An Escherichia coli K12 mutant resistant to thymineless death (TLD) was isolated, and its genetic analysis led us to identify a new mutation (recQ1) located between corA and metE on the standard linkage map. The mutation was found to result in increased sensitivity to ultraviolet light and deficiency in conjugational recombination when placed in the recBC sbcB background, indicating that it blocked the RecF pathway of recombination. It seemed likely that this mutation is also capable of causing partial resistance to TLD, but we reserve the possibility of a separate mutation closely linked to recQ1 giving rise to this phenotype. The original mutant was shown to carry an additional mutation probably in the vicinity of the uhp locus, which was also required for the full TLD resistance of the mutant to be expressed.
Background/Aims: In the present study, we examined whether DNA methylation of the brain-derived neurotrophic factor (BDNF) promoter is associated with the manifestation and clinical presentation of Alzheimer's disease (AD). Methods: Of 20 patients with AD and 20 age-matched normal controls (NCs), the DNA methylation of the BDNF promoter (measured using peripheral blood samples) was completely analyzed in 12 patients with AD and 6 NCs. The resulting methylation levels were compared statistically. Next, we investigated the correlation between the DNA methylation levels and the clinical presentation of AD. Results: The total methylation ratio (in %) of the 20 CpG sites was significantly higher in the AD patients (5.08 ± 5.52%) than in the NCs (2.09 ± 0.81%; p < 0.05). Of the 20 CpG sites, the methylation level at the CpG4 site was significantly higher in the AD subjects than in the NCs (p < 0.05). Moreover, the methylation level was significantly and negatively correlated with some neuropsychological test subscores (registration, recall, and prehension behavior scores; p < 0.05). Conclusion: These results suggest that the DNA methylation of the BDNF promoter may significantly influence the manifestation of AD and might be associated with its neurocognitive presentation.
In an approach to characterizing the nature of the lethal event in thymineless death (TLD), rec mutants of Escherichia coli K12 were examined for their sensitivity to TLD. The recB21 and recC22 mutations sensitized cells of the AB1157 line to TLD but not cells of the HF4733 line. This increased sensitivity was not suppressed substantially by either sbcB15 or xonA1 mutation. In contrast, a recF mutation appeared to make cells more resistant to TLD than rec+ cells. Three different recA alleles were shown not to affect TLD appreciably. These results not only provide further support for the view that the site of the lethal event in TLD is cellular DNA, but also strongly suggest the involvement of the recBC and recF gene products in TLD. The apparent indifference of recA mutation implies that the conventional recombination and repair pathways per se are not involved in TLD and that the hypothetical lethal damage to DNA may be unique in nature.
Background/Aims: To address the clinical neurocognitive roles of nerve growth factor (NGF) genetic polymorphism in early-stage Alzheimer’s disease (AD) and amnestic mild cognitive impairment (A-MCI), we investigated the association between this single-nucleotide polymorphism (SNP) and executive dysfunction as a nonmemory cognitive impairment. Methods: Among 200 outpatients with dementia and MCI whose NGF SNP rs6330 genotype was identified, those with A-MCI (n = 35) and early-stage AD (n = 67) were recruited and divided into three groups according to genotype (C/C: n = 58, C/T: n = 39, T/T: n = 5). Then, the Frontal Assessment Battery (FAB) scores were compared among the three (C/C, C/T, T/T) or two (C/C, T carrier) genotype groups. Results: Among the subtests, a significant difference was only noted for the go/no-go scores (p < 0.01) between C/C and T carriers. However, no significant differences in the demographic variables and other neuropsychological subtest scores reflecting attentional and memory function were observed among the genotypes. Conclusion: Regarding the functional roles of neurotrophin polymorphisms as they relate to executive dysfunction, the NGF gene rs6330 might influence the inhibition task in Japanese patients with early-stage AD or A-MCI.
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