SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex

Cpdm (chronic proliferative dermatitis) mice develop chronic dermatitis and an immunodeficiency with increased serum IgM, symptoms that resemble those of patients with X-linked hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED), which is caused by mutations in NEMO (NF-κB essential modulator; also known as IKBKG). Spontaneous null mutations in the Sharpin (SHANK-associated RH domain interacting protein in postsynaptic density) gene are responsible for the cpdm phenotype in mice. SHARPIN shows significant similarity to HOIL-1L (also known as RBCK1), a component of linear ubiquitin chain assembly complex (LUBAC), which induces NF-κB activation through conjugation of linear polyubiquitin chains to NEMO. Here, we identify SHARPIN as an additional component of LUBAC. SHARPIN-containing complexes can linearly ubiquitinate NEMO and activated NF-κB. Thus, we re-define LUBAC as a complex containing SHARPIN, HOIL-1L, and HOIP (also known as RNF31). Deletion of SHARPIN drastically reduced the amount of LUBAC, which resulted in attenuated TNF-α- and CD40-mediated activation of NF-κB in mouse embryonic fibroblasts (MEFs) or B cells from cpdm mice. Considering the pleomorphic phenotype of cpdm mice, these results confirm the predicted role of LUBAC-mediated linear polyubiquitination in NF-κB activation induced by various stimuli, and strongly suggest the involvement of LUBAC-induced NF-κB activation in various disorders.     

Human leukocyte and fibroblast interferons are structurally related

The coding sequences of the dDNAs of cloned human leukocyte interferon I and human fibroblast interferon show homologies of 45% at the nucleotide and 29% at the amino acid level. We conclude that the two genes were derived from a common ancestor.     

Uptake of3H-GABA (γ-aminobutyric acid) and3H-leucine in the pancreatic islets and substantia nigra of the rat

Summary Isolated pancreatic islets and thin slices of substantia nigra (SN) of the rat were incubated in a medium containing³H-GABA or³H-leucine to test the activity of both tissues in the uptake of those substances. Pancreatic islets showed a low uptake of both³H-GABA and³H-leucine, but SN had a high activity in the uptake of³H-GABA, though not for³H-leucine. This suggests that GABA contained at high levels in the pancreatic islets plays some functional role other than in neurotransmission as in the central nervous system (CNS).     

Direct observation of Tomonaga-Luttinger-liquid state in carbon nanotubes at low temperatures

The electronic transport properties of conventional three-dimensional metals are successfully described by Fermi-liquid theory. But when the dimensionality of such a system is reduced to one, the Fermi-liquid state becomes unstable to Coulomb interactions, and the conduction electrons should instead behave according to Tomonaga-Luttinger-liquid (TLL) theory. Such a state reveals itself through interaction-dependent anomalous exponents in the correlation functions, density of states and momentum distribution of the electrons. Metallic single-walled carbon nanotubes (SWNTs) are considered to be ideal one-dimensional systems for realizing TLL states. Indeed, the results of transport measurements on metal-SWNT and SWNT-SWNT junctions have been attributed to the effects of tunnelling into or between TLLs, although there remains some ambiguity in these interpretations. Direct observations of the electronic states in SWNTs are therefore needed to resolve these uncertainties. Here we report angle-integrated photoemission measurements of SWNTs. Our results reveal an oscillation in the pi-electron density of states owing to one-dimensional van Hove singularities, confirming the one-dimensional nature of the valence band. The spectral function and intensities at the Fermi level both exhibit power-law behaviour (with almost identical exponents) in good agreement with theoretical predictions for the TLL state in SWNTs.     

Epicatechin can cause the seedling growth inhibitor,nagilactone E,to induce growth stimulation

Summary A possible new role for the flavonoid (–)-epicatechin (II) is described. It has no growth effects on its own, but when it is added to lettuce and rice seeds together with the known seedling growth inhibitor nagilactone E (I), the growth inhibitor activity ofI can cease and growth stimulation can be observed.     

Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG

Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.     

Functional and molecular organisation of an antigen-specific suppressor factor from a T-cell hybridoma

Thymus-dependent (T) lymphocytes have been shown to have antigen specificity. The antigen receptor on T lymphocytes, in contrast to that on B lymphocytes, does not appear to be of the conventional immunoglobulin (Ig) type. Studies on the antigen-specific factors derived from helper and suppressor T cells (Ts) demonstrated that they possess determinants with antigen binding affinity and products of genes in the H-2 complex (MHC). Furthermore, antibodies against the variable region of Ig heavy chains or idiotypes have been shown to react with T-cell antigen receptors as well as antigen-specific helper and suppressor T-cell factors (TsF). It is, therefore, conceivable that at least two gene products are involved in the structural entity of these receptors: one each coded for by genes in either. To establish the molecular nature of the recognition component of T cells we have used homogeneous TsF from a T-cell hybridoma with a specific function. We report here that the antigen binding and I-J coded molecules on TsF are independently synthesised in the cytoplasm, and are secreted as an associated form of the two molecules; this association is required for antigen-specific suppression of antibody response.