Cannflavin A and B,prenylated flavones fromCannabis sativa L.

Summary Two novel prenylat flavones, termed Cannflavin A and B, were isolated from the cannabinoid free ethanolic extract ofCannabis sativa L. Both compounds inhibited prostaglandin E₂ production by human rheumatoid synovial cells in culture.This communication is dedicated to the memory of the late Professor J. W. Fairbairn and the late Dr. J. T. Pickens. We are grateful to the Medical Research Council for a project grant and to Ms J. Elliot of King's College London for NMR spectra.     

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.     

Cannflavin A and B, prenylated flavones from Cannabis sativa L

Two novel prenylated flavones, termed Cannflavin A and B, were isolated from the cannabinoid free ethanolic extract of Cannabis sativa L. Both compounds inhibited prostaglandin E2 production by human rheumatoid synovial cells in culture.     

Deterministic quantum teleportation of atomic qubits

Quantum teleportation provides a means to transport quantum information efficiently from one location to another, without the physical transfer of the associated quantum-information carrier. This is achieved by using the non-local correlations of previously distributed, entangled quantum bits (qubits). Teleportation is expected to play an integral role in quantum communication and quantum computation. Previous experimental demonstrations have been implemented with optical systems that used both discrete and continuous variables, and with liquid-state nuclear magnetic resonance. Here we report unconditional teleportation of massive particle qubits using atomic (9Be+) ions confined in a segmented ion trap, which aids individual qubit addressing. We achieve an average fidelity of 78 per cent, which exceeds the fidelity of any protocol that does not use entanglement. This demonstration is also important because it incorporates most of the techniques necessary for scalable quantum information processing in an ion-trap system.     

T-type calcium channel regulation by specific G-protein betagamma subunits

Low-voltage-activated (LVA) T-type calcium channels have a wide tissue distribution and have well-documented roles in the control of action potential burst generation and hormone secretion. In neurons of the central nervous system and secretory cells of the adrenal and pituitary, LVA channels are inhibited by activation of G-protein-coupled receptors that generate membrane-delimited signals, yet these signals have not been identified. Here we show that the inhibition of alpha1H (Ca(v)3.2), but not alpha(1G) (Ca(v)3.1) LVA Ca2+ channels is mediated selectively by beta2gamma2 subunits that bind to the intracellular loop connecting channel transmembrane domains II and III. This region of the alpha1H channel is crucial for inhibition, because its replacement abrogates inhibition and its transfer to non-modulated alpha1G channels confers beta2gamma2-dependent inhibition. betagamma reduces channel activity independent of voltage, a mechanism distinct from the established betagamma-dependent inhibition of non-L-type high-voltage-activated channels of the Ca(v)2 family. These studies identify the alpha1H channel as a new effector for G-protein betagamma subunits, and highlight the selective signalling roles available for particular betagamma combinations.     

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease

Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development.     

Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease

We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.