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Definitive diagnosis to sudden cardiac death (SCD) is often challenging since the postmortem examination on SCD victims could hardly demonstrate an adequate cause of death. It is therefore important to uncover the inherited risk component to SCD. Signal transducer and activators of transcription 5 A (STAT5A) is a member of the STAT family and a transcription factor that is activated by many cell ligands and associated with various cardiovascular processes. In this study, we performed a systematic variant screening on the STAT5A to filter potential functional genetic variations. Based on the screening results, an insertion/deletion polymorphism (rs3833144) in 3’UTR of STAT5A was selected as the candidate variant. A total of 159 SCD cases and 668 SCD matched healthy controls was enrolled to perform a case-control study and evaluate the association between rs3833144 and SCD susceptibility in Chinese populations. Logistic regression analysis showed that the deletion allele of rs3833144 had significantly increased the SCD risk (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.18–2.01; P = 0.000955). Further genotype-expression eQTL analysis showed that samples with deletion allele appeared to lower expression of STAT5A, and in silico prediction suggested the local 3 D structure changes of STAT5A mRNA caused by the variant. On the other hand, the bioinformatic analysis presented that promoters of RARA and PTGES3L-AARSD1 could interact with rs3833144, and eQTL analysis showed the higher expression of both genes in samples with deletion allele. Dual-luciferase activity assays also suggested the significant regulatory role of rs3833144 in gene transcription. Our current data thus suggested a possible involvement of rs3833144 to SCD predisposition in Chinese populations and rs3833144 with potential function roles may become a candidate marker for SCD diagnosis and prevention.

 

Abstract. New particle formation (NPF) consists of two steps: nucleation andsubsequent growth. At present, chemical and physical mechanisms that governthese two processes are not well understood. Here, we report initial resultsobtained from the TANGENT (Tandem Aerosol Nucleation and Growth EnvironmentTube) experiments. The TANGENT apparatus enables us to study these twoprocesses independently. The present study focuses on the effects oftemperature on sulfuric acid nucleation and further growth. Our results showthat lower temperatures enhance both the nucleation and growth rate.However, under temperatures below 268 K the effects of temperature on thenucleation rate become less significant and the nucleation rate becomes lessdependent on relative humidity, indicating that particle formation in the conditions of ourflow tube takes place via barrierless nucleation at lower temperatures. Wealso examined the growth of newly formed particles under differingtemperature conditions for nucleation and further growth. Our results showthat newly nucleated clusters formed at low temperatures can indeed surviveevaporation and grow in a warmer environment in the presence of SO2 andozone and potentially other contaminant vapors. These results implythat some heterogeneous reactions involving nanoparticles affect nucleationand growth of newly formed particles. 

New particle formation (NPF) represents the first step in the complex processes leading to formation of cloud condensation nuclei. Newly formed nanoparticles affect human health, air quality, weather, and climate. This review provides a brief history, synthesizes recent significant progresses, and outlines the challenges and future directions for research relevant to NPF. New developments include the emergence of state‐of‐the‐art instruments that measure prenucleation clusters and newly nucleated nanoparticles down to about 1 nm; systematic laboratory studies of multicomponent nucleation systems, including collaborative experiments conducted in the Cosmics Leaving Outdoor Droplets chamber at CERN; observations of NPF in different types of forests, extremely polluted urban locations, coastal sites, polar regions, and high‐elevation sites; and improved nucleation theories and parameterizations to account for NPF in atmospheric models. The challenges include the lack of understanding of the fundamental chemical mechanisms responsible for aerosol nucleation and growth under diverse environments, the effects of SO₂and NO_xon NPF, and the contribution of anthropogenic organic compounds to NPF. It is also critical to develop instruments that can detect chemical composition of particles from 3 to 20 nm and improve parameterizations to represent NPF over a wide range of atmospheric conditions of chemical precursor, temperature, and humidity.