Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases

This study aimed to identify what information triggered social media users’ responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education / information; alternative health information / Traditional Chinese Medicine; commercial advertisement / entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed.     

The Effect of Pollination on Cd Phytoextraction From Soil by Maize (Zea mays L.)

A pot experiment was conducted to investigate the effects of pollination on cadmium (Cd) phytoextraction from soil by mature maize plants. The results showed that the unpollinated maize plants accumulated 50% more Cd than that of the pollinated plants, even though the dry weight of the former plants was 15% less than that of the latter plants. The Cd accumulation in root and leaf of the unpollinated maize plant was 0.47 and 0.89 times higher than that of the pollinated plant, respectively. The Cd concentration in the cob was significantly decreased because of pollination. Preventing pollination is a promising approach for enhancing the effectiveness of phytoextraction in Cd-contaminated soils by maize. This study suggested that in low Cd-contaminated soil pollination should be encouraged because accumulation of Cd in maize grains is very little and maize seeds can bring farmers economic benefits, while in high Cd-contaminated soil, inhibition of pollination can be applied to enhance phytoextraction of Cd from soil by maize plant.     

Proteomics of Skin Proteins in Psoriasis: From Discovery and Verification in a Mouse Model to Confirmation in Humans

Herein, we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n = 3) were compared with littermate controls (n = 3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average p = 0.0082; cystatin A, human ortholog); slc25a5 (average fold change of 46.2 and an average p = 0.0318); serpinb3b (average fold change of 35.6 and an average p = 0.0345; serpinB1, human ortholog); and kallikrein related peptidase 6 (average fold change of 4.7 and an average p = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, p < 0.0001), KLK6 (9-fold, p = 0.002), stefin A1 (7.3-fold; p < 0.001), and slc25A5 (1.5-fold; p = 0.05) using qRT-PCR on a second cohort of animals (n = 8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; p < 0.05), 29,000-fold (stefinA1; p < 0.01), 322-fold (KLK6; p < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes versus healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3-fold), KLK6 (5.8-fold), and serpinB1 (76-fold; all p < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover, slc25a5, cystatin A, KLK6, and serpinB1 protein were all increased in lesional psoriasis skin compared with normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.One in three individuals in the United States is afflicted with a skin disease, with ∼2–3% of the American population suffering from psoriasis (1–3) a chronic, immune-mediated inflammatory skin disease characterized by well-demarcated areas of “involved” red, raised, and scaly skin adjacent to areas of “uninvolved” normal appearing skin. The underlying cause of psoriasis remains unknown and the specific signals that trigger disease onset have yet to be identified; however, several lines of evidence suggest the involvement of antigen-specific T cells, although the antigens involved remain elusive (4). A combination of human and animal studies have led to the understanding that in patients with a genetically susceptible background, some initiating stimulus, often a stressful event, an injury to the skin, or an infection, leads to a coordinated series of signaling events involving cytokines, resident skin cells, and skin-infiltrating immune cells, that once started, initiates a vicious pro-inflammatory hyperproliferative cycle. Once initiated, this cycle perpetuates sustained inflammatory responses. Intervention at several points in this cycle results in clinical resolution, however, durable remission and/or permanent clearance has not yet been achieved.Current psoriasis therapies are directed toward symptomatic relief and none of them represent a cure for this chronic illness. Current treatments include topical therapies, phototherapy, and systemic administration of immune-suppressants, anti-metabolites, oral retinoids, and biologics targeting immune cells or inflammatory cytokines (5, 6). Many of the most effective therapeutics however, also have the greatest adverse reactions; moreover, psoriasis can become resistant to specific therapies over time. Therefore, an ongoing need for discovery of new biological pathways and targets for psoriasis is obvious.We studied a mouse model of psoriasis using an unbiased proteomics screening approach to identify dysregulated peptides of interest in psoriasiform-inflamed mouse skin and ultimately compared these findings to psoriasis patient skin. We used in-gel label-free protein expression analysis to observe quantitative changes in protein expression. The peptides that were determined to be top-scoring from a statistical perspective and of biological interest were subjected to further analysis and confirmation using a targeted mass spectrometry approach along with qRT-PCR to assess gene expression in a distinct set of animal samples. Further validation of the translational importance of these novel proteins was then conducted in primary keratinocytes expanded from psoriasis skin as well as human skin taken directly from psoriasis patient lesional and nonlesional areas. The results of these experiments confirm the ability of a discovery in-gel label-free expression model to identify proteins that are in the moderate to high abundance range that are significantly different in their distribution between control and genetically modified psoriasiform mouse skin and demonstrate the usefulness of mouse models and proteomic approaches for identifying novel proteins that are differentially regulated in human psoriasis, providing future biomarkers and targets for development of translational approaches to disease improvement.     

Recombinant Murine Gamma Herpesvirus 68 Carrying KSHV G Protein-Coupled Receptor Induces Angiogenic Lesions in Mice

Human gamma herpesviruses, including Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are capable of inducing tumors, particularly in in immune-compromised individuals. Due to the stringent host tropism, rodents are resistant to infection by human gamma herpesviruses, creating a significant barrier for the in vivo study of viral genes that contribute to tumorigenesis. The closely-related murine gamma herpesvirus 68 (γHV68) efficiently infects laboratory mouse strains and establishes robust persistent infection without causing apparent disease. Here, we report that a recombinant γHV68 carrying the KSHV G protein-coupled receptor (kGPCR) in place of its murine counterpart induces angiogenic tumors in infected mice. Although viral GPCRs are conserved in all gamma herpesviruses, kGPCR potently activated downstream signaling and induced tumor formation in nude mouse, whereas γHV68 GPCR failed to do so. Recombinant γHV68 carrying kGPCR demonstrated more robust lytic replication ex vivo than wild-type γHV68, although both viruses underwent similar acute and latent infection in vivo. Infection of immunosuppressed mice with γHV68 carrying kGPCR, but not wild-type γHV68, induced tumors in mice that exhibited angiogenic and inflammatory features shared with human Kaposi’s sarcoma. Immunohistochemistry staining identified abundant latently-infected cells and a small number of cells supporting lytic replication in tumor tissue. Thus, mouse infection with a recombinant γHV68 carrying kGPCR provides a useful small animal model for tumorigenesis induced by a human gamma herpesvirus gene in the setting of a natural course of infection.     

TopBP1 Governs Hematopoietic Stem/Progenitor Cells Survival in Zebrafish Definitive Hematopoiesis

In vertebrate definitive hematopoiesis, nascent hematopoietic stem/progenitor cells (HSPCs) migrate to and reside in proliferative hematopoietic microenvironment for transitory expansion. In this process, well-established DNA damage response pathways are vital to resolve the replication stress, which is deleterious for genome stability and cell survival. However, the detailed mechanism on the response and repair of the replication stress-induced DNA damage during hematopoietic progenitor expansion remains elusive. Here we report that a novel zebrafish mutant^cas003 with nonsense mutation in topbp1 gene encoding topoisomerase II β binding protein 1 (TopBP1) exhibits severe definitive hematopoiesis failure. Homozygous topbp1^cas003 mutants manifest reduced number of HSPCs during definitive hematopoietic cell expansion, without affecting the formation and migration of HSPCs. Moreover, HSPCs in the caudal hematopoietic tissue (an equivalent of the fetal liver in mammals) in topbp1^cas003 mutant embryos are more sensitive to hydroxyurea (HU) treatment. Mechanistically, subcellular mislocalization of TopBP1^cas003 protein results in ATR/Chk1 activation failure and DNA damage accumulation in HSPCs, and eventually induces the p53-dependent apoptosis of HSPCs. Collectively, this study demonstrates a novel and vital role of TopBP1 in the maintenance of HSPCs genome integrity and survival during hematopoietic progenitor expansion.     

Recombination between Homologous Chromosomes Induced by Unrepaired UV-Generated DNA Damage Requires Mus81p and Is Suppressed by Mms2p

DNA lesions caused by UV radiation are highly recombinogenic. In wild-type cells, the recombinogenic effect of UV partially reflects the processing of UV-induced pyrimidine dimers into DNA gaps or breaks by the enzymes of the nucleotide excision repair (NER) pathway. In this study, we show that unprocessed pyrimidine dimers also potently induce recombination between homologs. In NER-deficient rad14 diploid strains, we demonstrate that unexcised pyrimidine dimers stimulate crossovers, noncrossovers, and break-induced replication events. The same dose of UV is about six-fold more recombinogenic in a repair-deficient strain than in a repair-proficient strain. We also examined the roles of several genes involved in the processing of UV-induced damage in NER-deficient cells. We found that the resolvase Mus81p is required for most of the UV-induced inter-homolog recombination events. This requirement likely reflects the Mus81p-associated cleavage of dimer-blocked replication forks. The error-free post-replication repair pathway mediated by Mms2p suppresses dimer-induced recombination between homologs, possibly by channeling replication-blocking lesions into recombination between sister chromatids.     

Aurantiamide acetate suppresses the growth of malignant gliomas in vitro and in vivo by inhibiting autophagic flux

We aim to investigate the effect of aurantiamide acetate isolated from the aerial parts of Clematis terniflora DC against gliomas. Human malignant glioma U87 and U251 cells were incubated with different concentrations (0–100 μM) of aurantiamide acetate. Aurantiamide acetate greatly decreased the cell viability in a dose‐ and time‐dependent manner. It induced moderate mitochondrial fragmentation and the loss of mitochondrial membrane potential. No significant difference was found in the alternation of other intracellular organelles, although F‐actin structure was slightly disturbed. Apparent ultrastructure alternation with increased autophagosome and autolysosome accumulation was observed in aurantiamide acetate‐treated cells. The expression of LC3‐II was greatly up‐regulated in cells exposed to aurantiamide acetate (P < 0.05 compared with control). The cytoplasmic accumulation of autophagosomes and autolysosomes induced by aurantiamide acetate treatment was confirmed by fluorescent reporter protein labelling. Administration of chloroquine (CQ), which inhibits the fusion step of autophagosomes, further increased the accumulation of autophagosomes in the cytoplasm of U87 cells. Autophagy inhibition by 3‐methyladenine, Bafilomycin A1 or CQ had no influence on aurantiamide acetate‐induced cytotoxicity, whereas autophagy stimulator rapamycin significantly suppressed aurantiamide acetate‐induced cell death. The anti‐tumour effects of aurantiamide acetate were further evaluated in tumour‐bearing nude mice. Intratumoural injection of aurantiamide acetate obviously suppressed tumour growth, and increased number of autophagic vacuoles was observed in tumour tissues of animals receiving aurantiamide acetate. Our findings suggest that aurantiamide acetate may suppress the growth of malignant gliomas by blocking autophagic flux.