The IL-33-ST2L Pathway Is Associated with Coronary Artery Disease in a Chinese Han Population

The effects of interleukin-33 (IL-33) on the immune system have been clearly demonstrated; however, in cardiovascular diseases, especially in coronary artery disease (CAD), these effects have not yet been clarified. In this study, we investigate the genetic role of the IL-33-ST2L pathway in CAD. We performed three-stage case-control association analyses on a total of 4,521 individuals with CAD and 4,809 controls via tag SNPs in the genes encoding IL-33 and ST2L-IL-1RL1. One tag SNP in each gene was significantly associated with CAD (rs7025417^T in IL33, p_adj = 1.19 × 10⁻²⁸, OR = 1.39, 95% CI: 1.31–1.47; rs11685424^G in IL1RL1, p_adj = 6.93 × 10⁻³⁰, OR = 1.40, 95% CI: 1.32–1.48). Combining significant variants in two genes, the risk for CAD increased nearly 5-fold (p_adj = 8.90 × 10⁻²¹, OR = 4.98, 95% CI: 3.56–6.97). Traditional risk factors for CAD were adjusted for the association studies by SPSS with logistic regression analysis. With the two variants above, both located within the gene promoter regions, reporter gene analysis indicated that the rs7025417 C>T and rs11685424 A>G changes resulted in altered regulation of IL33 and IL1RL1 gene expression, respectively (p < 0.005). Further studies revealed that the rs7025417 genotype was significantly associated with plasma IL-33 levels in the detectable subjects (n = 227, R² = 0.276, p = 1.77 × 10⁻¹⁷): the level of IL-33 protein increased with the number of rs7025417 risk (T) alleles. Based on genetic evidence in humans, the IL-33-ST2L pathway appears to have a causal role in the development of CAD, highlighting this pathway as a valuable target for the prevention and treatment of CAD.     

Cryptanalysis and Improvement of a Biometric-Based Multi-Server Authentication and Key Agreement Scheme

With the security requirements of networks, biometrics authenticated schemes which are applied in the multi-server environment come to be more crucial and widely deployed. In this paper, we propose a novel biometric-based multi-server authentication and key agreement scheme which is based on the cryptanalysis of Mishra et al.’s scheme. The informal and formal security analysis of our scheme are given, which demonstrate that our scheme satisfies the desirable security requirements. The presented scheme provides a variety of significant functionalities, in which some features are not considered in the most of existing authentication schemes, such as, user revocation or re-registration and biometric information protection. Compared with several related schemes, our scheme has more secure properties and lower computation cost. It is obviously more appropriate for practical applications in the remote distributed networks.     

Reliability and Validity of Dual-Task Mobility Assessments in People with Chronic Stroke

Background

The ability to perform a cognitive task while walking simultaneously (dual-tasking) is important in real life. However, the psychometric properties of dual-task walking tests have not been well established in stroke.

Objective

To assess the test-retest reliability, concurrent and known-groups validity of various dual-task walking tests in people with chronic stroke.

Design

Observational measurement study with a test-retest design.

Methods

Eighty-eight individuals with chronic stroke participated. The testing protocol involved four walking tasks (walking forward at self-selected and maximal speed, walking backward at self-selected speed, and crossing over obstacles) performed simultaneously with each of the three attention-demanding tasks (verbal fluency, serial 3 subtractions or carrying a cup of water). For each dual-task condition, the time taken to complete the walking task, the correct response rate (CRR) of the cognitive task, and the dual-task effect (DTE) for the walking time and CRR were calculated. Forty-six of the participants were tested twice within 3–4 days to establish test-retest reliability.

Results

The walking time in various dual-task assessments demonstrated good to excellent reliability [Intraclass correlation coefficient (ICC_2,1) = 0.70–0.93; relative minimal detectable change at 95% confidence level (MDC₉₅%) = 29%-45%]. The reliability of the CRR (ICC_2,1 = 0.58–0.81) and the DTE in walking time (ICC_2,1 = 0.11–0.80) was more varied. The reliability of the DTE in CRR (ICC_2,1 = -0.31–0.40) was poor to fair. The walking time and CRR obtained in various dual-task walking tests were moderately to strongly correlated with those of the dual-task Timed-up-and-Go test, thus demonstrating good concurrent validity. None of the tests could discriminate fallers (those who had sustained at least one fall in the past year) from non-fallers.

Limitation

The results are generalizable to community-dwelling individuals with chronic stroke only.

Conclusions

The walking time derived from the various dual-task assessments generally demonstrated good to excellent reliability, making them potentially useful in clinical practice and future research endeavors. However, the usefulness of these measurements in predicting falls needs to be further explored. Relatively low reliability was shown in the cognitive outcomes and DTE, which may not be preferred measurements for assessing dual-task performance.     

Proteomic dissection of plant responses to various pathogens

During their growth and development, plants are vulnerable to the effects of a variety of pathogens. Proteomics technology plays an important role in research studies of plant defense mechanisms by mining the expression changes of proteins in response to various biotic stresses. This review article provides a comprehensive overview of the latest developments in international proteomic research on plant biotic stress. It summarizes the methods commonly used in plant proteomic research to investigate biotic stress, analyze the protein responses of plants in adverse conditions, and reviews the applications of proteomics combined with transgenic technology in plant protection.     

Cloning of cDNAs with PDCD2C domain and their expressions during apoptosis of HEK293T cells

Modulation of the expression of genes involved in the control of cholesterol homeostasis by sterols in macrophages is crucial to foam cell formation. To characterize this regulation in THP-1 macrophages, we examined the effect of sterol loading and unloading on the expression of a number of genes that participate in lipoprotein uptake and cholesterol efflux. Sterol loading by exposure to acetylated LDL for 24 h resulted in an increase in free and esterified cholesterol of 1.4 and 1.8-fold, respectively. Under these conditions, the mRNA levels for SR-A were reduced a 59%, while those of CYP27 were increased by 4.6-fold. However, the expression of other genes involved in cholesterol efflux (ABCA1, ABCG1 and CLA-1) was not modified, despite a high intracellular cholesterol accumulation specially in the form of esterified cholesterol.On the other hand, HDL exposure reduced intracellular cholesterol content to 70%, and caused an increase in the expression of CD36 (78%), SR-A (51%) and CLA-1 (136%). Conversely, the expression of ABCA1, ABCG1 and CYP27 was decreased by 49, 67 and 57%, respectively. These findings indicate that in THP-1 macrophages, the expression of genes for receptors involved in lipoprotein binding and uptake tends to decrease upon cholesterol loading and to increase by cholesterol depletion, while the opposite pattern is found regarding the mRNA levels for proteins involved in cholesterol efflux.     

Long Non-coding RNAs in Parkinson’s Disease

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is associated with a range of motor and non-motor clinical symptoms. The underlying molecular pathogenesis of PD involves a variety of pathways and mechanisms, including α-synuclein proteostasis, mitochondrial dysfunction, oxidative stress, autophagy and apoptosis, neuroinflammation, and epigenetic regulation. Long non-coding RNAs (lncRNAs) are involved in the regulation of multiple pathological processes of PD. In this review, we provide an overview of large-scale studies on lncRNA expression profiling in PD patients and models, as well as highlight the impacts of lncRNAs on the pathogenesis of PD, which could provide basic information regarding the putative lncRNA-based biomarkers and therapeutic targets for the early diagnosis and treatment strategies for PD.

     

Structure determination of DNA methylation lesions N1-meA and N3-meC in duplex DNA using a cross-linked protein–DNA system

N¹-meA and N³-meC are cytotoxic DNA base methylation lesions that can accumulate in the genomes of various organisms in the presence of S_N2 type methylating agents. We report here the structural characterization of these base lesions in duplex DNA using a cross-linked protein–DNA crystallization system. The crystal structure of N¹-meA:T pair shows an unambiguous Hoogsteen base pair with a syn conformation adopted by N¹-meA, which exhibits significant changes in the opening, roll and twist angles as compared to the normal A:T base pair. Unlike N¹-meA, N³-meC does not establish any interaction with the opposite G, but remains partially intrahelical. Also, structurally characterized is the N⁶-meA base modification that forms a normal base pair with the opposite T in duplex DNA. Structural characterization of these base methylation modifications provides molecular level information on how they affect the overall structure of duplex DNA. In addition, the base pairs containing N¹-meA or N³-meC do not share any specific characteristic properties except that both lesions create thermodynamically unstable regions in a duplex DNA, a property that may be explored by the repair proteins to locate these lesions.