Estimation of the half-life of a secretory protein message

Synthesis of a specific secretory protein was followed in the presence of actinomycin D and cordycepin (3'-deoxyadenosine). The apparent half-life of the messenger RNA for this protein is significantly longer in the presence of actinomycin D than in the presence of cordycepin. These results suggest that actinomycin D studies of half-life in specialized cells may be inaccurate.     

Retention of xenon in quartz and Earth's missing xenon

The reactivity of xenon with terrestrial oxides was investigated by in situ synchrotron x-ray diffraction. At high temperature (T > 500 kelvin), some silicon was reduced, and the pressure stability of quartz was expanded, attesting to the substitution of some xenon for silicon. When the quartz was quenched, xenon diffused out and only a few weight percent remained trapped in samples. These results show that xenon can be covalently bonded to oxygen in quartz in the lower continental crust, providing an answer to the missing xenon problem; synthesis paths of rare gas compounds are also opened.     

The global circulation of seasonal influenza A (H3N2) viruses

Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.     

Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD

Acting as a signal, hydrogen peroxide circumvents antioxidant defense by overoxidizing peroxiredoxins (Prxs), the enzymes that metabolize peroxides. We show that sestrins, a family of proteins whose expression is modulated by p53, are required for regeneration of Prxs containing Cys-SO(2)H, thus reestablishing the antioxidant firewall. Sestrins contain a predicted redox-active domain homologous to AhpD, the enzyme catalyzing the reduction of a bacterial Prx, AhpC. Purified Hi95 (sestrin 2) protein supports adenosine triphosphate-dependent reduction of overoxidized PrxI in vitro, indicating that unlike AhpD, which is a disulfide reductase, sestrins are cysteine sulfinyl reductases. As modulators of peroxide signaling and antioxidant defense, sestrins constitute potential therapeutic targets.