Overloaded! Critical revision and a new conceptual approach for snow indicators in ski tourism.

Indicators are widely used in climate variability and climate change assessments to simplify the tracking of complex processes and phenomena in the state of the environment. Apart from the climatic criteria, the snow indicators in ski tourism have been increasingly extended with elements that relate to the technical, operational, and commercial aspects of ski tourism. These non-natural influencing factors have gained in importance in comparison with the natural environmental conditions but are more difficult to comprehend in time and space, resulting in limited explanatory power of the related indicators when applied for larger/longer scale assessments. We review the existing indicator approaches to derive quantitative measures for the snow conditions in ski areas, to formulate the criteria that the indicators should fulfill, and to provide a list of indicators with their technical specifications which can be used in snow condition assessments for ski tourism. For the use of these indicators, a three-step procedure consisting of definition, application, and interpretation is suggested. We also provide recommendations for the design of indicator-based assessments of climate change effects on ski tourism. Thereby, we highlight the importance of extensive stakeholder involvement to allow for real-world relevance of the achieved results.

Performance of complex snow cover descriptions in a distributed hydrological model system: A case study for the high Alpine terrain of the Berchtesgaden Alps.

[1] Runoff generation in Alpine regions is typically affected by snow processes. Snow accumulation, storage, redistribution, and ablation control the availability of water. In this study, several robust parameterizations describing snow processes in Alpine environments were implemented in a fully distributed, physically based hydrological model. Snow cover development is simulated using different methods from a simple temperature index approach, followed by an energy balance scheme, to additionally accounting for gravitational and wind-driven lateral snow redistribution. Test site for the study is the Berchtesgaden National Park (Bavarian Alps, Germany) which is characterized by extreme topography and climate conditions. The performance of the model system in reproducing snow cover dynamics and resulting discharge generation is analyzed and validated via measurements of snow water equivalent and snow depth, satellite-based remote sensing data, and runoff gauge data. Model efficiency (the Nash-Sutcliffe coefficient) for simulated runoff increases from 0.57 to 0.68 in a high Alpine headwater catchment and from 0.62 to 0.64 in total with increasing snow model complexity. In particular, the results show that the introduction of the energy balance scheme reproduces daily fluctuations in the snowmelt rates that trace down to the channel stream. These daily cycles measured in snowmelt and resulting runoff rates could not be reproduced by using the temperature index approach. In addition, accounting for lateral snow transport changes the seasonal distribution of modeled snowmelt amounts, which leads to a higher accuracy in modeling runoff characteristics.

NMDA receptor-mediated K+ efflux and neuronal apoptosis.

Neuronal death induced by activating N-methyl-D-aspartate (NMDA) receptors has been linked to Ca2+ and Na+ influx through associated channels. Whole-cell recording from cultured mouse cortical neurons revealed a NMDA-evoked outward current, INMDA-K, carried by K+ efflux at membrane potentials positive to -86 millivolts. Cortical neurons exposed to NMDA in medium containing reduced Na+ and Ca2+ (as found in ischemic brain tissue) lost substantial intracellular K+ and underwent apoptosis. Both K+ loss and apoptosis were attenuated by increasing extracellular K+, even when voltage-gated Ca2+ channels were blocked. Thus NMDA receptor-mediated K+ efflux may contribute to neuronal apoptosis after brain ischemia.

Usefulness of MR Arthrography of the Hip with and without leg Traction in Detection of Intra-articular Bodies.

RATIONALE AND OBJECTIVE: Although intra-articular bodies are a classic indication for MR arthrography and surgical removal, diagnostic studies are currently sparse. To assess the diagnostic performance of MR arthrography with and without leg traction in detection of intra-articular bodies in the hip joint. MATERIAL AND METHODS: The institutional hip arthroscopy data base (2009-2016: 631 hips) was retrospectively reviewed. Inclusion criteria were hips with and without intra-articular bodies and direct MR arthrography performed with and without leg traction. Twenty-one hips with intra-articular bodies constituted the "disease-positive" group. Seventy-nine randomly selected hips without intra-articular bodies constituted the "disease-negative" group. Images were reviewed independently for presence of intra-articular bodies by two blinded readers. Overall diagnosis and location of intra-articular bodies was recorded (peripheral or central). Arthroscopy served as goldstandard for diagnosis and location of intra-articular bodies. Diagnostic performance and kappa statistics of traction MR arthrography with and without traction were calculated. RESULTS: For both readers sensitivity/specificity of traction MR arthrography was 86%-95% respectively 90%-91% for overall diagnosis of intra-articular bodies and was 81%-86% respectively 90%-92%for MR arthrogrpahy without traction. For central intra-articular bodies sensitivity was higher for both readers with traction (79%-89%) than without traction (74% each). CONCLUSION: MR arthrography with and without traction of the hip is highly accurate in identifying central and peripheral intra-articular bodies. Application of traction was further useful for visualization of centrally located intra-articular bodies.

Isoform-selective deficit of glycine receptors in the mouse mutant spastic.

The mutant mouse spastic (spa) develops a characteristic motor disorder about 2 weeks after birth, with symptoms resembling sublethal poisoning by the glycinergic antagonist strychnine. Correspondingly, adult homozygotic mutants (spa/spa) exhibit a severe reduction of inhibitory glycine receptors in spinal cord and brain. Here we show that the spastic mutation selectively interferes with the postnatal accumulation of the adult isoform of the glycine receptor protein, whereas perinatal expression of the neonatal receptor isoform is not detectably affected. Heterologous expression in X. laevis oocytes of poly(A)+ RNA and Northern blot analysis indicate normal levels of glycine receptor alpha 1 subunit transcripts in spinal cord of adult spastic mutants. Thus, the age-dependent manifestation of spastic symptoms after birth reflects a selective effect of the mutation on the developmental expression of the adult glycine receptor isoform.

Molecular-cytogenetic characterisation of sex cord-stromal tumours: CGH analysis in sertoli cell tumours of the testis.

Sertoli cell tumours (SCT) are rare and poorly explored neoplasias, and the genetic features of these uncommon tumours are largely unknown. Data about chromosomal aberrations in human SCT of the testis are very rare. We present in this paper the first molecular-cytogenetic study of SCT of the testis. DNA was isolated from paraffin-embedded tumour material from 11 patients with unilateral SCT. We used comparative genomic hybridisation to investigate changes in DNA copy number. The detected DNA imbalances showed variation from case to case, indicating a high genetic heterogeneity. Chromosomal aberrations were detected in 9 of the 11 tumours evaluated, with 13 losses versus 14 gains. The most frequent aberrations detected were gain of chromosome X (5 of 11 cases) followed by losses of entire or part of chromosomes 2 and 19 in three cases. This study suggests a high variability in histomorphological and genetic patterns. Only gain of the entire chromosome X seems to be a frequent aberration in these tumours. Further studies of these tumour types are necessary to clarify the significance of chromosomal alterations in carcinogenesis of SCT.

Selective activation of group II mGluRs with LY354740 does not prevent neuronal excitotoxicity.

Recent reports have suggested a role for group II metabotropic glutamate receptors (mGluRs) in the attenuation of excitotoxicity. Here we examined the effects of the recently available group II agonist (+)-2-Aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740) on N-methyl-D-aspartate (NMDA)-induced excitotoxic neuronal death, as well as on hypoxic-ischemic neuronal death both in vitro and in vivo. At concentrations shown to be selective for group II mGluRs expressed in cell lines (0.1-100 nM), LY354740 did not attenuate NMDA-mediated neuronal death in vitro or in vivo. Furthermore, LY354740 did not attenuate oxygen-glucose deprivation-induced neuronal death in vitro or ischemic infarction after transient middle cerebral artery occlusion in rats. In addition, the neuroprotective effect of another group II agonist, (S)-4-carboxy-3-phenylglycine (4C3HPG), which has shown injury attenuating effects both in vitro and in vivo, was not blocked by the group II antagonists (2 S)-alpha-ethylglutamic acid (EGLU), (RS)-alpha-methyl-4-sulphonophenylglycine (MSPG), or the group III antagonist (S)-alpha-methyl-3-carboxyphenylalanine (MCPA), suggesting that this neuroprotection may be mediated by other effects such as upon group I mGluRs.

Prevention of neuronal apoptosis by phorbol ester-induced activation of protein kinase C: blockade of p38 mitogen-activated protein kinase.

Consistent with previous studies on cell lines and non-neuronal cells, specific inhibitors of protein kinase C induced mouse primary cultured neocortical neurons to undergo apoptosis. To examine the complementary hypothesis that activating protein kinase C would attenuate neuronal apoptosis, the cultures were exposed for 1 h to phorbol-12-myristate-13-acetate, which activated protein kinase C as evidenced by downstream enhancement of the mitogen-activated protein kinase pathway. Exposure to phorbol-12-myristate-13-acetate, or another active phorbol ester, phorbol-12,13-didecanoate, but not to the inactive ester, 4alpha-phorbol-12,13-didecanoate, markedly attenuated neuronal apoptosis induced by serum deprivation. Phorbol-12-myristate-13-acetate also attenuated neuronal apoptosis induced by exposure to beta-amyloid peptide 1-42, or oxygen-glucose deprivation in the presence of glutamate receptor antagonists. The neuroprotective effects of phorbol-12-myristate-13-acetate were blocked by brief (non-toxic) concurrent exposure to the specific protein kinase C inhibitors, but not by a specific mitogen-activated protein kinase 1 inhibitor. Phorbol-12-myristate-13-acetate blocked the induction of p38 mitogen-activated protein kinase activity and specific inhibition of this kinase by SB 203580 attenuated serum deprivation-induced apoptosis. c-Jun N-terminal kinase 1 activity was high at rest and not modified by phorbol-12-myristate-13-acetate treatment. These data strengthen the idea that protein kinase C is a key modulator of several forms of central neuronal apoptosis, in part acting through inhibition of p38 mitogen-activated protein kinase regulated pathways.

Neurotrophin-mediated potentiation of neuronal injury.

The neurotrophins are a diverse family of peptides which activate specific tyrosine kinase-linked receptors. Over the past five decades, since the pioneering work of Levi-Montalcini and colleagues, the critical role that neurotrophins play in shaping the developing nervous system has become increasingly established. These molecules, which include the nerve growth factor (NGF)-related peptides, NGF, brain-derived neurotrophic factor (BDNF), NT-4/5 and NT-3, promote differentiation and survival in the developing nervous system, and to a lesser extent in the adult nervous system. As survival-promoting molecules, neurotrophins have been studied as potential neuroprotective agents, and have shown beneficial effects in many model systems. However, a surprising "dark side" to neurotrophin behavior has emerged from some of these studies implying that, under certain pathological conditions, neurotrophins may exacerbate, rather than alleviate, injury. How neurotrophins cause these deleterious consequences is a question which is only beginning to be answered, but initial work supports altered free radical handling or modification of glutamate receptor expression as possible mechanisms underlying these effects. This review will focus on evidence suggesting that neurotrophins may enhance injury under certain circumstances and on the mechanisms behind these injury-promoting aspects.

Quantitative measurement of neuronal degeneration in organotypic hippocampal cultures after combined oxygen/glucose deprivation.

Organotypic hippocampal cultures were used to study cell degeneration during the recovery period after defined periods (30 and 60 min) of combined oxygen/glucose deprivation mimicking transient ischemic conditions. Staining with the fluorescent dye propidium iodide allowed detection of damaged cells. Fluorescence intensity was measured by an image analysis system and used to quantify cell damage at different time points during the recovery period (up to 22 h). At 30 min of oxygen/glucose deprivation cells in the CA1 area were relatively more sensitive compared to CA3 and dentate gyrus cells, with respect to the time course of degeneration and the percentage of affected cells. Expanding the oxygen/glucose deprivation period from 30 to 60 min drastically increased the percentage of cells dying in all hippocampal areas. Still, however, cells in CA1 degenerated faster compared to those in the CA3 area and dentate gyrus. A histological analysis of toluidine blue as well as MAP2-immunostained sections revealed that almost all neurons degenerated in all hippocampal areas following the 60-min deprivation period, whereas GFAP-stained astrocytes appeared to be unaffected. Therefore, neuronal degeneration could be quantified by taking the fluorescence intensity values 22 h after 60 min of oxygen/glucose deprivation as 100% neuronal damage. The possibility to quantify neuronal damage in organotypic cultures offers a useful tool for detailed studies on mechanisms of neuronal cell death in a cell culture system which is closer to in situ conditions than monolayer cell cultures.

Protection from neuronal damage induced by combined oxygen and glucose deprivation in organotypic hippocampal cultures by glutamate receptor antagonists.

Organotypic hippocampal cultures were exposed to defined periods (30 and 60 min) of combined oxygen and glucose deprivation, mimicking transient ischemic conditions. The involvement of different glutamate receptors in individual hippocampal subfields (CA1, CA3 and dentate gyrus) was studied using antagonists of NMDA (dizocilpine) and AMPA/kainate receptors (CNQX and GYKI 52466). Staining with the fluorescent dye propidium iodide (PI) allowed detection of damaged cells. For quantitative determination of neuronal damage, fluorescence intensity was measured after a 22 h recovery period and was related to maximal fluorescence intensity measured after fixation and PI restaining of the cultures at the end of the experiment. Dizocilpine (10 microM), CNQX (100 microM) and GYKI 52466 (100 microM) provided complete protection in CA1, CA3 and dentate gyrus following the moderate ischemic insult, when the antagonists were present permanently. This indicates that none of the ionotropic glutamate receptor subtypes dominated toxicity in the most sensitive subpopulation of neurons. When applied only during the recovery period protection with dizocilpine (10 microM) or CNQX (100 microM) was drastically reduced by about 60% in the most sensitive area (CA1), but only slightly by 15% in CA3. Therefore the onset of irreversible damage seems to occur earlier in CA1 than in CA3. Blockade of AMPA/kainate receptors by GYKI 52466 (100 microM) offered no neuroprotection if the compound was applied only during the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)

Gö 6976 is a potent inhibitor of neurotrophin-receptor intrinsic tyrosine kinase.

We report here that addition of the protein kinase C inhibitor Gö 6976 blocked neurotrophin-induced signaling and autophosphorylation of neurotrophin-specific tyrosine kinase (Trk) receptors, either Trk B in cortical neurons or Trk A in GT1-1-trk9 cells. The effect of Gö 6976 on Trk autophosphorylation was not inhibited by 100 microM orthovanadate, suggesting that the block was not due to the activation of tyrosine phosphatases. Moreover, addition of 10-100 nM concentrations of Gö 6976 inhibited either Trk B or Trk A intrinsic kinase activity in cell-free assays. Gö 6976 also blocked the ability of brain-derived neurotrophic factor to promote cortical neuronal survival and the ability of nerve growth factor to promote PC12 cell survival and differentiation. These results suggest that Gö 6976, besides its known inhibitory effects on lipid- and calcium-dependent isoforms of protein kinase C, can also inhibit neurotrophin signaling by directly inhibiting the intrinsic Trk.

Antagonists for group I mGluRs attenuate excitotoxic neuronal death in cortical cultures.

Activation of ion channel-linked glutamate receptors, especially N-methyl-D-aspartate (NMDA) receptors, mediates the excitotoxic effects of glutamate upon central neurons. We examined the hypothesis that activation of group I metabotropic glutamate receptors (mGluRs) would increase NMDA receptor-mediated cortical neuronal death. Addition of the selective group I mGluR agonists, dihydroxyphenylglycine (DHPG) or trans-azetidine-2,4-dicarboxylic acid (t-ADA) potentiated NMDA-induced neuronal death, and application of the group I mGluR-selective antagonist, aminoindan-1,5-dicarboxylic acid (AIDA), as well as the non-selective antagonists methyl-4-carboxyphenylglycine (MCPG) or 4-carboxyphenylglycine (4CPG) reduced NMDA- and kainate-induced neuronal death in murine cortical cultures. The pro-excitotoxic effect of group I mGluR activation may be mediated largely by enhancement of glutamate release, as DHPG potentiated high potassium-stimulated glutamate release, and the protective effects of both AIDA and MCPG were abolished when NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptors were blocked immediately after toxic NMDA receptor overstimulation. The present data support the possibility that antagonizing group I mGluRs may be a useful strategy for attenuating excitotoxic neuronal death in certain disease states.