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

Mitochondrial Oxidative Stress Causes Hyperphosphorylation of Tau

Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD): tau phosphorylation, and ß-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2) die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress. Treatment of these mice with catalytic antioxidants increases their lifespan and rescues the peripheral phenotypes, while uncovering central nervous system pathology. We examined sod2 null mice differentially treated with high and low doses of a catalytic antioxidant and observed striking elevations in the levels of tau phosphorylation (at Ser-396 and other phospho-epitopes of tau) in the low-dose antioxidant treated mice at AD-associated residues. This hyperphosphorylation of tau was prevented with an increased dose of the antioxidant, previously reported to be sufficient to prevent neuropathology. We then genetically combined a well-characterized mouse model of AD (Tg2576) with heterozygous sod2 knockout mice to study the interactions between mitochondrial oxidative stress and cerebral Aß load. We found that mitochondrial SOD2 deficiency exacerbates amyloid burden and significantly reduces metal levels in the brain, while increasing levels of Ser-396 phosphorylated tau. These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD

The Effects of Handling and Anesthetic Agents on the Stress Response and Carbohydrate Metabolism in Northern Elephant Seals

Free-ranging animals often cope with fluctuating environmental conditions such as weather, food availability, predation risk, the requirements of breeding, and the influence of anthropogenic factors. Consequently, researchers are increasingly measuring stress markers, especially glucocorticoids, to understand stress, disturbance, and population health. Studying free-ranging animals, however, comes with numerous difficulties posed by environmental conditions and the particular characteristics of study species. Performing measurements under either physical restraint or chemical sedation may affect the physiological variable under investigation and lead to values that may not reflect the standard functional state of the animal. This study measured the stress response resulting from different handling conditions in northern elephant seals and any ensuing influences on carbohydrate metabolism. Endogenous glucose production (EGP) was measured using [6-3H]glucose and plasma cortisol concentration was measured from blood samples drawn during three-hour measurement intervals. These measurements were conducted in weanlings and yearlings with and without the use of chemical sedatives—under chemical sedation, physical restraint, or unrestrained. We compared these findings with measurements in adult seals sedated in the field. The method of handling had a significant influence on the stress response and carbohydrate metabolism. Physically restrained weanlings and yearlings transported to the lab had increased concentrations of circulating cortisol (F11, 46 = 25.2, p<0.01) and epinephrine (F3, 12 = 5.8, p = 0.01). Physical restraint led to increased EGP (t = 3.1, p = 0.04) and elevated plasma glucose levels (t = 8.2, p<0.01). Animals chemically sedated in the field typically did not exhibit a cortisol stress response. The combination of anesthetic agents (Telazol, ketamine, and diazepam) used in this study appeared to alleviate a cortisol stress response due to handling in the field without altering carbohydrate metabolism. Measures of hormone concentrations and metabolism made under these conditions are more likely to reflect basal values

Cost-effectiveness of a complex intervention to reduce children’s exposure to second-hand smoke in the home

Background Second-hand smoke (SHS) causes numerous health problems in children such as asthma, respiratory tract infections and sudden infant death syndrome. The home is the main source of exposure to SHS for children, particularly for young children. We estimated the cost-effectiveness of a complex intervention designed to reduce SHS exposure of children whose primary caregiver feels unable or unwilling to quit smoking. Methods A cost-effectiveness analysis was carried out alongside an open-label, parallel, randomised controlled trial in deprived communities in Nottingham, England. A complex intervention combining behavioural support, nicotine replacement therapy and personalised feedback on home air quality was compared with usual care. A total number of 205 households were recruited, where the main caregivers were aged 18 and over, with a child aged under five years living in their household reporting smoking inside their home. Analyses for this study were undertaken from the National Health Service/Personal Social Services perspective. All costs were estimated in UK pounds (£) at 2013/14 prices. The primary outcome was the incremental cost-effectiveness of change in air quality in the home, measured as average 16–24 h levels of particulate matter of < 2.5 μm diameter (PM2.5), between baseline and 12 weeks. Secondary outcomes included incremental cost per quitter, quit attempts and cigarette consumption in the home. A non-parametric bootstrap re-sampling technique was employed to explore uncertainty around the calculated incremental cost-effectiveness ratios. Results The complex intervention achieved reduced PM2.5 by 21.6 μg/m3 (95% CI: 5.4 to 37.9), with an incremental cost of £283 (95% CI: £254–£313), relative to usual care. The incremental cost-effectiveness ratio was £131 (bootstrapped 95% CI: £72–£467) per additional 10μg/m3 reduction in PM2.5, or £71 (bootstrapped 95% CI: -£57-£309) per additional quitter. Conclusions This trial targeted a socio-economically disadvantaged population that has been neglected within the literature. The complex intervention was more costly but more effective in reducing PM2.5 compared with the usual care. It offers huge potential to reduce children’s’ tobacco-related harm by reducing exposure to SHS in the home. The intervention is considered cost-effective if the decision maker is willing to pay £131 per additional 10μg/m3 of PM2.5 reduction. Trial registration The Smoke Free Homes trial was registered with isrctn.com on 29 January 2013 with the identifier ISRCTN81701383

Substitutions in woolly mammoth hemoglobin confer biochemical properties adaptive for cold tolerance

We have genetically retrieved, resurrected and performed detailed structure-function analyses on authentic woolly mammoth hemoglobin to reveal for the first time both the evolutionary origins and the structural underpinnings of a key adaptive physiochemical trait in an extinct species. Hemoglobin binds and carries O2; however, its ability to offload O2 to respiring cells is hampered at low temperatures, as heme deoxygenation is inherently endothermic (that is, hemoglobin-O2 affinity increases as temperature decreases). We identify amino acid substitutions with large phenotypic effect on the chimeric b/d-globin subunit of mammoth hemoglobin that provide a unique solution to this problem and thereby minimize energetically costly heat loss. This biochemical specialization may have been involved in the exploitation of high-latitude environments by this African-derived elephantid lineage during the Pleistocene period. This powerful new approach to directly analyze the genetic and structural basis of physiological adaptations in an extinct species adds an important new dimension to the study of natural selection.Kevin L Campbell, Jason E E Roberts, Laura N Watson, Jörg Stetefeld, Angela M Sloan, Anthony V Signore, Jesse W Howatt, Jeremy R H Tame, Nadin Rohland, Tong-Jian Shen, Jeremy J Austin, Michael Hofreiter, Chien Ho, Roy E Weber & Alan Coope