Abstract
We demonstrate a local subunit-specific switch in NMDA receptors that alternately primes or prevents potentiation at single synapses. Prolonged suppression of neurotransmitter release enhances NMDA receptor currents, increases the number of functional NMDA receptors containing NR2B, and augments cal...
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PMID: 20620872
PDF is available here.
Abstract
We developed a reversible neurotransmission blocking technique, in which transmission of each pathway was selectively blocked by specific expression of transmission-blocking tetanus toxin in a doxycycline-dependent manner. The results indicated that the coordinated modulation of these two pathways w...
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PMID: 20620875
PDF is available here.
Abstract
This study aimed to determine the long-term change of seizure susceptibility and the role of nNOS on brain development following recurrent early-life seizures in rats. Video-EEG recordings were conducted between postnatal days 50 and 60. Alterations in seizure susceptibility were assayed on day 22 o...
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PMID: 20514313
PDF is available here.
Abstract
A simple, safe and efficient system that can specifically transfect peripheral sensorial neurons can bring new answers to address peripheral neuropathies. A multi-component non-viral gene delivery vector targeted to peripheral nervous system cells was developed, using poly(ethylene imine) (PEI) as s...
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PMID: 20093157
PDF is available here.
Abstract
We highlight novel genetic tracing approaches that enable visualization of specific neuronal pathways by introducing cDNA encoding a transsynaptic tracer. In contrast to conventional tracing methods, these genetic approaches use cell-type-specific promoters to express transsynaptic tracers such as w...
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PMID: 20367126
PDF is available here.
Abstract
Tetanus is a deadly disease of warm blooded animals and humans caused by an exotoxin called tetanospasmin or tetanus neurotoxin (TeNT) produced by anaerobic bacterium named Clostridium tetani TeNT is an A-B toxin; each molecule consists of a heavy chain (HC) containing cellular receptor binding doma...
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PMID: 20527521
PDF is available here.
Abstract
This study deals with the effects of the initial nitrogen source (NZ Case TT) level and the protocol of glucose addition during the fed-batch production of tetanus toxin by Clostridium tetani. An increase in the initial concentration of NZ Case TT (NZ(0)) accelerated cell growth, increased the consu...
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PMID: 19856382
PDF is available here.
Abstract
We have previously shown that CDR3-based DNA immunization can induce immune response against lymphoma and explored this strategy to provide protection in a murine B-cell lymphoma model. Here we performed vaccination employing as immunogen a naked DNA fusion product. The DNA vaccine was generated fol...
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PMID: 20445751
PDF is available here.
Mark J Kwakkenbos,
Sean A Diehl,
Etsuko Yasuda,
Arjen Q Bakker,
Caroline M M van Geelen,
Michaël V Lukens,
Grada M van Bleek,
Myra N Widjojoatmodjo,
Willy M J M Bogers,
Henrik Mei,
Andreas Radbruch,
Ferenc A Scheeren,
Hergen Spits and
Tim Beaumont
Abstract
We convert them to highly proliferating, cell surface B cell receptor (BCR)-positive, immunoglobulin-secreting B cells with features of germinal center B cells, including expression of activation-induced cytidine deaminase (AID). We generated cloned lines of B cells specific for respiratory syncytia...
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PMID: 20023635
PDF is available here.
Abstract
We have gained significant achievements against pneumococcal infections by using conjugated pneumococcal vaccines. In January 2009, the EMEA issued a positive opinion about, and recommended the approval of, GlaxoSmithKline's pediatric pneumococcal candidate vaccine, which is indicated for active imm...
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PMID: 19883326
PDF is available here.
Russell G Higbee,
Anthony M Byers,
Vipra Dhir,
Donald Drake,
Heather G Fahlenkamp,
Jyoti Gangur,
Anatoly Kachurin,
Olga Kachurina,
Del Leistritz,
Yifan Ma,
Riyaz Mehta,
Eric Mishkin,
Janice Moser,
Luis Mosquera,
Mike Nguyen,
Robert Parkhill,
Santosh Pawar,
Louis Poisson,
Guzman Sanchez-Schmitz,
Brian Schanen,
Inderpal Singh,
Haifeng Song,
Tenekua Tapia,
William Warren and
Vaughan Wittman
Abstract
We believe the best viable option available is to use human cells and/or tissues in a functional in vitro model of human physiology. Not only will this more accurately model human diseases, it will also eliminate any ethical, moral and scientific issues involved with use of live humans and animals....
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PMID: 19807200
PDF is available here.
Abstract
We employed the CA3-TeTX transgenic mouse, in which CA3 output can be specifically and inducibly controlled. We found that posttraining blockade of CA3 output for up to 4 weeks impairs the consolidation of contextual fear memory. Moreover, in vivo hippocampal recordings revealed a reduced intrinsic...
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PMID: 19555647
PDF is available here.
Abstract
We describe the assay validation process, during which the sensitivity, and precision of immunological endpoint assays were defined. The purpose was the evaluation of two multicentre phase I/II clinical trials from our unit in Southampton, UK, which assess the effects of DNA fusion vaccines on immun...
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PMID: 19066888
PDF is available here.
Abstract
The recombinant CT-1/TTC protein can be expressed and purified in BL21 (DE3) E. coli. This fusion protein has two biological activities of targeting delivery to central nervous system and protecting the cornu anterius medullae spinalis motoneurons....
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PMID: 19563075
PDF is available here.
Abstract
We used targeted neuronal silencing to assess the role of candidate neurons in the regulation of larval photobehavior. Inactivation of DOPA decarboxylase (Ddc) neurons increases the response to light throughout larval development, including during the later stages of the 3rd instar characterized by...
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PMID: 19549295
PDF is available here.
Abstract
Alcohol causes reactive hypoglycemia by attenuating the release of counter regulatory hormones, redistribution of pancreatic blood flow and direct stimulation of insulin secretion. Objective of this study was characterization of ethanol-induced insulin secretion. Signaling of ethanol- and glucose-in...
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PMID: 19910684
PDF is available here.
Abstract
We show the expression of CatE in primary human B cells and DC, which was only elevated in B cells after induction with phorbol 12-myristate 13-acetate (PMA), resulted in enhanced presentation of tetanus toxin C-fragment (TTC) to the respective T cells. Inhibition of aspartyl proteases using pepstat...
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PMID: 18996084
PDF is available here.
Abstract
Bcl-xL fusion proteins were found to bind specifically and undergo uptake into cultured rat spinal MNs. The fusion proteins were also taken up by DRG axonal terminals and transported back to the cell bodies in Campenot compartmentalized chambers (Tyler Research Corp., Edmonton, Canada). Finally, fus...
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PMID: 19057331
PDF is available here.
Abstract
We investigated the effects of prior exposure to the Salmonella typhimurium aroAD strain BRD509 on its ability to deliver the non-toxic C fragment of tetanus toxin (TT). BALB/c mice were orally immunised with BRD509 containing the C fragment expression plasmid pTETtac4, C fragment DNA vaccine pAT153...
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PMID: 18852007
PDF is available here.
Benjamin B BB Williams,
Meg M Wall,
Rebecca Yu RY Miao,
Brenda B Williams,
Ivan I Bertoncello,
Michael H MH Kershaw,
Theo T Mantamadiotis,
Michelle M Haber,
Murray D MD Norris,
Anand A Gautam,
Phillip K PK Darcy and
Robert G RG Ramsay
Abstract
We devised a DNA fusion vaccine to generate an anti-CRC immune response. c-Myb, like many tumor antigens, is weakly immunogenic as it is a "self" antigen and subject to tolerance. To break tolerance, a DNA fusion vaccine was generated comprising wild-type c-Myb cDNA flanked by two potent Th epitopes...
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PMID: 18386000
PDF is available here.
Abstract
We quantified circulating total, rotavirus (RV) and Tetanus toxin (TT) memory B cells (mBc) in healthy adults using a limiting dilution assay (LDA) and a flow cytometry assay (FCA) that permit evaluation of both CD27+ and CD27- mBc. RV mBc were enriched in the CD27-, IgG+ and in the CD27+, IgM+ subs...
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PMID: 18789807
PDF is available here.
Abstract
We provide evidence that amn plays a major role on sleep maintenance and onset in Drosophila. Flies with the amnesiac allele, loss-of-function amn(X8) mutation, showed a fragmented sleep pattern and short sleep latency. Moreover, homeostatic regulation was disrupted in amn(X8) mutants after sleep de...
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PMID: 18514063
PDF is available here.
Abstract
We and other groups developed the Gal4 gene trap and enhancer trap methods and established various transgenic fish expressing Gal4 in specific cells. By crossing such Gal4 lines with transgenic fish lines harboring various reporter genes and effector genes downstream of UAS (upstream activating sequ...
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PMID: 18482403
PDF is available here.
Abstract
We investigated whether C3 could modulate this step. Our results demonstrate for the first time that C3 can interfere with antigen proteolysis: (i) proteolysis of tetanus toxin (TT) by the lysosomal fraction from a human monocytic cell line (U937) is impaired in the presence of C3, (ii) this effect...
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PMID: 18585783
PDF is available here.
Abstract
We recently reported the development of a highly sensitive endopeptidase assay for the specific in vitro detection of active TeNT based on this proteolytic feature. Using this method, we could show that formaldehyde-inactivated TeNT preparations (toxoids), which are used for the production of tetanu...
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PMID: 18554757
PDF is available here.
Abstract
Botulinum neurotoxin (BoNT; serotypes A-G) and tetanus neurotoxin elicit flaccid and spastic paralysis, respectively. These neurotoxins are zinc proteases that cleave SNARE proteins to inhibit synaptic vesicle fusion to the plasma membrane. Although BoNT/B and tetanus neurotoxin (TeNT) cleave VAMP-2...
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PMID: 18511417
PDF is available here.
Abstract
We report the determination of all substrate residues that are involved in the interaction with BoNT/B, D, and F and TeNT by means of systematic mutagenesis of VAMP/synaptobrevin. For each of the toxins, three or more residues clustered at an N-terminal site remote from the respective scissile bond...
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PMID: 18511418
PDF is available here.
Abstract
Tetanus toxin (TeNT) elicits spastic paralysis through the cleavage of vesicle-associated membrane protein-2 (VAMP-2) in neurons at the interneuronal junction of the central nervous system. While TeNT retrograde traffics from peripheral nerve endings to the interneuronal junction, there is limited u...
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PMID: 18543947
PDF is available here.
Abstract
We have analyzed the masking effects of a lights-on (LOn) signal on Drosophila eclosion. The LOn response results in 12-21% of the flies that emerge on a given day eclosing within 10 min of the LOn signal. Flies that lack the neuropeptide eclosion hormone (EH), or in which its release is inhibited b...
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PMID: 18587121
PDF is available here.
Abstract
This review summarizes the microbiology, management and prevention of tetanus. Tetanus is an acute toxemic illness caused by Clostridium tetani infection at a laceration or break in the skin. It can also occur as a complication of burns, puerperal infections, umbilical stumps (tetanus neonatorum) an...
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PMID: 18588497
PDF is available here.
Abstract
We propose that insulin causes selective, dynamic relocalization of perinuclear GLUT4myc and VAMP2 and perinuclear GLUT4myc redistribution is a direct target of insulin-derived signals....
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PMID: 18417252
PDF is available here.
Abstract
To increase testing of vaccine induced humoral immunity in immune surveillance studies and vaccine trials, a rapid and simple microsphere-based multiplex assay (pentaplex) was developed for the quantitation of IgG serum antibodies directed against the Bordetella pertussis antigens: Pertussis Toxin (...
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PMID: 18407287
PDF is available here.
Abstract
Bead-based assay systems offer the possibility of measuring several specific antibodies in one sample simultaneously. This study evaluated a vaccine panel of a multianalyte system that measures antibodies to tetanus toxin, diphtheria toxin, and pertussis toxin (PT) from Bordetella pertussis. The ant...
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PMID: 18321880
PDF is available here.
Abstract
The effect of alpha-tocopherol, the major vitamin E component, on the release of endogenous glutamate has been investigated using rat cerebrocortical nerve terminals. Results showed that alpha-tocopherol facilitated the Ca2+-dependent but not the Ca2+-independent glutamate release evoked by 4-aminop...
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PMID: 18037536
PDF is available here.
Abstract
We identified two populations of neurons that are required for larval and adult ecdyses in the fruit fly, Drosophila melanogaster (Meigen). These neurons were identified by using the upstream region of two genes that code for atypical soluble guanylyl cyclases to drive tetanus toxin in the neurons t...
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PMID: 18456892
PDF is available here.
Abstract
We developed a generally applicable tetanus toxin-based method for transgenic mice that permits inducible and reversible inhibition of synaptic transmission and applied it to the trisynaptic pathway while preserving transmission in the monosynaptic pathway. We found that synaptic output from CA3 in...
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PMID: 18218862
PDF is available here.
Abstract
Live Salmonella vaccines are limited in use by the inherent toxicity of the lipopolysaccharide. The waaN gene encodes a myristyl transferase required for the secondary acylation of lipid A in lipopolysaccharide. A waaN mutant exhibits reduced induction of the inflammatory cytokines associated with l...
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PMID: 18177343
PDF is available here.
Abstract
Activation and expansion of T helper (Th) cells followed by regulation of activation are essential to the generation of immune responses while limiting concomitant autoreactivity. In order to characterize T cells reactive towards myeloma-derived monoclonal immunoglobulin (mIg), an autologous cocultu...
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PMID: 18156498
PDF is available here.
Abstract
We generated several gut-associated lymphoreticular tissue-null mice by treatment with anti-interleukin-7 receptor antibody, the fusion protein of lymphotoxin beta receptor and IgG Fc, and/or tumor necrosis factor receptor p55 and IgG Fc. These mice were then immunized with recombinant Salmonella ex...
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PMID: 18086815
PDF is available here.
Abstract
We show that mature MC isolated from human intestinal tissue express soluble N-ethylmaleide sensitive factor attachment protein (SNAP)-23, Syntaxin (STX)-1B, STX-2, STX-3, STX-4, and STX-6 but not SNAP-25. Furthermore, we found that primary human MC express substantial amounts of vesicle associated...
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PMID: 18253931
PDF is available here.
Abstract
We investigated the respiration of differentiated PC12 cells upon depolarization with 100 mm K+. Single cell confocal analysis identified a significant depolarization of the plasma membrane potential and a relatively minor depolarization of the mitochondrial membrane potential following K+ exposure....
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PMID: 18086678
PDF is available here.
Abstract
These results suggest that inhibitory basket cell synapses are optimized for rapid and precise temporal and spatial Ca(2+) coordination of synaptic vesicle fusion and replenishment, which may contribute to the unique physiology of inhibitory synaptic transmission, including phasic release during act...
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PMID: 18255033
PDF is available here.
Abstract
We describe induction of autoantibodies and self-reactive CTL in three types of OVA-transgenic mouse strains, RIP-OVA(low), RIP-mOVA and RIP-OVA(HI) exhibiting varying levels of OVA expression and tolerance. This was achieved by immunizing with DNA constructs where a foreign T-helper epitope, P30 fr...
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PMID: 18201366
PDF is available here.
Abstract
We show how we have introduced the light chain of the TeNT into nonneuronal cells and selected clones expressing this toxin by Western blotting and by immunofluorescence. We also present how we identified which cells express TeNT by searching for a soluble green fluorescent protein (GFP) pattern of...
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PMID: 18369946
PDF is available here.
Abstract
Botulinum (BoNT) and tetanus (TeNT) neurotoxins are bacterial zinc metalloproteases that cleave and inactivate cellular proteins essential for neurotransmitter release. There are seven serotypes of BoNT, while TeNT is found in one serotype. In order to characterize their enzymatic activities and to...
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PMID: 19075822
PDF is available here.
Abstract
In order to prevent atherosclerosis, a chimeric enzyme vaccine of AnsB-TTP-PADRE-CETPC was successfully constructed, expressed and purified to immunize New Zealand white rabbits for inducing high titers of anti-CETP antibodies to improve lipid abnormality. The protein was expressed as soluble protei...
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PMID: 18782072
PDF is available here.
Abstract
We demonstrated that GDNF-TTC induces the neuronal survival Akt kinase pathway in mouse cortical culture neurons and~maintains its antiapoptotic neuronal activity in Neuro2A cells. Moreover, we have found that genetic fusion is able to increase survival by 9 days and improves life quality in symptom...
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PMID: 19096133
PDF is available here.
Abstract
Tetanus neurotoxin (TeNT(1)) is a bacterial protease which specifically cleaves the vesicle protein synaptobrevin-2 (vesicle associated membrane protein-2, VAMP-2). This proteolytic feature of the toxin has been used to develop a sensitive endopeptidase assay for the detection of TeNT activity as an...
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PMID: 17826026
PDF is available here.
Abstract
We compared different biotin-binding proteins (avidin, streptavidin, or neutravidin) as crosslinkers to conjugate proteins to biodegradable nanoparticles prepared from poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-biotin polymers. Avidin gave the highest levels of overall protein co...
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PMID: 17854886
PDF is available here.
Abstract
Quite remarkably, when comparing the tetanus production process in our soy-based medium with the traditional animal/dairy-containing media, our medium does not require addition of expensive vitamins, uracil or carbon sources other than glucose. Furthermore, the l-tyrosine and l-cysteine components c...
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PMID: 17908228
PDF is available here.
Abstract
These results contrast with the perceived notion that tetanus toxoid responses are dominated by universal CD4+ T-cell epitopes. Rather these results illustrate heterogeneous T-cell responses for different class II alleles and individual-specific variation of the T-cell repertoire....
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PMID: 17906339
PDF is available here.
Abstract
We adopted a novel gene-manipulating technique, termed reversible neurotransmission blocking (RNB). In this technology, cerebellar granule cells specifically expressed neurotransmission-blocking tetanus toxin in a doxycycline (DOX)-dependent manner. Extracellular recording of Purkinje cells in awake...
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PMID: 17923666
PDF is available here.
Abstract
We have investigated at identified cholinergic inhibitory Aplysia synapses the cellular mechanism of post-tetanic potentiation (PTP) expressed under control conditions or after N has been depressed by applying lethal toxin (LT) from Clostridium sordellii or tetanus toxin (TeNT). The analysis of the...
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PMID: 17656428
PDF is available here.
Abstract
We coupled the foreign, immunodominant T-helper epitope of tetanus toxin to the N terminus of myostatin, and BALB/c mice were immunized with the recombinant vector. Sera from vaccinated mice showed the presence of specific antibodies against the recombinant protein. In addition, body weight, muscle...
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PMID: 17587222
PDF is available here.
Abstract
Low immunoglobulin G2 levels resolved completely within 0.6 years to 6 years (median: 1.5 years) in all patients. All 13 patients responded adequately to vaccination with protein antigens such as tetanus toxoid and polio as well as to immunization with pneumococcal vaccine. Four of 13 patients had a...
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PMID: 17682036
PDF is available here.