Who Are Better Informed Before Analysts’ Forecast Changes?

Using Korean data, we investigate information asymmetry among investors before analysts change their stock recommendations. By comparing trading activities between individuals, institutions, and foreign investors, we find that there is information asymmetry before analysts change their recommendations. Institutional investors buy/sell the stock before recommendation upgrades/downgrades, but individuals and foreign investors do not anticipate the upcoming news. We also document that the trade imbalance of institutional investors are associated with stock returns upon the announcements of recommendation changes. This result indicates that institutions take advantage of their superior information around the recommendation changes.     

Mechanical rolling formation of interpenetrated lithium metal/lithium tin alloy foil for ultrahigh-rate battery anode

To achieve good rate capability of lithium metal anodes for high-energy-density batteries, one fundamental challenge is the slow lithium diffusion at the interface. Here we report an interpenetrated, three-dimensional lithium metal/lithium tin alloy nanocomposite foil realized by a simple calendering and folding process of lithium and tin foils, and spontaneous alloying reactions. The strong affinity between the metallic lithium and lithium tin alloy as mixed electronic and ionic conducting networks, and their abundant interfaces enable ultrafast charger diffusion across the entire electrode. We demonstrate that a lithium/lithium tin alloy foil electrode sustains stable lithium stripping/plating under 30mAcm(-2) and 5mAhcm(-2) with a very low overpotential of 20mV for 200 cycles in a commercial carbonate electrolyte. Cycled under 6C (6.6mAcm(-2)), a 1.0mAhcm(-2) LiNi0.6Co0.2Mn0.2O2 electrode maintains a substantial 74% of its capacity by pairing with such anode

Duplex-specific nuclease efficiently removes rRNA for prokaryotic RNA-seq

Next-generation sequencing has great potential for application in bacterial transcriptomics. However, unlike eukaryotes, bacteria have no clear mechanism to select mRNAs over rRNAs; therefore, rRNA removal is a critical step in sequencing-based transcriptomics. Duplex-specific nuclease (DSN) is an enzyme that, at high temperatures, degrades duplex DNA in preference to single-stranded DNA. DSN treatment has been successfully used to normalize the relative transcript abundance in mRNA-enriched cDNA libraries from eukaryotic organisms. In this study, we demonstrate the utility of this method to remove rRNA from prokaryotic total RNA. We evaluated the efficacy of DSN to remove rRNA by comparing it with the conventional subtractive hybridization (Hyb) method. Illumina deep sequencing was performed to obtain transcriptomes from Escherichia coli grown under four growth conditions. The results clearly showed that our DSN treatment was more efficient at removing rRNA than the Hyb method was, while preserving the original relative abundance of mRNA species in bacterial cells. Therefore, we propose that, for bacterial mRNA-seq experiments, DSN treatment should be preferred to Hyb-based methods.

A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation

Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and there remains no pediatric vaccine. RSV live-attenuated vaccines (LAVs) have a history of safe testing in infants; however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we seek to engineer an RSV LAV with enhanced immunogenicity. Genetic mapping identifies strain line 19 fusion (F) protein residues that correlate with pre-fusion antigen maintenance by ELISA and thermal stability of infectivity in live RSV. We generate a LAV candidate named OE4 which expresses line 19F and is attenuated by codon-deoptimization of non-structural (NS1 and NS2) genes, deletion of the small hydrophobic (SH) gene, codon-deoptimization of the attachment (G) gene and ablation of the secreted form of G. OE4 (RSV-A2-dNS1-dNS2-ΔSH-dGm-Gsnull-line19F) exhibits elevated pre-fusion antigen levels, thermal stability, immunogenicity, and efficacy despite heavy attenuation in the upper and lower airways of cotton rats

Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo

BACKGROUND: Colorectal cancer (CRC) is a clinically challenging malignant tumor worldwide. As a natural product and sesquiterpene lactone, Costunolide (CTD) has been reported to possess anticancer activities. However, the regulation mechanism and precise target of this substance remain undiscovered in CRC. In this study, we found that CTD inhibited CRC cell proliferation in vitro and in vivo by targeting AKT. METHODS: Effects of CTD on colon cancer cell growth in vitro were evaluated in cell proliferation assays, migration and invasion, propidium iodide, and annexin V-staining analyses. Targets of CTD were identified utilizing phosphoprotein-specific antibody array; Costunolide-sepharose conjugated bead pull-down analysis and knockdown techniques. We investigated the underlying mechanisms of CTD by ubiquitination, immunofluorescence staining, and western blot assays. Cell-derived tumour xenografts (CDX) in nude mice and immunohistochemistry were used to assess anti-tumour effects of CTD in vivo. RESULTS: CTD suppressed the proliferation, anchorage-independent colony growth and epithelial-mesenchymal transformation (EMT) of CRC cells including HCT-15, HCT-116 and DLD1. Besides, the CTD also triggered cell apoptosis and cell cycle arrest at the G2/M phase. The CTD activates and induces p53 stability by inhibiting MDM2 ubiquitination via the suppression of AKT's phosphorylation in vitro. The CTD suppresses cell growth in a p53-independent fashion manner; p53 activation may contribute to the anticancer activity of CTD via target AKT. Finally, the CTD decreased the volume of CDX tumors without of the body weight loss and reduced the expression of AKT-MDM2-p53 signaling pathway in xenograft tumors. CONCLUSIONS: Our project has uncovered the mechanism underlying the biological activity of CTD in colon cancer and confirmed the AKT is a directly target of CTD. All of which These results revealed that CTD might be a new AKT inhibitor in colon cancer treatment, and CTD is worthy of further exploration in preclinical and clinical trials.1

Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis

CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported inToxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent conditional Blimp-1 knockout mixed bone marrow chimera as well as an adoptive transfer approach, we show that CD4 T cell–intrinsic deletion of Blimp-1 reversed CD8 T cell dysfunction and resulted in improved pathogen control. To the best of our knowledge, this is a novel finding, which demonstrates the role of Blimp-1 as a critical regulator of CD4 dysfunction and links it to the CD8 T cell dysfunctionality observed in infected mice. The critical role of CD4-intrinsic Blimp-1 expression in mediating CD4 and CD8 T cell exhaustion may provide a rational basis for designing novel therapeutic approaches

Mitochondrial dysfunction reduces yeast replicative lifespan by elevating RAS-dependent ROS production by the ER-localized NADPH oxidase Yno1

<div><p>Mitochondrial dysfunction leads to the accumulation of reactive oxygen species (ROS) which is associated with cellular dysfunction, disease etiology, and senescence. Here, we used the eukaryotic model <i>Saccharomyces cerevisiae</i>, commonly studied for cellular aging, to demonstrate how defective mitochondrial function affects yeast replicative lifespan (RLS). We show that RLS of respiratory-deficient cells decreases significantly, indicating that the maintenance of RLS requires active respiration. The shortening of RLS due to mitochondrial dysfunction was not related to the accumulation of extrachromosomal ribosomal DNA circles, a well-known cause of aging in yeast. Instead, intracellular ROS and oxidatively damaged proteins increased in respiratory-deficient mutants. We show that, while the protein kinase A activity is not elevated, ROS generation in respiratory-deficient cells depends on RAS signaling pathway. The ER-localized NADPH oxidase Yno1 also played a role in producing ROS. Our data suggest that a severe defect in mitochondrial respiration accelerates cellular aging by disturbing protein homeostasis in yeast.</p></div

Transcriptional silencing is not a major cause for shortening of RLS in respiratory-deficient cells.

<p>Silencing at the rDNA region was assessed by monitoring the growth of 10-fold serial dilution of cells on SC media lacking uracil or supplemented with FOA. SC medium was used as a control. (A) 10-fold serial dilutions of wild-type (WT) and rho⁰ cells were spotted on SC media without uracil or with FOA. (B) 10-fold serial dilutions of WT, <i>cyc3</i>Δ, and <i>shy1</i>Δ cells were spotted on SC media without uracil or with FOA. (C) 10-fold serial dilutions of WT cells were spotted on SC media without uracil containing 3 μg/ml antimycin A (AA) or 10 μg/ml oligomycin (OM). (D) 10-fold serial dilutions of WT, <i>cox5a</i>Δ, and <i>cyc1</i>Δ cells were spotted on SC media without uracil or with FOA. (E) Total RNA was extracted from WT, rho⁰, <i>cyc3</i>Δ, <i>shy1</i>Δ, <i>cox5a</i>Δ, <i>cyc1</i>Δ, and <i>sir2</i>Δ cells. Quantitative real-time reverse transcription-PCR analysis was performed to measure the <i>mURA3</i> transcript level. Amplification efficiencies were validated and normalized against <i>ACT1</i>. The relative transcript levels of the <i>mURA3</i> gene were calculated as the ratio of the normalized transcript levels of the <i>mURA3</i> gene inside the rDNA array (<i>NTS1</i>::<i>mURA3</i> and <i>NTS2</i>::<i>mURA3</i>) to that outside the rDNA array (<i>leu2</i>::<i>mURA3</i>). Values represent the average of three independent experiments, and error bars indicate the standard deviation. (F) rDNA recombination assay was performed to check rDNA stability of the indicated cells. rDNA recombination is represented by the frequency of loss of the <i>ADE2</i> marker gene integrated at the rDNA locus in the corresponding cells. Values represent the average of three independent experiments, and error bars indicate the standard deviation. Asterisks indicate <i>P</i><0.01, compared with WT cells (one-way ANOVA).</p

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In this study, to characterize PM1.0 concentrations and chemical composition, seasonal PM1.0 samples were collected using a single channel particulate sampler equipped with PM1.0 cyclone and quantified the chemical compositions of PM1.0. The sampling of PM1.0 was carried out at the Seoul Metropolitan Area Air Pollution Research Center located at Bulgwang in Seoul. The 8 ions (Cl-, NO3 -, SO4 2-, Na+, NH4 +, K+, Ca2+, and Mg2+), organic carbon (OC), elemental carbon (EC), and 13 elements (As, Cd, Cu, Zn, Pb, Cr, Mn, Fe, Ni, K, V, Se, and Al) were analyzed in the PM1.0 samples. The annual average of PM1.0 mass concentration was 18??10 ??g/m3 with the highest in winter as 30??9 ??g/m3 and the lowest of 12??6 ??g/m3 in fall. Among the chemical components of PM1.0, OC was the most dominating component, and variations of OC and SO4 2- were not significant, whereas NO3 - and EC showed distinct seasonal variations, highest in winter and lowest in summer. The distributions of precursor gases, oxidation ratio, and meteorological data were used to characterize the difference in PM1.0 chemical composition between normal and heavy pollution periods. High PM1.0 concentrations in the spring were associated with increases in precursor gas concentrations, whereas in the winter, transport of PM1.0 could cause a significant effect on PM1.0 concentrations with chemical components

Induction of Redox-Active Gene Expression by CoCl2 Ameliorates Oxidative Stress-Mediated Injury of Murine Auditory Cells

Free radicals formed in the inner ear in response to high-intensity noise, are regarded as detrimental factors for noise-induced hearing loss (NIHL). We reported previously that intraperitoneal injection of cobalt chloride attenuated the loss of sensory hair cells and NIHL in mice. The present study was designed to understand the preconditioning effect of CoCl2 on oxidative stress-mediated cytotoxicity. Treatment of auditory cells with CoCl2 promoted cell proliferation, with increases in the expressions of two redox-active transcription factors (hypoxia-inducible factor 1&alpha;, HIF-1&alpha;, nuclear factor erythroid 2-related factor 2; Nrf-2) and an antioxidant enzyme (peroxiredoxin 6, Prdx6). Hydrogen peroxide treatment resulted in the induction of cell death and reduction of these protein expressions, reversed by pretreatment with CoCl2. Knockdown of HIF-1&alpha; or Nrf-2 attenuated the preconditioning effect of CoCl2. Luciferase reporter analysis with a Prdx6 promoter revealed transactivation of Prdx6 expression by HIF-1&alpha; and Nrf-2. The intense immunoreactivities of HIF-1&alpha;, Nrf-2, and Prdx6 in the organ of Corti (OC), spiral ganglion cells (SGC), and stria vascularis (SV) of the cochlea in CoCl2-injected mice suggested CoCl2-induced activation of HIF-1&alpha;, Nrf-2, and Prdx6 in vivo. Therefore, we revealed that the protective effect of CoCl2 is achieved through distinctive signaling mechanisms involving HIF-1&alpha;, Nrf-2, and Prdx6