Opposing early and late effects of insulin-like growth factor I on differentiation and the cell cycle regulatory retinoblastoma protein in skeletal myoblasts.

The mechanisms by which insulin-like growth factors (IGFs) can be both mitogenic and differentiation-promoting in skeletal myoblasts are unclear because these two processes are believed to be mutually exclusive in this tissue. The phosphorylation state of the ubiquitous nuclear retinoblastoma protein (Rb) plays an important role in determining whether myoblasts proliferate or differentiate: Phosphorylated Rb promotes mitogenesis, whereas un- (or hypo-) phosphorylated Rb promotes cell cycle exit and differentiation. We hypothesized that IGFs might affect the fate of myoblasts by regulating the phosphorylation of Rb. Although long-term IGF treatment is known to stimulate differentiation, we find that IGFs act initially to inhibit differentiation and are exclusively mitogenic. These early effects of IGFs are associated with maintenance of Rb phosphorylation typical of proliferating cells; upregulation of the gene expression of cyclin-dependent kinase 4 and cyclin D1, components of a holoenzyme that plays a principal role in mediating Rb phosphorylation; and marked inhibition of the gene expression of myogenin, a member of the MyoD family of skeletal muscle-specific transcription factors that is essential in muscle differentiation. We also find that IGF-induced inhibition of differentiation occurs through a process that is independent of its mitogenic effects. We demonstrate, thus, that IGFs regulate Rb phosphorylation and cyclin D1 and cyclin-dependent kinase 4 gene expression; together with their biphasic effects on myogenin expression, these results suggest a mechanism by which IGFs are initially mitogenic and subsequently differentiation-promoting in skeletal muscle.

Synergy between T-cell immunity and inhibition of paracrine stimulation causes tumor rejection.

During tumor progression, variants may arise that grow more vigorously. The fate of such variants depends upon the balance between aggressiveness of the variant and the strength of the host immunity. Although enhancing host immunity to cancer is a logical objective, eliminating host factors necessary for aggressive growth of the variant should also be considered. The present study illustrates this concept in the model of a spontaneously occurring, progressively growing variant of an ultraviolet light-induced tumor. The variant produces chemotactic factors that attract host leukocytes and is stimulated in vitro by defined growth factors that can be produced or induced by leukocytes. This study also shows that CD8+ T-cell immunity reduces the rate of tumor growth; however, the variant continues to grow and kills the host. Treatment with a monoclonal anti-granulocyte antibody that counteracts the infiltration of the tumor cell inoculum by non-T-cell leukocytes did not interfere with the CD8+ T-cell-mediated immune response but resulted in rejection of the tumor challenge, indicating a synergy between CD8+ T-cell-mediated immunity and the inhibition of paracrine stimulation.

Redistribution of synaptic vesicles and their proteins in temperature-sensitive shibire(ts1) mutant Drosophila.

From an extract of Drosophila melanogaster head homogenates, a membrane fraction can be isolated that has the same sedimentation properties as vertebrate synaptic vesicles and contains Drosophila synaptotagmin. The fraction disappears from homogenates of temperature-sensitive (ts) mutant shibire(ts1) (shi(ts1)) flies paralyzed by exposure to non-permissive temperatures, and reappears on return to permissive temperatures. Since reversible, temperature-dependent depletion of synaptic vesicles is known to occur in shibire(ts1) flies, we conclude that the fraction we have identified contains synaptic vesicles. We have examined the fate of synaptic vesicle membrane proteins in shibire flies at nonpermissive temperatures and found that all of these vesicle antigens are transferred to rapidly sedimenting membranes and codistribute with a plasma membrane marker by both glycerol velocity and metrizamide density sedimentation and by confocal microscopy. Three criteria were used to establish that other neuron-specific antigens--neuronal synaptobrevin and cysteine-string proteins--are legitimate components of synaptic vesicles: cosedimentation with Drosophila synaptotagmin, immunoadsorption, and disappearance of these antigens from the vesicle fractions in paralyzed shibire flies.

The many lives of magnetized neutron stars

The magnetic field strength at birth is arguably one of the most important properties to determine the evolutionary path of a neutron star. Objects with very high fields, collectively known as magnetars, are characterized by high X-ray quiescent luminosities, occurrence of outbursts, and, for some of them, sporadic giant flares. While the magnetic field strength is believed to drive their collective behaviour, however, the diversity of their properties, and, especially, the observation of magnetar-like bursts from “low-field” pulsars, has been a theoretical puzzle. In this review, we discuss results of long-term simulations following the coupled evolution of the X-ray luminosity and the timing properties for a large, homogeneous sample of X-ray emitting isolated neutron stars, accounting for a range of initial magnetic field strengths, envelope compositions, and neutron star masses. In addition, by following the evolution of magnetic stresses within the neutron star crust, we can also relate the observed magnetar phenomenology to the physical properties of neutron stars, and in particular to their age and magnetic field strength and topology. The dichotomy of “high-B” field pulsars versus magnetars is naturally explained, and occasional outbursts from old, low B-field neutron stars are predicted. We conclude by speculating on the fate of old magnetars, and by presenting observational diagnostics of the neutron star crustal field topology.

The Berlin Republic. Evolution of Germany's politics of memory and German patriotism. OSW Point of View, August 2009

Important changes have occurred in recent years in the attitude of a majority of the German elite towards the history of the 20th century and the political identity built on collective memory. Until recently, the sense of guilt for the crimes of the Third Reich and the obligation to remember were prevalent. While these two elements of Germany's memory of World War II are still important, currently the focus increasingly shifts to the German resistance against Nazism and the fate of the Germans who suffered in the war. Positive references to Germany's post-war history also occupy more and more space in the German memory. In 2009, i.e. the year of the 60th anniversary of the Federal Republic of Germany and the 20th anniversary of the fall of Communism, the efforts of German public institutions concentrate on promoting a new canon of history built around the successful democratisation and Germany's post-war economic success. The purpose behind these measures is to build a common historical memory that could be shared by the eastern and western parts of Germany and appeal to Germany's immigrants, who account for a growing proportion of the society.

Tunisia: Changes and Challenges of Political Transition. MEDPRO Technical Report No. 3/May 2011

For 23 years, a combination of harsh repression and impressive socio-economic development in Tunisia ensured a certain level of stability of Ben Ali’s regime. However, on 14 January 2011, after several weeks of anti-government protests, the President fled the country, revealing the fallacy of the ‘Tunisian model’. While the departure of Ben Ali is an important step towards Tunisia’s political change, the fate of its democratic transition remains uncertain. In light of these changes and challenges, this paper first assesses the factors underpinning the former stability of Ben Ali’s regime; it then investigates the causes of its underlying unsustainability, culminating in the anti-government popular uprising in December 2010-January 2011 and the removal of Ben Ali; finally the paper evaluates the prospects for a real democratic transition in Tunisia, by highlighting the main political and socio-economic challenges that confront the country

Oxygen microprofiles and porewater chemistry in sediments of the Skagerrak

Sediment porewater oxygen profiles were measured with micro and needle electrodes in sediment cores of 27 stations in the Skagerrak (northeastern North Sea). Oxygen penetration depth ranged from 3 to 20 mm depth. Fluxes estimated from the oxygen gradients varied from 3 to 18 mmol m**-2 d**-1. Oxygen penetration and flux depend on water depth, but possibly more on the hydrological conditions, related to the import of fresh organic matter by primary production in the water column. Oxygen fluxes were not related to the total organic carbon (TOC) content of the sediments. Stations in the eastern part of the Skagerrak showed high burial rates of TOC. At 6 stations porewater chemistry of Fe, Mn and NO3- was strongly associated with the oxygen distribution. The average relative contribution of terminal electron acceptors to carbon mineralisation was estimated at 85% for O2, 0.5% for Mn, 4.5% for [NO3]3-, 1% for Fe and 9% for [SO4]2-. At one station the occurrence of exceptionally high solid manganese oxyhydroxides was probably related to an active internal manganese cycle.

Stable carbon and oxygen isotope ratios of benthic and planktic foraminifera from the Atlantic Ocean

Benthonic foraminifera in late Pleistocene deep-sea cores show significant variation in delta 13C with depth in sediment. This, and the report by Sommer et al., (in prep) of delta 13C variations in planktonic foraminifera, indicate that the delta13C in dissolved oceanic CO2 undergoes a significant change in a few thousand years. This is in apparent contradiction to the estimated 300 ka residence time for carbon in the ocean. It is suggested that this is a consequence of changes in the terrestrial plant biomass, which has a delta13C of about -25?. Postulated changes in world vegetation, particularly in tropical rainforests during the Late Pleistocene, were sufficient to produce change of the magnitude observed. Rapid expansions of forests between 13 ka and 8 ka ago may have resulted in the striking accumulation of aragonite pteropods in Atlantic Ocean sediments of the age. Rapid deforestation during an interglacial-glacial transition probably caused the intense carbonate dissolution which is observed in Equatorial Pacific Ocean sediments deposited over this interbal. The current rate of injection of fossil fuel CO2 into the atmosphere is substantially greater than the rate at which it was added during post-interglacial aridification in the tropics.

Being young in a changing world: how temperature and salinity changes interactively modify the performance of larval stages of the barnacle Amphibalanus improvisus

The fate of key species, such as the barnacle Amphibalanus improvisus, in the course of global change is of particular interest since any change in their abundance and/or performance may entail community-wide effects. In the fluctuating Western Baltic, species typically experience a broad range of environmental conditions, which may preselect them to better cope with climate change. In this study, we examined the sensitivity of two crucial ontogenetic phases (naupliar, cypris) of the barnacle toward a range of temperature (12, 20, and 28°C) and salinity (5, 15, and 30 psu) combinations. Under all salinity treatments, nauplii developed faster at intermediate and high temperatures. Cyprid metamorphosis success, in contrast, was interactively impacted by temperature and salinity. Survival of nauplii decreased with increasing salinity under all temperature treatments. Highest settlement rates occurred at the intermediate temperature and salinity combination, i.e., 20°C and 15 psu. Settlement success of "naive" cyprids, i.e., when nauplii were raised in the absence of stress (20°C/15 psu), was less impacted by stressful temperature/salinity combinations than that of cyprids with a stress history. Here, settlement success was highest at 30 psu particularly at low and high temperatures. Surprisingly, larval survival was not highest under the conditions typical for the Kiel Fjord at the season of peak settlement (20°C/15 psu). The proportion of nauplii that ultimately transformed to attached juveniles was, however, highest under these "home" conditions. Overall, only particularly stressful combinations of temperature and salinity substantially reduced larval performance and development. Given more time for adaptation, the relatively smooth climate shifts predicted will probably not dramatically affect this species.

Degradation of [14C]GlcDGD in the marine sediment by monitoring radioactivity in the aqueous and gas phase using liquid scintillation counting (LSC) techniques

An experiment was conceived in which we monitored degradation of GlcDGD. Independent of the fate of the [14C]glucosyl headgroup after hydrolysis from the glycerol backbone, the 14C enters the aqueous or gas phase whereas the intact lipid is insoluble and remains in the sediment phase. Total degradation of GlcDGD then is obtained by combining the increase of radioactivity in the aqueous and gaseous phases. We chose two different sediment to perform this experiment. One is from microbially actie surface sediment sampled in February 2010 from the upper tidal flat of the German Wadden Sea near Wremen (53° 38' 0N, 8° 29' 30E). The other one is deep subsurface sediments recovered from northern Cascadia Margin during Integrated Ocean Drilling Program Expedition 311 [site U1326, 138.2 meters below seafloor (mbsf), in situ temperature 20 °C, water depth 1,828 m. We performed both alive and killed control experiments for comparison. Surface and subsurface sediment slurry were incubated in the dark at in situ temperature, 4 °C and 20 °C for 300 d, respectively. The sterilized slurry was stored at 20 °C. All incubations were carried out under N2 headspace to ensure anaerobic conditions. The sampling frequency was high during the first half-month, i.e., after 1, 2, 7, and 14 d; thereafter, the sediment slurry was sampled every 2 months. At each time point, samples were taken in triplicate for radioactivity measurements. After 300 d of incubation, no significant changes of radioactivity in the aqueous phase were detected. This may be the result of either the rapid turnover of released [14C] glucose or the relatively high limit of detection caused by the slight solubility (equivalent to 2% of initial radioactivity) of GlcDGD in water. Therefore, total degradation of GlcDGD in the dataset was calculated by combining radioactivity of DIC, CH4, and CO2, leading to a minimum estimate.