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Graham L. Cromar Jonathan R. Epp Ana Popovic Yusing Gu Violet Ha Brandon J. Walters James St. Pierre Xuejian Xiong John G. Howland Sheena A. Josselyn Paul W. Frankland John Parkinson 《PLoS neglected tropical diseases》2022,16(7)
During chronic infection, the single celled parasite, Toxoplasma gondii, can migrate to the brain where it has been associated with altered dopamine function and the capacity to modulate host behavior, increasing risk of neurocognitive disorders. Here we explore alterations in dopamine-related behavior in a new mouse model based on stimulant (cocaine)-induced hyperactivity. In combination with cocaine, infection resulted in heightened sensorimotor deficits and impairment in prepulse inhibition response, which are commonly disrupted in neuropsychiatric conditions. To identify molecular pathways in the brain affected by chronic T. gondii infection, we investigated patterns of gene expression. As expected, infection was associated with an enrichment of genes associated with general immune response pathways, that otherwise limits statistical power to identify more informative pathways. To overcome this limitation and focus on pathways of neurological relevance, we developed a novel context enrichment approach that relies on a customized ontology. Applying this approach, we identified genes that exhibited unexpected patterns of expression arising from the combination of cocaine exposure and infection. These include sets of genes which exhibited dampened response to cocaine in infected mice, suggesting a possible mechanism for some observed behaviors and a neuroprotective effect that may be advantageous to parasite persistence. This model offers a powerful new approach to dissect the molecular pathways by which T. gondii infection contributes to neurocognitive disorders. 相似文献
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Litman GW; Rast JP; Shamblott MJ; Haire RN; Hulst M; Roess W; Litman RT; Hinds- Frey KR; Zilch A; Amemiya CT 《Molecular biology and evolution》1993,10(1):60-72
Immunoglobulins are encoded by a large multigene system that undergoes
somatic rearrangement and additional genetic change during the development
of immunoglobulin-producing cells. Inducible antibody and antibody-like
responses are found in all vertebrates. However, immunoglobulin possessing
disulfide-bonded heavy and light chains and domain-type organization has
been described only in representatives of the jawed vertebrates. High
degrees of nucleotide and predicted amino acid sequence identity are
evident when the segmental elements that constitute the immunoglobulin gene
loci in phylogenetically divergent vertebrates are compared. However, the
organization of gene loci and the manner in which the independent elements
recombine (and diversify) vary markedly among different taxa. One striking
pattern of gene organization is the "cluster type" that appears to be
restricted to the chondrichthyes (cartilaginous fishes) and limits
segmental rearrangement to closely linked elements. This type of gene
organization is associated with both heavy- and light-chain gene loci. In
some cases, the clusters are "joined" or "partially joined" in the germ
line, in effect predetermining or partially predetermining, respectively,
the encoded specificities (the assumption being that these are expressed)
of the individual loci. By relating the sequences of transcribed gene
products to their respective germ-line genes, it is evident that, in some
cases, joined-type genes are expressed. This raises a question about the
existence and/or nature of allelic exclusion in these species. The
extensive variation in gene organization found throughout the vertebrate
species may relate directly to the role of intersegmental
(V<==>D<==>J) distances in the commitment of the individual
antibody-producing cell to a particular genetic specificity. Thus, the
evolution of this locus, perhaps more so than that of others, may reflect
the interrelationships between genetic organization and function.
相似文献
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KR Rupesh PL PremKumar Vasanth V Shiva Kumar Seetharaman S Jayachandran 《BMC microbiology》2002,2(1):5-7
Background
Seeds of the legume plant Lathyrus sativus, which is grown in arid and semi arid tropical regions, contain Diamino Propionic acid (DAP). DAP is a neurotoxin, which, when consumed, causes a disease called Lathyrism. Lathryrism may manifest as Neurolathyrism or Osteolathyrism, in which the nervous system, and bone formation respectively, are affected. DAP ammonia lyase is produced by a few microorganisms such as Salmonella typhi, Salmonella typhimurium and Pseudomonas, and is capable of detoxifying DAP. 相似文献6.
A mathematical model is proposed which systematically investigates complex calcium oscillations in pancreatic acinar cells. This model is based on calcium-induced calcium release via inositol trisphosphate receptors (IPR) and ryanodine receptors (RyR) and includes calcium modulation of inositol (1,4,5) trisphosphate (IP3) levels through feedback regulation of degradation and production. In our model, the apical and the basal regions are separated by a region containing mitochondria, which is capable of restricting Ca2+ responses to the apical region. We were able to reproduce the observed oscillatory patterns, from baseline spikes to sinusoidal oscillations. The model predicts that calcium-dependent production and degradation of IP3 is a key mechanism for complex calcium oscillations in pancreatic acinar cells. A partial bifurcation analysis is performed which explores the dynamic behaviour of the model in both apical and basal regions. 相似文献
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N. Bolton M. Critchley R. Fabien N. Cromar H. Fallowfield 《Journal of applied microbiology》2010,109(1):239-247
Aims: To investigate the role of heterotrophic bacteria in the corrosion of galvanized steel in the presence of water. Methods and Results: Samples were taken from corroding galvanized steel pipes conveying water for specialist applications, and heterotrophic bacteria were isolated and cultured. The majority of bacteria were Gram‐negative aerobes and included Pseudomonas sp., Bacillus pumilus, Afipia spp. and Blastobacter denitrificans/Bradyrhizobium japonicum. Zinc tolerance was assessed through growth and zinc disc diffusion experiments. In general, zinc negatively influenced growth rates. An unidentified yeast also isolated from the system demonstrated a high tolerance to zinc at concentrations up to 4 g l?1. Coupon experiments were performed to assess corrosion by the bacteria on galvanized steel and steel coupons. The majority of isolates as pure culture biofilms (69%) accelerated corrosion of galvanized coupons, assessed as zinc release, relative to sterile control coupons (P < 0·05). Pure culture biofilms did not increase the corrosion of steel, with four isolates demonstrating protective effects. Conclusions: Pure culture biofilms of heterotrophic bacteria isolated from a corroding galvanized pipe system were found to accelerate the corrosion of galvanized steel coupons. Significance and Impact of the Study: Microbially influenced corrosion is a potential contributor to sporadically occurring failures in galvanized steel systems containing water. Management strategies should consider microbial control as a means for corrosion prevention in these systems. 相似文献
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Regeneration and reestablishment of synaptic connections is an important topic in neurobiological research. In the present study, the regeneration of auditory afferents and the accompanying effects in the central nervous system are investigated in nymphs and adults of the bush cricket Tettigonia viridissima L. (Orthoptera: Tettigoniidae). In all animals in which the tympanal nerve is crushed, neuronal tracing shows a regrowth of the afferents into the prothoracic ganglion. This regeneration is seen in both adult and nymphal stages and starts 10–15 days after nerve crushing. Physiological recordings from the leg nerve indicate a recovery of tympanal fibres and a formation of functional connections to interneurones in the same time range. Electrophysiological recordings from the neck connective suggest additional contralateral sprouting of interneurones and the formation of aberrant connections. The regeneration processes of the tympanal nerve in nymphal stages and adults appear to be similar. 相似文献
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ISABELLA URRU JOHANNES STÖKL JEANINE LINZ TAMARA KRÜGEL MARCUS C. STENSMYR BILL S. HANSSON 《Biological journal of the Linnean Society. Linnean Society of London》2010,101(4):991-1001
Flowers of the genus Arum are known to attract dung‐breeding flies and beetles through olfactory deceit. In addition to this strategy, the genus has evolved several other pollination mechanisms. The present study aimed to characterize the pollination strategies of the Cretan Arum species by investigating the flowering phenology, thermogeny, inflorescence odours, and the pollinating fauna. The results obtained show that Arum cyrenaicum and Arum concinnatum emit a strong dung smell and exhibit the distinctive features associated with this pollination syndrome. Both species are highly thermogenic, have a similar odour profile and attract small‐bodied Diptera. Although sharing the same habitat, these two plant species are never found growing sympatrically as a result of the early blooming period of A. cyrenaicum. By contrast, Arum creticum and Arum idaeum have evolved a more traditional and mutually beneficial pollination mechanism. The stinking smell has been replaced by a more flower‐like odour that attracts bees (Lasioglossum sp.) and, occasionally, bugs (Dionconotus cruentatus). Although attracting the same pollinator, the main compound present in the odour of A. creticum is different from that of A. idaeum. Principal component analysis (PCA), based on physiologically active components of the flower odours determined by testing on the antenna of the Lasioglossum bee, revealed two different clusters, indicating that pollinators can potentially discriminate between the odours of the two species. A further PCA on the main floral odour volatiles as identified by gas chroatography‐mass spectroscopy from all the Arum species under investigation displayed odour‐based similarities and differences among the species. The PCA‐gas chomotography‐electroantennographic detection active peaks analysis showed that the two species, A. creticum and A. idaeum, form two groups and are clearly separated from A. cyrenaicum and A. concinnatum, which, conversely, cluster together. The evolutionary forces and selective pressures leading to diversification of pollination mechanisms in the Cretan Arum spp. are discussed. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101 , 991–1001. 相似文献
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