Learning from Alfred Wegener's pioneering field observations in West Greenland after a century of climate change.

The cryosphere in Greenland is currently undergoing strong changes. While remote sensing improves our understanding of spatial and temporal changes across scales, particularly our knowledge of conditions during the pre-satellite era is fragmented. Therefore, high-quality field data from that period can be particularly valuable to better understand changes of the cryosphere in Greenland at climate time scales. At Graz University, the last work-place of Alfred Wegener we have access to the extensive expedition results from their epic 1929-1931 expedition to Greenland. The expedition coincides with the warmest phase of the Arctic early twentieth century warm period. We present an overview of the main findings of the Wegener expedition archive and set it into context with further monitoring activities that occurred since, as well as the results from reanalysis products and satellite imagery. We find that firn temperatures have increased significantly, while snow and firn densities and have remained similar or decreased since. Local conditions at the Qaamarujup Sermia have changed strongly, with a reduction in length of more than 2 km, in thickness by up to 120 m and a rise in terminus position of approximately 300 m. The elevation of the snow line of the years 1929 and 1930 was similar to the one from the extreme years 2012 and 2019. Compared to the satellite era, we find that during the time of the Wegener expedition fjord ice extent was smaller in early spring and larger in late spring. We demonstrate that a well-documented snapshot of archival data can provide a local and regional context for contemporary climate change and that it can serve as the basis for process-based studies on the atmospheric drivers of glacier changes.

Disentangling Drivers of Meteorological Droughts in the European Greater Alpine Region During the Last Two Centuries.

This study investigates the atmospheric drivers of severe precipitation deficits in the Greater Alpine Region during the last 210 years utilizing a daily atmospheric circulation type reconstruction. Precipitation deficit tends to be higher during periods with more frequent anticyclonic (dry) and less frequent cyclonic (wet) circulation types, as would be expected. However, circulation characteristics are not the main drivers of summer precipitation deficit. Dry soils in the warm season tend to limit precipitation, which is particularly the case for circulation types that are sensitive to a soil moisture-precipitation feedback. This mechanism is of specific relevance in explaining the major drought decades of the 1860s and 1940s. Both episodes show large negative precipitation anomalies in spring followed by increasing frequencies of circulation types sensitive to soil moisture precipitation feedbacks. The dry springs of the 1860s were likely caused by circulation characteristics that were quite different from those of recent decades as a consequence of the large spatial extent of Arctic sea ice at the end of the Little Ice Age. On the other hand, the dry springs of the 1940s developed under a persistent positive pressure anomaly across Western and Central Europe, triggered by positive sea surface temperatures in the western subtropical Atlantic.

The pi-helix formation between Asp369 and Thr375 as a key factor in E1-E2 conformational change of Na+/K+-ATPase.

Molecular modeling of the H4-H5-loop of the alpha2 isoform of Na+/K+-ATPase in the E1 and E2 conformations revealed that twisting of the nucleotide (N) domain toward the phosphorylation (P) domain is connected with the formation of a short pi-helix between Asp369 and Thr375. This conformational change close to the hinge region between the N-domain and the P-domain could be an important event leading to a bending of the N-domain by 64.7 degrees and to a shortening of the distance between the ATP binding site and the phosphorylation site (Asp369) by 1.22 nm from 3.22 nm to 2.00 nm. It is hypothesized that this shortening mechanism is involved in the Na+-dependent formation of the Asp369 phospho-intermediate as part of the overall Na+/K+-ATPase activity.

Functional relationship between Na/K-ATPase and NMDA-receptors in rat cerebellum granule cells.

Activation of rat cerebellum granule cells by N-methyl-D-aspartate (NMDA, 10(-4)-10(-3) M) results in progressive increase in reactive oxygen species (ROS) and suppression of the ouabain-sensitive part of Na/K-ATPase activity. When Na/K-ATPase was inhibited by high ouabain concentrations (10(-5)-5 x 10(-4) M), an increase in stationary ROS level in neuronal cells was noted, this effect being attenuated by NMDA antagonists, MK-801 and D-AP5. It is concluded that in cerebellum neurons, ouabain-resistant Na/K-ATPase is responsible for suppression of intracellular level of ROS, which, in turn, inhibit ouabain-sensitive Na/K-ATPase.

Application of the high-temperature ratio method for evaluation of the depth distribution of dose equivalent in a water-filled phantom on board space station Mir.

A water-filled tissue equivalent phantom with a diameter of 35 cm was developed at the Institute for Biomedical Problems. Moscow. Russia. It contains four channels perpendicular to each other, where dosemeters can be exposed at different depths. Between May 1997 and February 1999 the phantom was installed at three different locations on board the Mir space station. Thermoluminescence dosemeters (TLDs) were exposed at various depths inside the phantom either parallel or perpendicular to the hull of the spacecraft. The high-temperature ratio (HTR) method was used for the evaluation of the TLDs. The method was developed at the Atominstitute of the Austrian Universities. Vienna, Austria, and has already been used for measurements in mixed radiation fields on earth and in space with great success. It uses the changes of peak height ratios in LiF:Mg,Ti glow curves in dependence on the linear energy transfer (LET), and therefore allows determination of an 'averaged' LET as well as measurement of the absorbed dose. A mean quality factor and, subsequently, the dose equivalent can be calculated according to the Q(LETinfinity) relationship proposed by the ICRP. The small size of the LiF dosemeters means that the HTR method can be used to determine the gradient of absorbed dose and dose equivalent inside the tissue equivalent body.

Dose assessment of aircrew using passive detectors.

Radiation exposure of aircrew is a serious concern which has been given special emphasis in the European Council directive 96/29/Euratom. The cosmic ray induced neutron component can contribute more than 50% to the biologically relevant dose at aviation altitudes. Various computational approaches to route dose assessment, e.g. CARI, are in use nowadays and are compared with experimental data. Measurements of aircrew exposure usually involve extensive instrumentation in order to cover the whole particle spectrum and energy range present inside aircraft. Due to their small size and easy handling, thermoluminescence dosemeters represent an appropriate alternative. Previous measurements onboard aircraft applying the high-temperature ratio method with LiF:Mg,Ti dosemeters for the determination of an 'averaged' linear energy transfer of mixed radiation fields demonstrate the ability of this method to evaluate the dose equivalent, according to the Q(LETinfinity) relationship proposed by the ICRP. Measurements with CaF2:Tm dosemeters are currently in progress and are discussed here.

Advantages of passive detectors for the determination of the cosmic ray induced neutron environment.

Due to the pronounced energy dependence of the neutron quality factor, accurate assessment of the biologically relevant dose requires knowledge of the spectral neutron fluence rate. Bonner sphere spectrometers (BSSs) are the only instruments which provide a sufficient response over practically the whole energy range of the cosmic ray induced neutron component. Measurements in a 62 MeV proton beam at Paul Scherrer Institute, Switzerland, and in the CERN-EU high-energy reference field led to the assumption that conventional active devices for the detection of thermal neutrons inside the BSS, e.g. 6Lil(Eu) scintillators, also respond to charged particles when used in high-energy mixed radiation fields. The effects of these particles cannot be suppressed by amplitude discrimination and are subsequently misinterpreted as neutron radiation. In contrast, paired TLD-600 and TLD-700 thermoluminescence dosemeters allow the determination of a net thermal neutron signal.

Analysis of the neutron component at high altitude mountains using active and passive measurement devices.

The European Council directive 96/29/Euratom requires dosimetric precautions if the effective dose exceeds 1 mSv/a. On an average, this value is exceeded by aircrew members. Roughly half of the radiation exposure at flight altitudes is caused by cosmic ray-induced neutrons. Active (6LiI(Eu)-scintillator) and passive (TLDs) Bonner sphere spectrometers were used to determine the neutron energy spectra atop Mt. Sonnblick (3105 m) and Mt. Kitzsteinhorn (3029 m). Further measurements in a mixed radiation field at CERN as well as in a proton beam of 62 MeV at Paul Scherrer Institute, Switzerland, confirmed that not only neutrons but also charged particles contribute to the readings of active detectors, whereas TLD-600 and TLD-700 in pair allow the determination of the thermal neutron flux. Unfolding of the detector data obtained atop both mountains shows two relative maxima around 1 MeV and 85 MeV, which have to be considered for the assessment of the biologically relevant dose equivalent. By convoluting the spectra with appropriate conversion functions the neutron dose equivalent rate was determined to be 150 +/- 15 nSv/h. The total dose equivalent rate determined by the HTR-method was 210 +/- 15 nSv/h. The results are in good agreement with LET-spectrometer and Sievert counter measurements carried out simultaneously.

Endogenous cardiotonic steroids.

The search for endogenous digitalis led to the isolation of ouabain from blood adrenals and hypothalamus. Additional cardiotonic steroids of the cardenolid and bufadienolide type seem to circulate in blood. Adrenal cortical cells in tissue culture release ouabain upon addition of angiotensin 11. Ouabain in blood is increased in 50% of Caucasians with low renin hypertension. Analogous to other steroid hormones, cardiotonic steroid hormones in blood are bound to a specific cardiac glycoside binding globulin. Since ouabain induced growth of myocytes in tissue culture, this effect probably mediates by partial inhibition of the sodium pump and consecutive rise of intracellular Ca2+ the thickening of the wall of arteries and myocardium. PST 2238, an antagonist of cardiac glycoside function at the sodium pump, leads in rats under prolonged therapy to a decrease of hypertension. The finding of ouabain as a new adrenal hormone of the Na+ metabolism and of ouabain antagonists opens new possibilities of therapy of hypertension and congestive heart failure.

Measurement of the depth distribution of average LET and absorbed dose inside a water-filled phantom on board space station MIR.

The Atominstitute of the Austrian Universities developed the HTR-method for determination of absorbed dose and "averaged" linear energy transfer (LET) in mixed radiation fields. The method was applied with great success during several space missions (e.g. STS-60, STS-63, BION-10 and BION-11) and on space station MIR in the past 10 years. It utilises the changes of peak height ratios in LiF thermoluminescent glowcurves in dependence on the LET. Due to the small size of these dosemeters the HTR-method can be used also for measurements inside tissue equivalent phantoms. A water filled phantom with a diameter of 35 cm containing four channels where dosemeters can be exposed in different depths was developed by the Institute for Biomedical Problems. This opens the possibility to measure the depth distribution of the average LET and the dose equivalent simultaneously. During phase 1 dosemeters were exposed for 271 days (05.1997-02.1998) in 6 different depths inside the phantom, which was positioned in the commander cabin. In phase 2 dosemeters were exposed in 2 channels in 6 different depths for 102 days (05.1998-08.1998) in the board engineer cabin, following an exposure in different channels in 3 different depths for 199 days (08.1998- 02.1999) in the Modul KWANT 2.

Ouabain, a new steroid hormone of adrenal gland and hypothalamus.

Ouabain has been isolated and identified as a constituent of human blood, bovine adrenal glands and hypothalamus. This water soluble inhibitor of the sodium pump (Na+/K+-ATPase) circulates in elevated concentrations in blood plasma of 50% of Caucasians with elevated blood pressure. It is released from adrenal cortical cells in tissue culture by angiotensin II. A ouabain antagonist, PST2238, lowers blood pressure in hypertensive rats. Hence, ouabain is most probably a new steroid hormone formed in adrenal glands and hypothalamus. Consistent therewith is the demonstration of a specific binding globulin for cardiac glycosides in blood plasma.

Endogenous ouabain and its binding globulin: effects of physical exercise and study on the globulin's tissue distribution.

Ouabain, that has been isolated from bovine adrenals and hypothalamus, is a new cardiotonic steroid hormone, which is either synthesized in the adrenals or stored there after it has absorbed from the diet. Little is known in vivo which events may lead to the release of ouabain into blood. Moreover, a binding protein for cardiotonic steroids exists in blood, which binds cardiac glycosides with high affinity. It may affect the action of endogenous ouabain on heart and circulation, but the physiological function of this protein is unclear. To realize, which physiological stimuli in vivo may affect blood concentrations of endogenous ouabain and which function the cardiotonic binding protein may have in modulating ouabain effects, the effect of physical exercise on endogenous ouabain was studied and the tissue distribution of its binding protein was investigated. We found that endogenous ouabain changes rapidly in blood upon physical exercise and behaves like expected for a hormone of circulation. The cardiotonic steroid binding globulin shows the highest concentration in the kidney, which suggests that sodium pumps of the kidney are protected against its inhibition by ouabain which would lead not only to natriuresis but also to a deleterious loss of glucose, amino acids and phosphate.

Correlation of the LET-dependent TL-response of LIF:Mg,Ti TL-dosemeters and gentoxic endpoints after proton irradiation.

The high temperature ratio (HTR) method using LiF:Mg,Ti thermoluminescent dosemeters allows in addition to the measurement of absorbed dose, the evaluation of the biological effectiveness of radiation. In order to analyse the correlation of the measured parameter HTR and gentoxic endpoints irradiation of cell cultures and TLDs were performed in a 62 MeV proton beam. The gentoxic effects respectively the relative biological effectiveness RBE, show an excellent correlation with the HTR due to a similar dose and LET-dependent behaviour.

Effects of fluorescent pseudo-ATP and ATP-metal analogs on secondary structure of Na(+)/K(+)-ATPase.

The secondary structure of Na(+)/K(+)-ATPase after modification of the ATP-binding sites was analyzed. Consistently with recent reports, we found in trypsin-treated Na(+)/K(+)-ATPase additionally to alpha-helix also beta-sheet structures in the transmembrane segments. However, binding of fluorescein 5'-isothiocyanate (FITC), the pseudo-ATP analog, to the ATP-binding site did not affect the secondary structure of undigested Na(+)/K(+)-ATPase. Consequently, fluorescence intensity changes of FITC-labeled Na(+)/K(+)-ATPase commonly used to observe conformational transitions of the enzyme reflect physiological changes of the native structure. The metal complex analogues of ATP, Cr(H(2)O)(4)ATP and Co(NH(3))(4)ATP, on the other hand, affected the secondary structure of Na(+)/K(+)-ATPase. We propose that these changes in the secondary structure are responsible for inhibition of backdoor phosphorylation.

Functional expression and characterization of the wild-type mammalian renal cortex sodium/phosphate cotransporter and an 215R mutant in Saccharomyces cerevisiae.

The wild-type and an R215E mutant of the rat renal cortex sodium/phosphate cotransporter type 2 (NaPi-2) were functionally expressed in the yeast Saccharomyces cerevisiae strain MB192, a cell line lacking the high-affinity endogenous H+/P(i) cotransporter. The expression of the mRNA molecules and corresponding proteins was confirmed by Northern and Western blot analysis, respectively. As detected by indirect immunofluorescence and antibody capture assay, both wild-type and mutant NaPi-2 proteins are expressed in the yeast plasma membrane in comparable amounts. In the presence of 5 microM phosphate, Na+ promotes phosphate uptake into yeast cells expressing the wild-type NaPi-2 with a K(0.5) of 5.6 +/- 1.1 mM. The maximum uptake of phosphate (649 +/- 30 pmol/10 min) is approximately 8-fold higher than the uptake obtained with nontransformed cells (76.8 +/- 8 pmol/10 min). Yeast cells expressing the R215E mutant of NaPi-2 accumulate 213 +/- 9 pmol of phosphate/10 min under the same conditions. The K(0.5) for the stimulation of phosphate uptake by Na+ is 4.2 +/- 0.8 mM for the R215E mutant and thus not significantly different from the value obtained with cells expressing the wild-type cotransporter. The reduced level of accumulation of phosphate in yeast cells expressing the R215E mutant is probably due to a reduction of the first-order rate constant k for phosphate uptake: while cells expressing wild-type NaPi-2 accumulate phosphate with a k of 0.06 min(-1), the rate for phosphate uptake into cells expressing the R215E mutant (k) is 0.016 min(-1) and therefore about 4-fold lower. In comparison, the rate for phosphate uptake into nontransformed cells (k) is 0.0075 min(-1). Phosphate uptake into yeast cells that express the wild-type NaPi-2 in the presence of 150 mM NaCl is promoted by extracellular phosphate with a K(0.5) of 45 +/- 4 microM. A phosphate-dependent phosphate accumulation is also observed with cells expressing the R215E mutant, but the K(0.5) is twice as high (86 +/- 5 microM) as that obtained with the wild-type cotransporter. We conclude that the yeast expression system is a useful tool for the investigation of structure-function relationships of the renal sodium/phosphate cotransporter and that (215)R, although not involved in Na+ recognition, is a part of the structure involved in phosphate recognition and considerably influences the rate of phosphate uptake by the NaPi-2 cotransporter.

Affinity labelling with MgATP analogues reveals coexisting Na+ and K+ forms of the alpha-subunits of Na+/K+-ATPase.

To test the hypothesis that Na+/K+-ATPase works as an (alpha beta)2-diprotomer with interacting catalytic alpha-subunits, tryptic digestion of pig kidney enzyme, that had been inactivated with substitution-inert MgATP complex analogues, was performed. This led to the demonstration of coexisting C-terminal Na+-like 80-kDa as well as K+-like 60-kDa peptides and N-terminal 40-kDa peptides of the alpha-subunit. To localize the ATP binding sites on tryptic peptides, studies with radioactive MgATP complex analogues were performed: Co(NH3)4-8-N3-ATP specifically modified the E2ATP (low affinity) binding site of Na+/K+-ATPase with an inactivation rate constant (k2) of 12 x 10-3.min-1 at 37 degrees C and a dissociation constant (Kd) of 207 +/- 28 microm. Tryptic digestion of the [gamma32P]Co(NH3)4-8-N3-ATP-inactivated and photolabelled alpha-subunit (Mr = 100 kDa) led, in the absence of univalent cations, to a K+-like C-terminal 60-kDa fragment which was labelled in addition to an unlabelled Na+-like C-terminal 80-kDa fragment. Tryptic digestion of [alpha32P]-or [gamma32P]Cr(H2O)4ATP - bound to the E1ATP (high affinity) site - led to the labelling of a Na+-like 80-kDa fragment besides the immediate formation of an unlabelled K+-like N-terminal 40-kDa fragment and a C-terminal 60-kDa fragment. Because a labelled Na+-like 80-kDa fragment cannot result from an unlabelled K+-like 60-kDa fragment, and because unlabelled alpha-subunits did not show any catalytic activity, the findings are consistent with a situation in which Na+- and K+-like conformations are stabilized by tight binding of substitution-inert MgATP complex analogues to the E1ATP and E2ATP sites. Hence, all data are consistent with the hypothesis that ATP binding induces coexisting Na+ and K+ conformations within an (alphabeta)2-diprotomeric Na+/K+-ATPase.

Microenvironment of the high affinity ATP-binding site of Na+/K+-ATPase is slightly acidic.

Fluorescein-5'-isothiocyanate (FITC) was used to study the high-affinity ATP-binding site of Na+/K+-ATPase. The molar ratio of specifically bound FITC per alpha-subunit of Na+/K+-ATPase was found to be 0.5 as followed from pretreatment experiments with another specific E1ATP-inhibitor Cr(H2O)4AdoPP[CH2]P. This indicated an existence of one high affinity ATP-binding site (E1ATP-binding site) in the native (alphabeta)2-diprotomer of Na+/K+-ATPase. Fluorescence dual-excitation ratio of specifically bound FITC revealed that at external pH 7.5, the pH value inside the E1ATP-binding site is 6.95 +/- 0.18. In addition, FITC fluorescence quenching by anti-fluorescein and by iodide choline indicated the limited access of water into the small pocket of the E1ATP-binding site.