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Fu-hsiung Lin Ying Wang Susie Lin Zhen Cao † David A. Hosford 《Journal of neurochemistry》1995,65(5):2087-2095
Abstract: Previously, we have shown a significant increase in number of GABAB receptor binding sites in neocortex and thalamus of lethargic ( lh/lh ) mice, a mutant strain exhibiting absence seizures. This study was performed to test our hypothesis that presynaptic GABAB receptors would inhibit [3 H]GABA release to a greater degree in lh/lh mice compared with their nonepileptic littermates (designated +/+). Synaptosomes isolated from neocortex and thalamus of age-matched male lh/lh and +/+ mice were similar in uptake of [3 H]GABA. In the neocortical preparation, baclofen dose-dependently inhibited [3 H]GABA release evoked by 12 m M KCl, an effect mediated by GABAB receptors. The maximal inhibition ( I max ) value was significantly greater (80%) in lh/lh than +/+ mice, whereas the IC50 (3 µ M ) was unchanged. In the thalamic preparation, the effect of baclofen (50 µ M ) was 58% less robust in lh/lh mice. Other effects mediated by GABAB receptors (inhibitions in Ca2+ uptake and cyclic AMP formation) were also significantly reduced in thalamic synaptosomes from lh/lh mice. These data suggest a greater presynaptic GABAB receptor-mediated effect in neocortex and a reduced effect in thalamic nuclei of lh/lh mice. It is possible that selective effects of presynaptic GABAB receptors on GABA release in neocortex and thalamic nuclei of lh/lh mice may contribute to mechanisms underlying absence seizures. 相似文献
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Yadin Dudai Shoshana Zvi Susie Segel 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1984,155(4):569-576
Summary TheDrosophila X-linked mutantrutabaga (Duerr and Quinn 1982) fails to perform normally in olfactory conditioning paradigms, in spite of being able to sense odorants and shock (Figs. 1–3).rut is capable of forming an association between shock and odorant, but memory decays rapidly; the memory of the mutant following intensive training resembles that of normal flies following very brief training (Fig. 4).rut flies also display in vitro a defective adenylate cyclase activity (Fig. 6). The enzyme in the mutant is responsive to stimulation by a putative neurotransmitter and by a guanyl nucleotide (Fig. 8) but the activity is lower than normal even in the presence of forskolin (Fig. 8) and MnATP (Fig. 9), suggesting that the lesion is closely associated with the function of the catalytic subunit.rut/ + heterozygotes are semi-recessive with regard to both the behavioral defect and the biochemical defect (Figs. 5, 7). The behavioral and the biochemical lesions detected inrut flies are discussed in light of current molecular models of learning. 相似文献
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Background
The Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine is given to >120 million infants each year worldwide. Most studies investigating the immune response to BCG have focused on adaptive immunity. However the importance of TCR-gamma/delta (γδ) T cells and NK cells in the mycobacterial-specific immune response is of increasing interest.Methods
Participants in four age-groups were BCG-immunized. Ten weeks later, in vitro BCG-stimulated blood was analyzed for NK and T cell markers, and intracellular IFNgamma (IFNγ) by flow cytometry. Total functional IFNγ response was calculated using integrated median fluorescence intensity (iMFI).Results
In infants and children, CD4 and CD4-CD8- (double-negative (DN)) T cells were the main IFNγ-expressing cells representing 43-56% and 27-37% of total CD3+ IFNγ+ T cells respectively. The iMFI was higher in DN T cells compared to CD4 T cells in all age groups, with the greatest differences seen in infants immunized at birth (p=0.002) or 2 months of age (p<0.0001). When NK cells were included in the analysis, they accounted for the majority of total IFNγ-expressing cells and, together with DN Vδ2 γδ T cells, had the highest iMFI in infants immunized at birth or 2 months of age.Conclusion
In addition to CD4 T cells, NK cells and DN T cells, including Vδ2 γδ T cells, are the key populations producing IFNγ in response to BCG immunization in infants and children. This suggests that innate immunity and unconventional T cells play a greater role in the mycobacterial immune response than previously recognized and should be considered in the design and assessment of novel tuberculosis vaccines. 相似文献6.
Rick A. Brenneman Adam T. McLain Justin M. Taylor John R. Zaonarivelo Runhua Lei Susie M. McGuire Rambinintsoa Andriantompohavana Anthony B. Rylands Edward E. LouisJr. 《International journal of primatology》2016,37(3):460-477
Subspecies were traditionally defined by identifying gaps between phenotypes across the geographic range of a species, and may represent important units in the development of conservation strategies focused on preserving genetic diversity. Previous taxonomic research proposed that phenotypic variation between scattered Indri indri populations warranted the naming of two distinct subspecies, I. i. indri and I. i. variegatus. We tested these subspecific designations using mitochondrial sequence data generated from the control region or D-loop (569 bp) and a large section (2362 bp) of multiple genes and tRNAs known as Pastorini’s fragment and nuclear microsatellite markers. This study used 114 samples of I. indri from 12 rainforest sites in eastern Madagascar, encompassing the entire range of the species. These genetic samples represent multiple populations from low- and high-elevation forests from both putative subspecies. Molecular analyses of the mitochondrial sequence data did not support the two proposed subspecies. Furthermore, the microsatellite analyses showed no significant differences across the range beyond population level differentiation. This study demonstrates the utility of incorporating multiple lines of evidence in addition to phenotypic traits to define species or subspecies. 相似文献
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Diego de Souza Gonalves Marina da Silva Ferreira Kamilla Xavier Gomes Claudia Rodríguez‐de La Noval Susie Coutinho Liedke Giovani Carlo Veríssimo da Costa Patricia Albuquerque Juliana Reis Cortines Regina Helena Saramago Peralta Jos Mauro Peralta Arturo Casadevall Allan J. Guimares 《Cellular microbiology》2019,21(10)
Free‐living amoebae (FLAs) are major reservoirs for a variety of bacteria, viruses, and fungi. The most studied mycophagic FLA, Acanthamoeba castellanii (Ac), is a potential environmental host for endemic fungal pathogens such as Cryptococcus spp., Histoplasma capsulatum, Blastomyces dermatitides, and Sporothrix schenckii. However, the mechanisms involved in this interaction are poorly understood. The aim of this work was to characterize the molecular instances that enable Ac to interact with and ingest fungal pathogens, a process that could lead to selection and maintenance of possible virulence factors. The interaction of Ac with a variety of fungal pathogens was analysed in a multifactorial evaluation that included the role of multiplicity of infection over time. Fungal binding to Ac surface by living image consisted of a quick process, and fungal initial extrusion (vomocytosis) was detected from 15 to 80 min depending on the organism. When these fungi were cocultured with the amoeba, only Candida albicans and Cryptococcus neoformans were able to grow, whereas Paracoccidioides brasiliensis and Sporothrix brasiliensis displayed unchanged viability. Yeasts of H. capsulatum and Saccharomyces cerevisiae were rapidly killed by Ac; however, some cells remained viable after 48 hr. To evaluate changes in fungal virulence upon cocultivation with Ac, recovered yeasts were used to infect Galleria mellonella, and in all instances, they killed the larvae faster than control yeasts. Surface biotinylated extracts of Ac exhibited intense fungal binding by FACS and fluorescence microscopy. Binding was also intense to mannose, and mass spectrometry identified Ac proteins with affinity to fungal surfaces including two putative transmembrane mannose‐binding proteins (MBP, L8WXW7 and MBP1, Q6J288). Consistent with interactions with such mannose‐binding proteins, Ac–fungi interactions were inhibited by mannose. These MBPs may be involved in fungal recognition by amoeba and promotes interactions that allow the emergence and maintenance of fungal virulence for animals. 相似文献
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Crans DC Smee JJ Gaidamauskiene EG Anderson OP Miller SM Jin W Gaidamauskas E Crubellier E Grainda R Chi LH Willsky GR 《Journal of inorganic biochemistry》2004,98(11):1837-1850
The effects of Mo-hydroxylamido complexes on cell growth were determined in Saccharomyces cerevisiae to investigate the biological effects of four different Mo complexes as a function of pH. Studies with yeast, an eukaryotic cell, are particularly suited to examine growth at different pH values because this organism grows well from pH 3 to 6.5. Studies can therefore be performed both in the presence of intact complexes and when the complexes have hydrolyzed to ligand and free metal ion. One of the complexes we examined was structurally characterized by X-ray crystallography. Yeast growth was inhibited in media solutions containing added Mo-dialkylhydroxylamido complexes at pH 3-7. When combining the yeast growth studies with a systematic study of the Mo-hydroxylamido complexes' stability as a function of pH and an examination of their speciation in yeast media, the effects of intact complexes can be distinguished from that of ligand and metal. This is possible because different effects are observed with complex present than when ligand or metal alone is present. At pH 3, the growth inhibition is attributed to the forms of molybdate ion that exist in solution because most of the complexes have hydrolyzed to oxomolybdate and ligand. The monoalkylhydroxylamine ligand inhibited yeast growth at pH 5, 6 and 7, while the dialkylhydroxylamine ligands had little effect on yeast growth. Growth inhibition of the Mo-dialkylhydroxylamido complexes is observed when a complex exists in the media. A complex that is inert to ligand exchange is not effective even at pH 3 where other Mo-hydroxylamido complexes show growth inhibition as molybdate. These results show that the formation of some Mo complexes can protect yeast from the growth inhibition observed when either the ligand or Mo salt alone are present. 相似文献
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Role of the Rab GTP-binding protein Ypt3 in the fission yeast exocytic pathway and its connection to calcineurin function 下载免费PDF全文
Cheng H Sugiura R Wu W Fujita M Lu Y Sio SO Kawai R Takegawa K Shuntoh H Kuno T 《Molecular biology of the cell》2002,13(8):2963-2976
A genetic screen for mutations synthetically lethal with fission yeast calcineurin deletion led to the identification of Ypt3, a homolog of mammalian Rab11 GTP-binding protein. A mutant with the temperature-sensitive ypt3-i5 allele showed pleiotropic phenotypes such as defects in cytokinesis, cell wall integrity, and vacuole fusion, and these were exacerbated by FK506-treatment, a specific inhibitor of calcineurin. Green fluorescent protein (GFP)-tagged Ypt3 showed cytoplasmic staining that was concentrated at growth sites, and this polarized localization required the actin cytoskeleton. It was also detected as a punctate staining in an actin-independent manner. Electron microscopy revealed that ypt3-i5 mutants accumulated aberrant Golgi-like structures and putative post-Golgi vesicles, which increased remarkably at the restrictive temperature. Consistently, the secretion of GFP fused with the pho1(+) leader peptide (SPL-GFP) was abolished at the restrictive temperature in ypt3-i5 mutants. FK506-treatment accentuated the accumulation of aberrant Golgi-like structures and caused a significant decrease of SPL-GFP secretion at a permissive temperature. These results suggest that Ypt3 is required at multiple steps of the exocytic pathway and its mutation affects diverse cellular processes and that calcineurin is functionally connected to these cellular processes. 相似文献