Independent modulation of individual genomic component transcription and a cis-acting element related to high transcriptional activity in a multipartite DNA virus

Background: The genome of Banana bunchy top virus (BBTV) consists of at least six circular, single-stranded DNA components of 1kb in length. Some BBTV isolates may also carry satellite DNA molecules that are not essential for BBTV infection. The relation between multipartite DNA virus replication and their transcriptional levels and the underlying mechanism remain unclear. Results: To understand the coordinated replication and transcription of the multiple genomic components, the absolute amounts of each BBTV DNA component were measured by real-time PCR (qPCR), and their transcriptional levels were determined by RNAseq and reverse transcription-qPCR (qRT-PCR). Significant differences were found in the absolute amounts of individual BBTV genomic components. Transcriptional levels of each BBTV genomic component obtained from the RNAseq data matched closely to those obtained from qRT-PCR, but did not correspond to the absolute amount of each DNA component. The ratio of transcript over DNA copies ranged from 46.21 to 1059.44%, which was possibly regulated by the promoter region in the intergenic region of each component. To further determine this speculation, the promoter region of the DNA-S, -M or -N was constructed to the upstream of green fluorescent protein (GFP) gene for transient expression by agrobacterium-mediated transformation method. The qRT-PCR showed the highest transcriptional activity was promoted by DNA-N promoter, about 386.58% activity comparing with CaMV 35S promoter. Confocal microscopy observation showed that the intensity of green fluorescence was corresponding to that of qRT-PCR. Conclusions: Our data clearly showed that BBTV was able to control the transcriptional level of each DNA component independently by through the promoter sequences in the intergenic region. Moreover, a cis-acting element from DNA-N component had a high transcriptional activity.National Natural Science Foundation of China [31401709]; Hainan Provincial Natural Science Foundation [20153130]; Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences [19CXTD-33]; Young Elite Scientists Sponsorship Program, CSTC [CSTC-QN201704]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Diffusion entropy analysis on the scaling behavior of financial markets

In this paper the diffusion entropy technique is applied to investigate the scaling behavior of financial markets. The scaling behaviors of four representative stock markets, Dow Jones Industrial Average, Standard&Poor 500, Heng Seng Index, and Shang Hai Stock Synthetic Index, are almost the same; with the scale-invariance exponents all in the interval $[0.92, 0.95]$. These results provide a strong evidence of the existence of long-rang correlation in financial time series, thus several variance-based methods are restricted for detecting the scale-invariance properties of financial markets. In addition, a parsimonious percolation model for stock markets is proposed, of which the scaling behavior agrees with the real-life markets well.Comment: 5 pages, 3 figure

Testosterone-mediated endocrine function and TH1/TH2 cytokine balance after prenatal exposure to perfluorooctane sulfonate: by sex status

Little information exists about the evaluation of potential developmental immunotoxicity induced by perfluorooctane sulfonate (PFOS), a synthetic persistent and increasingly ubiquitous environmental contaminant. To assess potential sex-specific impacts of PFOS on immunological health in the offspring, using male and female C57BL/6 mice, pups were evaluated for developmental immunotoxic effects after maternal oral exposure to PFOS (0.1, 1.0 and 5.0 mg PFOS/kg/day) during Gestational Days 1—17. Spontaneous TH1/TH2-type cytokines, serum levels of testosterone and estradiol were evaluated in F1 pups at four and eight weeks of age. The study showed that male pups were more sensitive to the effects of PFOS than female pups. At eight weeks of age, an imbalance in TH1/TH2-type cytokines with excess TH2 cytokines (IL-4) was found only in male pups. As for hormone levels, PFOS treatment in utero significantly decreased serum testosterone levels and increased estradiol levels only in male pups, and a significant interaction between sex and PFOS was observed for serum testosterone at both four weeks of age (pinteraction = 0.0049) and eight weeks of age (pinteraction = 0.0227) and for estradiol alternation at four weeks of age (pinteraction = 0.0351). In conclusion, testosterone-mediated endocrine function may be partially involved in the TH1/TH2 imbalance induced by PFOS, and these deficits are detectable among both young and adult mice and may affect males more than females

Smoking Exposure and Survival of Patients with Esophagus Cancer: A Systematic Review and Meta-Analysis

Smoking is a well-known major risk factor in development of esophageal cancer, but few studies have reported the association between smoking status and prognosis of these patients. We conduct the present study to summarize current evidence. A computerized search of the PubMed and EMBASE was performed up to April 30, 2015. Eight studies, containing 4,286 patients, were analyzed. In the grouping analysis, among esophageal squamous-cell carcinoma patients, current and former smokers, compared to those who have never smoked, seemed to have a poorer prognosis (HR = 1.41, 95% CI 1.22–1.64, and HR = 1.35, 95% CI 0.92–1.97, resp.). In the subgroup analysis, adverse effects on current smoker compared with never smoker were also observed in China and the other countries (HR = 1.5, 95% CI 1.18–1.92, and HR = 1.36, 95% CI 1.12–1.65, resp.). In the group that ever smoked, we could not get a similar result. No significantly increased risk was found in esophageal adenocarcinoma patients compared to the squamous-cell histology ones. In the smoking intensity analysis, heavy smoking was associated with poor survival in esophageal squamous-cell carcinoma. Our pooled results supported the existence of harmful effects of smoking on survival after esophagus cancer diagnosis

A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts

Terminally differentiated cells can be generated by lineage reprogramming, which is, however, hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming.</p

NEDD9 Facilitates Hypoxia-Induced Gastric Cancer Cell Migration via MICAL1 Related Rac1 Activation

Aims and Hypothesis: NEDD9 is highly expressed in gastric cancer and has a significant involvement in its pathogenesis. However, the mechanism behind hypoxia-promoted cancer cell migration and its regulation because of NEDD9 is still unknown. The aim of this study is to investigate the involvement of NEDD9 in gastric cancer cell migration under hypoxia and explore the underlying potential molecular mechanisms.MethodsCell motility was measured by wound healing and transwell assay. NEDD9 and MICAL1 expressions were examined by western blot analysis. Interaction between NEDD9 and MICAL1 was assessed by immunohistochemistry and co-immunoprecipitation assay, respectively. Cells were transfected with plasmids or siRNA to upregulate or downregulate the expression of NEDD9 and MICAL1. Rac1, Cdc42, and RhoA activation was assessed by pulldown assay.ResultsThe mRNA and protein level of NEDD9 increased as a result of hypoxia in gastric cancer cell lines BGC-823 and SGC-7901 while decreased levels of NEDD9 caused reduced cell migratory potential in response to hypoxia. Hypoxia also caused the enhancement of MICAL1 expression. Furthermore, it was revealed that there is a positive correlation between NEDD9 and MICAL1 protein while hypoxia played role in increasing their interaction. Under hypoxic conditions, silencing of NEDD9 caused reduction in the stability of MICAL1 protein, while depletion of MICAL1 also inhibited the migration of NEDD9-overexpressing gastric cancer cells. In addition, silencing of NEDD9 or MICAL1 expression reversed the increased GTP forms of Rac1 and Cdc42 in hypoxic cells. However, only the upregulation of Rac1-GTP level was observed in gastric cancer cells that were already overexpressed by MICAL1.ConclusionIn all, it is concluded that MICAL1 is regulated by NEDD9 that facilitates hypoxia-induced gastric cancer cell migration via Rac1-dependent manner