SVAD: A genetic database curates non-ischemic sudden cardiac death-associated variants.

Sudden cardiac death (SCD) is an important cause of mortality worldwide. It accounts for approximately half of all deaths from cardiovascular disease. While coronary artery disease and acute myocardial infarction account for the majority of SCD in the elderly population, inherited cardiac diseases (inherited CDs) comprise a substantial proportion of younger SCD victims with a significant genetic component.

Force Dependence of Velocity and Run Length of Kinesin-1, Kinesin-2 and Kinesin-5 Family Molecular Motors.

Kinesin-1, kinesin-2 and kinesin-5 are three families of a superfamily of motor proteins; which can walk processively on microtubule filaments by hydrolyzing ATP. It was experimentally shown that while the three kinesin dimers show similar feature on the force dependence of velocity, they show rather different features on the force dependence of run length. However, why the three families of kinesins show these rather different features is unclear.

Diversity and enterotype in gut bacterial community of adults in Taiwan.

Background: Gastrointestinal microbiota, particularly gut microbiota, is associated with human health. The biodiversity of gut microbiota is affected by ethnicities and environmental factors such as dietary habits or medicine intake, and three enterotypes of the human gut microbiome were announced in 2011. These enterotypes are not significantly correlated with gender, age, or body weight but are influenced by long-term dietary habits.

Water-soluble ionic species of coarse and fine particulate matter and gas precursor characteristics at urban and rural sites of central Taiwan.

Coarse and fine particulate matter (PM) were taken by a dichotomous sampler, and gas precursors were determined by a denuder sampler at two stations in central Taiwan. Water-soluble ionic constituents of PM and their precursor gases were analyzed by ionic chromatograph. In summer, the daytime/nighttime PM10 concentrations were 37 ± 10/41 ± 18 μg m(-3) and 36 ± 14/34 ± 18 μg m(-3) for Xitun and Jhushan, respectively.

Oxypurinol-Specific T Cells Possess Preferential TCR Clonotypes and Express Granulysin in Allopurinol-Induced Severe Cutaneous Adverse Reactions.

Allopurinol, a first-line drug for treating gout and hyperuricemia, is one of the leading causes of severe cutaneous adverse reactions (SCARs). To investigate the molecular mechanism of allopurinol-induced SCAR, we enrolled 21 patients (13 Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and 8 drug reaction with eosinophilia and systemic symptoms (DRESS)), 11 tolerant controls, and 23 healthy donors. We performed in vitro T-cell activation assays by culturing peripheral blood mononuclear cells (PBMCs) with allopurinol, oxypurinol, or febuxostat and measuring the expression of granulysin and IFN-γ in the supernatants of cultures.

Mapping intracellular diffusion distribution using single quantum dot tracking: compartmentalized diffusion defined by endoplasmic reticulum.

The crowded intracellular environment influences the diffusion-mediated cellular processes, such as metabolism, signaling, and transport. The hindered diffusion of macromolecules in heterogeneous cytoplasm has been studied over years, but the detailed diffusion distribution and its origin still remain unclear. Here, we introduce a novel method to map rapidly the diffusion distribution in single cells based on single-particle tracking (SPT) of quantum dots (QDs).

Systematic analysis of the association between gut flora and obesity through high-throughput sequencing and bioinformatics approaches.

Eighty-one stool samples from Taiwanese were collected for analysis of the association between the gut flora and obesity. The supervised analysis showed that the most, abundant genera of bacteria in normal samples (from people with a body mass index (BMI) ≤ 24) were Bacteroides (27.7%), Prevotella (19.

Oxaliplatin and its enantiomer induce different condensation dynamics of single DNA molecules.

The interactions of DNA with oxaliplatin (Pt(R,R-DACH)) or its enantiomer (Pt(S,S-DACH)) were investigated using magnetic tweezers and atomic force microscope. In the process of DNA condensation induced by Pt-DACH, only diadducts and micro-loops are formed at low Pt-DACH concentrations, while at high Pt-DACH concentrations, besides the diadducts and micro-loops, long-range cross-links are also formed. The diadduct formation rate of Pt(R,R-DACH) is higher than that of Pt(S,S-DACH).

Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility.

Background: The molecular basis for the focal nature of atherosclerotic lesions is poorly understood. Here, we explored whether disturbed flow patterns activate an innate immune response to form the NLRP3 inflammasome scaffold in vascular endothelial cells via sterol regulatory element binding protein 2 (SREBP2).

Methods And Results: Oscillatory flow activates SREBP2 and induces NLRP3 inflammasome in endothelial cells.

Transplatin enhances effect of cisplatin on both single DNA molecules and live tumor cells.

Cisplatin is the main platinum antitumor drug applied in clinical settings. However, its trans isomer, transplatin, is known to have an ineffective antitumor activity. Despite intensive studies in this field, the structural and biophysical properties of DNA molecules reacting with these two platinum complexes have not been fully elucidated.

Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis.

Despite a general repression of translation under hypoxia, cells selectively upregulate a set of hypoxia-inducible genes. Results from deep sequencing revealed that Let-7 and miR-103/107 are hypoxia-responsive microRNAs (HRMs) that are strongly induced in vascular endothelial cells. In silico bioinformatics and in vitro validation showed that these HRMs are induced by HIF1α and target argonaute 1 (AGO1), which anchors the microRNA-induced silencing complex (miRISC).

Effects of paclitaxel on EGFR endocytic trafficking revealed using quantum dot tracking in single cells.

Paclitaxel (PTX), a chemotherapeutic drug, affects microtubule dynamics and influences endocytic trafficking. However, the mechanism and the dynamics of altered endocytic trafficking by paclitaxel treatment in single living cells still remain elusive. By labeling quantum dots (QDs) to the epidermal growth factor (EGF), we continuously tracked the endocytosis and post-endocytic trafficking of EGF receptors (EGFRs) in A549 cells for a long time interval.

miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4.

Metastasis is the major cause of poor prognosis in colorectal cancer (CRC), and increasing evidence supports the contribution of miRNAs to cancer progression. Here, we found that high expression of miR-103 and miR-107 (miR-103/107) was associated with metastasis potential of CRC cell lines and poor prognosis in patients with CRC. We showed that miR-103/107 targeted the known metastasis suppressors death-associated protein kinase (DAPK) and Krüppel-like factor 4 (KLF4) in CRC cells, resulting in increased cell motility and cell-matrix adhesion and decreased cell-cell adhesion and epithelial marker expression.

Elastic response and length change of single DNA molecules induced by a combination of cisplatin and transplatin.

Magnetic tweezers were employed to investigate the interactions between DNA and cisplatin (transplatin). Cisplatin shortened DNA and reduced its persistence length more significantly than transplatin due to the formation of many more diadducts than those formed by transplatin. Interestingly, the presence of transplatin could enhance the ability of cisplatin in shortening DNA.

Palladacycles bearing tridentate CNS-type benzamidinate ligands as catalysts for cross-coupling reactions.

Three pendant benzamidines, [Ph-C(=NC(6)H(5))-{NH(E)}] [E = -(CH(2))(2)SMe (1); -(CH(2))(2)S(t)Bu (2); -o-C(6)H(4)SMe (3)], are described. Reactions of 1, 2 or 3 with one molar equivalent of Pd(OAc)(2) in CH(2)Cl(2) give the palladacyclic complexes, [Ph-C{-NH(η(1)-C(6)H(4))}{=N(E)}]Pd(OAc) [E = -(CH(2))(2)SMe (4); -(CH(2))(2)S(t)Bu (5); -o-C(6)H(4)SMe (6)], as mononuclear palladium complexes respectively. A minor product described as 5', {[Ph-C{-N(C(6)H(5))}{-N(CH(2))(2)S(t)Bu}]Pd(OAc)}(2), was isolated as benzamidinate-bridged dinuclear palladium complex upon recrystallizing from Et(2)O/hexane solution.

Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a.

Background: Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2.

Clusters of nucleotide substitutions and insertion/deletion mutations are associated with repeat sequences.

The genome-sequencing gold rush has facilitated the use of comparative genomics to uncover patterns of genome evolution, although their causal mechanisms remain elusive. One such trend, ubiquitous to prokarya and eukarya, is the association of insertion/deletion mutations (indels) with increases in the nucleotide substitution rate extending over hundreds of base pairs. The prevailing hypothesis is that indels are themselves mutagenic agents.

Arabidopsis Argonaute 2 regulates innate immunity via miRNA393(∗)-mediated silencing of a Golgi-localized SNARE gene, MEMB12.

Argonaute (AGO) proteins are critical components of RNA silencing pathways that bind small RNAs and mediate gene silencing at their target sites. We found that Arabidopsis AGO2 is highly induced by the bacterial pathogen Pseudomonas syringae pv. tomato (Pst).

Health risk assessment of exposure to selected volatile organic compounds emitted from an integrated iron and steel plant.

Workplace air samples from sintering, cokemaking, and hot and cold forming processes in the integrated iron and steel industry were analyzed to determine their volatile organic compound (VOC) concentration. Sixteen VOC species including three paraffins (cyclohexane, n-hexane, methylcyclohexane), five chlorinated VOC species (trichloroethylene, 1,1,1-trichloroethane, tetrachloroethylene, chlorobenzene, 1,4-dichlorobenzene), and eight aromatics (benzene, ethylbenzene, styrene, toluene, m,p-xylene, o-xylene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene) were selected to measure their noncancer risk for workers. Concentrations of toluene, xylene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene, dichlorobenzene, and trichloroethylene were high in all four processes.

Global analyses of small interfering RNAs derived from Bamboo mosaic virus and its associated satellite RNAs in different plants.

Background: Satellite RNAs (satRNAs), virus parasites, are exclusively associated with plant virus infection and have attracted much interest over the last 3 decades. Upon virus infection, virus-specific small interfering RNAs (vsiRNAs) are produced by dicer-like (DCL) endoribonucleases for anti-viral defense. The composition of vsiRNAs has been studied extensively; however, studies of satRNA-derived siRNAs (satsiRNAs) or siRNA profiles after satRNA co-infection are limited.

miRExpress: analyzing high-throughput sequencing data for profiling microRNA expression.

Background: MicroRNAs (miRNAs), small non-coding RNAs of 19 to 25 nt, play important roles in gene regulation in both animals and plants. In the last few years, the oligonucleotide microarray is one high-throughput and robust method for detecting miRNA expression. However, the approach is restricted to detecting the expression of known miRNAs.

Formation of DNA toroids inside confined droplets adsorbed on mica surfaces.

We report observations of in vitro DNA compaction into toroids in the absence of any condensing agent. The DNA toroid formation is induced by geometry confinement from microdroplets on mica surfaces. With AFM imaging we show that the confined DNA molecules may take the form of random coils or semiordered folded loops with large microdroplets, while they readily take the form of compact and ordered toroids when the microdroplet sizes are small enough.

Characteristics of water-soluble ionic species in fine (PM2.5) and coarse particulate matter (PM10-2.5) in Kaohsiung, southern Taiwan.

Eleven ionic species and fine and coarse particle mass concentrations of fine (PM2.5) and coarse (PM10-2.5) particulate matter were investigated in Kaohsiung, southern Taiwan.

Cisplatin induces loop structures and condensation of single DNA molecules.

Structural properties of single lambda DNA treated with anti-cancer drug cisplatin were studied with magnetic tweezers and AFM. Under the effect of low-concentration cisplatin, the DNA became more flexible, with the persistence length decreased significantly from approximately 52 to 15 nm. At a high drug concentration, a DNA condensation phenomenon was observed.

Dynamic simulation of the effect of calcium-release activated calcium channel on cytoplasmic Ca2+ oscillation.

A mathematical model is proposed to illustrate the activation of STIM1 (stromal interaction molecule 1) protein, the assembly and activation of calcium-release activated calcium (CRAC) channels in T cells. In combination with De Young-Keizer-Li-Rinzel model, we successfully reproduce a sustained Ca(2+) oscillation in cytoplasm. Our results reveal that Ca(2+) oscillation dynamics in cytoplasm can be significantly affected by the way how the Orai1 CRAC channel are assembled and activated.