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Evolution ofMHC polymorphism: Extensive sharing of polymorphic sequence motifs between human and bovine DRB alleles 总被引:4,自引:0,他引:4
Leif Andersson Sunna Sigurdardóttir Carina Borsch Kenth Gustafsson 《Immunogenetics》1991,33(3):188-193
The evolution ofMHC polymorphism has been studied by comparing the amino acid and nucleotide sequences of 14 bovine and 32 humanDRB alleles. The comparison revealed an extensive sharing of polymorphic sequence motifs in the two species. Almost identical sets of residues were found at several highly polymorphic amino acid positions in the putative antigen recognition site. Consequently, certain bovine alleles were found to be more similar to certain human alleles than to other bovine alleles. In contrast, the frequencies of silent nucleotide substitutions were found to be much higher in comparisons between species than within species implying that none of the human or bovine DRB alleles originated before the divergence of these distantly related species. The results suggest that the observed similarity inDRB polymorphism is due to convergent evolution and possibly the sharing of short ancestral sequence motifs. However, the relative role of the latter mechanism is difficult to assess due to the biased base composition in the first domain exon of polymorphic class 11 genes. The frequency of silent substitutions betweenDRB alleles was markedly lower in cattle than in man suggesting that theDRB diversity has evolved more rapidly in the former species. 相似文献
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The effect of focused high energy microwave treatment (MW) on brain concentrations and molecular forms of substance P, neurokinin A, neuropeptide Y, neurotensin, galanin and calcitonin gene-related peptide was investigated. Groups of rats were treated as follows: 1) MW, storage for 60 min at 22°C, 2) Decapitation, storage for 60 min at 22°C, 3) Decapitation, storage for 60 min at 22°C, MW treatment, 4) MW, decapitation, storage for 2 min at 22°C and 5) Decapitation, storage for 2 min at 22°C. Peptide concentrations were in all instances highest in the MW sacrificed groups. MW increased the concentration of intact peptides by rapid inhibition of peptidase activity and increase in peptide solubility/extractability. 相似文献
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Summary Isolated cod brain microtubules from the cold-adapted Atlantic cod (Gadus morhua) have previously been shown to be highly detyrosinated, a post-translational modification of tubulin usually found in stable
subsets of microtubules. In this study we found this was not restricted only to isolated brain microtubules. Microtubules
in primary cultures of brain and skin cells were composed of both tyrosinated (Tyr)- and detyrosinated (Glu)-tubulin seen
by immunocytochemistry. Immunoelectron microscopy of isolated microtubules showed that individual microtubules were composed
of a mixture of Tyr- and Glu-tubulin. Leukocytes with extending lamellopodia contained only microtubules stained with the
antibody against Tyr-tubulin, and isolated heart tubulin lacked both Tyr- and Glu-tubulin, suggesting that a relative high
level of detyrosination is a characteristic of most, but not all, cod microtubules. Brain cell microtubules were more resistant
to mitotic inhibitors than skin cell microtubules, but this was not correlated to a difference in detyrosination. Brain and
skin cell microtubules were only partially disassembled when incubated at 0°C. Upon reassembly of microtubules at 12°C, microtubules
were still made of mixtures of Tyr- and Glu-tubulin, indicating that detyrosination of assembled microtubules is rapid and/or
that in cod cells, in contrast to mammalian cells, Glu-tubulin can reassemble to microtubules. Our data show that most cod
microtubules are highly detyrosinated, but this is not the cause of their cold adaptation or drug stability. 相似文献
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Carina Ämmälä Krister Bokvist Sheila Galt Patrik Rorsman 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1991,1092(3):347-349
The effects of a photoactivatable (DMNPE-caged) ATP-analogue on ATP-regulated K+-channels (KATP-channel) in mouse pancreatic β-cells were investigated using the inside-out patch configuration of the patch-clamp technique. The caged precursor caused a concentration-dependent reduction of channel activity with a Ki of 17 μM; similar to the 11 μM obtained for standard Mg-ATP. The small difference in the blocking capacity between the precursor and ATP is probably the reason why no change in channel activity was observed upon photolysis of the caged molecule and liberation of ATP. It is suggested that the part of the ATP molecule involved in the blocking reaction of the KATP-channel is not sufficiently protected in DMNPE-caged ATP making this compound unsuitable for studying the rapid kinetics of ATP-induced KATP-channel inhibition. 相似文献
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Nathan E. Stone Carina M. Hall Marielisa Ortiz Shelby M. Hutton Ella Santana-Propper Kimberly R. Celona Charles H. D. Williamson Nicole Bratsch Luis G. V. Fernandes Joseph D. Busch Talima Pearson Sarai Rivera-Garcia Fred Soltero Renee Galloway Jason W. Sahl Jarlath E. Nally David M. Wagner 《PLoS neglected tropical diseases》2022,16(5)
BackgroundLeptospirosis, caused by Leptospira bacteria, is a common zoonosis worldwide, especially in the tropics. Reservoir species and risk factors have been identified but surveys for environmental sources are rare. Furthermore, understanding of environmental Leptospira containing virulence associated genes and possibly capable of causing disease is incomplete, which may convolute leptospirosis diagnosis, prevention, and epidemiology.Methodology/Principal findingsWe collected environmental samples from 22 sites in Puerto Rico during three sampling periods over 14-months (Dec 2018-Feb 2020); 10 water and 10 soil samples were collected at each site. Samples were screened for DNA from potentially pathogenic Leptospira using the lipL32 PCR assay and positive samples were sequenced to assess genetic diversity. One urban site in San Juan was sampled three times over 14 months to assess persistence in soil; live leptospires were obtained during the last sampling period. Isolates were whole genome sequenced and LipL32 expression was assessed in vitro.We detected pathogenic Leptospira DNA at 15/22 sites; both soil and water were positive at 5/15 sites. We recovered lipL32 sequences from 83/86 positive samples (15/15 positive sites) and secY sequences from 32/86 (10/15 sites); multiple genotypes were identified at 12 sites. These sequences revealed significant diversity across samples, including four novel lipL32 phylogenetic clades within the pathogenic P1 group. Most samples from the serially sampled site were lipL32 positive at each time point. We sequenced the genomes of six saprophytic and two pathogenic Leptospira isolates; the latter represent a novel pathogenic Leptospira species likely belonging to a new serogroup.Conclusions/SignificanceDiverse and novel pathogenic Leptospira are widespread in the environment in Puerto Rico. The disease potential of these lineages is unknown but several were consistently detected for >1 year in soil, which could contaminate water. This work increases understanding of environmental Leptospira diversity and should improve leptospirosis surveillance and diagnostics. 相似文献
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Carina Proença Marisa Freitas Daniela Ribeiro Eduardo F. T. Oliveira Joana L. C. Sousa Sara M. Tomé 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):1216-1228
α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme’s activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure–activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC50 much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG. 相似文献