Air samples were collected in June of 2004 from four sites in the city of Guangzhou, a typical urban center in South China, to determine the levels, compositional profiles, and gas-particle distribution of 11 polybrominated diphenyl ether (PBDE) congeners (BDE-28, -47, -66, -100, -99, -85, -154, -153, -138, -183, and -209). The arithmetic mean atmospheric concentrations of sigmaPBDEs (sum of all target PBDE congeners except for BDE-209) in samples from the urban and city background sites were comparable to or slightly higher than those from other places around the world. The arithmetic mean atmospheric concentrations of BDE-209, however, were higherthan those in North America and Europe, and similar to the values from Japan. Congener compositions were dominated by BDE-209 in all (>70%) but an industrial site, with an average abundance of 48% for BDE-209. The PBDE patterns were generally similar to that in the technical penta-BDE mixture, Bromkal 70-5DE. Partitioning of PBDEs between the gas and particle phases (Kp) was well correlated with the subcooled liquid vapor pressure (PLO) for all of the samples, but the relationship differed between samples from different sites. The measured fractions of PBDEs in the particulate phase were compared to the predictions from the Junge-Pankow adsorption and KOA-based absorption models. The results indicated that the KOA-based model worked better than the Junge-Pankow model that tended to overestimate the particulate fractions for most PBDE congeners.

interferon ͉ MITA ͉ negative-feedback regulation ͉ IRF3 ͉ NF-B

The tripartite motif (TRIM)-containing proteins are a family of proteins that have been known to be involved in divergent biological processes, including important roles in immune responses through regulating various signaling pathways. In this study, we identified a member of the TRIM family, TRIM8, as a positive regulator of tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β)-triggered NF-κB activation. Overexpression of TRIM8 activated NF-κB and potentiated TNFα-and IL-1β-induced activation of NF-κB, whereas knockdown of TRIM8 had opposite effects. Coimmunoprecipitations indicated that TRIM8 interacted with TGFβ activated kinase 1 (TAK1), a serine/threonine kinase essential for TNFα-and IL-β-induced NF-κB activation. Furthermore, we found that TRIM8 mediated K63-linked polyubiquitination of TAK1 triggered by TNFα and IL-1β. Our findings demonstrate that TRIM8 serves as a critical regulator of TNFα-and IL-1β-induced NF-κB activation by mediating K63-linked polyubiquitination of TAK1.T he transcription factor NF-κB plays a pivotal role in many cellular events such as cell proliferation, inhibition of apoptosis, and innate immunity. NF-κB activation requires the signal-induced phosphorylation and degradation of IκB proteins (1). The kinase that phosphorylates IκB, termed IκB kinase (IKK) complex, consists of the catalytic subunits IKKα, IKKβ, and the regulatory subunit NEMO/IKKγ. The IKK complex is activated by a large variety of stimuli, including the proinflammatory cytokines tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) (2).Binding of TNFα to its receptor TNF-RI results in recruitment of the adaptor protein TRADD. TRADD further recruits TRAF2, TRAF5, and RIP1 to the receptor complex. TRAF2 mediates polyubiquitination of RIP1, mainly in a K63-linked manner. Ubiquitinated RIP further recruits TAB2 and TAK1 and mediates activation of the latter. The activated RIP1-TAK1-TAB2 complex subsequently activates the IKK complex, leading to phosphorylation of IκBα and activation of NF-κB (3). Similarly, binding of IL-1β to its receptor IL-1R leads to the recruitment of adaptor proteins and kinases, including MyD88, IRAK1, and IRAK4. IRAK4 phospholylates and activates IRAK1, which in turn recruits TRAF6. IRAK1 and TRAF6 form a complex that is released from the receptor. TRAF6 possesses an E3 ubiquitin ligase activity that mediates its K63-linked autopolyubiquitination. Ubiquitinated TRAF6 further recruits the TAK1-TAB2-TAB3 complex, resulting in the activation of TAK1. Activated TAK1 eventually phosphorylates and activates IKK, leading to activation of NF-κB (3, 4).TAK1 is a member of the MAPK kinase kinase family that was originally found to function in the transforming growth factor β (TGFβ)-mediated MAPK activation (5). TAK1 has been demonstrated to be essential in TNFα-and IL-1β-mediated activation of NF-κB and JNK (6, 7). In all of these pathways, activation of TAK1 is an important event that transmits the upstream signal from the receptor complex to the downstream signaling molecules (3, 4, 6, 7).S...

The nonhydrolyzable carbon (NHC) and black carbon (BC) in three contaminated soils and seven sediments from the Pearl River Delta and Estuary, China, were isolated upon treatments with an acid hydrolysis method and with a combustion method at 375 degrees C, respectively, and their sorption isotherms for phenanthrene (Phen) were established. It was found that NHC is chemically and structurally different from the biopolymer and humic substances and consists mainly of aliphatic and aromatic carbon using elemental analysis, 13C nuclear magnetic resonance spectroscopy (13C NMR), and Fourier transformed infrared spectroscopy (FTIR). All the sorption isotherms are nonlinear and are well fitted by the Freundlich model. The single-point organic carbon-normalized distribution coefficient (K(oc)) measured for the isolated NHC is 1.3-7.7 times higher than that for the bulk samples at the same aqueous concentration of Phen. The NHC fractions play a dominant role to the overall sorption in the bulk samples. The bulk soils and their NHC fractions have lower sorption capacity than the bulk sediments and their NHC fractions, relating to the different source of organic matter between soils and sediments. The Phen sorption capacity in the NHC samples is related significantlyto H/C ratios and aliphatic carbon, but negatively to aromatic carbon, demonstrating the important role of aliphatic carbon to the Phen sorption and the fate in the investigated soils and sediments.

Ubiquitination and deubiquitination have emerged as critical post-translational regulatory mechanisms for activation or attenuation of the virus-triggered type I interferon (IFN) 2 induction pathways. In this study, we identified two deubiquitinating enzymes, OTUB1 and OTUB2, as negative regulators of virus-triggered type I IFN induction. Overexpression of OTUB1 and OTUB2 inhibited virus-induced activation of IRF3 and NF-B, transcription of the IFNB1 gene as well as cellular antiviral response, whereas knockdown of OTUB1 and OTUB2 had opposite effects. Coimmunoprecipitations indicated OTUB1 and -2 interacted with TRAF3 and TRAF6, two E3 ubiquitin ligases required for virus-triggered IRF3 and NF-B activation, respectively. Furthermore, we found that OTUB1 and OTUB2 mediated virus-triggered deubiquitination of TRAF3 and -6. These findings suggest that OTUB1 and OTUB2 negatively regulate virus-triggered type I IFN induction and cellular antiviral response by deubiquitinating TRAF3 and -6. Viral infections triggered a series of signaling events that lead to induction of type I interferons (IFNs). Type I IFNs then activate the JAK-STAT signal transduction pathways, leading to transcriptional induction of a wide range of downstream antiviral genes and subsequent innate antiviral response (1-4). Transcriptional induction of type I IFN genes requires the coordinate activation of multiple transcription factors and their cooperative assembly into transcriptional enhancer complexes in vivo. For example, the IFNB1 gene promoter contains conserved enhancer elements recognized by NF-B (B site) and phosphorylated IRF3 (ISRE site, also known as PRDIII or IRF-E). It has been shown that transcriptional activation of the IFNB1 gene requires coordinate and cooperative assembly of an enhanceosome that contains all of these transcription factors (2, 5, 6).The innate immune system has developed at least two types of pathogen recognition receptors for the recognition of viral RNAs (7).One is mediated by membrane-bound Toll-like receptors (TLRs) such as TLR3. Engagement of TLR3 by double-stranded RNA triggers TRIF-mediated signaling pathways, leading to IRF3 and NF-B activation (8). The second one involves the cytosolic RIG-I-like receptor family members RIG-I, MDA5, and Lgp2. Both RIG-I and MDA5 contain two CARD modules at their N terminus and a DexD/H-box RNA helicase domain at their C terminus (9, 10). Upon viral infection, the RNA helicase domains of RIG-I and MDA5 serve as intracellular viral RNA receptors, whereas their CARD modules are associated with the downstream CARD-containing adapter protein VISA (also known as MAVS, IPS-1, and Cardif) (11-15). The essential roles of VISA in antiviral innate immune response were demonstrated by the observations that VISAdeficient mice failed to mount a proper IFN response to viral infections (14,16). Various studies have demonstrated that VISA plays a central role in assembling a complex that activates distinct signaling pathways leading to NF-B and IRF3 activation, respectively. VISA is as...

No abstract

Viral DNA sensing within the cytosol of infected cells activates type I interferon (IFN) expression. MITA/STING plays an essential role in this pathway by acting as both a sensor for the second messenger cGAMP and as an adaptor for downstream signaling components. In an expression screen for proteins that can activate the IFNB1 promoter, we identified the ER-associated protein ZDHHC1 as a positive regulator of virus-triggered, MITA/STING-dependent immune signaling. Zdhhc1(-/-) cells failed to effectively produce IFNs and other cytokines in response to infection with DNA but not RNA viruses. Zdhhc1(-/-) mice infected with the neurotropic DNA virus HSV-1 exhibited lower cytokine levels and higher virus titers in the brain, resulting in higher lethality. ZDHHC1 constitutively associated with MITA/STING and mediates dimerization/aggregation of MITA/STING and recruitment of the downstream signaling components TBK1 and IRF3. These findings support a role for ZDHHC1 in mediating MITA/STING-dependent innate immune response against DNA viruses.

Concentrations of persistent halogenated hydrocarbons (PHHs) were determined in 13 consumer fish species (a total of 390 individuals) collected from a major fish-farming region of China. The potential health risks of PHHs associated with consumption of fish from China was also systematically assessed regionally and globally. In all fish samples, DDTs, HCHs, PCBs, and PBDEs were the predominant PHH residues, with the median levels (ranges) being 6.0 (0.14-698.9), 0.50 (0.13-24.06), 0.10 (< 0.02-7.65), and 0.15 (< 0.0012-3.85) ng/g wet weight, respectively. The upper-bound (90th percentile) values of estimated daily intakes of DDT, HCHs, PCBs, and PBDEs via fish consumption were 45.5, 1.35, 0.46, and 0.30 ng/kg bw/d (urban), and 15.9, 0.47, 0.16, and 0.10 ng/kg bw/d (rural). Globally, the upper-bound outflows via fishery exportation of DDT, HCHs, PCBs, and PBDEs were 185, 5.51, 1.86, and 1.22 kg, respectively, in 2005. Japan was the largest recipient of PHHs, followed by Korea and the United States. Fish consumption assessments indicated that consumption of freshwater farmed and wild marine fish generally does not subject consumers to significant health risk as far as PHHs are concerned, while limited consumption of seawater farmed fish is advised.