TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease

B cells are important in the development of autoimmune disorders by mechanisms involving dysregulated polyclonal B-cell activation, production of pathogenic antibodies, and co-stimulation of autoreactive T cells. zTNF4 (BLyS, BAFF, TALL-1, THANK) is a member of the tumour necrosis factor (TNF) ligand family that is a potent co-activator of B cells in vitro and in vivo. Here we identify two receptors for zTNF4 and demonstrate a relationship between zTNF4 and autoimmune disease. Transgenic animals overexpressing zTNF4 in lymphoid cells develop symptoms characteristic of systemic lupus erythaematosus (SLE) and expand a rare population of splenic B-Ia lymphocytes. In addition, circulating zTNF4 is more abundant in NZBWF1 and MRL-lpr/lpr mice during the onset and progression of SLE. We have identified two TNF receptor family members, TACI and BCMA, that bind zTNF4. Treatment of NZBWF1 mice with soluble TACI-Ig fusion protein inhibits the development of proteinuria and prolongs survival of the animals. These findings demonstrate the involvement of zTNF4 and its receptors in the development of SLE and identify TACI-Ig as a promising treatment of autoimmune disease in humans.     

Forecasting international bandwidth capability

M‐competition studies provide a set of stylized recommendations to enhance forecast reliability. However, no single method dominates across series, leading to consideration of the relationship between selected data characteristics and the reliability of alternative forecast methods. This study conducts an analysis of predictive accuracy in relation to Internet bandwidth loads. Extrapolation techniques that perform best in M‐competitions perform relatively poorly in predicting Internet bandwidth loads. Such performance is attributed to Internet bandwidth data exhibiting considerably less structure than M‐competition data. Copyright © 2005 John Wiley & Sons, Ltd.     

Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.     

Jarosite as an indicator of water-limited chemical weathering on Mars

The Mars Exploration Rover Opportunity identified the ferric sulphate mineral jarosite and possible relicts of gypsum at the Meridiani Planum landing site. On Earth, jarosite has been found to form in acid mine drainage environments, during the oxidation of sulphide minerals, and during alteration of volcanic rocks by acidic, sulphur-rich fluids near volcanic vents. Jarosite formation is thus thought to require a wet, oxidizing and acidic environment. But jarosite on Earth only persists over geologically relevant time periods in arid environments because it rapidly decomposes to produce ferric oxyhydroxides in more humid climates. Here we present equilibrium thermodynamic reaction-path simulations that constrain the range of possible conditions under which such aqueous alteration phases are likely to have formed on Mars. These calculations simulate the chemical weathering of basalt at relevant martian conditions. We conclude that the presence of jarosite combined with residual basalt at Meridiani Planum indicates that the alteration process did not proceed to completion, and that following jarosite formation, arid conditions must have prevailed.