Overlapping population structures of nasal isolates of Staphylococcus aureus from healthy Dutch and American individuals

To understand Staphylococcus aureus nasal carriage and its relationship with subsequent disease, insight into the natural (nonclinical) bacterial population structure is essential. This study investigated whether the distributions of S. aureus genotypes that cause colonization differ by geographic locales. High-throughput amplified fragment length polymorphism (AFLP) analysis was performed on nasal isolates of S. aureus from healthy American (n = 391) and Dutch (n = 829) volunteers. In total, 164,970 binary outcomes, covering 135 different markers per isolate, were scored. Methicillin resistance was defined for all strains; pulsed-field gel electrophoresis typing was performed for the American isolates. The overall population structures of the American and Dutch S. aureus isolates were comparable. The same four major AFLP clusters (I to IV) and subclusters were identified for both collections. However, the Dutch methicillin-susceptible S. aureus (MSSA) isolates were overrepresented in AFLP cluster III (P = 0.0016). Furthermore, the majority of the American methicillin-resistant S. aureus isolates (90.5%) were located in AFLP cluster I (P < 0.0001). This result identifies differences in the local prevalence of certain S. aureus genotypes. AFLP clusters II and III, which represent multilocus sequence typing clonal complexes 30 and 45, respectively, account for 46.4% of all MSSA isolates in the study, suggesting that these two lineages have evolved as extremely successful pandemic colonizers of humans. In conclusion, the overall population structures of American and Dutch nasal carriage isolates of S. aureus are surprisingly similar, despite subtle geographic differences in the prevalence of certain S. aureus genotypes.     

The association between vascular function-related genes and age at natural menopause

OBJECTIVE: In this study we attempted to confirm recent findings suggesting that age at natural menopause might be affected by single nucleotide polymorphisms in certain cardiovascular risk factor genes, such as genes encoding for blood clotting factors II, V, and VII and the apolipoprotein E2 gene. Such validation might increase support for the theory that ovarian aging is partly due to aging of the vascular supply to the ovary. DESIGN: We used a random sample of 742 naturally postmenopausal women from a large population-based cross-sectional study. Data on age at natural menopause, smoking, body mass index, reproductive history, and other health factors were collected through questionnaires. We studied the association between single nucleotide polymorphisms in the genes encoding for coagulation factors II, V, and VII and the apolipoprotein E2 gene and age at natural menopause using linear regression analysis. We corrected for oral contraceptive use, parity, current smoking, and body mass index. RESULTS: Only the heterozygous deletion/insertion mutation in clotting factor VII was significantly associated with an increase of menopausal age of 0.81 year (95% CI: 0.12-1.50 y). The homozygous variant, however, was not. The single nucleotide polymorphisms in the other genes studied were not significantly associated with age at natural menopause. Adjustment for various lifestyle factors did not change the associations between single nucleotide polymorphisms and age at menopause. CONCLUSIONS: Earlier findings relating specific point mutations in cardiovascular risk factor genes with age of natural menopause could not be confirmed in the present study.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.     

HIV-1包膜蛋白2G12和2F5中和表位的改造对假病毒形成及中和活性的影响

目的 研究HIV-1膜蛋白(Env)特定中和表位的改造对功能性假病毒形成及中和活性的影响.方法 采用环形诱变及Dpn I筛选的方法对Env进行定点突变,将2G12和2F5两个中和表位整合入不含该表位的BC亚型的Env上,比较改造对假病毒的形成情况及对2G12和2F5单抗的中和活性的影响.结果 对5株假病毒(BC02、BE03、BC04、BC05和BC12)的Env特定中和表位进行改造,其中BC04和BCl2的2G12表位改造后,不能形成假病毒,BC02、BC03和BC05增加2G12和2F5两个表位后,仍能够形成假病毒,且假病毒滴度较改造前无明显变化,改造后的BC03假病毒较改造前对单抗2G12和2175的中和活性均有所提高,而改造后的BE02和BC05假病毒较改造前对单抗2F5的中和活性增强,而对单抗2G12的中和活性无变化.结论 2G12中和表位部分位点的改造影响假病毒的形成,中和表位的增加能够提高单抗2G12的中和活性,为免疫原的优化提供了新思路.