Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites.
Hum Mol Genet 21:12 (2012) 2768-2778
Abstract:
The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that has an extracellular bilobed venus flytrap domain (VFTD) predicted to contain five calcium (Ca(2+))-binding sites. To elucidate the structure-function relationships of the VFTD, we investigated 294 unrelated probands with familial hypocalciuric hypercalcaemia (FHH), neonatal severe primary hyperparathyroidism (NSHPT) or autosomal dominant hypocalcaemic hypercalciuria (ADHH) for CaSR mutations and performed in vitro functional expression studies and three-dimensional modelling of mutations involving the VFTD. A total of 70 different CaSR mutations were identified: 35 in FHH, 10 in NSHPT and 25 in ADHH patients. Furthermore, a CaSR variant (Glu250Lys) was identified in FHH and ADHH probands and demonstrated to represent a functionally neutral polymorphism. NSHPT was associated with a large proportion of truncating CaSR mutations that occurred in the homozygous or compound heterozygous state. Thirty-four VFTD missense mutations were identified, and 18 mutations were located within 10 Å of one or more of the predicted Ca(2+)-binding sites, particularly at the VFTD cleft, which is the principal site of Ca(2+) binding. Mutations of residues 173 and 221, which are located at the entrance to the VFTD cleft binding site, were associated with both receptor activation (Leu173Phe and Pro221Leu) and inactivation (Leu173Pro and Pro221Gln), thereby highlighting the importance of these residues for entry and binding of Ca(2+) by the CaSR. Thus, these studies of disease-associated CaSR mutations have further elucidated the role of the VFTD cleft region in Ca(2+) binding and the function of the CaSR.Amplitude analysis of D0→K +K -π +π -
Physical Review D - Particles, Fields, Gravitation and Cosmology 85:12 (2012)
Abstract:
The first flavor-tagged amplitude analysis of the decay D0 to the self-conjugate final state K +K -π +π - is presented. Approximately 3000 signal decays are selected from data acquired by the CLEO II.V, CLEO III, and CLEO-c detectors. The three most significant amplitudes, which contribute to the model that best fits the data, are ρ0, K 1(1270) ±K, and nonresonant K +K -π +π -. Separate amplitude analyses of D0 and D ̄0 candidates indicate no CP violation among the amplitudes at the level of 5% to 30% depending on the mode. In addition, the sensitivity to the CP-violating parameter γ/ 3 from a sample of 2000 B +→D0(K +K -π +π -)K + decays, where D is a D0 or D ̄0, collected at LHCb or a future flavor facility, is estimated to be (11.3±0.3)° using the favored model. © 2012 American Physical Society.Measurement of $b$-hadron branching fractions for two-body decays into charmless charged hadrons
(2012)
Determination of the sign of the decay width difference in the bs0 system
Physical Review Letters 108:24 (2012)
Abstract:
The interference between the K +K - S-wave and P-wave amplitudes in Bs0→J/ψK +K - decays with the K +K - pairs in the region around the (1020) resonance is used to determine the variation of the difference of the strong phase between these amplitudes as a function of K +K - invariant mass. Combined with the results from our CP asymmetry measurement in Bs0→J/ψ decays, we conclude that the Bs0 mass eigenstate that is almost CP=+1 is lighter and decays faster than the mass eigenstate that is almost CP=-1. This determines the sign of the decay width difference ΔΓ sΓ L-Γ H to be positive. Our result also resolves the ambiguity in the past measurements of the CP violating phase s to be close to zero rather than π. These conclusions are in agreement with the standard model expectations. © 2012 CERN.Searches for Majorana neutrinos in B - decays
Physical Review D - Particles, Fields, Gravitation and Cosmology 85:11 (2012)