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61.
In this report we investigated whether the modulation of drug permeability in Chinese hamster ovary (CHO) cells was an energy-dependent process. We observed that (1) in the absence of glucose, metabolic inhibitors such as cyanide, azide, and dinitrophenol stimulated the uptake of [3H]colchicine and other drug; (2) cyanide-induced stimulation of drug uptake could be prevented by the presence of metabolizable sugars such as glucose and ribose; (3) cyanide-treated cells were fully viable; (4) on the addition of cyanide and glucose the kinetics of drug permeability changes were very rapid. These data are consistent with the hypothesis that an energy-dependent membrane barrier against the uptake of a variety of drugs was operative in CHO cells.The nature of this energy-dependent membrane barrier was examined in colchicine-resistant mutants (CHRC4 and CHRC5 cells) previously characterized as membrane mutants with greatly reduced drug permeability (Ling and Thompson, (1974) J. Cell Physiol. 83, 103–116). The mutants were more refractile to the cyanide-induced stimulation of drug permeability but more sensitive to the glucose prevention cyanide-induction. In the presence of cyadine, the uptake rate of [3H] colchicine by CHRC4 cells increased by about 100-fold and approached a rate similar to that of wild-type cells. These results suggest that the colchicine-resistant mutants may be altered in their energy-dependent modulation of drug permeability. 相似文献
62.
Marit Valeur Ramstad Trond E. Ellingsen Kjell D. Josefsen Hilde K. Hidal
Svein Valla
Gudmund Skjk-Brk David W. Levine 《Enzyme and microbial technology》1999,24(10):23819-646
The mannuronan C-5-epimerase AlgE2 is one of a family of Ca2+-dependent epimerases secreted by Azotobacter vinelandii. These enzymes catalyze the conversion of β-
-mannuronic acid residues (M) to -
-guluronic acid residues (G) in alginate. AlgE2 has been produced by fermentation with a recombinant strain of Escherichia coli, isolated and partially purified. Epimerization with AlgE2 increased the content of G-residues in different alginates from starting values of 0–45% up to approximately 70%. The new G-residues were mainly present in short blocks. Although G-residues may be introduced next to pre-existing G-residues, AlgE2 was not able to epimerize strictly alternating MG-structures. The epimerization with AlgE2 was greatly affected by the concentration of Ca2+. The type of alginate used as substrate affected the reaction rate and the reaction pattern especially at low Ca2+ concentration. AlgE2 appears to act by a preferred attack mechanism where the enzyme associates with different sequences in the alginate depending on the concentration of Ca2+. During epimerization, AlgE2 occasionally causes cleavage of the alginate chain. The observed frequency corresponds to 1–3 breaks per 1,000 M-units epimerized. 相似文献
63.
Yngvild B. Haukeland Torun M. Vatne Svein Mossige Krister W. Fjermestad 《The Yale journal of biology and medicine》2021,94(4):537
Siblings of children with chronic disorders are at increased risk of psychosocial problems. The risk may be exacerbated when the chronic disorder is rare and limited medical knowledge is available, due to more uncertainty and feelings of isolation. We examined mental health, parent-child communication, child-parent relationship quality, and social support among 100 children aged 8 to 16 years (M age 11.5 years, SD = 2.2; 50.0% boys, 50.0% girls). Fifty-six were siblings of children with rare disorders, and 44 were controls. The siblings of children with rare disorders (herein, siblings) were recruited from a resource centre for rare disorders and comprised siblings of children with a range of rare disorders including neuromuscular disorders and rare chromosomal disorders with intellectual disability. Controls were recruited from schools. Self-reported child mental health was significantly poorer for siblings compared to controls (effect size difference d = 0.75). Parent-reported child mental health was not significantly different between the groups (d = -0.06 to 0.16). Most child-parent relationships (anxiety/avoidance; mothers/fathers) were significantly poorer for siblings compared to controls (d = 0.47 to 0.91). There was no difference between groups in anxious relation with mother. Parent-child communication was significantly poorer for siblings compared to controls (d = -0.87 to -0.75). Social support was significantly poorer for siblings compared to controls (d = 0.61). We conclude that siblings of children with rare disorders display more psychosocial problems than controls. Interventions are indicated to prevent further maladjustment for siblings. 相似文献
64.
A database system and computer programs for storage and retrieval of information about guanine nucleotide-binding protein (G protein) -coupled receptor mutants and associated biological effects have been developed. Mutation data on the receptors were collected from the literature and a database of mutants and effects of mutations was developed. The G protein-coupled receptor, family A, point mutation database (GRAP) provides detailed information on ligand-binding and signal transduction properties of more than 2130 receptor mutants. The amino acid sequences of receptors for which mutation experiments have been reported were aligned, and from this alignment mutation data may be retrieved. Alternatively, a search form allowing detailed specification of which mutants to retrieve may be used, for example, to search for specific amino acid substitutions, substitutions in specific protein domains or reported biological effects. Furthermore, ligand and bibliographic oriented queries may be performed. GRAP is available on the Internet (URL: http://www-grap.fagmed.uit.no/GRAP/homepage.html ) using the World-Wide Web system. © 1996 Wiley-Liss, Inc. 相似文献
65.
66.
Moen MN Knævelsrud I Haugland GT Grøsvik K Birkeland NK Klungland A Bjelland S 《Journal of bacteriology》2011,193(17):4495-4508
Hydrolytic deamination of cytosine to uracil in DNA is increased in organisms adapted to high temperatures. Hitherto, the uracil base excision repair (BER) pathway has only been described in two archaeons, the crenarchaeon Pyrobaculum aerophilum and the euryarchaeon Archaeoglobus fulgidus, which are hyperthermophiles and use single-nucleotide replacement. In the former the apurinic/apyrimidinic (AP) site intermediate is removed by the sequential action of a 5'-acting AP endonuclease and a 5'-deoxyribose phosphate lyase, whereas in the latter the AP site is primarily removed by a 3'-acting AP lyase, followed by a 3'-phosphodiesterase. We describe here uracil BER by a cell extract of the thermoacidophilic euryarchaeon Thermoplasma acidophilum, which prefers a similar short-patch repair mode as A. fulgidus. Importantly, T. acidophilumcell extract also efficiently executes ATP/ADP-stimulated long-patch BER in the presence of deoxynucleoside triphosphates, with a repair track of ~15 nucleotides. Supplementation of recombinant uracil-DNA glycosylase (rTaUDG; ORF Ta0477) increased the formation of short-patch at the expense of long-patch repair intermediates, and additional supplementation of recombinant DNA ligase (rTalig; Ta1148) greatly enhanced repair product formation. TaUDG seems to recruit AP-incising and -excising functions to prepare for rapid single-nucleotide insertion and ligation, thus excluding slower and energy-costly long-patch BER. 相似文献
67.
Suso EM Dueland S Rasmussen AM Vetrhus T Aamdal S Kvalheim G Gaudernack G 《Cancer immunology, immunotherapy : CII》2011,60(6):809-818
Immunotherapy targeting the hTERT subunit of telomerase has been shown to induce robust immune responses in cancer patients
after vaccination with single hTERT peptides. Vaccination with dendritic cells (DCs) transfected with hTERT mRNA has the potential
to induce strong immune responses to multiple hTERT epitopes and is therefore an attractive approach to more potent immunotherapy.
Blood samples from such patients provide an opportunity for identification of new, in vivo processed T-cell epitopes that
may be clinically relevant. A 62-year-old female patient underwent radical surgery for a pancreatic adenocarcinoma. After
relapse, she obtained stable disease on gemcitabine treatment. Due to severe neutropenia, the chemotherapy was terminated.
The patient has subsequently been treated with autologous DCs loaded with hTERT mRNA for 3 years. Immunomonitoring was performed
at regular intervals following start of vaccination and clinical outcome measured by CT and PET/CT evaluation. The patient
developed an immune response against several hTERT-derived Th and CTL epitopes. She presently shows no evidence of active
disease based on PET/CT scans. No serious adverse events were experienced and the patient continues to receive regular booster
injections. We here provide evidence for the induction of hTERT-specific immune responses following vaccination of a pancreas
cancer patient with DCs loaded with hTERT mRNA. These responses are associated with complete remission. A thorough analysis
of this patient immune response has provided a unique opportunity to identify novel epitopes, associated with clinical effects.
These will be included in future hTERT vaccines. 相似文献
68.
Svein Løkkeborg Sten Ivar Siikavuopio Odd-Børre Humborstad Anne Christine Utne-Palm Keno Ferter 《Reviews in Fish Biology and Fisheries》2014,24(4):985-1003
Better knowledge of food search behaviour in fish is essential for studies that aim to improve longline fishing, particularly through bait development. This review provides an overview of our understanding of how fish detect and locate sources of food odour, focusing on the stimuli and sensory modalities involved, and on factors that affect feeding activity. Studies that identify feeding attractants and efforts to develop alternative longline baits are presented. The review reveals that such studies are few in number, and that to date there are no alternatives to traditional baits in commercial longlining despite the growing demand for these resources, which are also used for human consumption. The chemical compounds that elicit food search behaviour differ from species to species, and species selectivity could be improved by incorporating specific feeding attractants in manufactured baits. The unique properties of chemical stimuli and odour dispersal form the basis for improving longline efficiency through the development of a long-lasting bait. Vision is important in prey capture, and manufactured baits can be made more visible than natural baits by increasing the contrast (e.g. via fluorescent or polarising coatings) and creating motion through buoyancy. Physical properties such as size, shape, texture and strength can also be manipulated in a manufactured bait to improve catch efficiency. Knowledge obtained from studies of various aspects of food search behaviour is of paramount importance for future research aimed at alternative bait development and improving longline fishing. 相似文献
69.
Background
Gene duplication and horizontal gene transfer are common processes in bacterial and archaeal genomes, and are generally assumed to result in either diversification or loss of the redundant gene copies. However, a recent analysis of the genome of the soil bacterium Azotobacter vinelandii DJ revealed an abundance of highly similar homologs among carbohydrate metabolism genes. In many cases these multiple genes did not appear to be the result of recent duplications, or to function only as a means of stimulating expression by increasing gene dosage, as the homologs were located in varying functional genetic contexts. Based on these initial findings we here report in-depth bioinformatic analyses focusing specifically on highly similar intra-genome homologs, or synologs, among carbohydrate metabolism genes, as well as an analysis of the general occurrence of very similar synologs in prokaryotes.Results
Approximately 900 bacterial and archaeal genomes were analysed for the occurrence of synologs, both in general and among carbohydrate metabolism genes specifically. This showed that large numbers of highly similar synologs among carbohydrate metabolism genes are very rare in bacterial and archaeal genomes, and that the A. vinelandii DJ genome contains an unusually large amount of such synologs. The majority of these synologs were found to be non-tandemly organized and localized in varying but metabolically relevant genomic contexts. The same observation was made for other genomes harbouring high levels of such synologs. It was also shown that highly similar synologs generally constitute a very small fraction of the protein-coding genes in prokaryotic genomes. The overall synolog fraction of the A. vinelandii DJ genome was well above the data set average, but not nearly as remarkable as the levels observed when only carbohydrate metabolism synologs were considered.Conclusions
Large numbers of highly similar synologs are rare in bacterial and archaeal genomes, both in general and among carbohydrate metabolism genes. However, A. vinelandii and several other soil bacteria harbour large numbers of highly similar carbohydrate metabolism synologs which seem not to result from recent duplication or transfer events. These genes may confer adaptive benefits with respect to certain lifestyles and environmental factors, most likely due to increased regulatory flexibility and/or increased gene dosage.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-192) contains supplementary material, which is available to authorized users. 相似文献70.