pode-se verificar após a pesquisa que 100,0% dos professores sabiam os nomes das fases da Lua, 97,0% entenderam que o Sistema Solar é composto por oito planetas, 78,1% foram capazes de explicar como ocorre um eclipse lunar, um eclipse solar e um solstício, 72,7% sabiam como explicar a ocorrência das estações do ano; 64,5% explicaram corretamente a ocorrência do equinócio, 89,7% foram capazes de definir adequadamente o termo cometa; 63,6% definiram asteróide, 54,5% meteoro, 58,1% galáxia, e 42,4% planeta. Os resultados obtidos indicam uma aprendizagem significativa por parte dos participantes.

  3. Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins.

    PubMed

    Cartwright, K; Morris, R; Rümke, H; Fox, A; Borrow, R; Begg, N; Richmond, P; Poolman, J

    1999-06-01

    The development of effective vaccines against serogroup B meningococci is of great public health importance. We assessed a novel genetically engineered vaccine containing six meningococcal class 1 (PorA) outer membrane proteins representing 80% of prevalent strains in the UK. 103 infants were given the meningococcal vaccine at ages 2, 3 and 4 months with routine infant immunisations, with a fourth dose at 12-18 months. The vaccine was well tolerated. Three doses evoked good immune responses to two of six meningococcal strains expressing PorA proteins contained in the vaccine. Following a fourth dose, larger bactericidal responses to all six strains were observed, suggesting that the initial course had primed memory lymphocytes and revaccination stimulated a booster response. This hexavalent PorA meningococcal vaccine was safe and evoked encouraging immune responses in infants. Vaccines of this type warrant further development and evaluation. PMID:10418910

  4. Crystallization and preliminary X-ray analysis of the C-terminal fragment of PorM, a subunit of the Porphyromonas gingivalis type IX secretion system.

    PubMed

    Stathopulos, Julien; Cambillau, Christian; Cascales, Eric; Roussel, Alain; Leone, Philippe

    2015-01-01

    PorM is a membrane protein involved in the assembly of the type IX secretion system (T9SS) from Porphyromonas gingivalis, a major bacterial pathogen responsible for periodontal disease in humans. The periplasmic domain of PorM was overexpressed in Escherichia coli and purified. A fragment of the purified protein was obtained by limited proteolysis. Crystals of this fragment belonged to the tetragonal space group P4(3)2(1)2. Native and MAD data sets were recorded to 2.85 and 3.1 Å resolution, respectively, using synchrotron radiation. PMID:25615973

  5. "Estudio tribologico de aceros para moldes. Aplicacion al moldeo por inyeccion de polibutilentereftalato reforzado con fibra de vidrio"

    NASA Astrophysics Data System (ADS)

    Martinez Mateo, Isidoro Jose

    Mould materials for injection moulding of polymers and polymer-matrix composites represent a relevant industrial economic sector due to the large quantity of pieces and components processed. The material selection for mould manufacturing, its composition and heat treatment, the hardening procedures and machining and finishing processes determine the service performance and life of the mould. In the first part of the present study, the relationship between the hardness and microstructure and the wear resistance of mould steels from large blocks has been studied by pin-on-disc tests, studying the main wear mechanisms. In order to determine the surface damage on mould steels under real injection conditions, different commercial steels have been studied by measuring the variation of surface roughness with the number of injected pieces with different reinforcement percentages and different mould geometries, by using optical profilometry and scanning electron microscopy techniques. It was important to determine the variation of surface roughness of the moulded pieces with the number of injection operations. The materials used were polybutyleneterephthalate pure and reinforced with either 20% or 50% glass fibre. For the different mould designs, the evolution of the glass fibre orientation with injection flow has been determined by image analysis and related to roughness changes and surface damage, both of the composite parts and of the mould steel surface. Finally, the abrasion resistance of the composite parts has been studied by scratch tests as a function of the number of injected parts and of the scratch direction with respect to injection flow and glass fibre orientation. Los materiales para moldes de inyeccion de polimeros y materiales compuestos representan un sector economicamente muy relevante debido al gran aumento del numero de componentes fabricados a partir de materiales polimericos obtenidos mediante moldeo por inyeccion. La seleccion del material para la

  6. P(O)R2-directed Pd-catalyzed C–H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands

    PubMed Central

    Hu, Rong-Bin; Wang, Hong-Li; Zhang, Hong-Yu; Zhang, Heng; Ma, Yan-Na

    2014-01-01

    Summary Chiral phosphorus ligands have been widely used in transition metal-catalyzed asymmetric reactions. Herein, we report a new synthesis approach of chiral biaryls containing a phosphorus moiety using P(O)R2-directed Pd-catalyzed C–H activation; the functionalized products are produced with good enantioselectivity. PMID:25246966

  7. Adult Student Retention and Achievement with Language-Based Modular Materials. POR FIN: Program Organizing Related Family Instruction in the Neighborhood.

    ERIC Educational Resources Information Center

    Bexar County School Board, San Antonio, TX.

    The goal of the POR FIN research design was to develop a language-based curriculum emphasizing the audiolingual approach and integrating academic and social-functioning subject matter. The modular curriculum is designed so that each lesson is independent and complete in itself, and provides a high degree of motivation, retention, and achievement…

  8. Informe a la nación indica que los índices de muertes por cáncer siguen bajando

    Cancer.gov

    Los índices de mortalidad por todos los cánceres combinados para hombres, mujeres y niños siguieron bajando en Estados Unidos entre 2004 y 2008, según el Informe Anual a la Nación sobre el Estado del Cáncer de 1975 a 2008. El índice general de diagnóstico

  9. El proceso hacia la integracion de la equidad por genero al curriculo.(The Process of the Integration of Gender Equity in the Curriculum.)

    ERIC Educational Resources Information Center

    Rivera-Bermudez, Carmen D.

    "El Proyecto Colaborativo de Equidad por Genero en la Educacion," or the Collaborative Project for Gender Equity in Education, was undertaken in Puerto Rico between 1990 and 1992 to study how to facilitate the integration of gender equity themes in the curriculum through the direct action of participating teachers. A study examined the attitudes…

  10. Community-based education in nutrition and cancer: the Por La Vida Cuidándome curriculum.

    PubMed

    Navarro, A M; Rock, C L; McNicholas, L J; Senn, K L; Moreno, C

    2000-01-01

    The Por La Vida (PLV) intervention model relies on community lay health advisors trained to conduct education sessions among members of their existing social networks. PLV Cuidándome was funded by the NCI to develop, implement, and evaluate the PLV model with respect to nutrition and cancer prevention, as well as early detection of breast and cervical cancers. The target population is the Latino community, for which substantial barriers to health care access exist. This article presents the curriculum that guides the sessions and describes its development, which was based on semi-structured interviews with Latina lay-health community workers to explore relevant attitudes and behaviors. Also key to the process was the work of the educational materials committee, whose members offered community representation as well as expertise in nutritional sciences, educational technologies, and community-based health promotion interventions and research. The 12-session curriculum's goal was to increase both the variety and the quality of fruits and/or vegetables consumed. It included information about consumption of fiber and fat in the importance of balance between energy intake and physical activity. The program has been well received. An ongoing study examines how it enhances nutrition and cancer prevention. PMID:11019766

  11. Estimaciones de Prevalencia del VIH por Género y Grupo de Riesgo en Tijuana, México: 2006

    PubMed Central

    Iñiguez-Stevens, Esmeralda; Brouwer, Kimberly C.; Hogg, Robert S.; Patterson, Thomas L.; Lozada, Remedios; Magis-Rodriguez, Carlos; Elder, John P.; Viani, Rolando M.; Strathdee, Steffanie A.

    2010-01-01

    OBJETIVO Estimar la prevalencia del VIH en adultos de 15-49 años de edad en Tijuana, México - en la población general y en subgrupos de riesgo en el 2006. METODOS Se obtuvieron datos demográficos del censo Mexicano del 2005, y la prevalencia del VIH se obtuvo de la literatura. Se construyó un modelo de prevalencia del VIH para la población general y de acuerdo al género. El análisis de sensibilidad consistió en estimar errores estándar del promedio-ponderado de la prevalencia del VIH y tomar derivados parciales con respecto a cada parámetro. RESULTADOS La prevalencia del VIH es 0.54%(N = 4,347) (Rango: 0.22%–0.86%, (N = 1,750–6,944)). Esto sugiere que 0.85%(Rango: 0.39%–1.31%) de los hombres y 0.22%(Rango: 0.04%–0.40%) de las mujeres podrían ser VIH-positivos. Los hombres que tienen sexo con hombres (HSH), las trabajadoras sexuales usuarias de drogas inyectables (MTS-UDI), MTS-noUDI, mujeres UDI, y los hombres UDI contribuyeron las proporciones más elevadas de personas infectadas por el VIH. CONCLUSIONES El número de adultos VIH-positivos entre subgrupos de riesgo en la población de Tijuana es considerable, marcando la necesidad de enforcar las intervenciones de prevención en sus necesidades específicas. El presente modelo estima que hasta 1 en cada 116 adultos podrían ser VIH-positivos. PMID:19685824

  12. Study of the interaction mechanisms between absorbed NO{sub 2} and por-Si/SnO{sub x} nanocomposite layers

    SciTech Connect

    Bolotov, V. V.; Kan, V. E. Makushenko, R. K.; Biryukov, M. Yu.; Ivlev, K. E.; Roslikov, V. E.

    2013-10-15

    The interaction mechanisms between NO{sub 2} molecules and the surface of por-Si/SnO{sub x} nanocomposites obtained by magnetron deposition and chemical vapor deposition (CVD) are studied by infrared absorption spectroscopy and electron paramagnetic resonance methods. The observed increase in the free carrier concentration in the por-Si/SnO{sub x} nanocomposite layers is explained by a change in the charge state of P{sub b} centers due to the formation of neutral 'surface defect-adsorbed NO{sub 2} molecule' complexes with free carrier generation in the crystallite bulk. In the nanocomposite layers grown by the CVD method, the increase in the free hole concentration during NO{sub 2} adsorption is much less pronounced in comparison with the composite grown by magnetron deposition, which is caused by the competing interaction channel of NO{sub 2} molecules with electrically neutral P{sub b} centers.

  13. Los índices de mortalidad por cáncer de pulmón siguen en descenso y contribuyen a la continua reducc

    Cancer.gov

    El Informe Anual a la Nación sobre el Estado del Cáncer (1975 a 2010), mostró un descenso más acelerado que en años anteriores de los índices de mortalidad por cáncer de pulmón. También contiene una sección especial que destaca los efectos significativos

  14. La doctora Amelie Ramírez y la investigación de desigualdades de salud por cáncer en la comunidad la

    Cancer.gov

    La doctora Ramírez es la investigadora principal de Redes en Acción, un centro del programa de redes comunitarias subvencionado por el NCI que se propone reducir la incidencia del cáncer en la comunidad latina a través de una red nacional de grupos comunitarios, investigadores, agencias de salud gubernamentales y la población en general.

  15. Binding of Complement Factor H to PorB3 and NspA Enhances Resistance of Neisseria meningitidis to Anti-Factor H Binding Protein Bactericidal Activity

    PubMed Central

    Giuntini, Serena; Pajon, Rolando; Ram, Sanjay

    2015-01-01

    Among 25 serogroup B Neisseria meningitidis clinical isolates, we identified four (16%) with high factor H binding protein (FHbp) expression that were resistant to complement-mediated bactericidal activity of sera from mice immunized with recombinant FHbp vaccines. Two of the four isolates had evidence of human FH-dependent complement downregulation independent of FHbp. Since alternative complement pathway recruitment is critical for anti-FHbp bactericidal activity, we hypothesized that in these two isolates binding of FH to ligands other than FHbp contributes to anti-FHbp bactericidal resistance. Knocking out NspA, a known meningococcal FH ligand, converted both resistant isolates to anti-FHbp susceptible isolates. The addition of a nonbactericidal anti-NspA monoclonal antibody to the bactericidal reaction also increased anti-FHbp bactericidal activity. To identify a role for FH ligands other than NspA or FHbp in resistance, we created double NspA/FHbp knockout mutants. Mutants from both resistant isolates bound 10-fold more recombinant human FH domains 6 and 7 fused to Fc than double knockout mutants prepared from two sensitive meningococcal isolates. In light of recent studies showing functional FH-PorB2 interactions, we hypothesized that PorB3 from the resistant isolates recruited FH. Allelic exchange of porB3 from a resistant isolate to a sensitive isolate increased resistance of the sensitive isolate to anti-FHbp bactericidal activity (and vice versa). Thus, some PorB3 variants functionally bind human FH, which in the presence of NspA enhances anti-FHbp resistance. Combining anti-NspA antibodies with anti-FHbp antibodies can overcome resistance. Meningococcal vaccines that target both NspA and FHbp are likely to confer greater protection than either antigen alone. PMID:25644002

  16. Corynebacterium jeikeium jk0268 Constitutes for the 40 Amino Acid Long PorACj, Which Forms a Homooligomeric and Anion-Selective Cell Wall Channel

    PubMed Central

    Norouzy, Amir; Schulz, Robert; Nau, Werner M.; Kleinekathöfer, Ulrich; Tauch, Andreas; Benz, Roland

    2013-01-01

    Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed. PMID:24116064

  17. Adjuvant Effects Elicited by Novel Oligosaccharide Variants of Detoxified Meningococcal Lipopolysaccharides on Neisseria meningitidis Recombinant PorA Protein: A Comparison in Mice

    PubMed Central

    Mehta, Ojas H.; Norheim, Gunnstein; Hoe, J . Claire; Rollier, Christine S.; Nagaputra, Jerry C.; Makepeace, Katherine; Saleem, Muhammad; Chan, Hannah; Ferguson, David J. P.; Jones, Claire; Sadarangani, Manish; Hood, Derek W.; Feavers, Ian; Derrick, Jeremy P.; Pollard, Andrew J.; Moxon, E . Richard

    2014-01-01

    Neisseria meningitidis lipopolysaccharide (LPS) has adjuvant properties that can be exploited to assist vaccine immunogenicity. The modified penta-acylated LPS retains the adjuvant properties of hexa-acylated LPS but has a reduced toxicity profile. In this study we investigated whether two modified glycoform structures (LgtE and IcsB) of detoxified penta-acylated LPS exhibited differential adjuvant properties when formulated as native outer membrane vesicles (nOMVs) as compared to the previously described LgtB variant. Detoxified penta-acylated LPS was obtained by disruption of the lpxL1 gene (LpxL1 LPS), and three different glycoforms were obtained by disruption of the lgtB, lgtE or icsB genes respectively. Mice (mus musculus) were immunized with a recombinant PorA P1.7-2,4 (rPorA) protein co-administered with different nOMVs (containing a different PorA serosubtype P1.7,16), each of which expressed one of the three penta-acylated LPS glycoforms. All nOMVs induced IgG responses against the rPorA, but the nOMVs containing the penta-acylated LgtB-LpxL1 LPS glycoform induced significantly greater bactericidal activity compared to the other nOMVs or when the adjuvant was Alhydrogel. Compared to LgtE or IcsB LPS glycoforms, these data support the use of nOMVs containing detoxified, modified LgtB-LpxL1 LPS as a potential adjuvant for future meningococcal protein vaccines. PMID:25545241

  18. Binding of complement factor H to PorB3 and NspA enhances resistance of Neisseria meningitidis to anti-factor H binding protein bactericidal activity.

    PubMed

    Giuntini, Serena; Pajon, Rolando; Ram, Sanjay; Granoff, Dan M

    2015-04-01

    Among 25 serogroup B Neisseria meningitidis clinical isolates, we identified four (16%) with high factor H binding protein (FHbp) expression that were resistant to complement-mediated bactericidal activity of sera from mice immunized with recombinant FHbp vaccines. Two of the four isolates had evidence of human FH-dependent complement downregulation independent of FHbp. Since alternative complement pathway recruitment is critical for anti-FHbp bactericidal activity, we hypothesized that in these two isolates binding of FH to ligands other than FHbp contributes to anti-FHbp bactericidal resistance. Knocking out NspA, a known meningococcal FH ligand, converted both resistant isolates to anti-FHbp susceptible isolates. The addition of a nonbactericidal anti-NspA monoclonal antibody to the bactericidal reaction also increased anti-FHbp bactericidal activity. To identify a role for FH ligands other than NspA or FHbp in resistance, we created double NspA/FHbp knockout mutants. Mutants from both resistant isolates bound 10-fold more recombinant human FH domains 6 and 7 fused to Fc than double knockout mutants prepared from two sensitive meningococcal isolates. In light of recent studies showing functional FH-PorB2 interactions, we hypothesized that PorB3 from the resistant isolates recruited FH. Allelic exchange of porB3 from a resistant isolate to a sensitive isolate increased resistance of the sensitive isolate to anti-FHbp bactericidal activity (and vice versa). Thus, some PorB3 variants functionally bind human FH, which in the presence of NspA enhances anti-FHbp resistance. Combining anti-NspA antibodies with anti-FHbp antibodies can overcome resistance. Meningococcal vaccines that target both NspA and FHbp are likely to confer greater protection than either antigen alone. PMID:25644002

  19. Immunogenicity studies with a genetically engineered hexavalent PorA and a wild-type meningococcal group B outer membrane vesicle vaccine in infant cynomolgus monkeys.

    PubMed

    Rouppe van der Voort, E; Schuller, M; Holst, J; de Vries, P; van der Ley, P; van den Dobbelsteen, G; Poolman, J

    2000-01-31

    The immunogenicity of two meningococcal outer membrane vesicle (OMV) vaccines, namely the Norwegian wild-type OMV vaccine and the Dutch hexavalent PorA OMV vaccine, were examined in infant cynomolgus monkeys. For the first time, a wild-type- and a recombinant OMV vaccine were compared. Furthermore, the induction of memory and the persistence of circulating antibodies were measured. The Norwegian vaccine contained all four classes of major outer membrane proteins (OMP) and wild-type L3/L8 lipopolysaccharide (LPS). The Dutch vaccine consisted for 90% of class 1 OMPs, had low expression of class 4 and 5 OMP, and GalE LPS. Three infant monkeys were immunised with a human dose at the age of 1.5, 2.5 and 4.5 months. Two monkeys of each group received a fourth dose at the age of 11 months. In ELISA, both OMV vaccines were immunogenic and induced booster responses, particularly after the fourth immunisation. The Norwegian vaccine mostly induced sero-subtype P1.7,16 specific serum bactericidal antibodies (SBA), although some other SBA were induced as well. The antibody responses against P1.7,16, induced by the Norwegian vaccine, were generally higher than for the Dutch vaccine. However, the Dutch vaccine induced PorA specific SBA against all six sero-subtypes included in the vaccine showing differences in the magnitude of SBA responses to the various PorAs. PMID:10618530

  20. Obtención de la curva de luz en la ocultación de 35 Sgr por Júpiter el 6 de marzo de 1996

    NASA Astrophysics Data System (ADS)

    Paolantonio, S.; Duffard, R.; Carranza, G.

    La ocultación de la estrella de quinta magnitud 35 Sgr por Júpiter, se produjo el 6 de Marzo de 1996 a las 13 hs. TU. El objetivo era medir el cambio del flujo de la estrella en el ingreso y egreso por el limbo del planeta. Con estos datos se pueden determinar parámetros físicos del planeta (radio, eccentricidad) y de su atmósfera (escala de altura, temperatura, densidad, presión) Para lograr ésto se programó la cámara CCD TH 7896 1024 x 1025 instalada en el telescopio de 1.54 m de Bosque Alegre con el objetivo de lograr 2 imágenes por segundo. De esta forma se obtuvieron 2100 imágenes de la inmersión y otras tantas de la emersión. Hubo que tener grandes precauciones para evitar la saturación del CCD ya que la observación se realizó de día. En este momento las imágenes se encuentran en el Department of Planetary Sciences, Lunar and Planetary Laboratory, University of Arizona, para su reducción.

  1. Astronomy in the Classroom: Why? (Spanish Title: Astronomía en la Clase: ¿Por Qué?) Astronomia na Sala de Aula: Por Quê?

    NASA Astrophysics Data System (ADS)

    Daros Gama, Leandro; Bagdonas Henrique, Alexandre

    2010-07-01

    There are many discussions about the relevance of the topics covered in classes. One subject in particular is the focus of this essay: astronomy. In what sense and to what extent it would be worth to teach it in science or other kind of classes? In this paper we discuss some aspects of the advantages of dealing with this area of knowledge in schools, taking into account the epistemological and axiological dimensions of astronomy, in light of the vision of science as an intelligent dialogue with the world (Bachelard), in addition to the "problematization" knowledge of Paulo Freire. We propose that in fact the Astronomy does not need to be seen as just a new set of contents to be taught, but appears as a set of motivational contents for historical-philosophical discussions, and permit the discussion of concepts of other disciplines. Numerosas discusiones se están llevando a cabo acerca de la pertinencia de los temas tradicionalmente tratados en las clases. Uno de los temas, en particular, es el foco de este ensayo: la astronomía. ¿En qué sentido y en qué medida sería conveniente tratarla en clase, ya sea en clases de ciencias naturales, específicamente en las de astronomía o asignaturas afines? Elaboramos en este artículo algunos aspectos de las ventajas de tratar esta área del conocimiento en las escuelas, teniendo en cuenta las dimensiones epistemológica y axiológica de la astronomía, a la luz de la visión de la ciencia como un diálogo inteligente con el mundo (Bachelard), además de la propuesta del conocimiento "problematizador" de Paulo Freire. Proponemos que en realidad la astronomía no tiene por qué ser vista sólo como un nuevo conjunto de contenidos que se enseñan, sino que aparece como un conjunto de temas de motivación para el debate histórico-filosófico y para permitir la discusión de los conceptos típicos de otras disciplinas. Muitas discussões vêm acontecendo sobre a relevância dos temas abordados em sala de aula. Um tema, em

  2. Pincharse sin infectarse: estrategias para prevenir la infección por el VIH y el VHC entre usuarios de drogas inyectables

    PubMed Central

    MATEU-GELABERT, P.; FRIEDMAN, S.; SANDOVAL, M.

    2011-01-01

    Resumen Objetivo Desde principios de los noventa, en la ciudad de Nueva York se han implementado con éxito programas para reducir la incidencia del virus de la inmunodeficiencia humana (VIH) y, en menor medida, del virus de la hepatitis C (VHC). A pesar de ello, aproximadamente el 70% de los usuario de drogas inyectables (UDI) están infectados por el VHC. Queremos investigar cómo el 30% restante se las ha arreglado para no infectarse. El Staying safe (nombre original del estudio) explora los comportamientos y mecanismos que ayudan a evitar la infección por el VHC y el VIH a largo plazo. Material y métodos Hemos utilizado el concepto de «desviación positiva» aplicado en otros campos de salud pública. Estudiamos las estrategias, prácticas y tácticas de prevención de aquellos UDI que, viviendo en contextos de alta prevalencia, se mantienen sin infectar por VIH y el VHC, a pesar de haberse inyectado heroína durante años. Los resultados preliminares presentados en este artículo incluyen el análisis de las entrevistas realizadas a 25 UDI (17 doble negativos, 3 doble positivos y 5 con infección por el VHC y sin infección por el VIH). Se usaron entrevistas semiestructuradas que exploraban con detalle la historia de vida de los sujetos, incluyendo su consumo de drogas, redes sociales, contacto con instituciones, relaciones sexuales y estrategias de protección y vigilancia. Resultados La intencionalidad es importante para no infectarse, especialmente durante períodos de involución (períodos donde hay un deterioro económico y/o social que llevan al que se inyecta a situaciones de mayor riesgo). Presentamos tres dimensiones independientes de intencionalidad que conllevan comportamientos que pueden ayudar a prevenir la infección: a) evitar «el mono» (síntomas de abstención) asegurando el acceso a la droga; b) «llevarlo bien» para no convertirse en un junkie y así evitar la «muerte social» y la falta de acceso a los recursos, y c) seguir sin

  3. [Ag20 {S2 P(OR)2 }12 ]: A Superatom Complex with a Chiral Metallic Core and High Potential for Isomerism.

    PubMed

    Dhayal, Rajendra S; Lin, Yan-Ru; Liao, Jian-Hong; Chen, Yuan-Jang; Liu, Yu-Chiao; Chiang, Ming-Hsi; Kahlal, Samia; Saillard, Jean-Yves; Liu, C W

    2016-07-11

    The synthesis and structural determination of a silver nanocluster [Ag20 {S2 P(OiPr)2 }12 ] (2), which contains an intrinsic chiral metallic core, is produced by reduction of one silver ion from the eight-electron superatom complex [Ag21 {S2 P(OiPr)2 }12 ](PF6 ) (1) by borohydrides. Single-crystal X-ray analysis displays an Ag20 core of pseudo C3 symmetry comprising a silver-centered Ag13 icosahedron capped by seven silver atoms. Its n-propyl derivative, [Ag20 {S2 P(OnPr)2 }12 ] (3), can also be prepared by the treatment of silver(I) salts and dithiophosphates in a stoichiometric ratio in the presence of excess amount of [BH4 ](-) . Crystal structure analyses reveal that the capping silver-atom positions relative to their icosahedral core are distinctly different in 2 and 3 and generate isomeric, chiral Ag20 cores. Both Ag20 clusters display an emission maximum in the near IR region. DFT calculations are consistent with a description within the superatom model of an 8-electron [Ag13 ](5+) core protected by a [Ag7 {S2 P(OR)2 }12 ](5-) external shell. Two additional structural variations are predicted by DFT, showing the potential for isomerism in such [Ag20 {S2 P(OR)2 }12 ] species. PMID:27189869

  4. A survey of homopteran species (Auchenorrhyncha) from coffee shrubs and poró and laurel trees in shaded coffee plantations, in Turrialba, Costa Rica.

    PubMed

    Rojas, L; Godoy, C; Hanson, P; Hilje, L

    2001-01-01

    A survey of homopteran species (Auchenorryncha) was conducted in coffee plantations with no shade (C), and in those with shade of either poró (Erythrina poeppigiana) (CP) or poró plus laurel (Cordia alliodora) (CPL), in Turrialba, Costa Rica. A total of 130 species in ten families were collected, dominated by Cicadellidae (82 species). Species richness was highest in the CP system (88), followed by CPL (74) and C systems (60). Five most common species for all systems were Fusigonalia lativittata, Hebralebra nicaraguensis, Neocoelidia sp., Oliarus sp. and Clastoptera sp. Diversification of the coffee agroecosystem favors some species while limiting others, and have no effect on the majority of species. Thus, only F. lativittata, Neocoelidia sp. and Scaphytopius ca. latidens were well represented in all systems, but were more abundant in coffee shrubs. Additionally, the following were the dominant species in each system: Graphocephala sp. 1 (C), F. lativittata (CP) and H. nicaraguensis (CPL). Four species abundant on laurel trees, including H. nicaraguensis, appeared almost exclusively on these tree species. Species similarity was highest on the CP and CPL systems (51% of the species in common), followed by the C and CP (39%) and the C and CPL systems (38%). These findings show that even disturbed systems can harbor many insect species, so that they deserve attention from conservation advocates and biologists. PMID:12189787

  5. TsTX-IV, a short chain four-disulfide-bridged neurotoxin from Tityus serrulatus venom which acts on Ca2+-activated K+ channels.

    PubMed

    Novello, J C; Arantes, E C; Varanda, W A; Oliveira, B; Giglio, J R; Marangoni, S

    1999-04-01

    The primary structure of TsTX-IV, a neurotoxin isolated from Tityrus serrulatus scorpion venom, is reported. Its amino acid sequence was determined by automated Edman sequential degradation of the reduced and carboxymethylated toxin and of relevant peptides obtained by digestion with Staphylococcus aureus strain V8 protease or trypsin and cleavage by CNBr. The complete sequence showed 41 amino acid residues, which account for an estimated molecular weight of 4520, and eight half-cystine residues which cross-link the toxin molecule with four disulfide bonds. The molecular weight determined by mass spectrometry was 4518. Comparison of this sequence with those from other scorpion toxins showed a resemblance with toxins which act on different types of K+ channels. TsTx-IV was able to block Ca2+-activated K+ channels of high conductance. TsTX-IV is the first four-disulfide-bridged short toxin from T. serrulatus so far completely sequenced. PMID:10082164

  6. Probing the pH-dependent structural features of α-KTx12.1, a potassium channel blocker from the scorpion Tityus serrulatus

    PubMed Central

    Oyama, Sérgio; Pristovšek, Primož; Franzoni, Lorella; Pertinhez, Thelma A.; Schininá, Eugenia; Lücke, Christian; Rüterjans, Heinz; Arantes, Eliane Candiani; Spisni, Alberto

    2005-01-01

    Potassium channels are widespread in living cells and are involved in many diseases. The scorpion toxin α-KTx12.1 interacts with various K+ channels, suggesting its capacity to match diverse channel pores. It is recognized that tissue injuries may affect the pH at toxins site of action, thereby modulating both protein conformation and activity. To better understand its molecular mechanism of action, we studied α-KTx12.1 using pH as a tool to explore its plasticity and NMR in combination with MD calculations to detect it. The toxin solution structure consists of an α-helix and a triple-stranded β-sheet stabilized by four disulfide bridges. The NMR results show, in addition, that His28 possesses an unusually low pKa of 5.2. The best set of protein conformers is obtained at pH 4.5, while at pH 7.0, the reduced number of NOEs resulting from a faster hydrogen exchange does not allow to reach a good structural convergence. Nonetheless, MD calculations show that the toxin structure does not vary significantly in that pH range, while conformational changes and modifications of the surface charge distribution occur when His28 is fully protonated. Moreover, essential dynamics analysis reveals variations in the toxin’s coherent motions. In conclusion, His28, with its low pKa value, provides α-KTx12.1 with the ability to preserve its active conformation over a wide pH interval, thus expanding the range of cellular conditions where the toxin can fully exhibit its activity. Overall, the results further underline the role of histidine as a natural controller of proteins’ functionality. PMID:15772309

  7. New Fossil Scorpion from the Chiapas Amber Lagerstätte

    PubMed Central

    Riquelme, Francisco; Villegas-Guzmán, Gabriel; González-Santillán, Edmundo; Córdova-Tabares, Víctor; Francke, Oscar F.; Piedra-Jiménez, Dulce; Estrada-Ruiz, Emilio; Luna-Castro, Bibiano

    2015-01-01

    A new species of scorpion is described based on a rare entire adult male preserved in a cloudy amber from Miocene rocks in the Chiapas Highlands, south of Mexico. The amber-bearing beds in Chiapas constitute a Conservation Lagerstätte with outstanding organic preservation inside plant resin. The new species is diagnosed as having putative characters that largely correspond with the genus Tityus Koch, 1836 (Scorpiones, Buthidae). Accordingly, it is now referred to as Tityus apozonalli sp. nov. Its previously unclear phylogenetic relationship among fossil taxa of the family Buthidae from both Dominican and Mexican amber is also examined herein. Preliminarily results indicate a basal condition of T. apozonalli regarding to Tityus geratus Santiago-Blay and Poinar, 1988, Tityus (Brazilotityus) hartkorni Lourenço, 2009, and Tityus azari Lourenço, 2013 from Dominican amber, as was Tityus (Brazilotityus) knodeli Lourenço, 2014 from Mexican amber. Its close relationships with extant Neotropic Tityus-like subclades such as ‘Tityus clathratus’ and the subgenus Tityus (Archaeotityus) are also discussed. This new taxon adds to the knowledge of New World scorpions from the Miocene that are rarely found trapped in amber. PMID:26244974

  8. Fuentes de variabilidad en el diagnóstico de gastritis atrófica multifocal asociada con la infección por Helicobacter pylori1

    PubMed Central

    Bravo, Luis Eduardo; Bravo, Juan Carlos; Realpe, José Luis; Zarama, Guillermo; Piazuelo, MarÍa Blanca; Correa, Pelayo

    2014-01-01

    RESUMEN Introducción El mapeo de las diferentes regiones del estómago y el número de fragmentos de mucosa gástrica disponibles para evaluación histopatológica son fuentes importantes de variación en el momento de clasificar y hacer la gradación de la gastritis crónica. Objetivos Estimar la sensibilidad del número de fragmentos de mucosa gástrica necesarios para establecer los diagnósticos de gastritis atrófica con metaplasia intestinal (MI), displasia y estado de infección por Helicobacter pylori. Además evaluar la variabilidad intra-observador en la clasificación de estas lesiones precursoras del cáncer gástrico. Materiales y métodos En una cohorte de 6 años de seguimiento se evaluaron 1,958 procedimientos de endoscopia realizados por dos gastroenterólogos. En cada procedimiento y de cada participante se obtuvieron 5 biopsias de mucosa gástrica que representaban antro, incisura angularis y cuerpo. Un único patólogo hizo la interpretación histológica de las 5 biopsias y proporcionó un diagnóstico definitivo global que se utilizó como patrón de referencia. Cada fragmento de mucosa gástrica examinado condujo a un diagnóstico individual para cada biopsia que se comparó con el patrón de referencia. La variabilidad intra-observador se evaluó en 127 personas que corresponden a una muestra aleatoria de 20% del total de endoscopias hechas a los 72 meses de seguimiento. Resultados La sensibilidad del diagnóstico de MI y displasia gástrica aumentó de manera significativa con el número de fragmentos de mucosa gástrica evaluados El sitio anatómico de mayor sensibilidad para el diagnóstico de MI y displasia fue la incisura angularis. Para descubrir H. pylori se logró alta sensibilidad con el estudio de un solo fragmento de mucosa gástrica (95.9%) y fue independiente del sitio de obtención de la biopsia. El acuerdo intra-observador para el diagnóstico de gastritis crónica fue 86.1% con valor kappa de 0.79 IC 95% (0.76-0.85). Las

  9. A UV-vis study of the effects of alcohols on formation and stability of Mn(por)(O)(OAc) complexes

    NASA Astrophysics Data System (ADS)

    Mohajer, Daryoush; Jahanbani, Maryam

    2012-06-01

    Interactions of three different (acetato) (tetraarylporphyrinato) manganese (III) MnIII(por) with tetra-n-butylammonium hydrogen monopersulfate (n-Bu4NHSO5), in the presence of excess tetra-n-butylammonium acetate (n-Bu4NOAc) and in the absence or presence of various alcohols (alcohols = CH3OH, C2H5OH, i-C3H7OH, t-C4H9OH) in CH2Cl2, were monitored by their UV-vis spectral changes, under identical conditions, at room temperature. (Acetato) (tetrakispentafluorophenylporphyrinato) manganese (III) MnIII(tpfpp)(OAc) and (acetato) (tetramesitylporphyrinato) manganese (III) MnIII(tmp)(OAc) produced their corresponding high valent Mn(tpfpp)(O)(OAc) and Mn(tmp)(O)(OAc) both in the absence or presence of alcohols. Whereas, (acetato) (tetraphenylporphyrinato) manganese (III) MnIII(tpp)(OAc) only generated Mn(tpp)(O)(OAc) in the presence of less bulky alcohols. In the absence of alcohols or in the presence of t-C4H9OH, the UV-vis spectra displayed a very weak sign of formation of Mn(tpp)(O)(OAc) complex. It was observed that alcohols generally increased the rate of formation of Mn-oxo species in accordance with their acidity or hydrogen bonding strength, and enhanced the stability of Mn-oxo complexes, as their size increases. Attempts are made to explain these effects. A mechanistic scheme is also suggested for the decomposition of HSO5- to O2 and HSO4-, through the formation and dimerization of Mn-oxo species.

  10. Estudio teórico de la desorción de Na y K de SiO2 estimulada por la acción de fotones o electrones

    NASA Astrophysics Data System (ADS)

    Domínguez Ariza, D.; López, N.; Illas, F.; Pacchioni, G.; Madey, T. E.

    Se ha estudiado el mecanismo de generación de sodio y potasio atómico a partir de muestras de SiO2 utilizando cálculos basados tanto en la teoría del funcional de la densidad como en métodos post-Hartree Fock, así como en el método de cluster para modelar el sólido. Como consecuencia del estudio se han propuesto distintos caminos posibles para la desorción, estimulada por la acción de fotones o electrones, de sodio y potasio desde el óxido de silicio, proporcionando por lo tanto una explicación a la atmósfera tenue de sodio y potasio de La Luna.