CpG and Interleukin-15 Synergize to Enhance IFN-γ Production by Activated CD8+ T Cells

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8+ T cells. Paradoxically, we previously reported that IL-15 could enhance CD8+ T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8+ T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN-γ by CD8+ T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN-γ production. The effect of CpG and IL-15 was also evident with CD8+ T cells recovered from mice infected with the parasite Trypanosoma cruzi (T. cruzi) and restimulated with antigen. The observed synergy between CpG and IL-15 occurred in an IL-12-dependent manner, and this effect could even be demonstrated in cocultures of activated CD8+ T cells and CD4+CD25+ regulatory T cells. Although IFN-γ was not essential for CpG-induced IL-12, the ability of CpG and IL-15 to act on CD8+ T cells required expression of the IFN-γ-inducible transcription factor T-bet. These data have important implications for development of vaccines and design of therapies to boost CD8+ T-cell responses to infectious agents and tumors

THE IMPACT OF INSTITUTIONAL HOLDING AND BANK LEVERAGE ON STOCK RETURN VOLATILITY

This paper analyses the relation between stock return volatility and institutional holdings and company\u27s leverage in the US banking industry in the period 1980 to 2013.  We find that institutional holdings and bank leverage have a negative relationship with stock return volatility.  Our results are not driven only by cross-sectional variation as we find that bank characteristics such as size, age and ROE are significant ina  fixed-effect specification. &nbsp

CpG and Interleukin-15 Synergize to Enhance IFN- Production by Activated CD8+ T Cells

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8+ T cells. Paradoxically, we previously reported that IL-15 could enhance CD8+ T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8+ T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN- by CD8+ T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN- production. The effect of CpG and IL-15 was also evident with CD8+ T cells recovered from mice infected with the parasite Trypanosoma cruzi (T. cruzi) and restimulated with antigen. The observed synergy between CpG and IL-15 occurred in an IL-12-dependent manner, and this effect could even be demonstrated in cocultures of activated CD8+ T cells and CD4+CD25+ regulatory T cells. Although IFN- was not essential for CpG-induced IL-12, the ability of CpG and IL-15 to act on CD8+ T cells required expression of the IFN--inducible transcription factor T-bet. These data have important implications for development of vaccines and design of therapies to boost CD8+ T-cell responses to infectious agents and tumors

Who Dominate TDI? A Big Data Evidence from DMO and UGC Short Videos

Abstract In the formation of tourism destination image (TDI), understanding and being able to measure, analyze, compare, and contrast the images projected by user-generated content(UGC) and destination marketing organizations(DMOs) is crucial in tourism management and destination marketing. This study aims to propose a specific way to measure and compare UGC and DMO projected images within 249 short videos. Using machine learning algorithms, four indicators (the number of short videos, the number of likes, comments and shares) were identified to measure the influences of DMO and UGC short videos, and extracted 7 dimensions representing the destination image extracted through video content analysis, namely, nature environment, infrastructure, culture and art, people, food and beverage, specific activities, and transportation. The data analysis further revealed statistical differences in several dimensions of these images at different destination’s life cycle. Theoretical and practical implications were also discussed. Keywords tourism destination image, destination’s life cycle, short video, video captaining，brand hijac

What Motivates People to Share Online Rumors? Deconstructing the Ambiguity of Rumors from a Perspective of Digital Storytelling

With the proliferation of social networks and the development of digital technology, the content structure and propagation mode of rumors have become more complicated with ambiguity, which has greatly influenced people’s behaviors when facing digitalized rumors. Based on the digital storytelling theory, this study takes an early initiative by deconstructing and identifying the basic components of online rumors and revealing the conditions under which people’s sharing behaviors in a social environment. A data set of health-related rumors related to Covid-19 was used to test the research hypotheses. The results indicated that causality explicitness, element integrality and source explicitness have different influences on rumor sharing behavior. And rumor vividness plays a negative moderating effect during the sharing process. This research offers insight to viewers and website authorities on ways to monitor and debunk online rumors

IL-15/IL-15Rα Heterodimeric Complex as Cancer Immunotherapy In Murine Breast Cancer Models

Interleukin 15 (IL-15) has been evaluated as a potential treatment for solid tumors in clinical trials, but the effectiveness of systemic IL-15 administration as a monotherapy has not been realized. IL-15 receptor alpha (IL-15Rα) can stabilize IL-15 and enhance its bioactivity. The goal of this study was to examine the activity of IL-15/IL-15Rα complex (IL-15cx) to CD8(+) T cells and evaluate its potential efficacy in murine breast cancer models. The antitumor efficacy was studied in mouse mammary carcinoma models (Her2/neu transgenic and 4T1-luc mammary cancers) treated with systemic recombinant protein with/without the depletion of myeloid-derived suppressor cells or intra-tumoral gene electrotransfer (GET). IL-15cx shows superior in vivo bioactivity to expand CD8 T cells in comparison to an equimolar single chain IL-15. T-bet is partially involved in CD8 T cell expansion ex vivo and in vivo due to IL-15 or IL-15cx. Intraperitoneal administration of IL-15cx results in a moderate inhibition of breast cancer growth that is associated with an increase in the frequency of cytotoxic CD8 T cells and the improvement of their function. The depletion of myeloid-derived suppressor cells (MDSCs) has no impact on mouse breast cancer growth. IL-15cx treatment diminishes MDSCs in murine tumors. However, it also antagonizes the effects of anti-Gr-1 depleting antibodies. Intratumoral GET with plasmid IL-15/IL-15Rα leads to a long-term survival benefit in 4T1 mammary carcinoma model. An early increase of local cytotoxic cells correlates with GET treatment and an increase of long-term memory T cells results from animals with complete tumor regression. Systemic and local administration of IL-15cx shows two distinct therapeutic responses, a moderate tumor growth inhibition or heterogeneous tumor regressions with survival improvement. Further studies are warranted to improve the efficacy of IL-15cx as an immunotherapy for breast cancer

Research on Online Reviews Reliability

This study examines the factors that have an impact on online reviews reliability. A theoretical framework was built and empirically tested with a sample of 200 interviewees. Results of structural equation model show that the online reviews quality and perceived risk have positive impact on online review reliability. Accordingly, online review value and number have positive impact on online review quality, customer involvement and reviewer acception have positive impact on perceived risk. The results of this study also suggest that the character of online review and reviewer indirectly impact review reliability by impacting intermediate variables

The Role of Reactive Oxygen Species in the Immunity Induced by Nano-Pulse Stimulation

Reactive oxygen species (ROS) are byproducts of tumor cells treated with Nano-Pulse Stimulation (NPS). Recently, ROS have been suggested as a contributing factor in immunogenic cell death and T cell-mediated immunity. This research further investigated the role of NPS induced ROS in antitumor immunity. ROS production in 4T1-luc breast cancer cells was characterized using three detection reagents, namely, Amplex Red, MitoSox Red, and Dihydroethidium. The efficiency of ROS quenching was evaluated in the presence or absence of ROS scavengers and/or antioxidants. The immunogenicity of NPS treated tumor cells was assessed by ex vivo dendritic cell activation, in vivo vaccination assay and in situ vaccination with NPS tumor ablation. We found that NPS treatment enhanced the immunogenicity of 4T1-luc mouse mammary tumor, resulted in a potent in situ vaccination protection and induced long-term T cell immunity. ROS production derived from NPS treated breast cancer cells was an electric pulse dose-dependent phenomenon. Noticeably, the dynamic pattern of hydrogen peroxide production was different from that of superoxide production. Interestingly, regardless of NPS treatment, different ROS scavengers could either block or promote ROS production and stimulate or inhibit tumor cell growth. The activation of dendritic cells was not influenced by blocking ROS generation. The results from in vivo vaccination with NPS treated cancer cells suggests that ROS generation was not a prerequisite for immune protection

Electro-Gene Transfer to Skin Using a Noninvasive Multielectrode Array

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene-expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest that EP with MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications