A genetic association study of D-dimer levels with 50 K SNPs from a candidate gene chip in four ethnic groups

Introduction

D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations.

Materials and Methods

We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis.

Results

Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p < 2.0 × 10^− 6. The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p = 0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p = 0.006). No additional SNPs were significantly associated with D-dimer.

Conclusions

Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics.     

Spiral chain O₄ form of dense oxygen

Oxygen is in many ways a unique element: It is the only known diatomic molecular magnet, and it exhibits an unusual O(8) cluster in its high-pressure solid phase. Pressure-induced molecular dissociation as one of the fundamental problems in physical sciences has been reported from theoretical or experimental studies of diatomic solids H(2), N(2), F(2), Cl(2), Br(2), and I(2) but remains elusive for molecular oxygen. We report here the prediction of the dissociation of molecular oxygen into a polymeric spiral chain O(4) structure (space group I4(1)/acd, θ-O(4)) above 1.92-TPa pressure using the particle-swarm search method. The θ-O(4) phase has a similar structure as the high-pressure phase III of sulfur. The molecular bonding in the insulating ε-O(8) phase or the isostructural superconducting ζ-O(8) phase remains remarkably stable over a large pressure range of 0.008-1.92 TPa. The pressure-induced softening of a transverse acoustic phonon mode at the zone boundary V point of O(8) phase might be the ultimate driving force for the formation of θ-O(4). Stabilization of θ-O(4) turns oxygen from a superconductor into an insulator by opening a wide band gap (approximately 5.9 eV) that originates from the sp(3)-like hybridized orbitals of oxygen and the localization of valence electrons.     

Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats

Lifelong dietary restriction (DR) is known to have many potential beneficial effects on brain function as well as delaying the onset of neurological diseases. In the present investigation, the effect of late-onset short-term intermittent fasting dietary restriction (IF-DR) regimen was studied on motor coordination and cognitive ability of ageing male rats. These animals were further used to estimate protein carbonyl content and mitochondrial complex I-IV activity in different regions of brain and peripheral organs, and the degree of age-related impairment and reversion by late-onset short-term IF-DR was compared with their levels in 3-month-old young rats. The results of improvement in motor coordination by rotarod test and cognitive skills by Morris water maze in IF-DR rats were found to be positively correlated with the decline in the oxidative molecular damage to proteins and enhanced mitochondrial complex IV activity in different regions of ageing brain as well as peripheral organs. The work was further extended to study the expression of synaptic plasticity-related proteins, such as synaptophysin, calcineurin and CaM kinase II to explore the molecular basis of IF-DR regimen to improve cognitive function. These results suggest that even late-onset short-term IF-DR regimen have the potential to retard age-associated detrimental effects, such as cognitive and motor performance as well as oxidative molecular damage to proteins.     

不同皮肤扩张方式对皮瓣的超微结构和回缩率的影响

目的研究反复快速扩张、单纯快速扩张及常规扩张对皮瓣的超微结构和回缩率的影响,以探讨适合于临床的最佳皮肤扩张方式。方法用兔制备动物模型,随机将动物分为反复快速扩张组(A组)、单纯快速扩张组(B组)、常规扩张组(C组)、植入不扩组(D组)和正常对照组(E组),扩张后分别维持1周、2周、3周、4周以及6周,透射电镜下观察扩张皮瓣超微结构的变化,分格测量法计算回缩率。结果透射电镜观察:维持扩张1周后,A、B、C三组的基底细胞胞质可见少量的表面张力细丝,基底膜部分断裂,成纤维细胞胞质内,有丰富的粗面内质网,线粒体数量明显增加,A组的细胞功能最为活跃;维持扩张4周后,A、B、C三组基底膜基本恢复,成纤维细胞胞质内,细胞器数量明显减少,线粒体大部分嵴或膜融合。回缩率比较:A、B、C及D组在相同扩张维持期,回缩率均高于E组;A、B、C组回缩率随时间延长均呈下降趋势;A、C组与B组比较,维持1、2、3和4周,回缩率均下降;A组与C组比较,维持1和2周,回缩率增加。结论采用反复快速扩张方式,能获取回缩率及质量相同的皮瓣,并可缩短疗程。     

牙龈卟啉单胞菌感染血管平滑肌细胞的超微结构观察

目的:观察牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg)对大鼠胸大动脉平滑肌细胞黏附及入侵情况,探讨Pg对血管平滑肌细胞的损伤途径,为牙周病在动脉粥样硬化发病机制中的研究提供依据.方法:用感染复数(multiplicity of infection,MOD为100∶1 Pg感染大鼠胸大动脉平滑肌细胞,分别于8、16 h TEM观察Pg对血管平滑肌细胞的黏附和入侵能力.结果:Pg感染大鼠胸大动脉平滑肌细胞16h时,Pg能利用表面菌毛黏附于血管平滑肌细胞表面并入侵胞质内.结论:Pg能够黏附于大鼠胸大动脉平滑肌细胞,并入侵细胞质,定植于细胞内.     

Awareness, anxiety, compliance: community perceptions and response to the threat and reality of an influenza pandemic

This study compared community response prior to and during the H1N1 2009 influenza pandemic using a cross-sectional phone survey of rural and metropolitan South Australia, conducted in 2007 and 2009. Awareness of pandemic influenza was significantly higher and anxiety lower in 2009 than in 2007. Reported seasonal influenza vaccine uptake increased from 51.7% in 2007 to 61.4% in 2009, but there was more interest in receiving pandemic vaccine in 2007 (87.5%) than in 2009 (57%).     

Pandemic A/H1N1 influenza: Transmission of the first cases in Spain

Introduction

Pandemic A/H1N1 influenza emerged in Mexico at the end of March 2009. Since then, it is still important to provide evidences that contributed to the international spread of the virus and to ascertain the attack rate of this new strain of influenza among the first cases in Spain that led to identify the first transmission in Europe.

Methods

Three pandemic A/H1N1 influenza groups related to an overseas flight were studied: 71 student group, 94 remaining passengers, and 68 contacts of confirmed cases. The attack rate with their 95% confidence interval (CI) among the student group and contacts was calculated. On April 26th, when the first cases were notified, strong preventive measures were implemented among the student group and the contacts of the confirmed cases.

Results

On 27th April, the first pandemic A/H1N1 influenza cases confirmed in Spain were three students that came back from Mexico by airplane. A student generated the first native case in Spain and one of the first cases in Europe. Similar attack rates were found between the student group (14.1%; CI: 12.1–16.1) and their contacts (13.2%; CI: 4.4–22.0), but no cases among remaining passengers were detected, suggesting low transmission risk during air travel.

Conclusion

The first cases of pandemic A/H1N1 influenza in Spain were imported by airplane from Mexico. Preventive efforts to reduce the impact of the influenza influenced that primary and secondary rates were lower than first estimations by WHO.     

Expression profile and thyroid hormone responsiveness of transporters and deiodinases in early embryonic chicken brain development

We used the chick embryo to study the mechanisms regulating intracellular TH availability in developing brain. TH-transporters OATP1C1 and MCT8, and deiodinases D1, D2, and D3 were expressed in a region-specific way, well before the onset of endogenous TH secretion. Between day 4 and 10 of development MCT8 and D2 mRNA levels increased, while OATP1C1 and D3 mRNA levels decreased. D2 and D3 mRNAs were translated into active protein, while no D1 activity was detectable. Injection of THs into the yolk 24 h before sampling increased TH levels in the brain and resulted in decreased OATP1C1 and increased MCT8 expression in 4-day-old embryos. A compensatory response in deiodinase activity was only observed at day 8. We conclude that THs are active in the early embryonic brain and TH-transporters and deiodinases can regulate their availability. However, the absence of clear compensatory mechanisms at day 4 makes the brain more vulnerable for changes in maternal TH supply.     

Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys

While the mechanisms of cellular aging remain controversial, a leading hypothesis is that mitochondrial oxidative stress and mitochondrial dysfunction play a critical role in this process. Here, we provide data in aging rhesus macaques supporting the hypothesis that increased oxidative stress is a major characteristic of aging and may be responsible for the age-associated increase in mitochondrial dysfunction. We measured mitochondrial DNA (mtDNA) damage by quantitative PCR in liver and peripheral blood mononuclear cells of young, middle age, and old monkeys and show that older monkeys have increases in the number of mtDNA lesions. There was a direct correlation between the amount of mtDNA lesions and age, supporting the role of mtDNA damage in the process of aging. Liver from older monkeys showed significant increases in lipid peroxidation, protein carbonylations and reduced antioxidant enzyme activity. Similarly, peripheral blood mononuclear cells from the middle age group showed increased levels in carbonylated proteins, indicative of high levels of oxidative stress. Together, these results suggest that the aging process is associated with defective mitochondria, where increased production of reactive oxygen species results in extensive damage at the mtDNA and protein levels. This study provides valuable data based on the rhesus macaque model further validating age-related mitochondrial functional decline with increasing age and suggesting that mtDNA damage might be a good biomarker of aging.