Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

A human MYBPC3 mutation appearing about 10 centuries ago results in a hypertrophic cardiomyopathy with delayed onset, moderate evolution but with a risk of sudden death.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a genetically heterogeneous disease. One specific mutation in the MYBPC3 gene is highly prevalent in center east of France giving an opportunity to define the clinical profile of this specific mutation. METHODS: HCM probands were screened for mutation in the MYH7, MYBPC3, TNNT2 and TNNI3 genes. Carriers of the MYBPC3 IVS20-2A>G mutation were genotyped with 8 microsatellites flanking this gene. The age of this MYBPC3 mutation was inferred with the software ESTIAGE. The age at first symptom, diagnosis, first complication, first severe complication and the rate of sudden death were compared between carriers of the IVS20-2 mutation (group A) and carriers of all other mutations (group B) using time to event curves and log rank test. RESULTS: Out of 107 HCM probands, 45 had a single heterozygous mutation in one of the 4 tested sarcomeric genes including 9 patients with the MYBPC3 IVS20-2A>G mutation. The IVS20-2 mutation in these 9 patients and their 25 mutation carrier relatives was embedded in a common haplotype defined after genotyping 4 polymorphic markers on each side of the MYBPC3 gene. This result supports the hypothesis of a common ancestor. Furthermore, we evaluated that the mutation occurred about 47 generations ago, approximately at the 10th century.We then compared the clinical profile of the IVS20-2 mutation carriers (group A) and the carriers of all other mutations (group B). Age at onset of symptoms was similar in the 34 group A cases and the 73 group B cases but group A cases were diagnosed on average 15 years later (log rank test p = 0.022). Age of first complication and first severe complication was delayed in group A vs group B cases but the prevalence of sudden death and age at death was similar in both groups. CONCLUSION: A founder mutation arising at about the 10th century in the MYBPC3 gene accounts for 8.4% of all HCM in center east France and results in a cardiomyopathy starting late and evolving slowly but with an apparent risk of sudden death similar to other sarcomeric mutations

Genetic approaches to studying mouse models of human seizure disorders.

In conclusion, we have discussed a reverse genetics approach to studying seizure disorders in mice (Fig. 1), employing a targeted mutagenesis method to exploit the genetic defects identified in human epilepsy families. After detailed characterization of the nature of the human mutation and the mouse counterpart gene, a targeting vector containing the human disease allele is created. The endogenous mouse gene is replaced by the human disease allele through homologous recombination in ES cells, leading to the generation of chimeric animals. Mice carrying one copy or both copies of the human mutation can be bred to study the phenotypic effect of heterozygous and homozygous mutations. At this stage, one may want to split the newly created mice into two groups. One group will go through seizure phenotyping tests, while the other group will be used to generate disease allele-carrying mice on a different genetic background. Phenotypic characterization of mice on different inbred strains includes behavioral monitoring and EEG analysis looking for the occurrence of spontaneous seizures, as well as routine cage examination looking for handling-provoked seizure and ECT- and PTZ- induced seizure paradigms looking for sensitivity to these stimuli. A complete evaluation of the seizure phenotype at the whole-animal level establishes the relevance of the mouse model to the human condition. Further investigation including imaging, electrophysiology and AED response in these mouse models will shed light on the mechanistic basis of the convulsive disorder. Current epilepsy research in mouse genetics offers promise for understanding the molecular mechanisms that underlie epileptogenesis in humans. A large-scale forward genetic effort to create novel mouse mutants with seizure phenotypes by in vivo chemical mutagenesis with ethyl-nitroso urea (ENU) is underway at the Jackson Laboratory (http://www.jax.org/nmf/). Genetic mapping and isolation of the affected genes in these seizure-prone models will provide additional molecular pathways involved in seizures. The mutant mice generated through both forward and reverse genetic approaches will be a valuable resource for the biomedical community to study epilepsy at the molecular level and to characterize the pathological consequences of seizures in the whole organism

Recent Advances in the Treatment of Acanthamoeba

Infection of the eye caused by Acanthamoeba species constitutes a burgeoning and unsolved problem. Of individuals with Acanthamoeba keratitis, 85% wear contact lenses; abrasion of the cornea is implicated. Corneal infection often can be prevented by good lens care and hygiene. Severe Acanthamoeba keratitis often can be very difficult to treat; surgery can be less than successful and may lead to further problems. The encysted stage in the life cycle of Acanthamoeba species appears to cause the most problems; many biocides are ineffective in killing the highly resistant cysts. Combination therapy—that is, use of 2 or 3 biocides, sometimes with antibacterial antibiotics—appears to work best. Recurrence is common if treatment is stopped prematurely. Immunologic methods are being investigated as a form of prevention, and oral immunization of animals recently has been successful in the prevention of Acanthamoeba keratitis by inducing immunity before infection occurs. Immunization thus may eventually become the best approach for reduction of the incidence of amebic infection in humans