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821.
Mel Campbell Kevin Y. Kim Pei-Ching Chang Steve Huerta Bogdan Shevchenko Don-Hong Wang Chie Izumiya Hsing-Jien Kung Yoshihiro Izumiya 《Journal of virology》2014,88(3):1843-1848
Latent Kaposi''s sarcoma-associated herpesvirus (KSHV) episomes are coated with viral latency-associated nuclear antigen (LANA). In contrast, LANA rapidly disassociates from episomes during reactivation. Lytic KSHV expresses polyadenylated nuclear RNA (PAN RNA), a long noncoding RNA (lncRNA). We report that PAN RNA promotes LANA-episome disassociation through an interaction with LANA which facilitates LANA sequestration away from KSHV episomes during reactivation. These findings suggest that KSHV may have evolved an RNA aptamer to regulate latent protein function. 相似文献
822.
Paşca SP Dronca E Nemeş B Kaucsár T Endreffy E Iftene F Benga I Cornean R Dronca M 《Journal of cellular and molecular medicine》2010,14(3):600-607
Autism spectrum disorders (ASD) comprise a complex and heterogeneous group of conditions of unknown aetiology, characterized by significant disturbances in social, communicative and behavioural functioning. Recent studies suggested a possible implication of the high-density lipoprotein associated esterase/lactonase paraoxonase 1 (PON1) in ASD. In the present study, we aimed at investigating the PON1 status in a group of 50 children with ASD as compared to healthy age and sex matched control participants. We evaluated PON1 bioavailability (i.e. arylesterase activity) and catalytic activity (i.e. paraoxonase activity) in plasma using spectrophotometric methods and the two common polymorphisms in the PON1 coding region (Q192R, L55M) by employing Light Cycler real-time PCR. We found that both PON1 arylesterase and PON1 paraoxonase activities were decreased in autistic patients (respectively, P < 0.001, P < 0.05), but no association with less active variants of the PON1 gene was found. The PON1 phenotype, inferred from the two-dimensional enzyme analysis, had a similar distribution in the ASD group and the control group. In conclusion, both the bioavailability and the catalytic activity of PON1 are impaired in ASD, despite no association with the Q192R and L55M polymorphisms in the PON1 gene and a normal distribution of the PON1 phenotype. 相似文献
823.
Research suggests that stress disrupts reinforcement learning and induces anhedonia. The mineralocorticoid receptor (MR) determines the sensitivity of the stress response, and the missense iso/val polymorphism (Ile180Val, rs5522) of the MR gene (NR3C2) has been associated with enhanced physiological stress responses, elevated depressive symptoms and reduced cortisol‐induced MR gene expression. The goal of these studies was to evaluate whether rs5522 genotype and stress independently and interactively influence reward learning. In study 1, participants (n = 174) completed a probabilistic reward task under baseline (i.e. no‐stress) conditions. In study 2, participants (n = 53) completed the task during a stress (threat‐of‐shock) and no‐stress condition. Reward learning, i.e. the ability to modulate behavior as a function of reinforcement history, was the main variable of interest. In study 1, in which participants were evaluated under no‐stress conditions, reward learning was enhanced in val carriers. In study 2, participants developed a weaker response bias toward a more frequently rewarded stimulus under the stress relative to no‐stress condition. Critically, stress‐induced reward learning deficits were largest in val carriers. Although preliminary and in need of replication due to small sample size, findings indicate that psychiatrically healthy individuals carrying the MR val allele, gene, which has been recently linked to depression, showed a reduced ability to modulate behavior as a function of reward when facing an acute, uncontrollable stressor. Future studies are warranted to evaluate whether rs5522 genotype interacts with naturalistic stressors to increase the risk of depression and whether stress‐induced anhedonia might moderate such risk. 相似文献
824.
Allosteric potentiation of acetylcholine nicotinic receptors is considered to be one of the most promising approaches for
the treatment of Alzheimer’s disease. However, the exact localization of the allosteric binding site and the potentiation
mechanism at the molecular level are presently unknown. We have performed the “blind docking” of three known allosteric modulators
(galanthamine, codeine and eserine) with the Acetylcholine Binding Protein and models of human α7, α3β4 and α4β2 nicotinic
receptors, created by homology modeling. Three putative binding sites were identified in the channel pore, each one showing
different affinities for the ligands. One of these sites is localized opposite to the agonist binding site and is probably
implicated in the potentiation process. On the basis of these results, a possible mechanism for nicotinic acetylcholine receptor
(nAChRs) activation is proposed. The present findings may represent an important advance for understanding the allosteric
modulation mechanism of nAChRs.
Electronic supplementary material Supplementary material is available for this article at 相似文献
825.
John A. Bogdan Wei Yuan Karen O. Long-Rowe Jawad Sarwar Eric Allen Brucker M. S. Blake 《Applied microbiology》2003,69(10):6272-6279
The introduction of acellular pertussis vaccines has greatly enhanced the safety profile of vaccines to prevent whooping cough. Pertussis toxin (Ptx) is one component produced by Bordetella pertussis that is contained in all of these vaccines, either in combination with other known pertussis virulence factors or as the sole pertussis component, combined with tetanus and diphtheria toxoids. A hydrogen peroxide toxoid of Ptx has been shown to be efficacious in preventing pertussis infections in a mass vaccination trial and is presently licensed in the United States and Europe (B. Trollfors, J. Taranger, T. Lagergard, L. Lind, V. Sundh, G. Zackrisson, C. U. Lowe, W. Blackwelder, and J. B. Robbins, N. Engl. J. Med. 333:1045-1050, 1995). The industrial production of Ptx can be performed through the cultivation of B. pertussis in well-defined growth media, in which the components can be well characterized and their origins can be documented. Once the bacteria are removed from the culture, Ptx can be isolated from the supernatant and purified by using the technique described by Sekura et al. (R. D. Sekura, F. Fish, C. R. Manclark, B. Meade, and Y. L. Zhang, J. Biol. Chem. 258:14647-14651, 1983). The only drawback of this procedure, which combines two affinity chromatography steps, one with Blue Sepharose and a second with matrix-bound bovine fetuin (BF), is the source and purity of the BF. Concern about vaccine preparations that may possibly risk contamination by material associated with bovine spongioform encephalopathy has continued to increase. We thus sought a replacement for the BF affinity chromatography and, more specifically, for the glycosidic moiety on BF. We describe here the identification of a seven-amino-acid peptide that mimics the glycosidic moiety on BF to which Ptx binds. Furthermore, we have constructed an affinity column containing this peptide that can be used to replace BF in Ptx purification. Finally, we used the X-ray crystallographic structure of Ptx bound to the oligosaccharide moiety of BF as a scaffold and replaced the oligosaccharide with the peptide. 相似文献
826.
Processing and secretion of guanylate binding protein‐1 depend on inflammatory caspase activity
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Elisabeth Naschberger Walter Geißdörfer Christian Bogdan Philipp Tripal Elisabeth Kremmer Michael Stürzl Nathalie Britzen‐Laurent 《Journal of cellular and molecular medicine》2017,21(9):1954-1966
Human guanylate binding protein‐1 (GBP‐1) belongs to the family of large GTPases. The expression of GBP‐1 is inducible by inflammatory cytokines, and the protein is involved in inflammatory processes and host defence against cellular pathogens. GBP‐1 is the first GTPase which was described to be secreted by eukaryotic cells. Here, we report that precipitation of GBP‐1 with GMP‐agarose from cell culture supernatants co‐purified a 47‐kD fragment of GBP‐1 (p47‐GBP‐1) in addition to the 67‐kD full‐length form. MALDI‐TOF sequencing revealed that p47‐GBP‐1 corresponds to the C‐terminal helical part of GBP‐1 and lacks most of the globular GTPase domain. In silico analyses of protease target sites, together with cleavage experiments in vitro and in vivo, showed that p67‐GBP‐1 is cleaved by the inflammatory caspases 1 and 5, leading to the formation of p47‐GBP‐1. Furthermore, the secretion of p47‐GBP‐1 was found to occur via a non‐classical secretion pathway and to be dependent on caspase‐1 activity but independent of inflammasome activation. Finally, we showed that p47‐GBP‐1 represents the predominant form of secreted GBP‐1, both in cell culture supernatants and, in vivo, in the cerebrospinal fluid of patients with bacterial meningitis, indicating that it may represent the biologically active form of extracellular GBP‐1. These findings confirm the involvement of caspase‐1 in non‐classical secretion mechanisms and open novel perspectives for the extracellular function of secreted GBP‐1. 相似文献
827.
Identification of glucose kinase‐dependent and ‐independent pathways for carbon control of primary metabolism,development and antibiotic production in Streptomyces coelicolor by quantitative proteomics
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828.
Carmen Fierbinteanu-Braticevici Crina Sinescu Alexandru Moldoveanu Ana Petrisor Sorina Diaconu Dragos Cretoiu Bogdan Braticevici 《Cell biology and toxicology》2017,33(1):5-14
Nonalcoholic fatty liver disease (NAFLD) is very prevalent and now considered the most common cause of chronic liver disease. Staging the severity of liver damage is very important because the prognosis of NAFLD is highly variable. The long-term prognosis of patients with NAFLD remains incompletely elucidated. Even though the annual fibrosis progression rate is significantly higher in patients with nonalcoholic hepatitis (NASH), both types of NAFLD (nonalcoholic fatty liver and nonalcoholic steatohepatitis) can lead to fibrosis. The risk for progressive liver damage and poor outcomes is assessed by staging the severity of liver injury and liver fibrosis. Algorithms (scores) that incorporate various standard clinical and laboratory parameters alongside imaging-based approaches that assess liver stiffness are helpful in predicting advanced fibrosis. 相似文献
829.
Glenn F. King Michael J. York Bogdan E. Chapman Philip W. Kuchel 《Biochemical and biophysical research communications》1983,110(1):305-312
In studies on human erythrocyte metabolism in situ, high resolution (400 MHz)1H spin-echo NMR spectroscopy was used to follow the time dependence of hydrolysis of glycylglycine and L-cysteinylglycine in intact cells and their lysates. The concentration dependence of the hydrolysis of L-cysteinylglycine was described by a rectangular hyperbola with Km, 3.5 ± 0.6 mmol/llysate and Vmax, 64.2 ± 3.2 mmol/llysate/h. We demonstrated that glycylglycine readily enters the erythrocyte and we introduce a means of analysing the data from the coupled reaction sequence; the sequence consists of transport followed by enzyme catalysed hydrolysis. 相似文献
830.