Structural basis for self-association and receptor recognition of human TRAF2

Tumour necrosis factor (TNF)-receptor-associated factors (TRAFs) form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily and the interleukin-1 receptor. They are important in the regulation of cell survival and cell death. The carboxy-terminal region of TRAFs (the TRAF domain) is required for self-association and interaction with receptors. The domain contains a predicted coiled-coil region that is followed by a highly conserved TRAF-C domain. Here we report the crystal structure of the TRAF domain of human TRAF2, both alone and in complex with a peptide from TNF receptor-2 (TNF-R2). The structures reveal a trimeric self-association of the TRAF domain, which we confirm by studies in solution. The TRAF-C domain forms a new, eight-stranded antiparallel beta-sandwich structure. The TNF-R2 peptide binds to a conserved shallow surface depression on one TRAF-C domain and does not contact the other protomers of the trimer. The nature of the interaction indicates that an SXXE motif may be a TRAF2-binding consensus sequence. The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands.     

Detection of marijuana smoke in the atmosphere of a room

Zusammenfassung Mit einer Analysenmethode gelingt es, Marijuanarauch von einer Zigarette oder weniger durch Kombination von Anreicherungsverfahren mit hochauflösender Gaschromatographie in Zimmerluft nachzuweisen. Charakteristische Profile von 200 bis 300 Komponenten (darunter Cannabinoide), die sich deutlich von denen von Tabakrauch unterscheiden, wurden mit Hilfe von Glaskapillarsäulen gewonnen.     

Birth of parthenogenetic mice that can develop to adulthood

Only mammals have relinquished parthenogenesis, a means of producing descendants solely from maternal germ cells. Mouse parthenogenetic embryos die by day 10 of gestation. Bi-parental reproduction is necessary because of parent-specific epigenetic modification of the genome during gametogenesis. This leads to unequal expression of imprinted genes from the maternal and paternal alleles. However, there is no direct evidence that genomic imprinting is the only barrier to parthenogenetic development. Here we show the development of a viable parthenogenetic mouse individual from a reconstructed oocyte containing two haploid sets of maternal genome, derived from non-growing and fully grown oocytes. This development was made possible by the appropriate expression of the Igf2 and H19 genes with other imprinted genes, using mutant mice with a 13-kilobase deletion in the H19 gene as non-growing oocytes donors. This full-term development is associated with a marked reduction in aberrantly expressed genes. The parthenote developed to adulthood with the ability to reproduce offspring. These results suggest that paternal imprinting prevents parthenogenesis, ensuring that the paternal contribution is obligatory for the descendant.     

Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf

Specific adaptors regulate the activation of initiator caspases; for example, FADD and Apaf-1 engage caspases 8 and 9, respectively. The adaptors ASC, Ipaf and RIP2 have each been proposed to regulate caspase-1 (also called interleukin (IL)-1 converting enzyme), which is activated within the 'inflammasome', a complex comprising several adaptors. Here we show the impact of ASC-, Ipaf- or RIP2-deficiency on inflammasome function. ASC was essential for extracellular ATP-driven activation of caspase-1 in toll-like receptor (TLR)-stimulated macrophages. Accordingly, ASC-deficient macrophages exhibited defective maturation of IL-1beta and IL-18, and ASC-null mice were resistant to lipopolysaccharide-induced endotoxic shock. Furthermore, activation of caspase-1 in response to an intracellular pathogen (Salmonella typhimurium) was abrogated severely in ASC-null macrophages. Unexpectedly, Ipaf-deficient macrophages activated caspase-1 in response to TLR plus ATP stimulation but not S. typhimurium. Caspase-1 activation was not compromised by loss of RIP2. These data show that whereas ASC is key to caspase-1 activation within the inflammasome, Ipaf provides a special conduit to the inflammasome for signals triggered by intracellular pathogens. Notably, cell death triggered by stimuli that engage caspase-1 was ablated in macrophages lacking either ASC or Ipaf, suggesting a coupling between the inflammatory and cell death pathways.     

Some new data concerning effect of actinomycin D on early chick embryos

Zusammenfassung Actinomycin D führte beim Hühnerembryo zu einer deutlichen Hemmung der Herzentwicklung nach Inkubation im Nährmedium während der Entwicklungsstadien 3 und 3⁺. Nach Vorbehandlung der Stadien 3–7 und anschliessender Kultur in actinomycin D-freiem Medium fanden sich Fehlbildungen von Herz, ZNS und Somiten, die in ihrer Häufigkeit von den betroffenen Entwicklungsphasen abhängig sind.

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This study was supported by a grant from the Rutgers University Research Council No. 07-2189.     

Histone hydrolase in tadpole liver

Résumé Le cytoplasme du foie de têtard contient une enzyme qui hydrolyse spécifiquement les protéines basiques telle que la polylysine, la protamine et les histones. L'addition d'autres protéines telles que l'albumine, la globuline et l'acide polyglutamique inhibe l'activité de cette enzyme. Les résultats obtenus montrent que cette hydrolysase extraite du foie de têtard diffère des cathépsines ou de l'histone-hydrolase du rein de rat.

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This work was supported by research grants from the National Institute of Arthritis and Metabolic Diseases No. AM 09602, National Science Foundation No. GB-22663 and from the National Cancer Institute No. CA 07174.