Mite allergen Der-p2 triggers human B lymphocyte activation and Toll-like receptor-4 induction

Background

Allergic disease can be characterized as manifestations of an exaggerated inflammatory response to environmental allergens triggers. Mite allergen Der-p2 is one of the major allergens of the house dust mite, which contributes to TLR4 expression and function in B cells in allergic patients. However, the precise mechanisms of Der-p2 on B cells remain obscure.

Methodology/Principal Findings

We investigated the effects of Der-p2 on proinflammatory cytokines responses and Toll-like receptor-4 (TLR4)-related signaling in human B cells activation. We demonstrated that Der-p2 activates pro-inflammatory cytokines, TLR4 and its co-receptor MD2. ERK inhibitor PD98059 significantly enhanced TLR4/MD2 expression in Der-p2-treated B cells. Der-p2 markedly activated mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) and decreased p38 phosphorylation in B cells. MKP-1-siRNA downregulated TLR4/MD2 expression in Der-p2-treated B cells. In addition, Der-p2 significantly up-regulated expression of co-stimulatory molecules and increased B cell proliferation. Neutralizing Der-p2 antibody could effectively abrogate the Der-p2-induced B cell proliferation. Der-p2 could also markedly induce NF-κB activation in B cells, which could be counteracted by dexamethasone.

Conclusions/Significance

These results strongly suggest that Der-p2 is capable of triggering B cell activation and MKP-1-activated p38/MAPK dephosphorylation-regulated TLR4 induction, which subsequently enhances host immune, defense responses and development of effective allergic disease therapeutics in B cells.     

Complete genome sequence of the obligate piezophilic hyperthermophilic archaeon Pyrococcus yayanosii CH1

Pyrococcus yayanosii CH1 is the first obligate piezophilic hyperthermophilic archaeon isolated from the deep-sea hydrothermal site Ashadze on the mid-Atlantic ridge at a depth of 4,100 m. This organism grows within a temperature range of 80 to 108°C and a hydrostatic pressure range of 20 to 120 MPa, with optima at 98°C and 52 MPa, respectively. Here, we report the complete genome sequence (1,716,817 bp, with a G+C content of 51.6%) of the type strain P. yayanosii CH1(T) (= JCM 16557). This genomic information reveals a systematic view of the piezoadaptation strategy and evolution scenario of metabolic pathways in Thermococcales.     

4.4 Å cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus

Venezuelan equine encephalitis virus (VEEV), a member of the membrane‐containing Alphavirus genus, is a human and equine pathogen, and has been developed as a biological weapon. Using electron cryo‐microscopy (cryo‐EM), we determined the structure of an attenuated vaccine strain, TC‐83, of VEEV to 4.4 Å resolution. Our density map clearly resolves regions (including E1, E2 transmembrane helices and cytoplasmic tails) that were missing in the crystal structures of domains of alphavirus subunits. These new features are implicated in the fusion, assembly and budding processes of alphaviruses. Furthermore, our map reveals the unexpected E3 protein, which is cleaved and generally thought to be absent in the mature VEEV. Our structural results suggest a mechanism for the initial stage of nucleocapsid core formation, and shed light on the virulence attenuation, host recognition and neutralizing activities of VEEV and other alphavirus pathogens.     

Performance of laboratory-scale constructed wetlands coupled with micro-electric field for heavy metal-contaminating wastewater treatment

This study reports the performance of laboratory-scale constructed wetlands coupled with micro-electric field (CWMEF) planted cannas (Canna generalis) for heavy metal-contaminating wastewater treatment. The CWMEF had a better performance for heavy metal (HM) removal from wastewater than did the ordinary constructed wetlands (CWs). Owing to the stimulation of the suitable voltage and electrical exposure time, cannas may grew better and in fact assimilated more metallic ions in CWMEF than in CWs. The environmental conditions in CWMEF, such as the higher pH by electrolysis of water, the presence of aluminum ions by anodizing of aluminum, caused chemical precipitation, physical adsorption and flocculation of metallic ions.     

Invasion dynamics of epidemic with the Allee effect

Investigating the likely success of epidemic invasion is important in the epidemic management and control. In the present study, the invasion of epidemic is initially introduced to a predator-prey system, both species of which are considered to be subject to the Allee effect. Mathematically, the invasion dynamics is described by three nonlinear diffusion-reaction equations and the spatial implicit and explicit models are designed. By means of extensive numerical simulations, the results of spatial implicit model show that the Allee effect has an opposite impact on the invasion criteria and local dynamics when that on the different species. As the intensity of the Allee effect increases, the domain of epidemic invasion reduces and the system dynamics is changed from the stable state to the limit cycle and finally becomes the chaotic state when the susceptible prey with the Allee effect, but the domain expands and the system dynamics is changed from limit cycle to a table point when the predator is subject to the Allee effect. Results from the spatial explicit model show that the strong intensity of the Allee effect can lead to the catastrophic global extinction of all species in the case of that on the susceptible prey. While the predator with the Allee effect, the increased intensity of which makes spatial species reach a stable state. Furthermore, numerical simulations reveal a certain relationship between the invasion speed and spatial patterns.     

Terminal amino acids disturb xylanase thermostability and activity

Protein structure is composed of regular secondary structural elements (α-helix and β-strand) and non-regular region. Unlike the helix and strand, the non-regular region consists of an amino acid defined as a disordered residue (DR). When compared with the effect of the helix and strand, the effect of the DR on enzyme structure and function is elusive. An Aspergillus niger GH10 xylanase (Xyn) was selected as a model molecule of (β/α)(8) because the general structure consists of ~10% enzymes. The Xyn has five N-terminal DRs and one C-terminal DR, respectively, which were deleted to construct three mutants, XynΔN, XynΔC, and XynΔNC. Each mutant was ~2-, 3-, or 4-fold more thermostable and 7-, 4-, or 4-fold more active than the Xyn. The N-terminal deletion decreased the xylanase temperature optimum for activity (T(opt)) 6 °C, but the C-terminal deletion increased its T(opt) 6 °C. The N- and C-terminal deletions had opposing effects on the enzyme T(opt) but had additive effects on its thermostability. The five N-terminal DR deletions had more effect on the enzyme kinetics but less effect on its thermo property than the one C-terminal DR deletion. CD data showed that the terminal DR deletions increased regular secondary structural contents, and hence, led to slow decreased Gibbs free energy changes (ΔG(0)) in the thermal denaturation process, which ultimately enhanced enzyme thermostabilities.