Physical capability and the advantages and disadvantages of ageing : Perceptions of older age by men and women in two British cohorts

In an increasingly ageing society, its older members are receiving considerable political and policy attention. However, much remains to be learnt about public perceptions of older age, particularly the views and experiences of older individuals themselves. Drawing on qualitative interviews carried out with members of two British cohorts (N = ??) who have reached the ‘third age’, this paper discusses perceptions of age, focusing particularly on how perceived advantages and disadvantages differ by respondents’ self-reported physical capability. The interviews were carried out in ???? as part of the HALCyon (Healthy Ageing across the Life Course) collaborative research programme. Findings suggest there is some difference in the way older people view aspects of ageing by capability and that although advantages are widely perceived, physical decline and associated health concerns were the overwhelming theme across the conversations. The article concludes by making tentative suggestions to inform the positive ageing agenda and its related policies

Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour

Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role

Two-dimensional N=(2,2) super Yang-Mills theory on computer

We carry out preliminary numerical study of Sugino's lattice formulation \cite{Sugino:2004qd,Sugino:2004qdf} of the two-dimensional $\mathcal{N}=(2,2)$ super Yang-Mills theory (2d $\mathcal{N}=(2,2)$ SYM) with the gauge group \SU(2). The effect of dynamical fermions is included by re-weighting a quenched ensemble by the pfaffian factor. It appears that the complex phase of the pfaffian due to lattice artifacts and flat directions of the classical potential are not problematic in Monte Carlo simulation. Various one-point supersymmetric Ward-Takahashi (WT) identities are examined for lattice spacings up to $a=0.5/g$ with the fixed physical lattice size $L=4.0/g$, where $g$ denotes the gauge coupling constant in two dimensions. WT identities implied by an exact fermionic symmetry of the formulation are confirmed in fair accuracy and, for most of these identities, the quantum effect of dynamical fermions is clearly observed. For WT identities expected only in the continuum limit, the results seem to be consistent with the behavior expected from supersymmetry, although we do not see clear distintion from the quenched simulation. We measure also the expectation values of renormalized gauge-invariant bi-linear operators of scalar fields.Comment: 24 pages, 10 figures, the distribution of the complex phase of the pffafian is also measured, the final version to appear in JHE

Molecular, Enzymatic, and Cellular Characterization of Soluble Adenylyl Cyclase From Aquatic Animals.

The enzyme soluble adenylyl cyclase (sAC) is the most recently identified source of the messenger molecule cyclic adenosine monophosphate. sAC is evolutionarily conserved from cyanobacteria to human, is directly stimulated by [Formula: see text] ions, and can act as a sensor of environmental and metabolic CO2, pH, and [Formula: see text] levels. sAC genes tend to have multiple alternative promoters, undergo extensive alternative splicing, be translated into low mRNA levels, and the numerous sAC protein isoforms may be present in various subcellular localizations. In aquatic organisms, sAC has been shown to mediate various functions including intracellular pH regulation in coral, blood acid/base regulation in shark, heart beat rate in hagfish, and NaCl absorption in fish intestine. Furthermore, sAC is present in multiple other species and tissues, and sAC protein and enzymatic activity have been reported in the cytoplasm, the nucleus, and other subcellular compartments, suggesting even more diverse physiological roles. Although the methods and experimental tools used to study sAC are conventional, the complexity of sAC genes and proteins requires special considerations that are discussed in this chapter

NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion

Overexpression of the NAD(+) biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD(+) or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD(+) metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD(+) synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD(+) consumption that is central to axon degeneration. DOI: http://dx.doi.org/10.7554/eLife.19749.00

Current cosmological bounds on neutrino masses and relativistic relics

We combine the most recent observations of large-scale structure (2dF and SDSS galaxy surveys) and cosmic microwave anisotropies (WMAP and ACBAR) to put constraints on flat cosmological models where the number of massive neutrinos and of massless relativistic relics are both left arbitrary. We discuss the impact of each dataset and of various priors on our bounds. For the standard case of three thermalized neutrinos, we find an upper bound on the total neutrino mass sum m_nu < 1.0 (resp. 0.6) eV (at 2sigma), using only CMB and LSS data (resp. including priors from supernovae data and the HST Key Project), a bound that is quite insensitive to the splitting of the total mass between the three species. When the total number of neutrinos or relativistic relics N_eff is left free, the upper bound on sum m_nu (at 2sigma, including all priors) ranges from 1.0 to 1.5 eV depending on the mass splitting. We provide an explanation of the parameter degeneracy that allows larger values of the masses when N_eff increases. Finally, we show that the limit on the total neutrino mass is not significantly modified in the presence of primordial gravitational waves, because current data provide a clear distinction between the corresponding effects.Comment: 13 pages, 6 figure

Sensitivity Projections for Dark Matter Searches with the Fermi Large Area Telescope

The nature of dark matter is a longstanding enigma of physics; it may consist of particles beyond the Standard Model that are still elusive to experiments. Among indirect search techniques, which look for stable products from the annihilation or decay of dark matter particles, or from axions coupling to high-energy photons, observations of the $\gamma$-ray sky have come to prominence over the last few years, because of the excellent sensitivity of the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope mission. The LAT energy range from 20 MeV to above 300 GeV is particularly well suited for searching for products of the interactions of dark matter particles. In this report we describe methods used to search for evidence of dark matter with the LAT, and review the status of searches performed with up to six years of LAT data. We also discuss the factors that determine the sensitivities of these searches, including the magnitudes of the signals and the relevant backgrounds, considering both statistical and systematic uncertainties. We project the expected sensitivities of each search method for 10 and 15 years of LAT data taking. In particular, we find that the sensitivity of searches targeting dwarf galaxies, which provide the best limits currently, will improve faster than the square root of observing time. Current LAT limits for dwarf galaxies using six years of data reach the thermal relic level for masses up to 120 GeV for the $b\bar{b}$ annihilation channel for reasonable dark matter density profiles. With projected discoveries of additional dwarfs, these limits could extend to about 250 GeV. With as much as 15 years of LAT data these searches would be sensitive to dark matter annihilations at the thermal relic cross section for masses to greater than 400 GeV (200 GeV) in the $b\bar{b}$ ($\tau^+ \tau^-$) annihilation channels.Comment: Updated with a few additional and corrected references; otherwise, text is identical to previous version. Submitted on behalf of the Fermi-LAT collaboration. Accepted for publication in Physics Reports, 59 pages, 34 figures; corresponding author: Eric Charles ([email protected]

Solution of the Nuclear Shell Model by Symmetry-Dictated Truncation

The dynamical symmetries of the Fermion Dynamical Symmetry Model are used as a principle of truncation for the spherical shell model. Utilizing the usual principle of energy-dictated truncation to select a valence space, and symmetry-dictated truncation to select a collective subspace of that valence space, we are able to reduce the full shell model space to one of manageable dimensions with modern supercomputers, even for the heaviest nuclei. The resulting shell model then consists of diagonalizing an effective Hamiltonian within the restricted subspace. This theory is not confined to any symmetry limits, and represents a full solution of the original shell model if the appropriate effective interaction of the truncated space can be determined. As a first step in constructing that interaction, we present an empirical determination of its matrix elements for the collective subspace with no broken pairs in a representative set of nuclei with $130\le A \le 250$. We demonstrate that this effective interaction can be parameterized in terms of a few quantities varying slowly with particle number, and is capable of describing a broad range of low-energy observables for these nuclei. Finally we give a brief discussion of extending these methods to include a single broken collective pair.Comment: invited paper for J. Phys. G, 57 pages, Latex, 18 figures a macro are available under request at [email protected]

Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the development and maintenance of cognitive function