Spermidine/spermine N1-acetyltransferase specifically binds to the integrin α9 subunit cytoplasmic domain and enhances cell migration

The integrin α9β1 is expressed on migrating cells, such as leukocytes, and binds to multiple ligands that are present at sites of tissue injury and inflammation. α9β1, like the structurally related integrin α4β1, mediates accelerated cell migration, an effect that depends on the α9 cytoplasmic domain. α4β1 enhances migration through reversible binding to the adapter protein, paxillin, but α9β1-dependent migration is paxillin independent. Using yeast two-hybrid screening, we identified the polyamine catabolizing enzyme spermidine/spermine N1-acetyltransferase (SSAT) as a specific binding partner of the α9 cytoplasmic domain. Overexpression of SSAT increased α9β1-mediated migration, and small interfering RNA knockdown of SSAT inhibited this migration without affecting cell adhesion or migration that was mediated by other integrin cytoplasmic domains. The enzyme activity of SSAT is critical for this effect, because a catalytically inactive version did not enhance migration. We conclude that SSAT directly binds to the α9 cytoplasmic domain and mediates α9-dependent enhancement of cell migration, presumably by localized effects on acetylation of polyamines or of unidentified substrates

Searching for Lee-Wick Gauge Bosons at the LHC

In an extension of the Standard Model(SM) based on the ideas of Lee and Wick, Grinstein, O'Connell and Wise have found an interesting way to remove the usual quadratically divergent contributions to the Higgs mass induced by radiative corrections. Phenomenologically, the model predicts the existence of Terascale, negative-norm copies of the usual SM fields with rather unique properties: ghost-like propagators and negative decay widths, but with otherwise SM-like couplings. The model is both unitary and causal on macroscopic scales. In this paper we examine whether or not such states with these unusual properties can be uniquely identified as such at the LHC. We find that in the extended strong and electroweak gauge boson sector of the model, which is the simplest one to analyze, such an identification can be rather difficult. Observation of heavy gluon-like resonances in the dijet channel offers the best hope for this identification.Comment: 17 pages, 4 figs; discussion adde

Equatorial scattering and the structure of the broad-line region in Seyfert nuclei: evidence for a rotating disc

Original article can be found at: http://www3.interscience.wiley.com/ Copyright Royal Astronomical Society. DOI: 10.1111/j.1365-2966.2005.08895.xWe present detailed scattering models confirming that distinctive variations in polarization across the broad Hα line, which are observed in a significant fraction of type 1 Seyfert galaxies, can be understood in terms of a rotating line-emitting disc surrounded by a coplanar scattering region (the equatorial scattering region). The predicted polarization properties are: (i) averaged over wavelength, the position angle (PA) of polarization is aligned with the projected disc rotation axis and hence also with the radio source axis; (ii) the polarization PA rotates across the line profile, reaching equal but opposite (relative to the continuum PA) rotations in the blue and red wings; and (iii) the degree of polarization peaks in the line wings and passes through a minimum in the line core. We identify 11 objects that exhibit these features to different degrees. In order to reproduce the large-amplitude PA rotations observed in some cases, the scattering region must closely surround the emission disc and the latter must itself be a relatively narrow annulus – presumably the Hα-emitting zone of a larger accretion disc. Asymmetries in the polarization spectra may be attributable to several possible causes, including bulk radial infall in the equatorial scattering region, or contamination by polar scattered light. The broad Hα lines do not, in general, exhibit double-peaked profiles, suggesting that a second Hα-emitting component of the broad-line region is present, in addition to the disc.Peer reviewe

Mammographic screening before age 50 years in the UK: comparison of the radiation risks with the mortality benefits

Mammographic screening before age 50 years is less effective than at older ages and the associated radiation risks are higher. We estimated how many breast cancer deaths could be caused and how many could be prevented by a decade of annual two-view mammographic screening starting at ages 20, 30 and 40 years, respectively, in the UK; for all women, and for women with first-degree relatives affected with breast cancer. We extrapolated from a radiation risk model to estimate the number of radiation-induced breast cancer deaths, and used results from randomised trials, which suggest a reduction in breast cancer mortality of 10–20% in women invited to screening before age 50 years, to estimate the number of deaths that could be prevented. The net change in breast cancer deaths was defined as the number of radiation-induced deaths minus the number of prevented deaths. For all women, assuming a reduction in mortality from screening of 20%, a decade of annual screening was estimated to induce more deaths than it prevents if started at age 20 years and at age 30 years (net increase=0.86 and 0.37 breast cancer deaths, respectively, per 1000 women screened). The corresponding estimate for screening starting at age 40 years was a net decrease of 0.46 deaths/1000 women screened and a zero net change assuming a 10% mortality reduction. Results for women with first-degree relatives with breast cancer were generally in the same direction but, because their background incidence rates are higher, the net increases or decreases were greater. In conclusion, our estimates suggest that a decade of annual two-view mammographic screening before age 40 years would result in a net increase in breast cancer deaths, and that starting at age 40 years could result in a material net decrease only if breast cancer mortality is reduced by about 20% or more in women screened. Although these calculations were based on a number of uncertain parameters, in general, the conclusions were not altered when these parameters were varied within a feasible range

Physiological Consequences of Compartmentalized Acyl-CoA Metabolism

Meeting the complex physiological demands of mammalian life requires strict control of the metabolism of long-chain fatty acyl-CoAs because of the multiplicity of their cellular functions. Acyl-CoAs are substrates for energy production; stored within lipid droplets as triacylglycerol, cholesterol esters, and retinol esters; esterified to form membrane phospholipids; or used to activate transcriptional and signaling pathways. Indirect evidence suggests that acyl-CoAs do not wander freely within cells, but instead, are channeled into specific pathways. In this review, we will discuss the evidence for acyl-CoA compartmentalization, highlight the key modes of acyl-CoA regulation, and diagram potential mechanisms for controlling acyl-CoA partitioning

Situationally edited empathy: an effect of socio-economic structure on individual choice

Criminological theory still operates with deficient models of the offender as agent, and of social influences on the agent’s decision-making process. This paper takes one ‘emotion’, empathy, which is theoretically of considerable importance in influencing the choices made by agents; particularly those involving criminal or otherwise harmful action. Using a framework not of rational action, but of ‘rationalised action’, the paper considers some of the effects on individual psychology of social, economic, political and cultural structure. It is suggested that the climate-setting effects of these structures promote normative definitions of social situations which allow unempathic, harmful action to be rationalised through the situational editing of empathy. The ‘crime is normal’ argument can therefore be extended to include the recognition that the uncompassionate state of mind of the criminal actor is a reflection of the self-interested values which govern non-criminal action in wider society

Negative modes in the four-dimensional stringy wormholes

We study the Giddings-Strominger wormholes in string theories. We found negative modes among O(4)-symmetric fluctuations about the non-singular wormhole background. Hence the stringy wormhole contribution to the euclidean functional integral is purely imaginary. This means that the stringy wormhole is a bounce (not an instanton) and describes the nucleation and growth of wormholes in the Minkowski spacetime.Comment: 12 pages 2 figures, RevTe

Asymptotic Giant Branch Stars in the Sculptor Dwarf Spheroidal Galaxy

JHK_S photometry is presented for a 35 arcmin square field centred on the Sculptor dwarf spheroidal galaxy. With the aid of published kinematic data definite galaxy members are identified and the width in J-K of the colour-magnitude diagram is shown to be consistent with an old population of stars with a large range in metal abundance. We identify two Asymptotic Giant Branch variables, both carbon Miras, with periods of 189 and 554 days, respectively, and discuss their ages, metallicities and mass loss as well as their positions in the Mira period-luminosity diagram. There is evidence for a general period-age relation for Local Group Miras. The mass-loss rate for the 554-day variable, MAG29, appears to be consistent with that found for Miras of comparable period in other Local Group galaxies.Comment: accepted for publication in MNRA