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411.
Daniel Landau Yael Segev Rina Eshet Allan Flyvbjerg Moshe Phillip 《Experimental diabetes research》2000,1(1):9-18
We investigated the changes in GH-IGF-I axis in
non-obese diabetic (NOD)-mice, a model of insulin dependent
diabetes mellitus. Diabetic female NOD
mice and their age- and sex-matched controls were
sacrificed at 4, 14, 21 and 30 days (30d DM) after the
onset of glycosuria. Serum GH levels increased and
serum IGF-I levels decreased in the 30d DM group
(182 ± 32% and 45 ± 24% of age-matched controls
respectively, p < 0.05). Another group (30d DM + I)
was given SC insulin, and its serum IGF-I levels
remained decreased. Liver GH receptor (GHR) and
GH binding protein (GHBP) mRNA levels, as well
as liver membrane GH binding assays were deeply
decreased in the 30d DM group in comparison to
controls. GHR message and binding capacity remained
decreased in the 30d DM + I group. Renal
GHR mRNA was decreased at 21d DM but not at
14d DM, whereas GHBP mRNA remained unchanged
throughout the experiment. In conclusion,
increased serum GH levels are documented in NOD
diabetic mice, similarly to the changes described in
humans. The decrease in GHR levels and decreased
serum IGF-I in spite of increased circulating GH
suggest a state of GH resistance. 相似文献
412.
Gilad Liberman Jennifer I.C. Benichou Yaakov Maman Jacob Glanville Idan Alter Yoram Louzoun 《Nucleic acids research》2016,44(5):e46
Incremental selection within a population, defined as limited fitness changes following mutation, is an important aspect of many evolutionary processes. Strongly advantageous or deleterious mutations are detected using the synonymous to non-synonymous mutations ratio. However, there are currently no precise methods to estimate incremental selection. We here provide for the first time such a detailed method and show its precision in multiple cases of micro-evolution. The proposed method is a novel mixed lineage tree/sequence based method to detect within population selection as defined by the effect of mutations on the average number of offspring. Specifically, we propose to measure the log of the ratio between the number of leaves in lineage trees branches following synonymous and non-synonymous mutations. The method requires a high enough number of sequences, and a large enough number of independent mutations. It assumes that all mutations are independent events. It does not require of a baseline model and is practically not affected by sampling biases. We show the method''s wide applicability by testing it on multiple cases of micro-evolution. We show that it can detect genes and inter-genic regions using the selection rate and detect selection pressures in viral proteins and in the immune response to pathogens. 相似文献
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Numerous applications in molecular biology and genomics require characterization of mutant DNA molecules present at low levels within a larger sample of non-mutant DNA. This is often achieved either by selectively amplifying mutant DNA, or by sequencing all the DNA followed by computational identification of the mutant DNA. However, selective amplification is challenging for insertions and deletions (indels). Additionally, sequencing all the DNA in a sample may not be cost effective when only the presence of a mutation needs to be ascertained rather than its allelic fraction. The MutS protein evolved to detect DNA heteroduplexes in which the two DNA strands are mismatched. Prior methods have utilized MutS to enrich mutant DNA by hybridizing mutant to non-mutant DNA to create heteroduplexes. However, the purity of heteroduplex DNA these methods achieve is limited because they can only feasibly perform one or two enrichment cycles. We developed a MutS-magnetic bead system that enables rapid serial enrichment cycles. With six cycles, we achieve complete purification of heteroduplex indel DNA originally present at a 5% fraction and over 40-fold enrichment of heteroduplex DNA originally present at a 1% fraction. This system may enable novel approaches for enriching mutant DNA for targeted sequencing. 相似文献