Subclinical Atherosclerosis, Vascular Risk Factors, and White Matter Alterations in Diffusion Tensor Imaging Findings of Older Adults With Cardiometabolic Diseases.

White matter abnormalities may reflect cerebral microvessel disease. Diffusion tensor imaging (DTI) can help detect early changes in white matter integrity in each tract. However, studies investigating the relationship between subclinical atherosclerosis markers and white matter alterations in DTI findings are limited. This study aimed to examine associations between cardiovascular risk factors and indices of subclinical atherosclerosis-ankle brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and carotid artery intima-media thickness (IMT)-and altered white matter integrity in older patients. A total of 224 patients (aged ≥65 years) with cardiometabolic disease who underwent magnetic resonance imaging (MRI) and either plethysmography or cervical ultrasound at the start of the 3-year observational study period were included in this study. We measured fractional anisotropy (FA) and mean diffusivity (MD), which are indices of white matter integrity in seven white matter tracts. In a univariate analysis, lower ABI and higher baPWV values were associated with FA or MD abnormalities in several tracts, whereas IMT was scarcely associated with such change. In addition, high blood pressure and glycoalbumin/glycohemoglobin ratio (GA/HbA1c) and low body mass index (BMI) and triglyceride (TG) levels were associated with FA or MD abnormalities. In a multivariate analysis adjusted for age, sex, BMI, diastolic blood pressure, TG, and GA/HbA1c, the associations between ABI and FA or MD remained in all of either side of the following tracts: anterior thalamic radiation, forceps minor, inferior frontooccipital fasciculus (p < 0.001 for all) and superior longitudinal fasciculus (SLF; p < 0.05), whereas most of those between baPWV and FA or MD disappeared except for SLF (p < 0.05). These results indicate that low ABI could be an indicator of white matter abnormalities.

The Adenine/Thymine Deleterious Selection Model for GC Content Evolution at the Third Codon Position of the Histone Genes in Drosophila.

The evolution of the GC (guanine cytosine) content at the third codon position of the histone genes (H1, H2A, H2B, H3, H4, H2AvD, H3.3A, H3.3B, and H4r) in 12 or more Drosophila species is reviewed. For explaining the evolution of the GC content at the third codon position of the genes, a model assuming selection with a deleterious effect for adenine/thymine and a size effect is presented. The applicability of the model to whole-genome genes is also discussed.

Evolution of GC content in the histone gene repeating units from Drosophila lutescens, D. takahashii and D. pseudoobscura.

A subset of histone genes (H1, H2A, H2B and H4), which are encoded along with H3 within repeating units, were analyzed in Drosophila lutescens, D. takahashii and D. pseudoobscura to investigate the evolutionary mechanisms influencing this multigene family and its GC content. Nucleotide divergence among species was more marked in the less functional regions. A strong inverse relationship was observed between the extent of evolutionary divergence and GC content within the repeating units; this finding indicated that the functional constraint on a region must be associated with both divergence and GC content. The GC content at 3(rd) codon positions in the histone genes from D. lutescens and D. takahashii was higher than that from D. melanogaster, while that from D. pseudoobscura was similar. These evolutionary patterns were similar to those of H3 gene regions. Based on these findings, we propose that the evolutionary mechanisms governing nucleotide content at 3(rd) codon positions tend to eliminate A and T nucleotides more frequently than G and C nucleotides. These changes might be the consequence of negative selection and would result in GC-rich 3(rd) codon positions. In addition, interspecific differences in GC content, which exhibited the same pattern for all histone genes, could be explained by different selection efficiencies that result from changes in population size.

Potential clinical benefit of the in situ hybridization method for the diagnosis of sepsis.

Despite the significant development of antibiotics, sepsis is still associated with high morbidity and mortality rates. The identification of pathologic organisms at an early stage of sepsis is critical to improve the outcome, but this is difficult to achieve with the conventional method of blood culture (BC). It has been demonstrated that the genes of pathogenic organisms surviving in neutrophils were detectable with in situ hybridization (ISH) and this method was useful for the accurate and rapid diagnosis of sepsis. In this study, we applied ISH to blood smears 60 patients with suspected sepsis. BC was also carried out using the same blood samples to investigate the diagnostic value of ISH. The number of positive results obtained by ISH was approximately four times higher than that obtained by BC (ISH, 25 [41.7%]; BC, 7 [11.7%]). The positive rate in the 21 patients given antibiotics was 61.9% by ISH (13 patients) and 4.7% by BC (1 patient). The antibiotic treatments targeting the organisms detected by either procedure showed a beneficial clinical outcome. Positive results by ISH were obtained earlier than those with BC (ISH, within 1 day; BC, several days). We conclude that ISH is a useful method for the rapid diagnosis of sepsis.

Divergence and heterogeneity of the histone gene repeating units in the Drosophila melanogaster species subgroup.

The repeating units of the histone gene cluster containing the H1, H2A, H2B and H4 genes were amplified by PCR from the Drosophila melanogaster species subgroup, i.e., D. yakuba, D. erecta, D. sechellia, D. mauritiana, D. teissieri and D. orena. The PCR products were cloned and their nucleotide sequences of about 4.6-4.8kbp were determined to elucidate the mechanism of molecular evolution of the histone gene family. The heterogeneity among the histone gene repeating units was 0.6% and 0.7% for D. yakuba and D. sechellia, respectively, indicating the same level of heterogeneity as in the H3 gene region of D. melanogaster. Divergence of the genes among species even in the most closely related ones was much greater than the heterogeneity among family members, indicating a concerted mode of evolution for the histone gene repeating units. Among the species in the D. melanogaster species subgroup, the histone gene regions as well as 3rd codon position of the coding region showed nearly the same GC contents. These results suggested that the previous conclusion on analysis of the H3 gene regions, the gene family evolution in a concerted fashion, holds true for the whole histone gene repeating unit.

Evolution of the GC content of the histone 3 gene in seven Drosophila species.

The molecular evolution of the histone multigene family was studied by cloning and determining the nucleotide sequences of the histone 3 genes in seven Drosophila species, D. takahashii, D. lutescens, D. ficusphila, D. persimilis, D.pseudoobscura, D. americana and D. immigrans. CT repeats, a TATA box and an AGTG motif in the 5' region, and a hairpin loop and purine-rich motifs (CAA(T/G)GAGA) in the 3' region were conserved even in distantly related species. In D. hydei and D.americana, the GC content at the third codon position in the protein coding region was relatively low (49% and 45%), while in D. takahashii and D. lutescens it was relatively high (64% and 65%). The non- significant correlation between the GC contents in the 3' region and at the third codon position as well as the evidence of less constraint in the 3' region suggested that mutational bias may not be the major mechanism responsible for the biased nucleotide change at the third codon position or for codon usage bias.