Recent evidence indicates that small noncoding RNA molecules known as microRNAs (miRNAs) can function as tumor suppressors and oncogenes. Mutation, misexpression, and altered mature miRNA processing are implicated in carcinogenesis and tumor progression. Because SNPs in pre-miRNAs could alter miRNA processing, expression, and/or binding to target mRNA, we conducted a systematic survey of common premiRNA SNPs and their surrounding regions and evaluated in detail the association of 4 of these SNPs with the survival of individuals with non-small cell lung cancer (NSCLC). When we assumed that disease susceptibility was inherited as a recessive phenotype, we found that the rs11614913 SNP in hsa-mir-196a2 was associated with survival in individuals with NSCLC. Specifically, survival was significantly decreased in individuals who were homozygous CC at SNP rs11614913. In the genotype-phenotype correlation analysis of 23 human lung cancer tissue samples, rs11614913 CC was associated with a statistically significant increase in mature hsa-mir-196a expression but not with changes in levels of the precursor, suggesting enhanced processing of the pre-miRNA to its mature form. Furthermore, binding assays revealed that the rs11614913 SNP can affect binding of mature hsa-mir-196a2-3p to its target mRNA. Therefore, the rs11614913 SNP in hsa-mir-196a2 may be a prognostic biomarker for NSCLC. Further characterization of miRNA SNPs may open new avenues for the study of cancer and therapeutic interventions.

Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with approximately 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing approximately 450000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples. We experimentally confirmed the frequencies of the most promising SNPs in a multiethnic panel of unrelated samples and identified 3011 as a MALD map (1.2 cM average spacing). We estimate that this map is approximately 70% informative in differentiating African versus European origins of chromosomal segments. This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts. The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations.

Objective Although the symptoms of autism exhibit quantitative distributions in nature, estimates of recurrence risk in families have never previously considered or incorporated quantitative characterization of the autistic phenotype among siblings. Method We report the results of quantitative characterization of 2,920 children from 1,235 families participating in a national volunteer register who met the criteria of having at least one child clinically-affected by an autism spectrum disorder (ASD) and at least one full biological sibling. Results The occurrence of a traditionally-defined ASD in an additional child occurred in 10.9% of the families. An additional 20% of non-ASD-affected siblings had a history of language delay, half of whom had exhibited autistic qualities of speech. Quantitative characterization using the Social Responsiveness Scale (SRS) supported previously-reported aggregation of a wide range of subclinical (quantitative) autistic traits among otherwise unaffected children in multiple-incidence families, and a relative absence of quantitative autistic traits among siblings in single-incidence autism families. Girls whose standardized severity ratings fell above a first percentile severity threshold (relative to the general population distribution) were significantly less likely to have elicited community diagnoses than their male counterparts. Conclusions These data suggest that, depending on how it is defined, sibling recurrence in ASD may exceed previously-published estimates, and varies as a function of family type. The results support differences in mechanisms of genetic transmission between simplex and multiplex autism, and advance current understanding of the genetic epidemiology of autism.

Background-Ischemic heart disease is the greatest cause of death in Western countries. The deleterious effects of cardiac ischemia are ameliorated by ischemic preconditioning (IPC), in which transient ischemia protects against subsequent severe ischemia/reperfusion injury. IPC activates multiple signaling pathways, including the reperfusion injury salvage kinase pathway (mainly PI3K-Akt-glycogen synthase kinase-3␤ [GSK3␤] and ERK1/2) and the survivor activating factor enhancement pathway involving activation of the JAK-STAT3 axis. Nevertheless, the fundamental mechanism underlying IPC is poorly understood. Methods and Results-In the present study, we define MG53, a muscle-specific TRIM-family protein, as a crucial component of cardiac IPC machinery. Ischemia/reperfusion or hypoxia/oxidative stress applied to perfused mouse hearts or neonatal rat cardiomyocytes, respectively, causes downregulation of MG53, and IPC can prevent ischemia/ reperfusion-induced decrease in MG53 expression. MG53 deficiency increases myocardial vulnerability to ischemia/ reperfusion injury and abolishes IPC protection. Overexpression of MG53 attenuates whereas knockdown of MG53 enhances hypoxia-and H 2 O 2 -induced cardiomyocyte death. The cardiac protective effects of MG53 are attributable to MG53-dependent interaction of caveolin-3 with phosphatidylinositol 3 kinase and subsequent activation of the reperfusion injury salvage kinase pathway without altering the survivor activating factor enhancement pathway. Conclusions-These results establish MG53 as a primary component of the cardiac IPC response, thus identifying a potentially important novel therapeutic target for the treatment of ischemic heart disease. (Circulation. 2010;121:2565-2574.)Key Words: hypoxia Ⅲ ischemia Ⅲ myocardial infarction Ⅲ myocytes Ⅲ stress I schemic heart disease remains the greatest cause of mortality in Western countries and the predicted leading source of mortality worldwide by 2020. 1 Blockage of heart blood flow leads to myocardial ischemia. Persistent ischemia causes myocardial infarctions, resulting in profound myocyte death, irreversible myocardial damage, and a permanent loss of contractile mass. Timely reperfusion of ischemic heart is the only way to preserve cardiac cell viability. However, reperfusion can trigger further damage to the myocardium (ie, ischemia/reperfusion [IR] injury) via reactive oxygen species-induced oxidative stress, calcium overload, or calpain activation. [2][3][4] Both ischemic injury and subsequent IR injury after restoration of blood flow represent important therapeutic targets. Editorial on p 2547 Clinical Perspective on p 2574Interventional approaches against IR injury have centered on the study of ischemic preconditioning (IPC), in which nonlethal ischemic stress to the heart (IPC) protects against subsequent lethal IR injury in the heart. 5-7 IPC is the most powerful intrinsic cellular mechanism to protect the heart as well as other organs, such as brain, liver, and kidney, from IR injury. 8 -11 A variety of signaling mo...

In this communication, we report the coexistence of liquid and solid phases of room temperature ionic liquid (IL) [Bmim][PF6] on mica surfaces, observed by tapping mode atomic force microscopy (AFM) in air. Multilayers as well as drop-on-the-layer structures of the ionic liquid are revealed. The solid layers were very stable, and their orientations were affected by the mica lattice, indicating that the ionic liquid undergoes a template-induced ordering process. These results are helpful for advancing the understanding of interfacial structures of ILs on solid surfaces, the analogous structural patterns in both of its solid and liquid phases, and its heterogeneity.

Background: It has been reported that the triglyceride-glucose (TyG) index may serve as a simple and credible surrogate marker of insulin resistance (IR). However, its association with macrovascular and microvascular damage is unclear. Accordingly, the objective of the present study is to investigate the association of macrovascular and microvascular damage with the TyG index. Methods: A total of 2830 elderly participants from the Northern Shanghai Study (NSS) were enrolled. The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Parameters of vascular damage, including carotid-femoral pulse wave velocity (cf-PWV), brachial-ankle pulse wave velocity (ba-PWV), ankle-brachial index (ABI), carotid intima-media thickness (CMT), carotid plaque, estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR), were measured and calculated. Results: In univariate logistic regression, an increased TyG index was associated with a higher risk of cf-PWV > 10 m/s, ba-PWV > 1800 cm/s, ABI < 0.9, microalbuminuria (MAU) and chronic kidney disease (CKD). In multivariable logistic regression, there was a significant increase in the risk of cf-PWV > 10 m/s (OR = 1.86, 95% confidence interval [95% CI] 1.37-2.53, P for trend < 0.001), ba-PWV > 1800 cm/s (OR = 1.39, [95% CI] 1.05-1.84, P for trend = 0.02), MAU (OR = 1.61, [95% CI] 1.22-2.13, P for trend < 0.001) and CKD (OR = 1.67, [95% CI] 1.10-1.50, P for trend = 0.02) after adjustment for age, sex, BMI, waist circumference, smoking habit, hypertension, family history of premature CVD, diabetes, HDL-C, LDL-C, insulin therapy and statin therapy. However, no significant relationship was observed between the TyG index and lower extremity atherosclerosis, carotid hypertrophy or carotid plaque. Conclusion: An elevated TyG index was significantly associated with a higher risk of arterial stiffness and nephric microvascular damage. This conclusion lends support to the clinical significance of the TyG index for the assessment of vascular damage.

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

Ionic liquids (ILs) have been claimed as "greener" replacements to molecular solvents. However, the environmental impacts of the life cycle phases and comparison with alternative methods have not been studied. Such a life cycle assessment (LCA) is essential before any legitimate claims of "greenness" can be made and is the subject of this paper. The model IL selected is 1-butyl-3-methyl-imidazolium tetrafluoroborate ([Bmim][BF4]) and its use as a solvent for the manufacture of cyclohexane and in a Diels-Alder reaction was assessed. These uses are compared with more conventional synthesis methods. The results indicate that processes that use IL are highly likely to have a larger life cycle environmental impact than more conventional methods. Sensitivity analysis shows that the result is robust to errors and variation in the data. For cyclohexane synthesis, the industrial gas phase process is the greenest, but the three solvents compared for the Diels-Alder reaction showed comparable life cycle impact. Although ILs are not the most attractive alternatives, the result may change if their separation efficiency, stability and recyclability are improved. Because there are many kinds of ILs, with many applications, two examples are not enough to reach any general conclusions about the greenness of all ILs. However, the life cycle data and approach of this study can be used for evaluating the greenness of more kinds of solvents, processes, and emerging technologies.