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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have previously shown that progesterone (PROG) is synthesized by Schwann cells and promotes myelin formation in the peripheral nervous system (PNS). We now report that this neurosteroid also stimulates myelination in organotypic slice cultures of 7-day-old (P7) rat and mouse cerebellum. Myelination was evaluated by immunofluorescence analysis of the myelin basic protein (MBP). After 7 days in culture (7DIV), we found that adding PROG (2–5 × 10−5 M) to the culture medium caused a fourfold increase in MBP expression when compared to control slices. The effect of PROG on MBP expression involves the classical intracellular PROG receptor (PR): the selective PR agonist R5020 significantly increased MBP expression and the PR antagonist mifepristone (RU486) completely abolished the effect of PROG on this MBP expression. Moreover, treatment of P7-cerebellar slice cultures from PR knockout (PRKO) mice with PROG had no significant effect on MBP expression. PROG was metabolized in the cerebellar slices to 5α-dihydroprogesterone (5α-DHP) and to the GABAA receptor-active metabolite 3α,5α-tetrahydroprogesterone (3α,5α-THP, allopregnanolone). The 5α-reductase inhibitor L685-273 partially inhibited the effect of PROG, and 3α,5α-THP (2–5 × 10−5 M) significantly stimulated the MBP expression, although to a lesser extent than PROG. The increase in MBP expression by 3α,5α-THP involved GABAA receptors, as it could be inhibited by the selective GABAA receptor antagonist bicuculline. These findings suggest that progestins stimulate MBP expression and consequently suggest an increase in CNS myelination via two signalling systems, the intracellular PR and membrane GABAA receptors, and they confirm a new role of GABAA receptors in myelination.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 7 (1995), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Basal forebrain cholinergic neurons, which degenerate in Alzheimer's disease, respond to multiple trophic factors, including the neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). This dual responsiveness prompted us to investigate the effects of a synthetic chimaeric molecule, containing the active domains of both NGF and BDNF. The NGF/BDNF chimaeric factor exhibited synergistic actions, and was 100-fold more potent than wild-type BDNF in enhancing survival of cultured dissociated basal forebrain cholinergic neurons. This effect was apparently due to true BDNF/NGF synergy, since addition of the two wild-type trophins simultaneously reproduced the effect of the chimaera. Synergy was selective for neurons which respond to both factors; substantia nigra dopaminergic neurons, which respond to BDNF but not NGF, exhibited no potentiation. The chimaeric factor thus revealed a synergy that may normally occur in the brain, and constitutes a potentially novel therapeutic agent with greater potency than naturally occurring individual trophins.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Phytochemistry 30 (1991), S. 2289-2293 
    ISSN: 0031-9422
    Keywords: Lamiaceae ; Thymus willkomii ; chemotypes ; essential oil ; multivariate analysis.
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Bulletin of environmental contamination and toxicology 52 (1994), S. 231-237 
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Bulletin of environmental contamination and toxicology 50 (1993), S. 871-877 
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7284
    Keywords: Typhoid fever ; Epidemiology ; Salmonella typhi ; Plasmid analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A typhoid fever outbreak affecting 54 school students occurred in a Public School of Móstoles, Madrid. The date of onset was 11 June 1991 and the last detected case was 8 July 1991. Salmonella typhi was cultured from blood and/or stool samples corresponding to 54 patients and one food-handler. There were no secondary cases detected. Epidemiological investigation suggested a salad or a custard as the common source. Patients and the food-handler were treated with ampicillin/amoxicillin for up to three weeks. There were seven relapses that were also treated with the same antibiotics with success. None were found to be excreting the organisms when tested after four months. All the Salmonella ryphi isolated strains were phagetype 34, biotype Xylose +, Tetrationate Reductase + and harboured a similar 22 Mdal plasmid, they were also susceptible to the antibiotics tested.
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2021-08-24
    Description: Many members of the benthic fauna of the Antarctic continental shelf share close phylogenetic relationships to the deep-sea fauna adjacent to Antarctica and in other ocean basins. It has been suggested that connections between the Southern Ocean and the deep sea have been facilitated by the presence of a deep Antarctic continental shelf coupled with submerging Antarctic bottom water and emerging circumpolar deep water. These conditions may have allowed ‘polar submergence’, whereby shallow Southern Ocean fauna have colonised the deep sea and ‘polar emergence’, whereby deep-sea fauna colonised the shallow Southern Ocean. A recent molecular study showed that a lineage of deep-sea and Southern Ocean octopuses with a uniserial sucker arrangement on their arms appear to have arisen via polar submergence. A distantly related clade of octopuses with a biserial sucker arrangement on their arms (historically placed in the genus Benthoctopus) is also present in the deep-sea basins of the world and the Southern Ocean. To date their evolutionary history has not been examined. The present study investigated the origins of this group using 3133 base pairs (bp) of nucleotide data from five mitochondrial genes (12S rRNA, 16S rRNA, cytochrome c oxidase subunit I, cytochrome c oxidase subunit III, cytochrome b) and the nuclear gene rhodopsin from at least 18 species (and 7 outgroup taxa). Bayesian relaxed clock analyses showed that Benthoctopus species with a high-latitude distribution in the Southern Hemisphere represent a paraphyletic group comprised of three independent clades. The results suggest that the Benthoctopus clade originated in relatively shallow Northern Hemisphere waters. Benthoctopus species distributed in the Southern Ocean are representative of polar emergence and occur at shallower depths than non-polar Benthoctopus species.
    Type: Article , PeerReviewed
    Format: text
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  • 8
    Publication Date: 2016-10-08
    Description: Background Toca 511, a gamma retroviral replicating vector encoding cytosine deaminase, used in combination with 5-fluorocytosine (5-FC) kills tumor by local production of 5-fluorouracil (5-FU), inducing local and systemic immunotherapeutic response resulting in long-term survival after cessation of 5-FC. Toca 511 and Toca FC (oral extended-release 5-FC) are under investigation in patients with recurrent high-grade glioma. Lomustine is a treatment option for patients with high-grade glioma. Methods We investigated the effects of lomustine combined with Toca 511 + 5-FC in syngeneic orthotopic glioma models. Safety and survival were evaluated in immune-competent rat F98 and mouse Tu-2449 models comparing Toca 511 + 5-FC to lomustine + 5-FC or the combination of Toca 511 + 5-FC + lomustine. After intracranial implantation of tumor, Toca 511 was delivered transcranially followed by cycles of intraperitoneal 5-FC with or without lomustine at the first or fourth cycle. Results Coadministration of 5-FC with lomustine was well tolerated. In F98, combination Toca 511 + 5-FC and lomustine increased median survival, but "cures" were not achieved. In Tu-2449, combination Toca 511 + 5-FC and lomustine increased median survival and resulted in high numbers of cure. Rejection of tumor rechallenge occurred after treatment with Toca 511 + 5-FC or combined with lomustine, but not with lomustine + 5-FC. Mixed lymphocyte–tumor cell reactions using splenocytes from cured animals showed robust killing of target cells in an effector:target ratio–dependent manner with Toca 511 + 5-FC and Toca 511 + 5-FC + lomustine day 10. Conclusion The combination of Toca 511 + 5-FC and lomustine shows promising efficacy with no additive toxicity in murine glioma models. Immunotherapeutic responses resulting in long-term survival were preserved despite lomustine-related myelosuppression.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
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  • 9
    Publication Date: 2014-01-22
    Description: Papillomaviruses (PVs) are widespread pathogens. However, the extent of PV infections in bats remains largely unknown. This work represents the first comprehensive study of PVs in Iberian bats. We identified four novel PVs in the mucosa of free-ranging Eptesicus serotinus (EserPV1, EserPV2, and EserPV3) and Rhinolophus ferrumequinum (RferPV1) individuals and analyzed their phylogenetic relationships within the viral family. We further assessed their prevalence in different populations of E. serotinus and its close relative E. isabellinus . Although it is frequent to read that PVs co-evolve with their host, that PVs are highly species-specific, and that PVs do not usually recombine, our results suggest otherwise. First, strict virus–host co-evolution is rejected by the existence of five, distantly related bat PV lineages and by the lack of congruence between bats and bat PVs phylogenies. Second, the ability of EserPV2 and EserPV3 to infect two different bat species ( E. serotinus and E. isabellinus ) argues against strict host specificity. Finally, the description of a second noncoding region in the RferPV1 genome reinforces the view of an increased susceptibility to recombination in the E2-L2 genomic region. These findings prompt the question of whether the prevailing paradigms regarding PVs evolution should be reconsidered.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 10
    Publication Date: 2011-08-03
    Description: Hedgehog (Hh) moves from the producing cells to regulate the growth and development of distant cells in a variety of tissues. Here, we have investigated the mechanism of Hh release from the producing cells to form a morphogenetic gradient in the Drosophila wing imaginal disk epithelium. We describe that Hh reaches both apical and basolateral plasma membranes, but the apical Hh is subsequently internalized in the producing cells and routed to the basolateral surface, where Hh is released to form a long-range gradient. Functional analysis of the 12-transmembrane protein Dispatched, the glypican Dally-like (Dlp) protein, and the Ig-like and FNNIII domains of protein Interference Hh (Ihog) revealed that Dispatched could be involved in the regulation of vesicular trafficking necessary for basolateral release of Hh, Dlp, and Ihog. We also show that Dlp is needed in Hh-producing cells to allow for Hh release and that Ihog, which has been previously described as an Hh coreceptor, anchors Hh to the basolateral part of the disk epithelium.
    Keywords: Feature Articles
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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