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Published: 4 June 2021

Last updated: 7 February 2022

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1

Guttenberg, Gregor [Verfasser], and Manfred [Akademischer Betreuer] Jung. "Clostridiale Glukosylierende Toxine: Untersuchungen zur Autoprozessierung von Clostridium sordellii Letalem Toxin und Clostridium novyi alpha-Toxin sowie funktionelle Charakterisierung von Clostridium perfringens TpeL-Toxin." Freiburg : Universität, 2012. http://d-nb.info/1123467994/34.

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2

Eaton, Julian Timothy. "Structural studies of Clostridium perfringens alpha toxin." Thesis, Birkbeck (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417896.

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3

Justin, Neil. "Structural studies of clostridium perfringens alpha toxin." Thesis, Birkbeck (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392355.

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4

Reutemann, Mathias. "ICAM-1 abhängige Akkumulation neutrophiler Granulozyten und Leukotrien-vermittelte Kardiodepression in Staphylococcus aureus [alpha]-Toxin-perfundierten [Alpha-Toxin-perfundierten] Rattenherzen." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=965811611.

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5

Carnegie, Andrew Mark. "Effects of C.perfringens alpha toxin on cell signalling." Thesis, Birkbeck (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416052.

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6

Wegner, Judith. "Exotoxin-Schock, ausgelöst durch Staphylococcus-aureus-[alpha]-Toxin [Staphylococcus-aureus-alpha-Toxin], am Tiermodell Ratte Auswirkungen auf Gefässendothel, Leukozytenakkumulation und Thrombozytenaggregation /." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=97606538X.

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7

Sawicki, Maria. "Immunological studies on staphylococcal alpha toxin and its fragments." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0020/MQ52656.pdf.

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8

Penha, Marcelo De Luca. "Detecção dos genes das toxinas alfa, beta e épsilon de Clostridium perfringens isolados a partir de amostras clínicas de bovinos pela reação em cadeia da polimerase." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/10/10134/tde-06072005-101119/.

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O Clostridium perfringens é um microrganismo anaeróbio que está presente no solo e no trato intestinal dos mamíferos. Provoca intoxicação alimentar nos seres humanos, doenças enterotoxêmicas nos animais domésticos e gangrena gasosa em ambos os grupos. O C. perfringens é classificado em cinco tipos (A, B, C, D e E) mediante a produção de quatro toxinas principais (alfa, beta, épsilon e iota). Neste trabalho foi possível padronizar a técnica de PCR para detectar a presença dos genes cpa, cpb e etx a partir de culturas de C. perfringens. A sensibilidade analítica da técnica de PCR a partir de culturas de C. perfringens foi de 2,27 ng/µL para o gene cpa, 22,7 pg/µL para o gene cpb e 22,7 pg/µL para o gene etx. A pesquisa dos genes cpa, cpb e etx partir de 35 amostras de C. perfringens isoladas de bovinos revelou que 16 (45,7%) eram do tipo A; 18 (51,4%) eram do tipo C e 1 (2,9%) era do tipo B. Não foi observada nenhuma amostra do tipo D. A metodologia de PCR revelou-se útil na tipificação de amostras de C. perfringens isoladas de bovinos, contribuindo para o diagnóstico dessa bacteriose neste país, eliminando as dificuldades de tipificação oriundas do alto custo e da indisponibilidade de anti-soros para a tipificação pela reação de soroneutralização e evitando a utilização de animais de laboratório.
Clostridium perfringens is an anaerobic micro-organism that is present in the soil and gastrointestinal tract of mammals. It causes food poisoning in humans, enterotoxemic diseases in domestic animals and gas gangrene in both. C. perfringens is classified into five types (A, B, C, D and E) according to the production of four major toxins (alpha, beta, epsilon and iota). In this trial was possible to standardize the PCR?s technique to detect cpa, cpb and etx genes from cultures of C. perfringens. PCR?s analythical sensibility was 2.27 ng/µL for cpa gene, 22.7 pg/µL for cpb gene and 22.7 pg/µL for etx gene. The research of cpa, cpb and etx genes from 35 samples of C. perfringens isolated from cattle reveals that 16 (45.7%) were classified as type A, 18 (51.4%) as type C and 1 (2.9%) as type B. No sample of type D was observed. PCR?s technique reveals to be usefull to typify samples of C. perfringens isolated from cattle, contributing to diagnose of this bacterial disease in this country and solving typifing problems represented by the high costs of the process and by the lack of antiserum that is required to typify the micro-organism by seroneutralization. PCR?s technique avoid the use of laboratory animals, too.

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9

Leslie, Dario Lyall. "Genetic analysis of alpha toxin (phospholipase C) from Clostridium perfringens." Thesis, University of Newcastle Upon Tyne, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.346420.

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10

Sylvester, Ian David. "The characterisation and conjugation of the fungal toxin #alpha#-sarcin." Thesis, University of Warwick, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308083.

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11

Bullifent, Helen Lisa. "The regulation of the alpha-toxin gene of Clostridium perfringens." Thesis, University of Sheffield, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296729.

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12

Eger, Frank. "Durch Staphylococcus-aureus-[alpha]-Toxin [Staphylococcus-aureus-Alpha-Toxin] permeabilisierte, mit Simian Virus 40 infizierte CV1-Zellen als Modellsystem zum Studium der DNA-Replikation höherer Zellen." Tübingen, Stäudach 107 : F. Eger, 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963193643.

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13

Thompson, James Russell. "Imaging the assembly of the Staphylococcal pore-forming toxin alpha-Hemolysin." Thesis, University of Oxford, 2009. http://ora.ox.ac.uk/objects/uuid:e320004a-6118-4dac-af2a-eca6e90be7ac.

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Alpha-hemolysin is a pore-forming toxin secreted by pathogenic Staphylococcus aureus. Its spontaneous oligomerization and assembly into a trans-bilayer beta-barrel pore is a model for the assembly of many other pore-forming toxins. It is studied here in vitro as a means to probe general membrane protein oligomerization and lipid bilayer insertion. This thesis details the results of experiments to develop and implement a novel in vitro lipid bilayer system, Droplet-on-Hydrogel Bilayers (DHBs) for the single-molecule imaging of alpha-hemolysin assembly. Chapter 2 describes the development of DHBs and their electrical characterization. Experiments show the detection of membrane channels in SDS-PAGE gels post-electrophoresis and DHBs use as a platform for nanopore stochastic sensing. Chapter 3 describes the engineering and characterization of fluorescently-labelled monomeric alpha-hemolysin for use in protein assembly imaging experiments described in Chapter 6. Chapter 4 describes the characterization of DHB lipid fluidity and suitability for single-molecule studies of membrane protein diffusion. In addition, a novel single-particle tracking algorithm is described. Chapter 5 describes experiments demonstrating simultaneous electrical and fluorescence measurements of alpha-hemolysin pores embedded within DHBs. The first multiple-pore stochastic sensing in a single-lipid bilayer is also described. Chapter 6 describes experiments studying the assembly of alpha-hemolysin monomers in DHBs. Results show that alpha-hemolysin assembles rapidly into its oligomeric state, with no detection of long-lived intermediate states.

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14

Berger, Katharina [Verfasser]. "Integritätsstörung endothelialer Junktionsproteine durch Staphylococcus aureus Alpha-Toxin-Stabilisierung durch Adrenomedullin / Katharina Berger." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2010. http://d-nb.info/1024784266/34.

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15

Miyashiro, Simone. "Caracterização de isolados de Clostridium perfringens de ruminantes." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/10/10134/tde-16092014-155341/.

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C. perfringens é uma bactéria anaeróbia presente no intestino delgado do homem e animais em equilíbrio e, sob a ação de alguns fatores predisponentes como mudança brusca de alimentação ou super alimentação, stress no manejo ou alto parasitismo intestinal, há a proliferação do microrganismo com a consequente produção de potentes toxinas que provocam a morte do animal. Dentre as toxinas principais destaca-se a toxina alfa, importante fator de virulência, produzida por todos os tipos de C. perfringens, sendo os pertencentes ao tipo A os maiores produtores. A fim de caracterizar o microrganismo em suspeitas de enterotoxemia em ruminantes, trabalhamos com 61 amostras de intestino delgado de bovinos e 12 de ovinos como grupo estudo e no grupo controle composto de animais hígidos levados ao abate, 73 amostras de intestino delgado de bovinos e 24 de ovinos. Foram realizados procedimentos de isolamento e tipagem molecular de C. perfringens e quantificação celular, detecção molecular da toxina β2, além de avaliações moleculares qualitativa (PCR convencional) e quantitativa (PCR em tempo real) do gene da toxina alfa dos diferentes isolados. Em 29 amostras do grupo estudo bovino (47,54%) e em 4 (33,33%) do grupo estudo ovino isolou-se o microrganismo, em contrapartida no grupo controle bovino não houve isolamento do bacilo e 5 amostras do grupo controle ovino (20,83%) foram positivas. Houve diferença estatisticamente significante somente entre os grupos de bovinos (p<0,05). Todos os isolados (100%) foram classificados como tipo A, e os resultados das quantificações celulares de C. perfringens revelaram que todos os bovinos controle apresentaram <10 UFC/g de conteúdo enquanto que o grupo estudo apresentou mediana de 104 UFC/g com variações de <10 UFC/g até 108 UFC/g. Nos ovinos, a mediana no grupo controle foi 101 UFC/g assim como no grupo estudo, entretanto com clara separação de valores entre os grupos. Tanto na PCR convencional quanto na PCR em tempo real para detecção do RNAm da toxina alfa foi observado limiar de detecção de 102 cópias de cDNA por reação, porém provavelmente devido aos valores das amostras estarem próximos ao limite da sensibilidade analítica da reação, não foi observada boa reprodutibilidade da última. Já na reação molecular convencional, observou-se a presença de detecção de RNAm da toxina alfa em 60,52% dos isolados o que revela alguma diferença da presença do transcrito entre as culturas, já que nas cepas restantes não foi detectada a presença do RNAm em questão. A pesquisa do gene da toxina β2 revelou sua presença em 54,55% dos isolados de C. perfringens corroborando com a afirmativa de que o gene está amplamente distribuído entre os ruminantes. A metodologia aplicada para avaliação da expressão do gene da toxina alfa nos isolados mostrou que há diferenças dos níveis de transcrição porém não permitiu quantificar esses valores. A tipagem molecular corrobora com outros estudos quanto à importância epidemiológica do tipo A nos quadros de enterotoxemia em ruminantes, e os dados da quantificação celular permite-nos concluir que animais sadios possuem um nível basal de C. perfringens <10 UFC/g de conteúdo que não possibilita o seu isolamento.
C. perfringens is an anaerobe present in small intestine of man and animals in equilibrium, and under some predisposing factors such as sudden feeding change or super feeding, rough management or high intestinal parasitism, the microorganism multiplies with the consequent production of potent toxins that can cause animal death. Amongst the main toxins, alpha toxin is an important virulence factor, that is produced by all C. perfringens types, and those belonging to type A are its higher producer. Aiming to characterize the microorganism in ruminants suspect of enterotoxaemia, we evaluated 61 bovine small intestinal samples and 12 sheep small intestines as the study group, and for the control group composed by higid animals led to slaughterhousing, 73 bovine small intestines and 24 ovine samples. We performed microbiological culture and molecular typing of C. perfringens isolates, cellular quantification, molecular detection of 2 toxin, and qualitative and quantitative molecular evaluations of alpha toxin from different isolates by means of conventional PCR and real time PCR, respectively. In 29 samples from the bovine study group (47.54%) and in 4 (33.33%) from ovine study group the microorganism was isolated, however in the bovine control group there was no isolation success and 5 samples from sheep control group (20.83%) were positive. There was statistically significant difference only between bovine groups (p<0,05). All isolates (100%) were classified as type A, and C. perfringens cellular quantification results showed that every control bovine presented <10 CFU/g of intestinal contents while the study group presented a median of 104 CFU/g with results ranging from <10 CFU/g to 108 CFU/g. In sheep, the median value in the control group was 101 CFU/g as in the study group, but with a clear division of values between the groups. We observed the threshold detection of 102 cDNA copies per reaction in both conventional and real time PCR reactions for alpha toxin mRNA detection, however since the samples quantification values were close to the analytical sensitivity of the test, we could not observe the reproducibility in the last technique. In the conventional PCR reaction, alpha toxin mRNA was detected in 60.52% of the isolates. This result reveals some difference in the transcript presence among the cultures, since we could not detect the presence of the described mRNA in the other isolates. Beta2 toxin gene was detected in 54.55% of C. perfringens isolates corroborating with the affirmative that this gene is widely distributed among ruminants. The methodology presented herein for the evaluation of alpha toxin gene expression showed that there are differences in the transcription levels, however it didnt allow to quantify these values. Molecular typing results agree with other studies regarding the epidemiological importance of type A in the enterotoxaemia processes in ruminants, and the cellular quantification data allow us to conclude that healthy animals show a basal level of C. perfringens <10 CFU/g of intestinal content that doesnt allow its isolation.

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16

Russo, Michael J. (Michael Joseph). "Controlled poration of the cell membrane using alpha-toxin with a metal-actuated switch." Thesis, Massachusetts Institute of Technology, 1995. http://hdl.handle.net/1721.1/11491.

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Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1995.
On t.p., "[alpha]" appears as the lower-case Greek letter.
Includes bibliographical references (leaves 73-80).
by Michael J. Russo.
M.S.

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17

Simon, Melanie Eva Maria [Verfasser]. "α-Toxin [Alpha-Toxin] von Staphylococcus aureus induziert ein Nierenversagen durch Aktivierung der intrarenalen Thromboxansynthese im Modell der isolierten Rattenniere / eingereicht von Melanie Eva Maria Simon." Giessen : VVB Laufersweiler, 2010. http://d-nb.info/1008284920/34.

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18

Hoven, Gisela von [Verfasser]. "Induktion von Pro-Autophagie-Signalen durch einen extra- oder intrazellulären Alpha-Toxin-Angriff / Gisela von Hoven." Mainz : Universitätsbibliothek Mainz, 2013. http://d-nb.info/1032940409/34.

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19

Cargnelutti, Marilisa [Verfasser]. "Sequencing of alpha- and beta2- toxin-genes from C. perfringens strains isolated from rabbits / Marilisa Cargnelutti." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/102362172X/34.

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20

Zhang, Guangtao. "Design, synthesis, and evaluation of cholera toxin inhibitors and [alpha]-helix mimetics of dormancy survival regulator /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/8485.

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21

Ghosh, Gargi. "A WHOLE CELL BASED BIOSENSOR FOR MONITORING PHYSIOLOGICAL TOXINS AND EARLY SCREENING OF CANCER." UKnowledge, 2008. http://uknowledge.uky.edu/gradschool_diss/578.

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Recently a whole cell based biosensor has been developed in our laboratory that consists of a monolayer of human umbilical vein endothelial cells (HUVECs) on the asymmetric cellulose triacetate (CTA) membrane of an ion selective electrode (ISE). When a confluent cell monolayer is formed across the membrane, response from the sensor is inhibited due to inhibited ion transport across the membrane. When the cell based biosensor is exposed to permeability modifying agents, the permeability across the cell monolayer is altered facilitating more ion transport and as a result the response from the sensor increases. This sensor response can be related to the concentration of these agents. One objective of this research was to investigate the ability of the sensor to detect a physiological toxin, alpha toxin from Staphylococcus aureus. Studies demonstrated that the biosensor can detect 0.1ng/ml alpha toxin. Considering the fact that the concentration of this toxin is 100-250 ng/ml in whole blood in humans, this biosensor has the ability to act as the diagnostic tool for staphylococcal diseases. Another part of this research was to investigate the ability of the biosensor to measure angiogenesis by measuring the changes in permeability induced by cytokines such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and tumor necrosis factor andamp;aacute; (TNF- andamp;aacute;) individually and in combination. The sensor response was then compared with the common in vitro assays for angiogenesis. The study demonstrated that at the concentrations studied the sensor response in the presence of cytokines was much higher than that observed for other angiogenesis assays, thereby bolstering the potential of the biosensor to act as a quick screening tool for angiogenesis. Furthermore, epithelial cell based sensor responses to the same cytokines were compared with the responses from endothelial cell based sensor and the mechanisms behind the increased sensor response were elucidated. Finally, to investigate the ability of the sensor to screen cancer, the biosensor was exposed to the serum from healthy individuals and cancer patients. The results showed that the sensor can distinguish between healthy individuals and cancer patients and the results correlate with the stages of cancer.

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22

Rogers, Tara Marie. "Investigation of Alpha-Toxin Secretions in Biofilm Conditioned Medium as a Potential Pro-Inflammatory Disruptor to Macrophages." Kent State University Honors College / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1557145132511741.

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23

O'Brien, David Kenneth. "The Interactions of Clostridium Perfringens With Phagocytic Cells." Diss., Virginia Tech, 2003. http://hdl.handle.net/10919/27164.

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Clostridium perfringens is the most common cause of gas gangrene (clostridial myonecrosis), a disease that begins when ischemic tissues become contaminated with C. perfringens. C. perfringens quickly multiplies in ischemic tissues and spreads to healthy areas, leading to high levels of morbidity and mortality. As a species, the bacterium can synthesize thirteen different toxins. The alpha toxin (PLC) and perfringolysin O (PFO) are thought to be important virulence factors in gangrene. We wished to understand how C. perfringens is capable of avoiding killing by the host immune system, and determine if PLC and PFO play a role in this avoidance. We found C. perfringens was not killed by J774-33 cells or mouse peritoneal macrophages under aerobic or anaerobic conditions. Using electron microscopy, we showed that C. perfringens could escape the phagosome of J774-33 and mouse peritoneal macrophages. We believe the ability of C. perfringens to survive in the presence of macrophages is due to its ability to escape the phagosome. Using a variety of inhibitors of specific receptors, we identified those used by J774-33 cells to phagocytose C. perfringens. The scavenger receptor, mannose receptor(s), and complement receptor (CR3) were involved in the phagocytosis of C. perfringens. To determine if PFO or PLC were involved in the ability of C. perfringens to survive in the presence of macrophages, we constructed C. perfringens strains lacking these toxins. The ability of C. perfringens to survive in the presence of J774-33 cells is dependent on PFO, while survival in mouse peritoneal macrophages is dependent on PFO and PLC. The ability of C. perfringens to escape the phagosome of J774-33 cells and mouse peritoneal macrophages is mediated by either PFO or PLC. Using a mouse model, we found that PFO and PLC were necessary for C. perfringens to survive in vivo using infectious doses 1000 times lower than those required to initiate a gangrene infection. We propose that PFO and PLC play a critical role in the survival of C. perfringens during the early stages of gangrene infections, when phagocytic cells are present and bacterial numbers are low.
Ph. D.

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24

Eger, Frank [Verfasser]. "Durch Staphylococcus-aureus-α-Toxin [Staphylococcus-aureus-Alpha-Toxin] permeabilisierte, mit Simian Virus 40 infizierte CV1-Zellen als Modellsystem zum Studium der DNA-Replikation höherer Zellen / vorgelegt von Frank Eger." Tübingen, Stäudach 107 : F. Eger, 2001. http://d-nb.info/963193643/34.

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25

Gatsos, Xenia, and xgatsos@optusnet com au. "The development of live vectored vaccines targeting the alpha-toxin of Clostridium perfringens for the prevention of necrotic enteritis in poultry." RMIT University. Applied Sciences, 2007. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080212.142403.

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The Ñ-toxin of Clostridium perfringens is a toxin involved in numerous diseases of humans and agriculturally important animals. One of these diseases is necrotic enteritis (NE), a sporadic enteric disease which affects avian species world-wide. This study involved the inactivation of alpha-toxin (Ñ-toxin) for use as a potential vaccine candidate to combat NE in chickens, and other diseases caused by C. perfringens type A. During the course of this research a number of Ñ-toxin recombinant proteins were developed through molecular inactivation of the Ñ-toxin gene, plc. Proteins plc316 and plc204 were developed by the deletion of the first three and seven Ñ-helices of the N-terminal domain respectively. These deletions resulted in proteins which were unstable in solution, constantly aggregated into insoluble masses and elicited lower overall antibody responses when administered to mice. A third protein, plcInv3 was developed from the deletion of part of the catalytic domain of the Ñ-toxin. PlcInv3 was highly soluble and upon immunisation of mice elicited a significant antibody response which was also capable of protecting mice against a live challenge of C. perfringens. The fourth and final protein developed was plc104. The smallest of the recombinant Ñ-toxin proteins, it consisted entirely of the C-terminal domain of Ñ-toxin. Its small size did not affect its ability to induce a strong antibody response when administered to mice, the antibodies of which were also protective during a challenge with C. perfringens. STM1, an attenuated strain of S. Typhimurium was used in the development of a vectored vaccine for the expression and oral delivery of plcInv3 and plc104 within the mouse host. The proteins were expressed within STM1 from expression plasmids containing the in vivo inducible promoters PhtrA and PpagC. A measurable humoral immune response against Ñ-toxin was absent following three oral vaccinations with the vectored vaccines, although, cytokine profiling of splenocytes from vaccinated mice revealed an increase in the number of interleukin-4 (IL-4)secreting cells and the lack of interferon-gamma (IFN-×) secreting cells. This indicated the stimulation of a T-helper type 2 (TH2) immune response which also lead to partial protection against a live C. perfringens challenge. This study demonstrates the feasibility of using STM1 as a carrier for the in vivo expression of the C. perfringens Ñ-toxin recombinant proteins plcInv3 and plc104. It is the first study to express C. perfringens antigens within an attenuated strain of S. Typhimurium, STM1.The partial protection of mice immunised with these vaccines indicates there is potential for this vectored vaccine system to be used in the protection of diseases caused by the Ñ-toxin of C. perfringens.

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26

Johansson, David. "Bacterial toxins for cancer treatment." Doctoral thesis, Umeå universitet, Medicinsk biovetenskap, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1637.

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Even though anti‐cancer chemotherapy has been continuously improved during the last decades. problems with adverse effects and drug resistance still constitutes a considerable obstacle and sets a demand for new effective treatment options. Tissue homeostasis in multi‐cellular organisms is maintained through intrinsic cell death, apoptosis, which removes unwanted or damaged cells. Disrupted apoptosis is an important factor in tumorgenesis and drug resistance, therefore induction or restoration of apoptotic pathways is also important for the treatment of cancer. Several naturally occurring bacterial toxins have the ability to induce apoptosis and could thus be candidates to complement or improve the therapeutic effect of other anticancer drugs. The bacterial toxins, adenylate cyclase (AC) toxin from Bordetella pertussis, α‐toxin from Staphylococcus aureus and verotoxin‐1 (VT‐1) from Escherichia coli were investigated for their ability to induce apoptosis in different tumor cell lines. Toxin induction of cell death was investigated by cell viability assays, end‐stage apoptosis induction by DNA‐fregmentation (TUNEL) assay. Toxin receptor expression and signal transduction pathways to apoptosis were investigated by flow cytometry, caspase enzyme activity assays and western blot. Immunohistochemistry was used for identification of toxin receptor expression in tumor tissue samples. AC‐toxin was cytotoxic and induced apoptosis in cultured malignant plural mesothelioma (MPM) and small‐cell lung cancer (SCLC) cells. Low‐toxic concentrations of AC‐toxin enhanced cisplatin cytotoxicity and apoptosis in both cell lines. MPM‐cells with acquired cisplatin resistance were more sensitive to α‐toxin than the less resistant parental MPM cell line. A low‐toxic concentration of α‐toxin re‐sensitized resistant MPM cells to cisplatin cytotoxicity by apoptosis induced through the mitochondrial pathway without detectable activation of common up‐stream apoptosis signalling proteins. VT‐1 was highly cytotoxic and induced apoptosis in globotriosylceramide (Gb3) ‐expressing glioma, breast cancer and non‐small‐cell lung cancer (NSCLC) cells but was not cytotoxic to non‐Gb3‐expressing cells. PPMP, an inhibitor of glucosylceramide synthesis which makes exposed cells unable to synthesize Gb3 rendered Gb3‐expressing cells resistant to VT‐1. MPM cells with acquired‐cisplatin resistance expressed Gb3 in contrast to the absent of expression in the less resistant parental cell line. Gb3, could however be up‐regulated by cisplatin in Gb3‐negative MPM‐cells. Presence of a low‐toxic concentration of VT‐1 potentiated cisplatin‐induced cytotoxicity and apoptosis in the cisplatin‐resistance MPM cell line. VT‐1 was a potent inducer of apoptosis, probably via stress‐induced Mitogen‐activated protein kinase (MAPK)‐signaling involving c‐Jun N‐terminal kinase (JNK) and p38, leading to disruption of the mitochondrial membrane integrety, activation of caspase‐9 and ‐3, and ultimately DNA fragmentation and cell death. Gb3 expression was demonstrated in clinical specimens of glioblastoma and breast cancer making these tumor types interesting for further VT‐1 studies. We conclude that bacterial toxins may be used to induce apoptosis in several types of cancer cells. Low concentrations of verotoxin‐1 and α‐toxin may potentially be used to overcome acquired cisplatin‐resistance in cancer patients.

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27

Kostova, Vesela. "Shiga toxin targeted strategy for chemotherapy and cancer immunotherapy application using copper-free « Click » chemistry." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB144.

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Pas de résumé
Recently targeted therapies appeared as attractive alternatives to classical antitumoral treatments. The approach, developed on the concept of targeting drug to cancer cells, aims to spear normal tissues and decrease the side effects. This doctoral dissertation focuses on developing new anticancer targeted treatments in the field of chemotherapy and cancer immunotherapy by exploiting an original targeting moiety, the B subunit of Shiga toxin (STxB). Its specific properties, such as, recognition with its receptor Gb3 overexpressed in cancer cells or in antigen-presenting cells, its unconventional intracellular trafficking, guided the choice of this protein as targeting carrier. This project is based in the use of copper-free Huisgen [3+2] cycloaddition as a coupling method, which led to successful preparation of various conjugates for their respective applications. The concept was first validated by STxB-biotin conjugate. The high yield of the reaction and the compatibility between the targeting carrier and the chemical ligation promoted the design of conjugates for chemotherapy and immunotherapy. Two therapeutical optimizations of previously developed strategy in STxB drug targeting delivery were investigated: synthesis of multivalent drug-conjugates and synthesis of conjugates containing a highly potent anticancer agent. Both approaches exploited three anticancer agents: SN38, Doxorubicin and Monomethyl auristatin F. The disulfide spacer, combined with various self-immolative systems, insured drug release. Two cytotoxic conjugates STxB–doxorubicin (STxB-Doxo) and STxB-monomethyl auristatin F (STxB-MMAF) were obtained in very high yield and demonstrated strong tumor inhibition activity in the nanomolar range on Gb3-positive cells. Based on the results the STxB-MMAF conjugate was investigated on a mouse model. The project aimed also to develop STxB bioconjugates for vaccine applications. Previous studies used B subunit as a targeting carrier coupled to an antigenic protein in order to induce a more potent immune response against cancer. The conjugates were prepared using a commercial linker, requiring modifying the antigen at first place, or by oxime ligation, where slightly acidic conditions promoted the coupling. Thus, the work presented herein proposed an alternative ligation via copper-free click chemistry especially for more sensitive antigenic proteins. Various types of conjugates were synthesised and investigated for their immune stimulation properties. The STxB targeting strategy was also applied to the development of a new vaccine based on coupling the targeting carrier to alpha-GalCer, one of the most potent immune stimulating agents known. The work focused on the synthesis of functionalised alpha-Galcer with an azide handle

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28

Möller, Nils [Verfasser], Jan-Peter [Akademischer Betreuer] Hildebrandt, Jan-Peter [Gutachter] Hildebrandt, and Wolf-Michael [Gutachter] Weber. "Determinanten der Sensitivität von humanen Atemwegsepithelzellen gegenüber dem alpha-Toxin von Staphylococcus aureus und die Prozessierung des Toxins nach der Porenbildung / Nils Möller ; Gutachter: Jan-Peter Hildebrandt, Wolf-Michael Weber ; Betreuer: Jan-Peter Hildebrandt." Greifswald : Universität Greifswald, 2021. http://d-nb.info/1238233279/34.

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29

Clelland, Lyndsay Jacquelyn. "Role of ROK and PKC in Permeabilized Rabbit Femoral Artery." VCU Scholars Compass, 2007. http://hdl.handle.net/10156/1581.

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30

Félix, Mellanie Karoline do Carmo. "Antígeno inativado de Clostridium Novyi tipo B em emulsão W/O: uma prova de conceito em camundongos Swiss visando o controle de necrose hepática de ruminantes." Universidade Federal do Tocantins, 2018. http://hdl.handle.net/11612/965.

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A bovinocultura brasileira possui grande ênfase no mercado nacional. Doenças que acometem rebanhos comprometem o mercado além de gerarem grandes prejuízos econômicos. O Clostridium novyi tipo B provoca necrose hepática em bovinos através da produção da alfa toxina, uma potente exotoxina que reduz a produtividade através de alterações como hemoglobinúria, redução do apetite, febre, letargia, diminuição da produção de leite e sangue nas fezes. Conter o microrganismo causador torna-se uma busca necessária tanto do ponto de vista econômico quanto social. Entretanto, o controle da doença ainda é realizado por vacinas formuladas com múltiplos antígenos. A emulsão pode ser uma alternativa promissora para a melhoria da adsorção de antígenos nas formulações vacinais. Camundongos da linhagem Swiss foram utilizados a fim de se avaliar aspectos clínicos e validar resultados referentes a composição de uma nova formulação vacinal contendo adjuvante Montanide ISA 61 VG e antígeno inativado de C. novyi. Os testes de caracterização e antigenicidade indicaram a presença da proteína alfa toxina na composição avaliada. A imunogenicidade do antígeno inativado em emulsão W/O (água/óleo) foi verificada e a proporção empregada (40/60) mostrou ser ideal no uso de múltiplos antígenos, apresentando inocuidade, estabilidade do produto, liberação controlada e estímulo da resposta imune. A determinação da concentração de antígeno foi averiguada pela relação antígeno ativo e inativado com soros de animais doentes, visto a eficácia vacinal de 40%. A adequação da concentração de alfa toxina inativada na emulsão mostrou ser necessária para atingir melhores valores de proteção animal. Análises de hemograma, bioquímicas e morfologia de fígado, baço e coxa contribuíram para elucidar os efeitos da emulsão e comprovar necrose hepática nos grupos não imunizados, além de sugerir avanços na adsorção de vacinas. Os resultados possibilitaram o estabelecimento de um modelo murino de infecção de C. novyi com futuras aplicações relacionadas à produção vacinal com múltiplos antígenos emulsificados para controle das clostridioses.
Brazilian cattle breeding has great emphasis on the national market. Diseases that affect herds compromise the market as well as generate great economic losses. Clostridium novyi type B causes hepatic necrosis in cattle through the production of alpha toxin, a potent exotoxin that reduces productivity through changes such as hemoglobinuria, reduced appetite, fever, lethargy, decreased milk and stool production. Containing the causative micro-organism becomes a necessary quest both economically and socially. However, control of the disease is still performed by vaccines formulated with multiple antigens. The emulsion may be a promising alternative for the improvement of antigen adsorption in vaccine formulations. Swiss strain mice were used to evaluate clinical aspects and validate results regarding the composition of a new vaccine formulation containing Montanide ISA 61 VG adjuvant and C. novyi inactivated antigen. Characterization and antigenicity tests indicated the presence of the alpha toxin protein in the evaluated composition. The immunogenicity of antigen inactivated in W / O emulsion (water / oil) was verified and the ratio employed (40/60) showed to be ideal in the use of multiple antigens, presenting innocuousness, product stability, controlled release and stimulation of the immune response. The determination of the antigen concentration was investigated by the active antigen ratio and inactivated with sera from sick animals, since the vaccine efficacy was 40%. The suitability of the inactivated alpha toxin concentration in the emulsion was shown to be necessary to achieve better animal protection values. Hemogram, biochemical and liver, spleen and thigh morphology contributed to elucidate the effects of the emulsion and to verify hepatic necrosis in the nonimmunized groups, in addition to suggesting advances in the adsorption of vaccines. The results allowed the establishment of a murine model of C. novyi infection with future applications related to the vaccine production with multiple emulsified antigens to control clostridia.

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31

Jansen, Katja. "Methodische Untersuchungen zu Eigenschaften, Nachweis, Reinigung und Antigenität des a-Toxins [Alpha-Toxins] von Clostridium septicum." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=961183098.

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32

Sullivan, Derek J. "Regulation of #alpha#-haemolysin gene expression in Staphylococcus aureus." Thesis, University of Newcastle Upon Tyne, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287423.

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33

GUILLOUARD, ISABELLE. "Organisation structurale et fonctionnelle de la toxine alpha de clostridium perfringens." Paris 7, 1997. http://www.theses.fr/1997PA077115.

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La toxine-alpha de clostridium perfringens, principal facteur de virulence produit par les souches pathogenes, joue un role preponderant dans le developpement de la gangrene gazeuse. Phospholipase c, elle peut hydrolyser la phosphatidylcholine (lecithine) et la sphingomyeline, acides gras majeurs des membranes des cellules eucaryotes. Elle est aussi letale, necrosante et hemolytique. Bien caracterisee biochimiquement, les relations existant entre la structure et le mode d'action de la toxine alpha sont encore imprecises. Grace a la remarquable similitude existant entre les 2/3 n-terminaux de la toxine-alpha et la phospholipase c de bacillus cereus (pc-plc) bien decrite structuralement, nous avons determine la position du site catalytique dans la region n-terminale de la toxine alpha. Par mutagenese dirigee, nous avons identife les residus qui composent son site actif et qui sont tous conserves dans la pc-plc : residus histidine impliques dans la coordination avec les atomes de zinc, residus acides (asp et glu) constituant la partie chargee du site actif et residus aliphatiques necessaires pour sa structure. De plus, grace au variant asp56asn completement inactif, nous avons montre que l'activite phospholipasique etait responsable de la letalite due a la toxine-alpha. Pour determiner le role du domaine c-terminal de 120 acides amines completement depourvu d'activite enzymatique in vitro, nous avons examine les residus tyrosine indispensables pour l'interaction avec les membranes cellulaires et la reconnaissance du phospholipide. De plus, un site de fixation a faible affinite pour le calcium, cation necessaire a l'activite de la toxine-alpha, a aussi ete caracterise au niveau de residus aspartate de la partie c-terminale. Le calcium interviendrait dans l'interface entre la proteine et les membranes cellulaires.

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Maïga, Arhamatoulaye. "Caractérisation de l'interaction entre la toxine peptidique AdTx1 et le récepteur α1A adrénergique." Paris 6, 2011. http://www.theses.fr/2011PA066037.

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AdTx1 est une toxine à trois doigts de 65 acides aminés découverte dans notre laboratoire à partir du venin du mamba vert (Dendroaspis angusticeps). Elle a une haute affinité et sélectivité pour le récepteur adrénergique α1A-AR par rapport aux autres récepteurs adrénergiques α1. Ces différentes caractéristiques font de cette toxine un outil original pour étudier le récepteur et également une molécule thérapeutique potentielle dans le traitement de l’hypertrophie bénigne de la prostate. Le but de ma thèse est de caractériser le profil pharmacologique de cette toxine et de comprendre l'origine moléculaire de la haute affinité et sélectivité d’AdTx1 pour le récepteur α1A-AR. Au préalable à l’étude moléculaire, nous avons confirmé la grande sélectivité d’AdTx1 pour le récepteur α1A-AR par rapport à 8 autres récepteurs adrénergiques et mis en évidence son caractère d’antagoniste insurmontable sur ce récepteur. Nous avons également entrepris des tests de liaison cinétique et à l’équilibre qui mettent en évidence un mode d’action compétiteur entre AdTx1 et les ligands orthostériques du récepteur. Par conséquent, malgré sa grande taille, AdTx1 arriverait à atteindre le site orthostérique du récepteur situé dans les domaines transmembranaires. L’approche mutationnelle, entreprise pour comprendre l’origine de la forte interaction entre AdTx1 et α1A-AR, a mis en évidence quatre acides aminés des domaines transmembranaires du récepteur (Phe86, Phe288, Phe312A et Asp106) et 2 acides aminés sur la boucle 1 de la toxine (Phe10 et Lys7), impliqués dans l’interaction. Cette étude valide l’utilisation d’AdTx1 comme outil d’étude du récepteur α1A-AR dont il est sélectif et fournit des bases moléculaires pouvant servir à la conception de ligands aux propriétés prédéfinies comme une forte sélectivité et affinité utile pour l’étude du récepteur α1A-AR et pour un traitement plus spécifique de l’hypertrophie bénigne de la prostate.

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35

Thet, Naing Tun. "Modified tethered bilayer lipid membranes for detection of pathogenic bacterial toxins and characterization of ion channels." Thesis, University of Bath, 2010. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.530158.

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Pathogenic bacteria secrete various virulence factors as their biochemical weapons to gain access to and destroy the target cells. They can directly interact with the outer lipid bilayer membrane of eukaryotic cells, inducing the premature cell death by either apoptosis or necrosis. Such virulence factors account for much of the toxic actions associated with bacterial infection; therefore the detection of such proteins could provide a methodology for sensing/detection of pathogenic bacteria in, for example, food or human tissue. Detection and identification of pathogenic bacteria by conventional methods such as plating and counting in laboratory is expensive and time consuming. With growing concerns over emergence and re-emergence of pathogenic bacteria with high resistant to current antibiotics, there is a potential need for effective detection of pathogenic toxins invitro. On the other hand, artificially prepared lipid bilayer membrane on planar metallic surfaces provides the cell membrane mimics which are extremely useful in exploring the cellular functions and processes at the molecular level. Therefore in this work, an application of planar tethered bilayer lipid membrane (pTBLM) as a biomimetic sensing platform for the detection of clinically important pathogens, Staphylococcus aureus and Pseudomonas aeruginosa via their secreted virulence factors was presented. Planar TBLM was modified by incorporation of cholesterol and detection of bacterial toxins at human body temperature was examined by impedance and surface plasmon resonance methods. The results of pathogenic bacterial toxin detection were compared with those of Escherichia coli (DH5α), the human gut normal flora with non-pathogenic strain, as a control. Additionally pTBLM was transferred onto single nanoporous Si3N4 membrane to enhance the toxin sensitivity and extend the lifetime for the possible realization of future membrane chips for ion channel characterizations and drug screenings. Then the single ion channel measurement was demonstrated with nanopore-suspended TBLM (Nano-psTBLM) using α-toxin of S. aureus. The results presented in this work therefore, may pave the more effective and efficient ways for future pathogenic bacterial detection in which the sensing mechanism was solely based on the nature of interactions as well as modes of action between bacterial toxins and artificial lipid bilayer membranes.

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36

TENETTE, CATHERINE. "Modelisation du site de combinaison d'un anticorps libre et lie a son antigene, la toxine alpha." Paris 11, 1996. http://www.theses.fr/1996PA112141.

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Ce travail porte sur la prediction de la structure tridimensionnelle du complexe entre un anticorps monoclonal et son antigene, la toxine alpha. Cet anticorps est capable de neutraliser les toxines curarisantes courtes de serpent et de reconnaitre une partie du site fonctionnel de ces toxines, c'est-a-dire que son epitope sur les toxines recouvre en partie le site toxique reconnu par le recepteur nicotinique a l'acetylcholine. Pour cela, le fragment variable de l'anticorps a ete modelise a partir de sa sequence en acides amines. La modelisation par homologie a ete utilisee pour construire la region du fragment dont la structure est la mieux conservee. La structure du site de combinaison a ete predite a l'aide de trois methodes independantes: la dynamique moleculaire a haute temperature, dans le vide et en presence d'eau explicite, un algorithme de recherche conformationnelle uniforme et une procedure combinant l'utilisation les banques de donnees structurales et une methode de recherche conformationnelle uniforme. Puis des calculs de positionnement ont ete effectues pour predire la nature de l'association anticorps-antigene. La structure de la toxine a ete resolue par resonance magnetique nucleaire et l'epitope de l'anticorps sur la toxine cartographie par plusieurs experiences biochimiques. A l'aide de ces donnees, le nombre de modeles acceptables a pu etre reduit a huit. A partir de ces etudes de modelisation, nous avons propose plusieurs series d'experiences de mutagenese dirigee pour etablir une discrimination entre les differentes solutions. Certains de ces mutants devraient aussi permettre d'analyser certaines caracteristiques importantes du site de combinaison. Les premiers resultats de ces experiences sont discutes. Cette etude permettra l'elaboration d'un nouvel anticorps aux proprietes de liaison voisines de celles du recepteur nicotinique a l'acetylcholine

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Thiersé, Danièle. "Perméabilisation des cellules chromaffines par la toxine alpha : Rôle des protéines G dans le mécanismes d'exocytose." Université Louis Pasteur (Strasbourg) (1971-2008), 1991. http://www.theses.fr/1991STR1A005.

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38

Pan-Montojo, Francisco, Mathias Schwarz, Clemens Winkler, Mike Arnhold, Sullivan Gregory A. O', Arun Pal, Jonas Said, et al. "Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice." Nature Publishing Group, 2012. https://tud.qucosa.de/id/qucosa%3A28923.

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Pathological studies on Parkinson's disease (PD) patients suggest that PD pathology progresses from the enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is up-taken by presynaptic sympathetic neurites and retrogradely transported to the soma, where it accumulates. These results strongly suggest that pesticides can initiate the progression of PD pathology and that this progression is based on the transneuronal and retrograde axonal transport of alpha-synuclein. If confirmed in patients, this study would have crucial implications in the strategies used to prevent and treat PD.

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Pan-Montojo, Francisco, Mathias Schwarz, Clemens Winkler, Mike Arnhold, Sullivan Gregory A. O', Arun Pal, Jonas Said, et al. "Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-180702.

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Pathological studies on Parkinson's disease (PD) patients suggest that PD pathology progresses from the enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is up-taken by presynaptic sympathetic neurites and retrogradely transported to the soma, where it accumulates. These results strongly suggest that pesticides can initiate the progression of PD pathology and that this progression is based on the transneuronal and retrograde axonal transport of alpha-synuclein. If confirmed in patients, this study would have crucial implications in the strategies used to prevent and treat PD.

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40

Miles, Jr George Emmett. "On the structure and assembly of staphylococcal leukocidin: a study of the molecular architecture of beta-barrel pore-forming toxins." Texas A&M University, 2003. http://hdl.handle.net/1969.1/3952.

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Staphylococcal leukocidin pores are formed by the obligatory interaction of two distinct polypeptides, one of class F and one of class S, making them unique in the family of β-barrel pore-forming toxins (β-PFTs). By contrast, other β-PFTs form homooligomeric pores. For example, the staphylococcal α- hemolysin is a homoheptamer. Limited and controversial data exist on the assembly and molecular architecture of the leukocidin pore. In this work, biochemical and biophysical methods were used to characterize the leukocidin pore produced by the LukF (HlgB) and LukS (HlgC) components encoded by Staphylococcus aureus. I demonstrate that LukF and LukS assemble to form an SDS-stable pore on rabbit erythrocyte membranes. In addition, the pore-forming properties of recombinant leukocidin were investigated with planar lipid bilayers. Although leukocidins and staphylococcal α-hemolysin share partial sequence identity and related folds, LukF and LukS produce a pore with a unitary conductance of 2.5 nS (1 M KCl, 5 mM HEPES, pH 7.4), which is over three times greater than that of α-hemolysin measured under the same conditions. The subunit composition and stoichiometry of a leukocidin pore were determined by two independent methods, gel shift electrophoresis and sitespecific chemical modification during single channel recording. Four LukF and four LukS subunits were shown to co-assemble into an octameric transmembrane structure. The existence of an additional subunit in part explains properties of the leukocidin pore, such as its high conductance. Additionally, this is the first time that either technique has been applied successfully to assess the composition of a heteromeric membrane protein. It is also relevant to understanding the mechanism of assembly of β-PFT pores, and suggests new possibilities for engineering these proteins. In additional studies, the HlyII pore encoded by Bacillus cereus was found to form a homoheptameric transmembrane pore with properties conforming in general with those of other members of the class of β-PFTs. HlyII possesses additional properties which make it an attractive candidate for applications in biotechnology, such as an oligomer with a high thermal stability in the presence of SDS and the ability of the pore to remain open at high transmembrane potentials.

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41

Benoit, Evelyne. "Électrophysiologie et pharmacologie du courant sodium de la fibre nerveuse myélinisée de grenouille : contributions à la mise en évidence de trois formes interconvertibles du canal sodium." Paris 11, 1986. http://www.theses.fr/1986PA112131.

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Cette thèse présente une analyse du courant sodium de la fibre nerveuse myélinisée de grenouille à l'aide de la technique du potentiel imposé. Le courant sodium de la membrane nodale est activé par des impulsions dépolarisantes. Ce courant montre une activation et une inactivation dépendantes du potentiel. La cinétique d'inactivation du courant sodium est bien décrite par la somme de deux phases exponentielles et une phase constante. Ces trois phases présentent des propriétés cinétiques (courbes courant-potentiel, courbes inactivation stationnaire-potentiel, potentiels d'inversion, levées de l'inactivation, cinétiques d'activation) et pharmacologiques (effets de : acide niflumique, tétrodotoxine, kétamine, ciguatoxine, toxine alpha de scorpion) différentes. De plus, une diminution de température de l6°C à 4°C affecte différemment les deux phases exponentielles de l'inactivation. Les résultats suggèrent fortement l'existence, au niveau de la membrane nodale, de trois formes interconvertibles du canal sodium, l'expression de ces trois formes serait sous la dépendance de l'environnement protéolipidique membranaire de la protéine-canal. Par ailleurs, une étude des effets stationnaires et des cinétiques d'action de la tétrodotoxine sur le courant sodium permet de présenter un modèle selon lequel deux molécules de toxine, et non pas une, sont nécessaires pour bloquer chaque canal sodium
This thesis presents an analysis of the sodium current in the frog myelinated nerve fiber using the voltage-clamp technique. Depolarizing voltage-clamp steps stimulate the sodium current in the nodal membrane. This current shows bath voltage-dependent activation and inactivation. The time course of the inactivation of the sodium current can be well fitted by the sum of two exponential phases and one constant phase. These three phases show different kinetic (current-voltage curves, steady state inactivation-voltage curves, reversal potentials, recovery from inactivation, activation kinetics) and pharmacological (effects of: niflumic acid, tetrodotoxin, ketamine, ciguatoxine, scorpion alpha toxin) properties. In addition, a decrease in temperature from l6°C to 4°C differentially affects the two exponential phases of inactivation. The results strongly suggest that there are three interconvertible forms of the sodium channel in the nodal membrane, the expression of these three forms depending on the membrane proteolipid environment of the channel-protein. A separate study of the steady state effects and the onset and offset kinetics of the action of tetrodotoxin on the sodium current suggests a model where two molecules of toxin, instead of one, are required to black each sodium channel

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42

Gross, Grégori. "Modification des voies de repliement d'une petite protéine riche en ponts disulfure : la toxine alpha de Naja nigricollis." Phd thesis, Museum national d'histoire naturelle - MNHN PARIS, 2008. http://tel.archives-ouvertes.fr/tel-00364212.

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Le repliement des protéines, dernière étape du processus d'expression de l'information génétique, demeure imparfaitement expliqué. Pendant ma thèse, j'ai étudié le repliement oxydant d'une petite protéine riche en ponts disulfure, la toxine a de Naja nigricollis. J'ai pu montrer que l'addition d'un acide aminé dans une boucle de la structure entraîne un ralentissement global du repliement in vitro causé par une permutation des intermédiaires productifs. L'étude en RMN des intermédiaires de repliement a permis de proposer une explication structurale à cette modification de comportement cinétique. Par ailleurs, pour tester l'importance de l'aspect vectoriel du repliement in vivo, j'ai développé une méthode ayant pour but de vectoriser le repliement in vitro. J'ai pu montrer qu'il est possible grâce à des anticorps dirigés contre la toxine a réduite d'inhiber son repliement oxydant, de lever cette inhibition et finalement de modifier sa voie de repliement.

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Gross, Grégori. "Modification des voies de repliement d’une petite protéine riche en ponts disulfure : la toxine alpha de Naja nigricollis." Paris, Muséum national d'histoire naturelle, 2008. http://www.theses.fr/2008MNHN0010.

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Le repliement des protéines, dernière étape du processus d’expression de l’information génétique, demeure imparfaitement expliqué. Pendant ma thèse, j’ai étudié le repliement oxydant d’une petite protéine riche en ponts disulfure, la toxine  de Naja nigricollis. J’ai pu montrer que l’addition d’un acide aminé dans une boucle de la structure entraîne un ralentissement global du repliement in vitro causé par une permutation des intermédiaires productifs. L’étude en RMN des intermédiaires de repliement a permis de proposer une explication structurale à cette modification de comportement cinétique. Par ailleurs, pour tester l’importance de l’aspect vectoriel du repliement in vivo, j’ai développé une méthode ayant pour but de vectoriser le repliement in vitro. J’ai pu montrer qu’il est possible grâce à des anticorps dirigés contre la toxine  réduite d’inhiber son repliement oxydant, de lever cette inhibition et finalement de modifier sa voie de repliement
Protein folding is the last stage of genetic expression. The mechanism by which proteins acquire their 3D structure remains poorly understood. During my project,. I showed that the addition of one residue in one loop of the structure of toxin  from Naja nigricollis slows its oxidative folding process down in vitro. This decrease in the folding rate is due to a switch of productive pathway. NMR analysis of folding intermediates enabled me to hypothesize a structural explanation for this kinetic modification. Additionally, in order to test the influence of vectorial folding on the folding of a small disulfide-rich protein in vitro, I developed a method using antibodies raised against various parts of the reduced protein. My results showed that one of these antibodies is able to inhibit the oxidative folding of toxin . This inhibition is reversible. Most interestingly, the use of this antibody modifies the folding pathway

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44

Teixeira-Clerc, Fatima. "Etude de l'interaction entre le récepteur nicotinique de l'acetylcholine et la toxine alpha de Naja nigricollis par ingénierie chimique du ligand." Paris 6, 2003. http://www.theses.fr/2003PA066316.

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45

Gilles, Nicolas. "Effets pharmacologiques des toxines de type alpha de scorpion sur les canaux sodiques de l'insecte et du mammifère." Paris 5, 2000. http://www.theses.fr/2000PA05P601.

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46

Petitcolin, Marie-Anne. "Vieillissement artériel et sensibilité au calcium de la contraction : couplage entre récepteurs [alpha]1-adrénergiques et protéines G[indice i/o]." Nancy 1, 2000. http://www.theses.fr/2000NAN12012.

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Thèse de doctorat en sciences du médicament. Ce travail de thèse a eu pour objectif : 1] l'étude des mécanismes intracellulaires de régulation de la sensibilité au calcium intracellulaire ([Ca2+][indice i]) de la réponse contractile des cellules musculaires lisses, lors d'une stimulation par un agoniste, la noradrénaline, 2] la comparaison de ces mécanismes dans une artère musculaire de faible diamètre, l'artère caudale, et une artère de transfert, l'aorte, chez le rat, et 3] l'analyse des perturbations de ces mécanismes lors du vieillissement vasculaire. L'originalité de ce travail repose sur l'utilisation simultanée et sur la même artère d'une approche fonctionnelle et biochimique. La première a consisté à évaluer l'impact d'un traitement par la toxine pertussique, un inhibiteur des protéines G[indice i] et G[indice 01] sur le couplage [Ca2+][indice i]-vasoréactivité dans un segment perfusé d'artère caudale dé-endothélialisée ou sur la réponse contractile d'anneaux d'aorte dé-endothélialisée. L'approche biochimique a permis d'étudier le rôle des protéines G[indice i/o] dans la sensibilité au [Ca2+][indice i] de l'appareil contractile lors d'une stimulation par la noradrénaline. Ces deux approches ont été réalisées sur deux souches de rats normotendus (Wistar et WAG/Rij). [. . . ]

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Huang, Mengying [Verfasser], and Martin [Akademischer Betreuer] Borggrefe. "Alpha 1-adrenoceptor signaling contributes to toxic effects of catecholamine on electrical properties in human-induced stem cell-derived cardiomyocytes / Mengying Huang ; Betreuer: Martin Borggrefe." Heidelberg : Universitätsbibliothek Heidelberg, 2021. http://d-nb.info/1228539898/34.

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[Verfasser], Gunnaporn Veerachato. "On the cellular stress response to Staphylococcus aureus alpha-toxin / Gunnaporn Veerachato." 2007. http://d-nb.info/982704682/34.

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Reutemann, Mathias [Verfasser]. "ICAM-1 abhängige Akkumulation neutrophiler Granulozyten und Leukotrien-vermittelte Kardiodepression in Staphylococcus aureus α-Toxin-perfundierten [Alpha-Toxin-perfundierten] Rattenherzen / vorgelegt von Mathias Reutemann." 2002. http://d-nb.info/965811611/34.

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Wegner, Judith [Verfasser]. "Exotoxin-Schock, ausgelöst durch Staphylococcus-aureus-α-Toxin [Staphylococcus-aureus-alpha-Toxin], am Tiermodell Ratte : Auswirkungen auf Gefäßendothel, Leukozytenakkumulation und Thrombozytenaggregation / eingereicht von Judith Wegner." 2005. http://d-nb.info/97606538X/34.

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