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31.
Bacteria communicate with each other by the use of signaling molecules, a process called ‘quorum sensing’. One group of quorum sensing molecules includes the oligopeptides, which are mainly produced by Gram-positive bacteria. Recently, these quorum sensing peptides were found to biologically influence mammalian cells, promoting i.a. metastasis of cancer cells. Moreover, it was found that bacteria can influence different central nervous system related disorders as well, e.g. anxiety, depression and autism. Research currently focuses on the role of bacterial metabolites in this bacteria-brain interaction, with the role of the quorum sensing peptides not yet known. Here, three chemically diverse quorum sensing peptides were investigated for their brain influx (multiple time regression technique) and efflux properties in an in vivo mouse model (ICR-CD-1) to determine blood-brain transfer properties: PhrCACET1 demonstrated comparatively a very high initial influx into the mouse brain (Kin = 20.87 μl/(g×min)), while brain penetrabilities of BIP-2 and PhrANTH2 were found to be low (Kin = 2.68 μl/(g×min)) and very low (Kin = 0.18 μl/(g×min)), respectively. All three quorum sensing peptides were metabolically stable in plasma (in vitro) during the experimental time frame and no significant brain efflux was observed. Initial tissue distribution data showed remarkably high liver accumulation of BIP-2 as well. Our results thus support the potential role of some quorum sensing peptides in different neurological disorders, thereby enlarging our knowledge about the microbiome-brain axis.  相似文献   
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Casein kinase 1 (CK1) is a pleiotropic protein kinase implicated in several fundamental processes of eukaryotic cell biology. Plasmodium falciparum encodes a single CK1 isoform, PfCK1, that is expressed at all stages of the parasite’s life cycle. We have previously shown that the pfck1 gene cannot be disrupted, but that the locus can be modified if no loss-of-function is incurred, suggesting an important role for this kinase in intra-erythrocytic asexual proliferation. Here, we report on the use of parasite lines expressing GFP- or His-tagged PfCK1 from the endogenous locus to investigate (i) the dynamics of PfCK1 localisation during the asexual cycle in red blood cells, and (ii) potential interactors of PfCK1, so as to gain insight into the involvement of the enzyme in specific cellular processes. Immunofluorescence analysis reveals a dynamic localisation of PfCK1, with evidence for a pool of the enzyme being directed to the membrane of the host erythrocyte in the early stages of infection, followed by a predominantly intra-parasite localisation in trophozoites and schizonts and association with micronemes in merozoites. Furthermore, we present strong evidence that a pool of enzymatically active PfCK1 is secreted into the culture supernatant, demonstrating that PfCK1 is an ectokinase. Our interactome experiments and ensuing kinase assays using recombinant PfCK1 to phosphorylate putative interactors in vitro suggest an involvement of PfCK1 in many cellular processes such as mRNA splicing, protein trafficking, ribosomal, and host cell invasion.  相似文献   
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The overproduction of specialized metabolites requires plants to manage the inherent burdens, including the risk of self-intoxication. We present a control mechanism that stops the expression of phytoalexin biosynthetic enzymes by blocking the antecedent signal transduction cascade. Cultured cells of Eschscholzia californica (Papaveraceae) and Catharanthus roseus (Apocynaceae) overproduce benzophenanthridine alkaloids and monoterpenoid indole alkaloids, respectively, in response to microbial elicitors. In both plants, an elicitor-responsive phospholipase A2 (PLA2) at the plasma membrane generates signal molecules that initiate the induction of biosynthetic enzymes. The final alkaloids produced in the respective plant inhibit the respective PLA, a negative feedback that prevents continuous overexpression. The selective inhibition by alkaloids from the class produced in the “self” plant could be transferred to leaves of Nicotiana benthamiana via recombinant expression of PLA2. The 3D homology model of each PLA2 displays a binding pocket that specifically accommodates alkaloids of the class produced by the same plant, but not of the other class; for example, C. roseus PLA2 only accommodates C. roseus alkaloids. The interaction energies of docked alkaloids correlate with their selective inhibition of PLA2 activity. The existence in two evolutionary distant plants of phospholipases A2 that discriminate “self-made” from “foreign” alkaloids reveals molecular fingerprints left in signal enzymes during the evolution of species-specific, cytotoxic phytoalexins.  相似文献   
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Rat liver macrophages express a galactose-specific receptor which mediates endocytosis of particles or neuraminidase-treated blood cells. From rat serum we now have isolated and purified a galactose-specific lectin by affinity chromatography. Comparative analysis of this serum galactose-binding protein with the galactose-particle receptor protein purified from rat liver macrophages and with C-reactive protein (CRP) reveals close relation or identity of these proteins. An apparent m.w. of 30,000 was determined for all three proteins by SDS-PAGE under reducing conditions and m.w. of about 130,000 by native PAGE. All three proteins exhibit the same pentameric, ring-shaped structure in electron microscopy after negative staining. Antibodies raised against the serum galactose-binding protein or against the macrophage receptor cross-react. A mAb specific for rat neo-CRP labels liver macrophages but not hepatocytes and reacts with the isolated protein in a Western blot assay. Furthermore, the galactose-particle receptor can be functionally replaced by purified CRP: the binding capacity for neuraminidase-treated E of receptor-depleted liver macrophages can be restored by preincubation with purified rat CRP. We therefore conclude that CRP occurs as a membrane-associated protein constitutively expressed on liver macrophages functioning as a receptor mediating galactose-specific binding of particulate ligands.  相似文献   
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The viviparous-1 (vp1) locus in maize is a developmental gene that controls diverse aspects of the maturation phase of seed development. Mutations of vp1 alter embryo sensitivity to the hormone abscisic acid and block formation of anthocyanin pigment. Molecular cloning of a Robertson Mutator-induced mutant allele, vp1-mum-1, by transposable element tagging has allowed analysis of several transposon-induced vp1 mutants. In the vp1-Mc mutation, the gene is disrupted by 4.0 kbp insertion, which results in expression of a 3′ truncated mRNA. Phenotypically, this allele is at least partially functional in causing embryo dormancy, but is ineffective in controlling anthocyanin expression. This result suggests that disruption of the C-terminal domain of the Vp1 protein specifically affects regulation of the anthocyanin pathway. A second Mutator- derived allele, vp1-mum2, exhibits an unusual form of somatic mutability in which endosperm cells revert from wild-type vp1 expression to a mutant condition. The vp1-mum2 allele contains a 1.5 kbp Insertion that has no detectable homology to known Mu elements. This element is retained In wild-type germinal revertants derived from vp1-mum2 An apparent DNA modification affecting cleavage at an internal Sstl restriction site in the element correlates with vp1-mum2 states that exhibit wild-type Vp1 expression. A model involving mitotic assortment of modified and unmodified DNA strands during development is proposed for vp1-mum2 somatic mutation.  相似文献   
38.
Xylulose-1,5-bisphosphate in preparations of ribulose-1,5-bisphosphate (ribulose-P2) arises from non-enzymic epimerization and inhibits the enzyme. Another inhibitor, a diketo degradation product from ribulose-P2, is also present. Both compounds simulate the substrate inhibition of ribulose-P2 carboxylase/oxygenase previously reported for ribulose-P2. Freshly prepared ribulose-P2 had little inhibitory activity. The instability of ribulose-P2 may be one reason for a high level of ribulose-P2 carboxylase in chloroplasts where the molarity of active sites exceeds that of ribulose-P2. Because the KD of the enzyme/substrate complex is ≤1 μM, all ribulose-P2 generated in situ may be stored as this complex to prevent decomposition.  相似文献   
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