Cognitive and disease-modifying effects of 11ß-hydroxysteroid dehydrogenase type 1 inhibition in male Tg2576 mice, a model of Alzheimer's disease

Chronic exposure to elevated levels of glucocorticoids has been linked to age-related cognitive decline and may play a role in Alzheimer's disease. In the brain, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid levels. We show that short-term treatment of aged, cognitively impaired C57BL/6 mice with the potent and selective 11β-HSD1 inhibitor UE2316 improves memory, including after intracerebroventricular drug administration to the central nervous system alone. In the Tg2576 mouse model of Alzheimer's disease, UE2316 treatment of mice aged 14 months for 4 weeks also decreased the number of β-amyloid (Aβ) plaques in the cerebral cortex, associated with a selective increase in local insulin-degrading enzyme (involved in Aβ breakdown and known to be glucocorticoid regulated). Chronic treatment of young Tg2576 mice with UE2316 for up to 13 months prevented cognitive decline but did not prevent Aβ plaque formation. We conclude that reducing glucocorticoid regeneration in the brain improves cognition independently of reduced Aβ plaque pathology and that 11β-HSD1 inhibitors have potential as cognitive enhancers in age-associated memory impairment and Alzheimer's dementia

'Sexercise': Working out heterosexuality in Jane Fonda’s fitness books

This is an Author's Accepted Manuscript of an article published in Leisure Studies, 30(2), 237 - 255, 2011, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/02614367.2010.523837.This paper explores the connection between the promotion of heterosexual norms in women’s fitness books written by or in the name of Jane Fonda during the 1980s and the commodification of women’s fitness space in both the public and private spheres. The paper is set in the absence of overt discussions of normative heterosexuality in leisure studies and draws on critical heterosexual scholarship as well as the growing body of work theorising geographies of corporeality and heterosexuality. Using the principles of media discourse analysis, the paper identifies three overlapping characteristics of heterosexuality represented in Jane Fonda’s fitness books, and embodied through the exercise regimes: respectable heterosexual desire, monogamous procreation and domesticity. The paper concludes that the promotion and prescription of exercise for women in the Jane Fonda workout books centred on the reproduction and embodiment of heterosexual corporeality. Set within an emerging commercial landscape of women’s fitness in the 1980s, such exercise practices were significant in the legitimation and institutionalisation of heteronormativity

Partial Deficiency or Short-Term Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Improves Cognitive Function in Aging Mice

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids (GCs) from intrinsically inert 11-keto substrates inside cells, including neurons, thus amplifying steroid action. Excess GC action exerts deleterious effects on the hippocampus and causes impaired spatial memory, a key feature of age-related cognitive dysfunction. Mice with complete deficiency of 11β-HSD1 are protected from spatial memory impairments with ageing. Here, we tested whether life-long or short-term decreases in 11β-HSD1 activity are sufficient to alter cognitive function in aged mice. Aged 24m heterozygous male 11β-HSD1 knockout mice, with ~60% reduction in hippocampal 11β-reductase activity throughout life, were protected against spatial memory impairments in the Y-maze compared to age-matched congenic C57Bl/6J controls. Pharmacological treatment of aged C57Bl/6J mice with a selective 11β-HSD1 inhibitor (UE1961) for 10 days improved spatial memory performance in the Y-maze (59% greater time in novel arm than vehicle control). These data support the use of selective 11β-HSD1 inhibitors in the treatment of age-related cognitive impairments

Search for CP Violation in the Decay Z -> b (b bar) g

About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, ${\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab}$ and $h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}$, limits of \hat{h}_b < 0.59$and$h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure

Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV

A search for pair-production of supersymmetric particles under the assumption that R-parity is violated via a dominant LQDbar coupling has been performed using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV. The observed candidate events in the data are in agreement with the Standard Model expectation. This result is translated into lower limits on the masses of charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81 GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the 95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure

Effects of G/A polymorphism, rs266882, in the androgen response element 1 of the PSA gene on prostate cancer risk, survival and circulating PSA levels

Prostate-specific antigen (PSA) is a protease produced in the prostate that cleaves insulin-like growth factor binding protein-3 and other proteins. Production is mediated by the androgen receptor (AR) binding to the androgen response elements (ARE) in the promoter region of the PSA gene. Studies of a single nucleotide polymorphism (PSA −158 G/A, rs266882) in ARE1 of the PSA gene have been conflicting for risk of prostate cancer and effect on plasma PSA levels. In this nested case–control analysis of 500 white cases and 676 age- and smoking-matched white controls in the Physicians' Health Study we evaluated the association of rs266882 with risk and survival of prostate cancer and prediagnostic total and free PSA plasma levels, alone or in combination with AR CAG repeats. We used conditional logistic regression, linear regression and Cox regression, and found no significant associations between rs266882 (GG allele vs AA allele) and overall prostate cancer risk (RR=1.21, 95% confidence intervals (CI): 0.88–1.67) or prostate cancer-specific survival (RR=0.94, 95%CI: 0.56–1.58). Similarly, no associations were found among high grade or advanced stage tumours, or by calendar year of diagnosis. There was no significant association between rs266882 and baseline total or free PSA levels or the AR CAG repeats, nor any interaction associated with prostate cancer risk. Meta-analysis of 12 studies of rs266882 and overall prostate cancer risk was null

New explanation of the GAMS results on the f0(980)f_0(980) production in the reaction π−p→π0π0n\pi^-p\to \pi^0\pi^0n

The observed alteration of the S-wave $\pi^0\pi^0$ mass spectrum in the reaction $\pi^-p\to\pi^0\pi^0n$ with increasing $-t$, i.e., the disappearance of a dip and the appearance of a peak in the region of the $f_0(980)$ resonance as $-t$ increases, is explained by the contribution of the $\pi^-p\to f_0(980)n$ reaction amplitude with the quantum numbers of the $a_1$ Regge pole in the $t$ channel. It is very interesting that nontrivial evidence for the $a_1$ exchange mechanism in the reaction $\pi^-p\to \pi^0\pi^0n$ follows for the first time from the experiment on an unpolarized target. The explanation of the GAMS results suggested by us is compared with that reported previously. Two ways of experimentally testing these explanations are pointed out.Comment: 20 pages (RevTex), 5 figures (PS), minor typos corrected (in particular in Fig. 4), replaced to match the version accepted in Phys. Rev.