Patrilineal Background of Esophageal Cancer and Gastric Cardia Cancer Patients in a Chaoshan High-Risk Area in China

The Taihang Mountain range of north-central China, the Southern region area of Fujian province, and the Chaoshan plain of Guangdong province are 3 major regions in China well known for their high incidence of esophageal cancer (EC). These areas also exhibit high incidences of gastric cardia cancer (GCC). The ancestors of the Chaoshanese, now the major inhabitants in the Chaoshan plain, were from north-central China. We hypothesized that EC and GCC patients in Chaoshan areas share a common ancestry with Taihang Mountain patients. We analyzed 16 East Asian-specific Y-chromosome biallelic markers (single nucleotide polymorphisms; Y-SNPs) and 6 Y-chromosome short tandem repeat (Y-STR) loci in 72 EC and 48 GCC patients from Chaoshan and 49 EC and 63 GCC patients from the Taihang Mountain range. We also compared data for 32 Chaoshan Hakka people and 24 members of the aboriginal She minority who live near the Chaoshan area. Analysis was by frequency distribution and principal component, correlation and hierarchical cluster analysis of Y-SNP. Chaoshan patients were closely related to Taihang Mountain patients, even though they are geographically distant. Y-STR analysis revealed that the 4 patient groups were more closely related with each other than with other groups. Network analysis of the haplogroup O3a3c1-M117 showed a high degree of patient-specific substructure. We suggest that EC and GCC patients from these 2 areas share a similar patrilineal genetic background, which may play an important role in the genetic factor of EC and GCC in these populations.     

Elevation,Temperature, and Aquatic Connectivity All Influence the Infection Dynamics of the Amphibian Chytrid Fungus in Adult Frogs

Infectious diseases can cause population declines and even extinctions. The amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), has caused population declines and extinctions in amphibians on most continents. In the tropics, research on the dynamics of this disease has focused on amphibian populations in mountainous areas. In most of these areas, high and low elevation sites are connected by an assemblage of streams that may transport the infectious stage of the pathogen from high to low elevations, and, also, this pathogen, which grows well at cool temperatures, may persist better in cooler water flowing from high elevations. Thus, the dynamics of disease at low elevation sites without aquatic connections to higher elevation sites, i.e., non-contiguous low elevation sites, may differ from dynamics at contiguous low elevation sites. We sampled adult common mistfrogs (Litoria rheocola) at six sites of three types: two at high (> 400m) elevations, two at low elevations contiguous with high elevation streams, and two at low elevations non-contiguous with any high elevation site. Adults were swabbed for Bd diagnosis from June 2010 to June 2011 in each season, over a total of five sampling periods. The prevalence of Bd fluctuated seasonally and was highest in winter across all site types. Site type significantly affected seasonal patterns of prevalence of Bd. Prevalence remained well above zero throughout the year at the high elevation sites. Prevalence declined to lower levels in contiguous low sites, and reached near-zero at non-contiguous low sites. Patterns of air temperature fluctuation were very similar at both the low elevation site types, suggesting that differences in water connectivity to high sites may have affected the seasonal dynamics of Bd prevalence between contiguous and non-contiguous low elevation site types. Our results also suggest that reservoir hosts may be important in the persistence of disease at low elevations.     

Aliskiren Attenuates Steatohepatitis and Increases Turnover of Hepatic Fat in Mice Fed with a Methionine and Choline Deficient Diet

Background & Aims

Activation of the renin-angiotensin-system is known to play a role in nonalcoholic steatohepatitis. Renin knockout mice manifest decreased hepatic steatosis. Aliskiren is the first direct renin inhibitor to be approved for clinical use. Our study aims to evaluate the possible therapeutic effects and mechanism of the chronic administration of aliskiren in a dietary steatohepatitis murine model.

Methods

Male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet to induce steatohepatitis. After 8 weeks of feeding, the injured mice were randomly assigned to receive aliskiren (50 mg_·kg^-1 per day) or vehicle administration for 4 weeks. Normal controls were also administered aliskiren (50 mg_·kg^-1 per day) or a vehicle for 4 weeks.

Results

In the MCD mice, aliskiren attenuated hepatic steatosis, inflammation and fibrosis. Aliskiren did not change expression of lipogenic genes but increase turnover of hepatic fat by up-regulating peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1a, cytochrome P450-4A14 and phosphorylated AMP-activated protein kinase. Furthermore, aliskiren decreased the hepatic expression of angiotensin II and nuclear factor κB. The levels of oxidative stress, hepatocyte apoptosis, activation of Kupffer cells and hepatic stellate cells, and pro-fibrotic markers were also reduced in the livers of the MCD mice receiving aliskiren.

Conclusions

Aliskiren attenuates steatohepatitis and fibrosis in mice fed with a MCD diet. Thus, the noted therapeutic effects might come from not only the reduction of angiotensin II but also the up-regulation of fatty acid oxidation-related genes.     

BCRP/ABCG2 Inhibition Sensitizes Hepatocellular Carcinoma Cells to Sorafenib

The multikinase inhibitor, sorafenib (Nexavar®, BAY43-9006), which inhibits both the Raf/MEK/ERK pathway and several receptor tyrosine kinases (RTKs), has shown significantly therapeutic benefits in advanced hepatocellular carcinoma (HCC). However, not all HCC patients respond to sorafenib well and new therapeutic strategies to optimize the efficacy of sorafenib are urgently required. Overexpression of breast cancer resistance protein (BCRP/ABCG2) mediates the drug-efflux of several tyrosine kinase inhibitors (TKIs) to attenuate their efficacy. This study aimed to investigate the role of BCRP/ABCG2 in the sensitivity of HCC to sorafenib. Our data showed that BCRP/ABCG2 mediated the efflux of sorafenib. Co-treatment with a BCRP/ABCG2 inhibitor greatly augmented the cytotoxicity of sorafenib in HCC cells. Similar results were also achieved by the competitive inhibitor of BCRP/ABCG2, gefitinib, in combination with sorafenib. These results suggest not only that BCRP/ABCG2 is a potential predictor for the sorafenib sensitivity in HCC, but also that blockage of BCRP/ABCG2 may be a potential strategy to increase the response of HCC cells to sorafenib.     

抗花叶病烟草种质资源的鉴定与筛选

本研究以不同来源、不同类型的46个烟草品种为试验材料,进行抗烟草普通花叶病（TMV）特性的田间鉴定和分子鉴定,为筛选抗病烟草种质奠定基础。结果表明,22个品种的烟草抗TMV特性田间鉴定结果与前人鉴定结果基本相同,从24个前人未鉴定的烟草品种中初步筛选出14个中抗品种,8个中感品种和2个感病品种;通过抗TMV基因（CN）的特异引物进行扩增,36个烟草品种的基因组DNA具有特异性片段;通过分子鉴定和田间鉴定的结果比较,62.9%的具有CN或其同源基因的烟草品种田间鉴定表现为中抗或高抗,83.3%的具有CN或其同源基因的选育烟草品种田间鉴定表现为中抗或高抗;结合两种方法,初步确定了3个中感品种和11个中抗品种。     

Distribution of 2-kb miniplasmid pBMB2062 from Bacillus thuringiensis kurstaki YBT-1520 strain in Bacillus species

A multi-copy and small plasmid pBMB2062 from Bacillus thuringiensis kurstaki YBT-1520 strain was cloned and characterized and its distribution was analyzed using dot-blot analysis with the ORF1 fragment as a probe. Bacillus species of 84 serotypes were evaluated. The pBMB2062 plasmid was found to be present in commercial B. thuringiensis kurstaki (H3abc) and aizawai (H7) insecticides of various serotypes, and one Bacillus cereus UW85 strain (produced Zwittermicin fungicide and Cry toxin synergist). The sequences of 7 pBMB2062-like plasmids from randomly selected Bacillus species (positive signal in the dot-blot analysis) were highly conserved. Two open reading frames (ORFs), ORF1 and ORF2, were present in this plasmid. ORF1 was found to be necessary for plasmid replication, whereas ORF2 did not play a role in replication or stability. Based on its sequence homology, ORF2 was a putative solitary antitoxin. Furthermore, the copy number of the replicon of pBMB2062 was higher than those of ori1030 and ori44 based on the thermogenic data, and ori2062 could drive the stable replication of a recombinant plasmid (11 kb total size) in B. thuringiensis.     

Using fluorochemical as oxygen carrier to enhance the growth of marine microalga Nannochloropsis oculata

The commercial value of marine Nannochloropsis oculata has been recognized due to its high content of eicosapentaenoic acid (>50 % w/w). To make it as a profitable bioresource, one of the most desirable goals is to develop a quality-controlled, cost-effective, and large-scale photobioreactor for N. oculata growth. Generally, closed culture system can offer many advantages over open system such as small space requirement, controllable process and low risk of contamination. However, oxygen accumulation is often a detrimental factor for enclosed microalgal culture that has seriously hampered the development of microalga-related industries. In this study, we proposed to use fluorochemical as oxygen carrier to overcome the challenge where four liquid fluorochemicals namely perfluorooctyl bromide, perfluorodecalin, methoxynonafluorobutane, and ethoxynonafluorobutane were investigated separately. Our results showed that the microalgal proliferation with different fluorinated liquids was similar and comparable to the culture without a fluorochemical. When cultured in the photobioreactor with 60 % oxygen atmosphere, the N. oculata can grow up in all the fluorochemical photobioreactors, but completely inhibited in the chamber without a fluorochemical. Moreover, the perfluorooctyl bromide system exhibited the most robust efficacy of oxygen removal in the culture media (perfluorooctyl bromide > perfluorodecalin > methoxynonafluorobutane > ethoxynonafluorobutane), and yielded a >3-fold increase of biomass production after 5 days. In summary, the developed fluorochemical photobioreactors offer a feasible means for N. oculata growth in closed and large-scale setting without effect of oxygen inhibition.     

Synthesis of High Aspect Ratio BaTiO3 Nanowires for High Energy Density Nanocomposite Capacitors

High energy density capacitors are critically important in advanced electronic devices and power systems since they can reduce the weight, size and cost required to meet a desired application. Nanocomposites hold strong potential for increasing the performance of high power energy sources; however, the energy density of most nanocomposites is still low compared to commercial capacitors and neat polymers. Here, we develop a new synthesis method for the growth of high aspect ratio barium titanate nanowires (BaTiO₃) nanowires (NWs) with high yield. High energy density nanocomposite capacitors are fabricated using surface‐functionalized high aspect ratio BaTiO₃ NWs in a poly(vinylidene fluoride‐trifluoroethylene‐chlorofluoroethylene) (P(VDF‐TrFE‐CFE)) matrix. At a 17.5% volume fraction, the nanocomposites show more than 45.3% increase in energy density above that of the pure P(VDF‐TrFE‐CFE) polymer (10.48 J/cc compared to 7.21 J/cc) at electric field 300 MV/m. This value is significant and exceeds those reported for the conventional polymer‐ceramic nanocomposites; it is also more than seven times larger than high performance commercial polypropylene capacitor (1.2 J/cc at 640 MV/m). In addition, our nanocomposite capacitor has a maximum power density as high as 1.2 MW/cc occurring only 1.52 μs after the start of discharge. The findings of this research could lead to enhanced interest in nanowires based nanocomposites due to their potential for achieving next generation energy storage devices.     

Proteomic analysis for Type I interferon antagonism of Japanese encephalitis virus NS5 protein

Japanese encephalitis virus (JEV) nonstructural protein 5 (NS5) exhibits a Type I interferon (IFN) antagonistic function. This study characterizes Type I IFN antagonism mechanism of NS5 protein, using proteomic approach. In human neuroblastoma cells, NS5 expression would suppress IFNβ‐induced responses, for example, expression of IFN‐stimulated genes PKR and OAS as well as STAT1 nuclear translocation and phosphorylation. Proteomic analysis showed JEV NS5 downregulating calreticulin, while upregulating cyclophilin A, HSP 60 and stress‐induced‐phosphoprotein 1. Gene silence of calreticulin raised intracellular Ca²⁺ levels while inhibiting nuclear translocalization of STAT1 and NFAT‐1 in response to IFNβ, thus, indicating calreticulin downregulation linked with Type I IFN antagonism of JEV NS5 via activation of Ca²⁺/calicineurin. Calcineurin inhibitor cyclosporin A attenuated NS5‐mediated inhibition of IFNβ‐induced responses, for example, IFN‐sensitive response element driven luciferase, STAT1‐dependent PKR mRNA expression, as well as phosphorylation and nuclear translocation of STAT1. Transfection with calcineurin (vs. control) siRNA enhanced nuclear translocalization of STAT1 and upregulated PKR expression in NS5‐expressing cells in response to IFNβ. Results prove Ca²⁺, calreticulin, and calcineurin involvement in STAT1‐mediated signaling as well as a key role of JEV NS5 in Type I IFN antagonism. This study offers insights into the molecular mechanism of Type I interferon antagonism by JEV NS5.