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11.
Socrates J. Tzartos Heleni V. Loutrari Fen Tang Anna Kokla Susan L. Walgrave Robert P. Milius† Bianca M. Conti-Tronconi 《Journal of neurochemistry》1990,54(1):51-61
Most anti-nicotinic acetylcholine receptor (AChR) antibodies in myasthenia gravis are directed against an immunodominant epitope or epitopes [main immunogenic region (MIR)] on the AChR alpha-subunit. Thirty-two synthetic peptides, corresponding to the complete Torpedo alpha-subunit sequence and to a segment of human muscle alpha-subunit, were used to map the epitopes for 11 monoclonal antibodies (mAbs) directed against the Torpedo and/or the human MIR and for a panel of anti-AChR mAbs directed against epitopes on the alpha-subunit other than the MIR. A main constituent loop of the MIR was localized within residues alpha 67-76. Residues 70 and 75, which are different in the Torpedo and human alpha-subunits, seem to be crucial in determining the binding profile for several mAbs whose binding to the peptides correlated very well with their binding pattern to native Torpedo and human AChRs. This strongly supports the identification of the peptide loop alpha 67-76 as the actual location of the MIR on the intact AChR molecule. Residues 75 and 76 were necessary for binding of some mAbs and irrelevant for others, in agreement with earlier suggestions that the MIR comprises overlapping epitopes. Structural predictions for the sequence segment alpha 67-76 indicate that this segment has a relatively high segmental mobility and a very strong turning potential centered around residues 68-71. The most stable structure predicted for this segment, in both the Torpedo and human alpha-subunits, is a hairpin loop, whose apex is a type I beta-turn and whose arms are beta-strands. This loop is highly hydrophilic, and its apex is negatively charged. All these structural properties have been proposed as characteristic of antibody binding sites. We also localized the epitopes for mAbs against non-MIR regions. Among these, the epitope for a monoclonal antibody (mAb 13) that noncompetitively inhibits channel function was localized within residues alpha 331-351. 相似文献
12.
A. Cavallini L. Natali C. Balconi E. Rizzi M. Motto G. Cionini F. D. Amato 《Protoplasma》1995,189(3-4):156-162
Summary Chromosome endoreduplication is a very common process in higher plants but its function and genetic control are still to be clarified. In our experiments we analyzed, by Feulgen cytophotometry, chromosome endoreduplication in endosperm cells of two maize genotypes, IHP and ILP, having high and low protein content in their seed, respectively. Chromosome endoreduplication occurs in both lines within 24 days after pollination, attaining a maximum ploidy level of 384C (7 DNA replication rounds) in IHP and of 192C (6 replication rounds) in ILP. In the mature seed, endosperms of the two lines show different mean ploidy level. In reciprocal crosses between IHP and ILP the f1 endosperms have mean ploidy levels analogous to that of the maternal parent, showing that the difference in ploidy level between the two genotypes is maintained. After selfing of the f1 plants, the difference in ploidy level between the two F2 populations is reduced. In F2 the mean ploidy level is as variable as in f1, indicating the absence of genetic segregation. From our data, it is apparent that both the genetic constitution (cytoplasmic and nuclear) of the maternal parent and the genotype of the individual endosperms influence the ploidy level. An analysis of the protein content in endosperms carried out on the same seed sample as analyzed cytophotometrically showed that the protein content increases, during seed development, parallel to chromosome endoreduplication and varies, in the two lines, in reciprocal crosses and their progeny, according to the same trend as mean ploidy level, suggesting a correlation between the two parameters. 相似文献
13.
Characterization of a Small Family (CAIII) of Microsatellite-Containing Sequences with X-Y Homology 总被引:4,自引:0,他引:4
Patrizia Malaspina Bianca Maria Ciminelli Luigi Viggiano Carla Jodice Fulvio Cruciani Piero Santolamazza Daniele Sellitto Rosaria Scozzari Luciano Terrenato Mariano Rocchi Andrea Novelletto 《Journal of molecular evolution》1997,44(6):652-659
Four X-linked loci showing homology with a previously described Y-linked polymorphic locus (DYS413) were identified and characterized.
By fluorescent in situ hybridization (FISH), somatic cell hybrids, and YAC screening, the X-linked members of this small family
of sequences (CAIII) all map in Xp22, while the Y members map in Yq11. These loci contribute to the overall similarity of
the two genomic regions. All of the CAIII loci contain an internal microsatellite of the (CA)n type. The microsatellites display extensive length polymorphism in two of the X-linked members as well as in the Y members.
In addition, common sequence variants are found in the portions flanking the microsatellites in two of the X-linked members.
Our results indicate that, during the evolution of this family, length variation on the Y chromosome was accumulated at a
rate not slower than that on the X chromosome. Finally, these sequences represent a model system with which to analyze human
populations for similar X- and Y-linked polymorphisms.
Received: 29 July 1996 / Accepted: 15 January 1997 相似文献
14.
15.
Concetta Compagno Aldo Tura Bianca Maria Ranzi Enzo Martegani 《Applied microbiology and biotechnology》1992,36(4):535-537
Summary One of the methods commonly used for manufacturing fructose 1,6-diphosphate is based on the enzymatic phosphorylation of glucose with inorganic phosphate using permeabilized brewer's yeast cells. Our results demonstrate that a substantial improvement in the yield of bioconversion can be achieved using fed-batch-grown Saccharomyces cerevisiae cells. Under an appropriate glucose and phosphate to cell ratio the efficiency of bioconversion reaches 70% of the theoretical value.
Offprint requests to: C. Compagno 相似文献
16.
17.
Six calves were exposed in succession 12 days at 400 m altitude (control), 12 days at a simulated altitude of 5000 m in a low pressure chamber (experimental), and 14 days at 400 m altitude (recovery). Exposure to 5000 m produced the following changes: intake of feed and water decreased by 47 and 35% respectively, and body weight gain ceased. Rectal temperature rose by 0.4°C. Heart rate increased by 65%. Respiratory rate and blood pH increased moderately. There was an S-shaped rise of haematocrit (from 33 to 45%), which was paralleled by blood viscosity. Plasma viscosity showed a sharp, but transient rise. Short term measurements made during ascent to and descent from 5000 m altitude, both lasting for four hours, showed that some of the changes developed rapidly. 相似文献
18.
Birgitta Lindqvist Bianca B. Jütte Luca Love Wlaa Assi Julie Roux Anders Snnerborg Tugsan Tezil Eric Verdin J. Peter Svensson 《PLoS pathogens》2022,18(6)
The reservoir of latently HIV-1 infected cells is heterogeneous. To achieve an HIV-1 cure, the reservoir of activatable proviruses must be eliminated while permanently silenced proviruses may be tolerated. We have developed a method to assess the proviral nuclear microenvironment in single cells. In latently HIV-1 infected cells, a zinc finger protein tethered to the HIV-1 promoter produced a fluorescent signal as a protein of interest came in its proximity, such as the viral transactivator Tat when recruited to the nascent RNA. Tat is essential for viral replication. In these cells we assessed the proviral activation and chromatin composition. By linking Tat recruitment to proviral activity, we dissected the mechanisms of HIV-1 latency reversal and the consequences of HIV-1 production. A pulse of promoter-associated Tat was identified that contrasted to the continuous production of viral proteins. As expected, promoter H3K4me3 led to substantial expression of the provirus following T cell stimulation. However, the activation-induced cell cycle arrest and death led to a surviving cell fraction with proviruses encapsulated in repressive chromatin. Further, this cellular model was used to reveal mechanisms of action of small molecules. In a proof-of-concept study we determined the effect of modifying enhancer chromatin on HIV-1 latency reversal. Only proviruses resembling active enhancers, associated with H3K4me1 and H3K27ac and subsequentially recognized by BRD4, efficiently recruited Tat upon cell stimulation. Tat-independent HIV-1 latency reversal of unknown significance still occurred. We present a method for single cell assessment of the microenvironment of the latent HIV-1 proviruses, used here to reveal how T cell stimulation modulates the proviral activity and how the subsequent fate of the infected cell depends on the chromatin context. 相似文献
19.
Ahrens B 《New biotechnology》2011,28(5):530-537
In the past century, incidences of chronic metabolic diseases, such as obesity and type II diabetes, have increased dramatically. Obesity and abnormal insulin level are associated with a wide variety of health problems including a markedly increased risk for type II diabetes, fatty liver, hepato-biliary and gallbladder diseases, cardiovascular pathologies, neurodegenerative disorders, asthma and a variety of cancers. The development of therapeutic antibodies has evolved over the past decades into a mainstay of therapeutic options for patients with inflammatory diseases and cancer, while other indication areas such as metabolic diseases have so far only been rarely addressed. Although therapeutic antibodies might have advantages over current type II diabetes treatments like favorable serum half-life and high specificity, their development is also likely to face obstacles. For example the technical feasibility of antibody generation against G protein coupled receptors and transporters is challenging, patient compliance for a likely needle application might be limited, bioavailability in organs involved in the pathogenesis like the brain might be suboptimal and reimbursement issues for high treatment costs have to be taken into account. The current review focuses on the pathogenesis and standard therapeutic approaches as well as antibodies in development and potential antibody targets for type II diabetes. 相似文献
20.
van Leeuwen BN van der Wulp AM Duijnstee I van Maris AJ Straathof AJ 《Applied microbiology and biotechnology》2012,93(4):1377-1387
Isobutene (2-methylpropene) is one of those chemicals for which bio-based production might replace the petrochemical production
in the future. Currently, more than 10 million metric tons of isobutene are produced on a yearly basis. Even though bio-based
production might also be achieved through chemocatalytic or thermochemical methods, this review focuses on fermentative routes
from sugars. Although biological isobutene formation is known since the 1970s, extensive metabolic engineering is required
to achieve economically viable yields and productivities. Two recent metabolic engineering developments may enable anaerobic
production close to the theoretical stoichiometry of 1isobutene + 2CO2 + 2H2O per mol of glucose. One relies on the conversion of 3-hydroxyisovalerate to isobutene as a side activity of mevalonate diphosphate
decarboxylase and the other on isobutanol dehydration as a side activity of engineered oleate hydratase. The latter resembles
the fermentative production of isobutanol followed by isobutanol recovery and chemocatalytic dehydration. The advantage of
a completely biological route is that not isobutanol, but instead gaseous isobutene is recovered from the fermenter together
with CO2. The low aqueous solubility of isobutene might also minimize product toxicity to the microorganisms. Although developments
are at their infancy, the potential of a large scale fermentative isobutene production process is assessed. The production
costs estimate is 0.9 € kg−1, which is reasonably competitive. About 70% of the production costs will be due to the costs of lignocellulose hydrolysate,
which seems to be a preferred feedstock. 相似文献