Guomei Lin

Post-orogenic bimodal volcanism along the Sulu Orogenic Belt in eastern China

Abstract The early Cretaceous volcanism occurring along the Sulu orogenic belt, east Shandong Province, demonstrates a bimodal characteristic. The volcanic rocks belong to high-K alkaline series, dominated by alkali basalt, basaltic trachyandesite, latite and trachyte with LILE (e.g. K, Sr and Ba) and LREE enrichment but HFSE depletion (especially for Nb and P) in the primitive mantle-normalized spidergrams and steeply right-declined REE patterns. The enriched initial Sr-Nd isotopic ratios ( 87 Sr/ 86 Sr = 0.70724 to 0.70750 and e Nd (t) = −17.0 to −15.9) of the basaltic samples suggest their origin from an enriched lithospheric mantle, which might had undergone a fluid metasomatism or source mixing by the continental crust during or shortly after the Triassic continental subduction. Significantly negative Nb anomalies observed in the spidergrams and other “crustal” signatures of these rocks suggest an important role of continental material in their petrogenesis. The felsic rocks demonstrate geochemical and Sr-Nd isotopic features (initial 87 Sr/ 86 Sr = 0.70814 to 0.70961 and e Nd (t) = −18.9 to −17.0) similar to those of the post-collisional granitic plutons, probably derived from the anatexis of lower/middle crust in response to basaltic magma underplating. The widespread melting of the metasomatized mantle was probably attributed to the thermal perturbation or lithospheric extension induced by the mega-large displacement along the Tan-Lu wrench fault system when northward strike-slipping movement of the Izanagi Plate occurred during the late Mesozoic.

Late mesozoic mafic intrusive complexes in North China Block: constraints on the nature of subcontinental lithospheric mantle

The nature of Mesozoic subcontinental lithospheric mantle (SCLM) has been rarely iscussed in detail even though it might be crucial to understanding of the lithospheric thinning process and mechanism in North China Block (NCB). Late Mesozoic ultramafic to mafic intrusive complexes occurring in west Shandong Province, eastern China, provide a possible approach to constrain the nature of the SCLM in NCB. These mafic rocks are characterized by LILE and LREE enrichment, HFSE depletion and apparently positive Eu anomalies with EM1-like Sr and Nd isotopic compositions. A long-term metasomatism by carbonatitic fluid can be inferred in accordance to their LREE enrichment, HFSE depletion and low 87Sr/86Sr ratios. Additionally, the strong LILE enrichment (such as Rb, Ba and K) and the relatively wider range of eNd(t) values indicate that the mantle source had undergone recent metasomatism by high-potassium OIB-like melt during or shortly before partial melting, resulting in mantle heterogeneity. The geochemical and Sr-Nd isotopic characteristics of the ultramafic to mafic intrusives suggest their origin from enriched lithospheric mantle, which was probably dominated by phlogopite-bearing harzburgites at 80 to 160km depths. A combination of the partial melting of such a heterogeneously enriched mantle with fractional crystallization of olivine and pyroxene during magma ascent can well interpret their petrogenesis. When comparing the nature of the Mesozoic SCLM with that in the early Paleozoic, lithospheric extension or thinning occurred in response to the widespread basaltic generation during the late Mesozoic. It is favorable that the Archaean lithospheric keel in NCB was removed by means of the decompressional melting of the preexistent metasome defined by Menzies (1993).

TRIM30α Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING

Uncontrolled immune responses to intracellular DNA have been shown to induce autoimmune diseases. Homeostasis regulation of immune responses to cytosolic DNA is critical for limiting the risk of autoimmunity and survival of the host. Here, we report that the E3 ubiquitin ligase tripartite motif protein 30α (TRIM30α) was induced by herpes simplex virus type 1 (HSV-1) infection in dendritic cells (DCs). Knockdown or genetic ablation of TRIM30α augmented the type I IFNs and interleukin-6 response to intracellular DNA and DNA viruses. Trim30α-deficient mice were more resistant to infection by DNA viruses. Biochemical analyses showed that TRIM30α interacted with the stimulator of interferon genes (STING), which is a critical regulator of the DNA-sensing response. Overexpression of TRIM30α promoted the degradation of STING via K48-linked ubiquitination at Lys275 through a proteasome-dependent pathway. These findings indicate that E3 ligase TRIM30α is an important negative-feedback regulator of innate immune responses to DNA viruses by targeting STING.

Guanylate Binding Protein 4 Negatively Regulates Virus-Induced Type I IFN and Antiviral Response by Targeting IFN Regulatory Factor 7

IRF7 is known as the master regulator in virus-triggered induction of type I IFNs (IFN-I). In this study, we identify GBP4 virus-induced protein interacting with IRF7 as a negative regulator for IFN-I response. Overexpression of GBP4 inhibits virus-triggered activation of IRF7-dependent signaling, but has no effect on NF-κB signaling, whereas the knockdown of GBP4 has opposite effects. Furthermore, the supernatant from Sendai virus-infected cells in which GBP4 have been silenced inhibits the replication of vesicular stomatitis virus more efficiently. Competitive coimmunoprecipitation experiments indicate that overexpression of GBP4 disrupts the interactions between TRAF6 and IRF7, resulting in impaired TRAF6-mediated IRF7 ubiquitination. Our results suggest that GBP4 is a negative regulator of virus-triggered IFN-I production, and it is identified as a novel protein targeting IRF7 and inhibiting its function.

Negative Regulation of Nmi on Virus-Triggered Type I IFN Production by Targeting IRF7

Viral infection causes host cells to produce type I IFNs, which play a critical role in viral clearance. IFN regulatory factor (IRF) 7 is the master regulator of type I IFN-dependent immune responses. In this article, we report that N-Myc and STATs interactor (Nmi), a Sendai virus–inducible protein, interacted with IRF7 and inhibited virus-triggered type I IFN production. The overexpression of Nmi inhibited the Sendai virus–triggered induction of type I IFNs, whereas the knockdown of Nmi promoted IFN production. Furthermore, the enhanced production of IFNs resulting from Nmi knockdown was sufficient to protect cells from infection by vesicular stomatitis virus. In addition, Nmi was found to promote the K48-linked ubiquitination of IRF7 and the proteasome-dependent degradation of this protein. Finally, an impairment of antiviral responses is also detectable in Nmi-transgenic mice. These findings suggest that Nmi is a negative regulator of the virus-triggered induction of type I IFNs that targets IRF7.

ECM1 controls T(H)2 cell egress from lymph nodes through re-expression of S1P(1).

Type 2 helper T cells (TH2) are critically involved in allergies and asthma. Here we demonstrate that extracellular matrix protein-1 (ECM1) is highly and selectively expressed in TH2 cells. ECM1 deficiency caused impaired TH2 responses and reduced allergic airway inflammation in vivo. Functional analysis demonstrated that although the TH2 polarization of ECM1-deficient cells was unimpaired, these cells had a defect in migration and were retained in peripheral lymphoid organs. This was associated with reduced expression of KLF2 and S1P1. We also found that ECM1 could directly bind the interleukin-2 (IL-2) receptor to inhibit IL-2 signaling and activate S1P1 expression. Our data identify a previously unknown function of ECM1 in regulating TH2 cell migration through control of KLF2 and S1P1 expression.

Dec2 Promotes Th2 Cell Differentiation by Enhancing IL-2R Signaling

Th cell differentiation is precisely regulated by thousands of genes at different stages. In the present study, we demonstrate that Dec2, a transcription factor belonging to the bHLH (basic helix-loop-helix) superfamily, is progressively induced during the course of Th2 differentiation, especially at the late stage. The up-regulated Dec2 can strongly promote Th2 development under Th2-inducing conditions, as evidenced by retrovirus-mediated gene transfer or transgenic manipulation. In addition, an enhancement of Th2 responses is also detectable in Dec2 transgenic mice in vivo. Conversely, RNA interference-mediated suppression of endogenous Dec2 could attenuate Th2 differentiation. Finally, we show that the enhanced Th2 development is at least in part due to substantial up-regulation of CD25 expression elicited by Dec2, thereby resulting in hyperresponsiveness to IL-2 stimulation.

Immune Protection Induced on Day 10 Following Administration of the 2009 A/H1N1 Pandemic Influenza Vaccine

Background The 2009 swine-origin influenza virus (S-OIV) H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation. Methodology/Principal Findings 58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose). The sera were collected before Day 0 (pre-vaccination) and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%). This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21). However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1) more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer <1∶40, Group 2). The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21) than that in Group 2 (geometric mean titer: 70 on Day 21). Conclusions/Significance Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a stronger pre-existing seasonal influenza antibody response may have a relatively higher potential for developing a stronger humoral immune response after vaccination with the 2009 A/H1N1 pandemic influenza vaccine.

Synthetic peptides derived from SARS coronavirus S protein with diagnostic and therapeutic potential

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS‐CoV) is an important viral structural protein. Based on bioinformatics analysis, 10 antigenic peptides derived from the S protein sequence were selected and synthesized. The antigenicity and immunoreactivity of all the peptides were tested in vivo and in vitro. Four peptides (P6, P8, P9 and P10) which contain B cell epitopes of the S protein were identified, and P8 peptide was confirmed in vivo to have a potential in serological diagnosis. By using a syncytia formation model, we tested the neutralization ability of all 10 peptides and their corresponding antibodies. It is interesting to find that P8 and P9 peptides inhibited syncytia formation, suggesting that the P8 and P9 spanning regions may provide a good target for anti‐SARS‐CoV drug design. Our data suggest that we have identified peptides derived from the S protein of SARS‐CoV, which are useful for SARS treatment and diagnosis.

Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation.

It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin (TCS) could induce airway inflammation even without the help of alum. Furthermore, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accumulation of IL-4-producing eosinophils in peritoneum at an early stage and the adjuvant function of TCS was eliminated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4-deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-type adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.