Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways

Focal adhesion kinase family interacting protein of 200 kD (FIP200) has been shown to regulate diverse cellular functions such as cell size, proliferation, and migration in vitro. However, the function of FIP200 in vivo has not been investigated. We show that targeted deletion of FIP200 in the mouse led to embryonic death at mid/late gestation associated with heart failure and liver degeneration. We found that FIP200 knockout (KO) embryos show reduced S6 kinase activation and cell size as a result of increased tuberous sclerosis complex function. Furthermore, FIP200 KO embryos exhibited significant apoptosis in heart and liver. Consistent with this, FIP200 KO mouse embryo fibroblasts and liver cells showed increased apoptosis and reduced c-Jun N-terminal kinase phosphorylation in response to tumor necrosis factor (TNF) α stimulation, which might be mediated by FIP200 interaction with apoptosis signal–regulating kinase 1 (ASK1) and TNF receptor–associated factor 2 (TRAF2), regulation of TRAF2–ASK1 interaction, and ASK1 phosphorylation. Together, our results reveal that FIP200 functions as a regulatory node to couple two important signaling pathways to regulate cell growth and survival during mouse embryogenesis

Accumulation of the Mutations in Basal Core Promoter of Hepatitis B Virus Subgenotype C1 Increase the Risk of Hepatocellular Carcinoma in Southern China

Background: Hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC). In addition, HBV subgenotype C1 is the major subgenotype in Southern China. The aim of this study was to investigate whether there were the specific mutation patterns in HBV/C1 associated with Southern Chinese patients with HCC. Methods: Mutations in HBV basal core promoter (BCP) and their association with HCC were assessed in a matched cross-sectional control study of 102 HCC and 105 chronic hepatitis (CH) patients (from Guangdong, China) infected with HBV/C1. Functional analysis of HBx mutants was performed by the colony formation assay and the luciferase assays. Results: T1762/A1764 double mutations was frequently found in patients infected with HBV/C1, regardless of clinical status (64.7% in HCC and 51.4% in CH, P0.05). Unexpectedly, the adjacent V1753 or A1768 mutation significantly increased the risk of HCC (P0.05). Moreover, the prevalence of triple or quadruple mutations in BCP was significantly higher in patients with HCC than those with CH, particularly for HBeAg-positive-carriers (P0.05). Functional analysis revealed that T1762/A1764 mutation alone did not alter the transcriptional activity and the inhibitory effects on cell proliferation of HBx, but triple or quadruple mutations largely abrogated this effect.Conclusions: Accumulation of mutations involving V1753 or/and A1768 in addition to T1762/A1764 in BCP region were closely related to HCC among the patients infected with HBV/C1, particularly for HBeAg-positive-carriers. The increased risk of HCC caused by BCP variants may be attributable partially to modifying the biological functions of HBx

Study of the Global Alignment for the DAMPE Detector

The Dark Matter Particle Explorer (DAMPE) is designed as a high energy particle detector for probing cosmic-rays and $\gamma-$rays in a wide energy range. The trajectory of the incident particle is mainly measured by the Silicon-Tungsten tracKer-converter (STK) sub-detector, which heavily depends on the precise internal alignment correction as well as the accuracy of the global coordinate system. In this work, we carried out a global alignment method to validate the potential displacement of these sub-detectors, and particularly demonstrated that the track reconstruction of STK can well satisfy the required objectives by means of comparing flight data and simulations.Comment: 18 pages, 11 figure

Visualizing the elongated vortices in γ\gamma-Ga nanostrips

We study the magnetic response of superconducting $\gamma$-Ga via low temperature scanning tunneling microscopy and spectroscopy. The magnetic vortex cores rely substantially on the Ga geometry, and exhibit an unexpectedly-large axial elongation with aspect ratio up to 40 in rectangular Ga nano-strips (width $l$ $<$ 100 nm). This is in stark contrast with the isotropic circular vortex core in a larger round-shaped Ga island. We suggest that the unusual elongated vortices in Ga nanostrips originate from geometric confinement effect probably via the strong repulsive interaction between the vortices and Meissner screening currents at the sample edge. Our finding provides novel conceptual insights into the geometrical confinement effect on magnetic vortices and forms the basis for the technological applications of superconductors.Comment: published in Phys. Rev. B as a Rapid Communicatio

Overexpression of focal adhesion kinase in vascular endothelial cells promotes angiogenesis in transgenic mice

Objective: Focal adhesion kinase is implicated in the regulation of cell adhesion, migration, survival, and cell-cycle progression. However, the functions of focal adhesion kinase in endothelial cell (EC) in vivo remain unclear. This study aims to examine the role of FAK in EC function and angiogenesis in vivo by transgenic mice approach. Method: We generated transgenic mice which overexpressed chicken FAK in vascular endothelial cell under the control of the Tie-2 promoter and enhancer. FAK transgene was detected by RT-PCR, immunoprecipitation, and Western blot. The effect of FAK overexpression on angiogenesis was determined using skin wound healing and ischemia skeleton muscle models. Results: Expression of FAK transgene was detected in all vessel-rich tissues. Expression of FAK protein was verified by antibody specific for the exogenous chicken FAK in lung homogenates and isolated EC. In the wound-induced angiogenesis model, the number of vessels in the granulation tissue of healing wound was significantly increased in the transgenic mouse compared to that of wild-type control mice. Similarly, in the ischemia skeleton muscle model, the density of capillaries was significantly increased in the transgenic mouse. Conclusion: These results indicate that FAK may play an important role in the promotion of angiogenesis in viv

Screening immune adjuvants for an inactivated vaccine against Erysipelothrix rhusiopathiae

In this study, we screened adjuvants for an inactivated vaccine against Erysipelothrix rhusiopathiae (E. rhusiopathiae). Inactivated cells of E. rhusiopathiae strain HG-1 were prepared as the antigen in five adjuvanted inactivated vaccines, including a mineral-oil-adjuvanted vaccine (Oli vaccine), aluminum-hydroxide-gel-adjuvanted vaccine (Alh vaccine), ISA201-biphasic-oil-emulsion-adjuvanted vaccine (ISA201 vaccine), GEL02-water-soluble-polymer-adjuvanted vaccine (GEL vaccine), and IMS1313-water-soluble-nanoparticle-adjuvanted vaccine (IMS1313 vaccine). The safety test results of subcutaneous inoculation in mice showed that Oli vaccine had the most severe side effects, with a combined score of 35, followed by the ISA201 vaccine (25 points), Alh vaccine (20 points), GEL vaccine (10 points), and IMS1313 vaccine (10 points). A dose of 1.5LD50 of strain HG-1 was used to challenge the mice intraperitoneally, 14 days after their second immunization. The protective efficacy of Oli vaccine and Alh vaccine was 100% (8/8), whereas that of the other three adjuvanted vaccines was 88% (7/8). Challenge with 2.5LD50 of strain HG-1 resulted in a 100% survival rate, demonstrating the 100% protective efficacy of the Oli vaccine, followed by the GEL vaccine (71%, 5/7), IMS1313 vaccine (57%, 4/7), ISA201 vaccine (43%, 3/7), and Alh vaccine (29%, 2/7). Challenge with 4LD50 of strain HG-1 showed 100% (7/7) protective efficacy of the Oli vaccine and 71% (5/7) protective efficacy of the GEL vaccine, whereas the protective efficacy of other three adjuvanted vaccine was 14% (1/7). The Alh and GEL vaccines were selected for comparative tests in piglets, and both caused minor side effects. A second immunization with these two adjuvanted vaccines conferred 60 and 100% protective efficacy, respectively, after the piglets were challenged via an ear vein with 8LD100 of strain HG-1. After challenge with 16LD100 of strain HG-1, the Alh and GEL vaccines showed 40% and 100% protective efficacy, respectively. Our results suggested that GEL is the optimal adjuvant for an inactivated vaccine against E. rhusiopathiae