TRAF6 is a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. We have purified a heterodimeric protein complex that links TRAF6 to IKK activation. Peptide mass fingerprinting analysis reveals that this complex is composed of the ubiquitin conjugating enzyme Ubc13 and the Ubc-like protein Uev1A. We find that TRAF6, a RING domain protein, functions together with Ubc13/Uev1A to catalyze the synthesis of unique polyubiquitin chains linked through lysine-63 (K63) of ubiquitin. Blockade of this polyubiquitin chain synthesis, but not inhibition of the proteasome, prevents the activation of IKK by TRAF6. These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains.

The cycloaddition of carbon dioxide to epoxides to produce cyclic carbonates is quite promising and does not result in any side products. A discrete single-walled metal-organic nanotube was synthesized by incorporating a tetraphenyl-ethylene moiety as the four-point connected node. The assembled complex has a large cross-section, with an exterior wall diameter of 3.6 nm and an interior channel diameter of 2.1 nm. It features excellent activity toward the cycloaddition of carbon dioxide, with a turnover number of 17,500 per mole of catalyst and an initial turnover frequency as high as 1000 per mole of catalyst per hour. Only minimal decreases in the catalytic activity were observed after 70 h under identical reaction conditions, and a total turnover number as high as 35,000 was achieved. A simple comparison of relative porous MOFs suggested that the cross-section of the channels is an important factor influencing the transport of the substrates and products through the channel.

Previous studies have found a strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome in Asian areas including Taiwan, Hongkong and Thailand. This study explores the association between HLA-B*1502 allele and carbamazepine-induced cutaneous adverse reactions in Han Chinese of southern China mainland, and find the genetic marker that can predict carbamazepine-induced cutaneous adverse reactions. HLA-B*1502 allele genotyping was performed by a polymerase chain reaction-sequence specific primers (PCR-SSP) method in 48 Han Chinese subjects who had carbamazepine-induced cutaneous adverse reactions, including 9 severe cutaneous adverse reaction patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) and 39 cutaneous adverse reaction patients with maculopapular eruption (MPE). Meanwhile 80 carbamazepine-tolerant controls and 62 healthy individuals were also tested. The frequency of HLA-B*1502 allele among SJS/TEN patients (100%) is significantly higher than carbamazepine-tolerant controls (13.75%, P<0.001) and healthy individuals (17.74%, P<0.001). But the frequency between MPE patients and carbamazepine-tolerant controls (25.64% vs.13.75%, P=0.110) did not have any significant difference. The data showed that HLA-B*1502 allele is strongly associated with carbamazepine-induced SJS/TEN but not MPE in Han Chinese of southern China mainland.

The widely studied porous coordination polymers, possessing large pores to adsorb waste carbon dioxide gas and further transform it into valuable chemical products, have been attracting research interest, both industrially and academically. The active silver­(I) ions endow the specific alkynophilicity to activate CC bonds of alkyne-containing molecules via π activation. Incorporating catalytic Ag metal sites into the porous frameworks represents a promising approach to construct heterogeneous catalysts that cyclize propargylic alcohols with CO2, which is highly desirable for the environmentally benign conversion of carbon dioxide to fine chemicals. We report the preparation of porous coordination polymers (PCPs) with active silver sites and efficient silver–silver bond formation by carefully modifying the coordination geometries of the silver sites. The decentralized silver­(I) chains in the porous frameworks enable the efficient conversion of CO2 and derivatives of acetylene to α-alkylidene cyclic carbonates in a heterogeneous manner. X-ray structure analysis reveals two kinds of substrate molecules positioned within the pores of the framework, which correspond to trapping and activated modes through the multiple interactions with the functional Ag chains. The example of tandem conversion of simple alkynes and carbon dioxide to α-alkylidene cyclic carbonates is also presented. The well-positioned catalytic silver­(I) sites and the crystalline properties of the frameworks facilitated the structural analyses of the intermediates of each catalytic step, providing knowledge of the synergistic nature of the σ and π activation of CC bonds. The successful catalysis of azide–alkyne cycloaddition and synthesis of propargylic alcohols via terminal alkynes could also give another indicator for the activation properties of Ag sites.