In Vitro Aging of Human Skin Fibroblasts: Age-Dependent Changes in 4-Hydroxynonenal Metabolism

Evidence suggests that the increased production of free radicals and reactive oxygen species lead to cellular aging. One of the consequences is lipid peroxidation generating reactive aldehydic products, such as 4-hydroxynonenal (HNE) that modify proteins and form adducts with DNA bases. To prevent damage by HNE, it is metabolized. The primary metabolic products are the glutathione conjugate (GSH-HNE), the corresponding 4-hydroxynonenoic acid (HNA), and the alcohol 1,4-dihydroxynonene (DHN). Since HNE metabolism can potentially change during in vitro aging, cell cultures of primary human dermal fibroblasts from several donors were cultured until senescence. After different time points up to 30 min of incubation with 5 \ub5M HNE, the extracellular medium was analyzed for metabolites via liquid chromatography coupled with electrospray ionization mass spectrometry (LC/ESI-MS). The metabolites appeared in the extracellular medium 5 min after incubation followed by a time-dependent increase. But, the formation of GSH-HNL and GSH-DHN decreased with increasing in vitro age. As a consequence, the HNE levels in the cells increase and there is more protein modification observed. Furthermore, after 3 h of incubation with 5 \ub5M HNE, younger cells showed less proliferative capacity, while in older cells slight increase in the mitotic index was noticed

Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice

Human myelin disorders are commonly studied in mouse models. Since both clades evolutionarily diverged approximately 85 million years ago, it is critical to know to what extent the myelin protein composition has remained similar. Here, we use quantitative proteomics to analyze myelin purified from human white matter and find that the relative abundance of the structural myelin proteins PLP, MBP, CNP, and SEPTIN8 correlates well with that in C57Bl/6N mice. Conversely, multiple other proteins were identified exclusively or predominantly in human or mouse myelin. This is exemplified by peripheral myelin protein 2 (PMP2), which was specific to human central nervous system myelin, while tetraspanin-2 (TSPAN2) and connexin-29 (CX29/GJC3) were confined to mouse myelin. Assessing published scRNA-seq-datasets, human and mouse oligodendrocytes display well-correlating transcriptome profiles but divergent expression of distinct genes, including Pmp2, Tspan2, and Gjc3. A searchable web interface is accessible via www.mpinat.mpg.de/myelin. Species-dependent diversity of oligodendroglial mRNA expression and myelin protein composition can be informative when translating from mouse models to humans

Company ‘Emigration’ and EC Freedom of Establishment: Daily Mail Revisited

Following the ECJ’s recent case law on EC freedom of establishment (the Centros, Überseering and Inspire Art cases), regulatory competition for corporate law within the European Union takes place at an early stage of the incorporation of new companies. In contrast, as regards the ‘moving out’ of companies from the country of incorporation, the ECJ once considered a tax law restriction against the transfer abroad of a company’s administrative seat as compatible with EC freedom of establishment (the Daily Mail case). For years, this decision has been regarded as applicable to all restrictions imposed by countries of incorporation, even the forced liquidation of the ‘emigrating’ company. This paper addresses the question whether EC freedom of establishment really allows Member States to place any limit on the ‘emigration’ of nationally registered companies. It argues that EC freedom of establishment covers the transfer of the administrative seat as well as the transfer of the registered office and, therefore, that the country of incorporation cannot liquidate ‘emigrating’ companies. In addition, it addresses the question whether a new Directive is needed to allow the transfer of a com- pany’s registered office and the identity-preserving company law changes. It argues that such a Directive is necessary to avoid legal uncertainty and to protect the interests of employees, creditors and minority shareholders, among others, who could be detrimentally affected by the ‘emigration’ of national companies

The unidentified TeV source (TeVJ2032+4130) and surrounding field: Final HEGRA IACT-System results

The unidentified TeV source in Cygnus is now confirmed by follow-up observations from 2002 with the HEGRA stereoscopic system of Cherenkov Telescopes. Using all data (1999 to 2002) we confirm this new source as steady in flux over the four years of data taking, extended with radius 6.2 arcmin (+-1.2 arcmin (stat) +-0.9 arcmin (sys)) and exhibiting a hard spectrum with photon index -1.9. It is located in the direction of the dense OB stellar association, Cygnus OB2. Its integral flux above energies E>1 TeV amounts to \~5% of the Crab assuming a Gaussian profile for the intrinsic source morphology. There is no obvious counterpart at radio, optical nor X-ray energies, leaving TeVJ2032+4130 presently unidentified. Observational parameters of this source are updated here and some astrophysical discussion is provided. Also included are upper limits for a number of other interesting sources in the FoV, including the famous microquasar Cygnus X-3.Comment: 7 pages, 3 figures. Accepted for publication in Astronomy & Astrophysic

Simultaneous X-Ray and TeV Gamma-Ray Observations of the TeV Blazar Markarian 421 during February and May 2000

In this paper we present the results of simultaneous observations of the TeV blazar Markarian 421 (Mrk 421) at X-ray and TeV Gamma-ray energies with the Rossi X-Ray Timing Explorer (RXTE) and the stereoscopic Cherenkov Telescope system of the HEGRA (High Energy Gamma Ray Astronomy) experiment, respectively. The source was monitored from February 2nd to February 16th and from May 3rd to May 8th, 2000. We discuss in detail the temporal and spectral properties of the source. Remarkably, the TeV observations of February 7th/8th showed statistically significant evidence for substantial TeV flux variability on 30 min time scale. We show the results of modeling the data with a time dependent homogeneous Synchrotron Self-Compton (SSC) model. The X-ray and TeV gamma-ray emission strengths and energy spectra together with the rapid flux variability strongly suggest that the emission volume is approaching the observer with a Doppler factor of 50 or higher. The different flux variability time scales observed at X-rays and TeV Gamma-rays indicate that a more detailed analysis will require inhomogeneous models with several emission zones.Comment: Accepted for Publication in ApJ, 21 Pages, 5 Figure

Rejection of the hypothesis that Markarian 501 TeV photons are pure Bose-Einstein condensates

The energy spectrum of the Blazar type galaxy Markarian 501 (Mrk 501) as measured by the High-Energy-Gamma-Ray Astronomy (HEGRA) air Cerenkov telescopes extends beyond 16 TeV and constitutes the most energetic photons observed from an extragalactic object. A fraction of the emitted spectrum is possibly absorbed in interactions with low energy photons of the diffuse extragalactic infrared radiation, which in turn offers the unique possibility to measure the diffuse infrared radiation density by TeV spectroscopy. The upper limit on the density of the extragalactic infrared radiation derived from the TeV observations imposes constraints on models of galaxy formation and stellar evolution. One of the recently published ideas to overcome severe absorption of TeV photons is based upon the assumption that sources like Mrk 501 could produce Bose-Einstein condensates of coherent photons. The condensates would have a higher survival probability during the transport in the diffuse radiation field and could mimic TeV air shower events. The powerful stereoscopic technique of the HEGRA air Cerenkov telescopes allows to test this hypothesis by reconstructing the penetration depths of TeV air shower events: Air showers initiated by Bose-Einstein condensates are expected to reach the maximum of the shower development in the atmosphere earlier than single photon events. By comparing the energy-dependent penetration depths of TeV photons from Mrk 501 with those from the TeV standard-candle Crab Nebula and simulated air shower events, we can reject the hypothesis that TeV photons from Mrk 501 are pure Bose-Einstein condensates.Comment: 9 pages, 2 figures, published by ApJ Letters, revised version (simulation results added

Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5

Oligodendrocytes facilitate rapid impulse propagation along the axons they myelinate and support their long-term integrity. However, the functional relevance of many myelin proteins has remained unknown. Here, we find that expression of the tetraspan-transmembrane protein CMTM5 (chemokine-like factor-like MARVEL-transmembrane domain containing protein 5) is highly enriched in oligodendrocytes and central nervous system (CNS) myelin. Genetic disruption of the Cmtm5 gene in oligodendrocytes of mice does not impair the development or ultrastructure of CNS myelin. However, oligodendroglial Cmtm5 deficiency causes an early-onset progressive axonopathy, which we also observe in global and tamoxifen-induced oligodendroglial Cmtm5 mutants. Presence of the WldS mutation ameliorates the axonopathy, implying a Wallerian degeneration-like pathomechanism. These results indicate that CMTM5 is involved in the function of oligodendrocytes to maintain axonal integrity rather than myelin biogenesis

Is the giant radio galaxy M 87 a TeV gamma-ray emitter?

For the first time an excess of photons above an energy threshold of 730 GeV from the giant radio galaxy M 87 has been measured at a significance level above 4 σ. The data have been taken during the years 1998 and 1999 with the HEGRA stereoscopic system of 5 imaging atmospheric Cherenkov telescopes. The excess of 107.4 ± 26.8 events above 730 GeV corresponds to an integral flux of 3.3% of the Crab flux or Nγ (E > 730 GeV) = (0.96 ± 0.23) × 10-12 phot cm-2 s-1. M 87 is located at the center of the Virgo cluster of galaxies at a relatively small redshift of z = 0.00436 and is a promising candidate among the class of giant radio galaxies for the emission of TeV γ-radiation. The detection of TeV γ-rays from M 87 - if confirmed - would establish a new class of extragalactic source in this energy regime since all other AGN detected to date at TeV energies are BL Lac type objects.F. A. Aharonian ...G. P. Rowell...et al

Transition Rates between Mixed Symmetry States: First Measurement in 94Mo

The nucleus 94Mo was investigated using a powerful combination of gamma-singles photon scattering experiments and gamma-gamma-coincidence studies following the beta-decay of 94mTc. The data survey short-lived J^pi=1+,2+ states and include branching ratios, E2/M1 mixing ratios, lifetimes, and transition strengths. The mixed-symmetry (MS) 1+ scissors mode and the 2+ MS state are identified from M1 strengths. A gamma transition between MS states was observed and its rate was measured. Nine M1 and E2 strengths involving MS states agree with the O(6) limit of the interacting boson model-2 using the proton boson E2 charge as the only free parameter.Comment: 9 pages, 3 PostScript figures included, ReVTeX, accepted for publication in Physical Review Letters, tentatively scheduled for August 9, 199