PERK Activation Promotes Medulloblastoma Tumorigenesis by Attenuating Premalignant Granule Cell Precursor Apoptosis.

Evidence suggests that activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress negatively or positively influences cell transformation by regulating apoptosis. Patched1 heterozygous deficient (Ptch1(+/-)) mice reproduce human Gorlin's syndrome and are regarded as the best animal model to study tumorigenesis of the sonic hedgehog subgroup of medulloblastomas. It is believed that medulloblastomas in Ptch1(+/-) mice results from the transformation of granule cell precursors (GCPs) in the developing cerebellum. Here, we determined the role of PERK signaling on medulloblastoma tumorigenesis by assessing its effects on premalignant GCPs and tumor cells. We found that PERK signaling was activated in both premalignant GCPs in young Ptch1(+/-) mice and medulloblastoma cells in adult mice. We demonstrated that PERK haploinsufficiency reduced the incidence of medulloblastomas in Ptch1(+/-) mice. Interestingly, PERK haploinsufficiency enhanced apoptosis of premalignant GCPs in young Ptch1(+/-) mice but had no significant effect on medulloblastoma cells in adult mice. Moreover, we showed that the PERK pathway was activated in medulloblastomas in humans. These results suggest that PERK signaling promotes medulloblastoma tumorigenesis by attenuating apoptosis of premalignant GCPs during the course of malignant transformation.Grant numbers and sources of support: National Institutes of Health (NS73132, NS37956, and CA21765), National Multiple Sclerosis Society (RG4813-A-2 and RG5239-A-3), and Wellcome Trust.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.ajpath.2016.03.00

The social security rights of older international migrants in the European Union

Europe is now home to a significant and diverse population of older international migrants. Social and demographic changes have forced the issue of social security in old age onto the European social policy agenda in the last decade. In spite of an increased interest in the financial well-being of older people, many retired international migrants who are legally resident in the European Union face structured disadvantages. Four linked factors are of particular importance in shaping the pension rights and levels of financial provision available to individual older migrants: migration history, socio-legal status, past relationship to the paid labour market, and location within a particular EU Member State. Building on a typology of older migrants, the paper outlines the ways in which policy at both the European Union and Member State levels serves to diminish rather than enhance the social security rights of certain older international migrants

On the Molecular and Submolecular Structure of the Semiquinone Cations of Alloxazines and Isoalloxazines as Revealed by Electron-Paramagnetic-Resonance Spectroscopy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66144/1/j.1432-1033.1981.tb05295.x.pd

Spin-Dependent Cyclotron Decay Rates in Strong Magnetic Fields

Cyclotron decay and absorption rates have been well studied in the literature, focusing primarily on spectral, angular and polarization dependence. Astrophysical applications usually do not require retention of information on the electron spin state, and these are normally averaged in obtaining the requisite rates. In magnetic fields, higher order quantum processes such as Compton scattering become resonant at the cyclotron frequency and its harmonics, with the resonances being formally divergent. Such divergences are usually eliminated by accounting for the finite lifetimes of excited Landau states. This practice requires the use of spin-dependent cyclotron rates in order to obtain accurate determinations of process rates very near cyclotronic resonances, the phase space domain most relevant for certain applications to pulsar models. This paper develops previous results in the literature to obtain compact analytic expressions for cyclotron decay rates/widths in terms of a series of Legendre functions of the second kind; these expressions can be expediently used in astrophysical models. The rates are derived using two popular eigenstate formalisms, namely that due to Sokolov and Ternov, and that due to Johnson and Lippmann. These constitute two sets of eigenfunctions of the Dirac equation that diagonalize different operators, and accordingly yield different spin-dependent cyclotron rates. This paper illustrates the attractive Lorentz transformation characteristics of the Sokolov and Ternov formulation, which is another reason why it is preferable when electron spin information must be explicitly retained.Comment: 11 pages, 2 embedded figures, apjgalley format, To appear in The Astrophysical Journal, Vol 630, September 1, 2005 issu

Use of the Extended Fujita method for representing the molecular weight and molecular weight distributions of native and processed oat beta-glucans

Beta 1–3, 1–4 glucans (“beta-glucans”) are one of the key components of the cell wall of cereals, complementing the main structural component cellulose. Beta-glucans are also an important source of soluble fbre in foods containing oats with claims of other benefcial nutritional properties such as plasma cholesterol lowering in humans. Key to the function of beta-glucans is their molecular weight and because of their high polydispersity - molecular weight distribution. Analytical ultracentrifugation provides a matrix-free approach (not requiring separation columns or media) to polymer molecular weight distribution determination. The sedimentation coefficient distribution is converted to a molecular weight distribution via a power law relation using an established procedure known as the Extended Fujita approach. We establish and apply the power law relation and Extended Fujita method for the frst time to a series of native and processed oat beta-glucans. The application of this approach to beta-glucans from other sources is considered