X-Irradiation-Induced Changes of the Prelysosomal and Lysosomal Compartments and Proteolysis in HT-29 Cells

As a consequence of external and internal ionizing radiation, lysosome-like bodies have been observed to increase both in size and number in some cell types. We investigated this process by morphological methods (electron microscopy, cationized ferritin uptake, acid phosphatase histochemistry, morphometry) in cultured HT-29 cells. In parallel with these studies, we measured the rate of protein degradation on the basis of 14C-valine release from prelabeled cellular proteins. We found that at 2 and 4 Gy doses of X-irradiation the volume of the vacuolar (probably lysosomal) compartment increased without detectable changes of acid phosphatase activity. A 2 Gy irradiation dose did not change protein degradation rate. However, 4 Gy caused a significant inhibition of 14C-valine release from prelabeled proteins. Our results indicate, that the radiation induced expansion of the lysosomal compartment is not necessarily accompanied by increased lytic activity of HT-29 cells

Eruptive history of the Late Quaternary Ciomadul (Csomád) volcano, East Carpathians, part II: magma output rates

This study, which builds on high-precision unspiked Cassignol-Gillot K-Ar age determinations, presents an advanced DEMbased volumetrical analysis to infer long-term magma output rates for the Late Quaternary Ciomadul (Csomád) dacitic lava dome complex (East Carpathians, Romania). The volcanic field of Ciomadul developed on the erosional surface of Lower Cretaceous flysch and ~ 2 Ma old andesites and experienced an extended eruptive history from ~ 850 to < 30 ka. Predominantly effusive activity took place during the first stage (~ 850 to ~ 440 ka), producing volumetrically minor, isolated, peripheral domes. Subsequently, after a ~ 250 ky repose interval, a voluminous central dome cluster developed in the second stage (~ 200 to < 30 ka). During the youngest phase of evolution (~ 60 to < 30 ka), highly explosive eruptions also occurred, resulting in the formation of two craters (Mohos and St. Ana). The calculated ~ 8.00 ± 0.55 km3 total volume of the lava domes, which includes the related volcaniclastic (1.57 km3 ) as well as erosionally removed (0.18 km3 ) material, is in line with dimensions of other medium-sized dacitic lava domes worldwide. This volume was extruded at an average long-term magma output rate of 9.76 km3 / My (0.0098 km3 /ky). However, most of the domes (7.53 ± 0.51 km3 ) were formed in the 200 to < 30 ka period, implying a significantly increased magma output rate of 37.40 km3 /My (0.0374 km3 /ky), more than 30 times higher than in the first stage. Within these long-term trends, individual lava domes of Ciomadul (e.g. those with volumes between 0.02 and 0.40 km3 ) would have been emplaced at much higher rates over a period of years to tens of years. The active periods, lasting up to hundreds of years, would have been followed by repose periods ~ 30 times longer. The most recent eruption of Ciomadul has been dated here at 27.7 ± 1.4 ka. This age, which is in agreement with radiocarbon dates for the onset of lake sediment accumulation in St. Ana crater, dates fragmented lava blocks which are possibly related to a disrupted dome. This suggests that during the last, typically explosive, phase of Ciomadul, lava dome extrusion was still ongoing. In a global context, the analysis of the volumetric dynamism of Ciomadul’s activity gives insights into the temporal variations in magma output; at lava domes, short-term (dayor week-scale) eruption rates smooth out in long-term (millenia-scale) output rates which are tens of times lower

ICONE12-49300 DEVELOPMENT OF THE METHODOLOGY OF THE SAFETY ANALYSIS PERFORMED BY THE COUPLED KIKO3D/ATHLET CODE SYSTEM IN VVER-440 TYPE NPP

ABSTRACT In the deterministic safety analysis codes are required in order to provide evaluations of potential nuclear plant accidents. In the fields of the core transient behaviour, the computer codes have achieved a high degree of realistic modelling. Nevertheless, some further tools for the investigations of the wide range of physical phenomena in the whole plant transient, such as modeling the ex-core detector signals and the malfunctioning of the emergency control system are unavoidable, too. The programs and methods used in KFKI-AEKI for safety analysis of VVER-440 NPP are presented. The accident analysis methodology for a boron dilution scenario, in which an inactive coolant loop is started, is shown

Clinically relevant mutations in the ABCG2 transporter uncovered by genetic analysis linked to erythrocyte membrane protein expression

The ABCG2 membrane protein is a key xeno- and endobiotic transporter, modulating the absorption and metabolism of pharmacological agents and causing multidrug resistance in cancer. ABCG2 is also involved in uric acid elimination and its impaired function is causative in gout. Analysis of ABCG2 expression in the erythrocyte membranes of healthy volunteers and gout patients showed an enrichment of lower expression levels in the patients. By genetic screening based on protein expression, we found a relatively frequent, novel ABCG2 mutation (ABCG2-M71V), which, according to cellular expression studies, causes reduced protein expression, although with preserved transporter capability. Molecular dynamics simulations indicated a stumbled dynamics of the mutant protein, while ABCG2-M71V expression in vitro could be corrected by therapeutically relevant small molecules. These results suggest that personalized medicine should consider this newly discovered ABCG2 mutation, and genetic analysis linked to protein expression provides a new tool to uncover clinically important mutations in membrane proteins. © 2018 The Author(s)

Drainage development, neotectonics and base-level change in the Kalahari Desert, southern Africa

The Kalahari Desert contains extensive networks of ephemeral and fossil drainage which are potential indicators of past and present neotectonic activity and climatedriven environmental change. An absence of topographic data has hindered our understanding of their development. We present long-profile information for twentynine valley networks derived from Shuttle Radar Topographic Mission (SRTM) digital elevation data. In total, 8354 km of valley talweg was measured for x, y and z information. Most valleys exhibit concave-up profiles. Fifty-five previously unknown knickpoints were identified. The majority coincide with lithological boundaries or fractures, but many developed in response to Neogene uplift and/or downwarping or occur where valleys cross palaeolake shorelines. The headwaters of four valleys cross the Kalahari–Limpopo drainage divide and predate the presumed Miocene uplift of the Kalahari–Zimbabwe axis, suggesting that they are of considerable antiquity

Autophagy–physiology and pathophysiology

“Autophagy” is a highly conserved pathway for degradation, by which wasted intracellular macromolecules are delivered to lysosomes, where they are degraded into biologically active monomers such as amino acids that are subsequently re-used to maintain cellular metabolic turnover and homeostasis. Recent genetic studies have shown that mice lacking an autophagy-related gene (Atg5 or Atg7) cannot survive longer than 12 h after birth because of nutrient shortage. Moreover, tissue-specific impairment of autophagy in central nervous system tissue causes massive loss of neurons, resulting in neurodegeneration, while impaired autophagy in liver tissue causes accumulation of wasted organelles, leading to hepatomegaly. Although autophagy generally prevents cell death, our recent study using conditional Atg7-deficient mice in CNS tissue has demonstrated the presence of autophagic neuron death in the hippocampus after neonatal hypoxic/ischemic brain injury. Thus, recent genetic studies have shown that autophagy is involved in various cellular functions. In this review, we introduce physiological and pathophysiological roles of autophagy

AUTOPHAGY IN HEPATOCYTES AND ERYTHROPOIETIC CELLS ISOLATED FROM THE TWENTY-ONE DAY OLD RAT EMBRYO

Liver cells of the twenty-one day old rat embryo are isolated by a modified method and autophagy is studied in them by electron microscopic morphology and morphometry. Immediately after isolation or 2.5 h incubation in nutrient-free medium, embryonic hepatocytes contain high amount of glycogen and only very few autophagic vacuoles. In contrast, all glycogen is lost and 15% of the cytoplasmic volume is occupied by late autophagic vacuoles in hepatocytes after 18 h in the same medium. Presence of 3- methyladenine in the latter case inhibits both the loss of glycogen and the appearance of autophagic vac- uoles while enlarging the multivesicular body compartment. Our findings reveal major differences between isolated embryonic and adult hepatocytes concerning autophagy. Several types of autophagic vacuoles are described in the cell types of the erythropoietic cell lineage. This means that autophagy is an integral part of erythropoiesis not only in bone marrow, but also in embryonic liver that is investigat- ed here for the first time from this point of view. The presence of unclosed isolation membranes and the predominance of early autophagic vacuoles in reticulocytes indicates that the molecular machinery of segregation is still active in this functionally and structurally highly reduced cell type