Changes in calcium dynamics following the reversal of the sodium-calcium exchanger have a key role in AMPA receptor-mediated neurodegeneration via calpain activation in hippocampal neurons

Proteolytic cleavage of the Na(+)/Ca(2+) exchanger (NCX) by calpains impairs calcium homeostasis, leading to a delayed calcium overload and excitotoxic cell death. However, it is not known whether reversal of the exchanger contributes to activate calpains and trigger neuronal death. We investigated the role of the reversal of the NCX in Ca(2+) dynamics, calpain activation and cell viability, in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-stimulated hippocampal neurons. Selective overactivation of AMPA receptors caused the reversal of the NCX, which accounted for approximately 30% of the rise in intracellular free calcium concentration ([Ca(2+)](i)). The NCX reverse-mode inhibitor, 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R7943), partially inhibited the initial increase in [Ca(2+)](i), and prevented a delayed increase in [Ca(2+)](i). In parallel, overactivation of AMPA receptors strongly activated calpains and led to the proteolysis of NCX3. KB-R7943 prevented calpain activation, cleavage of NCX3 and was neuroprotective. Silencing of NCX3 reduced Ca(2+) uptake, calpain activation and was neuroprotective. Our data show for the first time that NCX reversal is an early event following AMPA receptor stimulation and is linked to the activation of calpains. Since calpain activation subsequently inactivates NCX, causing a secondary Ca(2+) entry, NCX may be viewed as a new suicide substrate operating in a Ca(2+)-dependent loop that triggers cell death and as a target for neuroprotectio

Genome-Wide Analysis of Subependymomas Shows Underlying Chromosomal Copy Number Changes Involving Chromosomes 6, 7, 8 and 14 in a Proportion of Cases

Subependymomas (SE) are slow-growing brain tumors that tend to occur within the ventricles of middle-aged and elderly adults. The World Health Organization classifies these tumors within the ependymoma group. Previous limited analysis of this tumor type had not revealed significant underlying cytogenetic abnormalities

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

The prevalence of self-reported underuse of medications due to cost for the elderly: Results from seven European urban communities

Background: The aim of this study was to evaluate the prevalence of self-reported underuse of medications due to procurement costs amongst older persons from seven European urban communities. Methods: The data were collected in a cross-sectional study (“ABUEL, Elder abuse: A multinational prevalence survey”) in 2009. Randomly selected people aged 60–84 years (n = 4,467) from seven urban communities: Stuttgart (Germany), Athens (Greece), Ancona (Italy), Kaunas (Lithuania), Porto (Portugal), Granada (Spain) and Stockholm (Sweden) were interviewed. Response rate - 45.2 %. Ethical permission was received in each country. Results: The results indicate that 3.6 % (n = 162) of the respondents self-reported refraining from buying prescribed medications due to cost. The highest prevalence of this problem was identified in Lithuania (15.7 %, n = 99) and Portugal (4.3 %, n = 28). Other countries reported lower percentages of refraining from buying medications (Germany – 2.0 %, Italy – 1.6 %, Sweden – 1.0 %, Greece – 0.6 %, Spain – 0.3 %). Females refrained more often from buying medications than males (2.6 % vs. 4.4 %, p < 0.0001). The prevalence of this refraining tended to increase with economic hardship. Discussion: These differences between countries can be only partly described by the financing of health-care systems. In spite of the presence of cost reimbursement mechanisms, patients need to make co-payments (or in some cases to pay the full price) for prescribed medications. This indicates that the purchasing power of people in 10.1186/s12913-015-1089-4 the particular country can play a major role and be related with the economic situation in the country. Lithuania, which has reported the highest refrain rates, had the lowest gross domestic product (at the time of conducting this study) of all participating countries in the study. Conclusions: Refraining from buying the prescribed medications due to cost is a problem for women and men in respect to ageing people in Europe. Prevalence varies by country, sex, and economic hardship.The ABUEL was supported by the Executive Agency for Health and Consumers (EAHC) (Grant No., A/2007123) and participating institutions

Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations

SCOPUS: ar.jinfo:eu-repo/semantics/publishe