Markus Stoffel

The State and Fate of Himalayan Glaciers

Going More Slowly Himalayan glaciers sometimes are called the “Third Pole” because of the amount of snow and ice they contain. Despite their importance as a global water reservoir and their essential role in Asian hydrology, how their mass is changing in response to global warming is not well known. Bolch et al. (p. 310) review the contemporary evolution of glaciers in the Himalayan region, including those of the less well sampled region of the Karakoram to the Northwest, in order to provide a current, comprehensive picture of how they are changing. Most Himalayan glaciers are retreating at rates comparable to glaciers elsewhere in the world. In the Karakorum, on the other hand, advancing glaciers are more common. Himalayan glaciers are a focus of public and scientific debate. Prevailing uncertainties are of major concern because some projections of their future have serious implications for water resources. Most Himalayan glaciers are losing mass at rates similar to glaciers elsewhere, except for emerging indications of stability or mass gain in the Karakoram. A poor understanding of the processes affecting them, combined with the diversity of climatic conditions and the extremes of topographical relief within the region, makes projections speculative. Nevertheless, it is unlikely that dramatic changes in total runoff will occur soon, although continuing shrinkage outside the Karakoram will increase the seasonality of runoff, affect irrigation and hydropower, and alter hazards.

miR-375 maintains normal pancreatic alpha- and beta-cell mass.

Altered growth and development of the endocrine pancreas is a frequent cause of the hyperglycemia associated with diabetes. Here we show that microRNA-375 (miR-375), which is highly expressed in pancreatic islets, is required for normal glucose homeostasis. Mice lacking miR-375 (375KO) are hyperglycemic, exhibit increased total pancreatic α-cell numbers, fasting and fed plasma glucagon levels, and increased gluconeogenesis and hepatic glucose output. Furthermore, pancreatic β-cell mass is decreased in 375KO mice as a result of impaired proliferation. In contrast, pancreatic islets of obese mice (ob/ob), a model of increased β-cell mass, exhibit increased expression of miR-375. Genetic deletion of miR-375 from these animals (375/ob) profoundly diminished the proliferative capacity of the endocrine pancreas and resulted in a severely diabetic state. Bioinformatic analysis of transcript data from 375KO islets revealed that miR-375 regulates a cluster of genes controlling cellular growth and proliferation. These data provide evidence that miR-375 is essential for normal glucose homeostasis, α- and β-cell turnover, and adaptive β-cell expansion in response to increasing insulin demand in insulin resistance.

21st century climate change in the European Alps—A review☆

Reliable estimates of future climate change in the Alps are relevant for large parts of the European society. At the same time, the complex Alpine region poses considerable challenges to climate models, which translate to uncertainties in the climate projections. Against this background, the present study reviews the state-of-knowledge about 21st century climate change in the Alps based on existing literature and additional analyses. In particular, it explicitly considers the reliability and uncertainty of climate projections. Results show that besides Alpine temperatures, also precipitation, global radiation, relative humidity, and closely related impacts like floods, droughts, snow cover, and natural hazards will be affected by global warming. Under the A1B emission scenario, about 0.25 °C warming per decade until the mid of the 21st century and accelerated 0.36 °C warming per decade in the second half of the century is expected. Warming will probably be associated with changes in the seasonality of precipitation, global radiation, and relative humidity, and more intense precipitation extremes and flooding potential in the colder part of the year. The conditions of currently record breaking warm or hot winter or summer seasons, respectively, may become normal at the end of the 21st century, and there is indication for droughts to become more severe in the future. Snow cover is expected to drastically decrease below 1500-2000 m and natural hazards related to glacier and permafrost retreat are expected to become more frequent. Such changes in climatic parameters and related quantities will have considerable impact on ecosystems and society and will challenge their adaptive capabilities.

Contribution of GIRK2-mediated postsynaptic signaling to opiate and α2-adrenergic analgesia and analgesic sex differences

The analgesia produced by inhibitory G protein-coupled receptor agonists involves coordinated postsynaptic inhibition via G protein-coupled inwardly rectifying potassium channels (GIRKs) and presynaptic inhibition of neurotransmitter release through regulation of voltage-gated Ca2+ channels. Here, we used mice lacking the GIRK2 channel subunit to assess the relative contribution of these two effector systems to nociceptive processing in male and female mice. Compared with female WT mice, male WT mice exhibited higher pain thresholds and enhanced opioid (morphine) and α2-adrenergic (clonidine) receptor-induced antinociception in a spinal reflex test. The GIRK2-null mutation reduced the “pain” threshold in male but not in female mice, effectively eliminating the sex differences in pain threshold. In addition, deletion of GIRK2 channels in mutant mice largely eliminated clonidine antinociception and significantly decreased morphine antinociception. Furthermore, the more pronounced morphine and clonidine-induced antinociception in male mice disappeared in the GIRK2 mutants. Based on the almost complete loss of clonidine-induced antinociception in the mutant mice, we conclude that it is primarily mediated by postsynaptic α2-adrenergic receptors. In contrast, the significant residual morphine effect in the mutant mice points to the presynaptic μ opioid receptor as a major contributor to its analgesic action. Finally, our results suggest that the reduced pain responsiveness of male compared with female mice results in part from GIRK2-coupled postsynaptic receptors that are activated by endogenous antinociceptive systems.

Insulin regulates the activity of forkhead transcription factor Hnf-3β/Foxa-2 by Akt-mediated phosphorylation and nuclear/cytosolic localization

Hepatocyte nuclear factors 3 α, β, and γ (Foxa-1, -2, and -3) are transcriptional activators of important metabolic genes in the liver that are suppressed by the actions of insulin. Here, we show that the activation of phosphatidylinositol 3-kinase–Akt by insulin induces Foxa-2 phosphorylation, nuclear exclusion, and inhibition of Foxa-2-dependent transcriptional activity. Foxa-2 physically interacts with Akt, a key mediator of the phosphatidylinositol 3-kinase pathway and is phosphorylated at a single conserved site (T156) that is absent in Foxa-1 and Foxa-3 proteins. This Akt phosphorylation site in Foxa-2 is highly conserved from mammals to insects. Mutant Foxa-2T156A is resistant to Akt-mediated phosphorylation, nuclear exclusion, and transcriptional inactivation of Foxa-2-regulated gene expression. These results implicate an evolutionarily conserved mechanism in the regulation of Foxa-2-dependent transcriptional control by extracellular signals such as insulin.

Common SNPs in HMGCR in Micronesians and Whites Associated With LDL-Cholesterol Levels Affect Alternative Splicing of Exon13

Background—Variation in LDL-cholesterol (LDL-C) among individuals is a complex genetic trait involving multiple genes and gene–environment interactions. Methods and Results—In a genome-wide association study (GWAS) to identify genetic variants influencing LDL-C in an isolated population from Kosrae, we observed associations for SNPs in the gene encoding 3hydroxy–3–methylglutaryl (HMG)-coenzyme A (CoA) reductase (HMGCR). Three of these SNPs (rs7703051, rs12654264, and rs3846663) met the statistical threshold of genome-wide significance when combined with data from the Diabetes Genetics Initiative GWAS. We followed up the association results and identified a functional SNP in intron13 (rs3846662), which was in linkage disequilibrium with the SNPs of genome-wide significance and affected alternative splicing of HMGCR mRNA. In vitro studies in human lymphoblastoid cells demonstrated that homozygosity for the rs3846662 minor allele was associated with up to 2.2-fold lower expression of alternatively spliced HMGCR mRNA lacking exon13, and minigene transfection assays confirmed that allele status at rs3846662 directly modulated alternative splicing of HMGCR exon13 (42.9±3.9 versus 63.7±1.0%&Dgr;exon13/total HMGCR mRNA, P=0.02). Further, the alternative splice variant could not restore HMGCR activity when expressed in HMGCR deficient UT-2 cells. Conclusion—We identified variants in HMGCR that are associated with LDL-C across populations and affect alternative splicing of HMGCR exon13.

MicroRNA-7a regulates pancreatic β cell function

Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic β cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of β cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in β cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates β cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in β cells developed diabetes due to impaired insulin secretion and β cell dedifferentiation. Interestingly, perturbation of miR-7a expression in β cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine β cell mass. Furthermore, we found that miR-7a levels are decreased in obese/diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated β cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic β cells and support a role for miR-7 in the adaptation of pancreatic β cell function in obesity and type 2 diabetes.

400 Years of Debris-Flow Activity and Triggering Weather Conditions: Ritigraben, Valais, Switzerland

Abstract Three major rainfall events have caused considerable damage in the Valais region (Swiss Alps) since 1987. Substantial debris flows originating from periglacial environments were recorded during the August 1987 and September 1993 rainfall events, whereas no debris flows occurred in October 2000. This paper aims at putting these large-area events and the apparent increase in debris-flow frequency into a wider context by reconstructing the past debris-flow activity in the Ritigraben torrent (Mattertal, Valais) with dendrogeomorphological methods. Tree-ring analysis allowed the reconstruction of 53 events, going back to the year 1605. Previously, only 10 debris flows had been known for the torrent, and these were limited to the period between 1922 and 2002. Results further show that the apparently above-average concentration of events since 1987 was mainly caused by insufficient and short archival data. In fact, debris flows occurred even more frequently in the nineteenth century than they do today. The spatial distribution of injured trees in particular years further indicates that significant events, like the one in 1993, always occurred in the torrent. Finally, reconstructed event years were compared with archival data on flooding in neighboring catchments. The comparisons prove that large-area events like those in 1987, 1993, or 2000 have at least been as common in the past as they are today.

Dendroecological Dating of Geomorphic Disturbance in Trees

Abstract The initial employment of tree rings in geomorphic studies was simply as a dating tool and only rarely were other environmental information and records of damage contained within the tree exploited. However, these annually resolved tree-ring records also preserve valuable archives of past geomorphic processes on timescales of decades to centuries. As many of these processes are significant natural hazards, understanding their distribution, timing and controls provides crucial information that can assist in the prediction, mitigation and defense against these hazards and their effects on society. This contribution aims at presenting a proposal on the types of growth disturbances to be included in future work focusing on geomorphic disturbance, the intensity of reactions, and on the minimum requirements needed for growth disturbances to be considered in event histories. We present possibilities and limitations of dendrogeomorphic applications in geomorphic research and propose a range of techniques and approaches that may become standard practice in the analysis and understanding of earth-surface processes and related natural hazards in the future.

Source of the great A.D. 1257 mystery eruption unveiled, Samalas volcano, Rinjani Volcanic Complex, Indonesia

Significance Based on ice core archives of sulfate and tephra deposition, one of the largest volcanic eruptions of the historic period and of the past 7,000 y occurred in A.D. 1257. However the source of this “mystery eruption” remained unknown. Drawing on a robust body of new evidence from radiocarbon dates, tephra geochemistry, stratigraphic data, a medieval chronicle, this study argues that the source of this eruption is Samalas volcano, part of the Mount Rinjani Volcanic Complex on Lombok Island, Indonesia. These results solve a conundrum that has puzzled glaciologists, volcanologists, and climatologists for more than three decades. In addition, the identification of this volcano gives rise to the existence of a forgotten Pompeii in the Far East. Polar ice core records attest to a colossal volcanic eruption that took place ca. A.D. 1257 or 1258, most probably in the tropics. Estimates based on sulfate deposition in these records suggest that it yielded the largest volcanic sulfur release to the stratosphere of the past 7,000 y. Tree rings, medieval chronicles, and computational models corroborate the expected worldwide atmospheric and climatic effects of this eruption. However, until now there has been no convincing candidate for the mid-13th century “mystery eruption.” Drawing upon compelling evidence from stratigraphic and geomorphic data, physical volcanology, radiocarbon dating, tephra geochemistry, and chronicles, we argue the source of this long-sought eruption is the Samalas volcano, adjacent to Mount Rinjani on Lombok Island, Indonesia. At least 40 km3 (dense-rock equivalent) of tephra were deposited and the eruption column reached an altitude of up to 43 km. Three principal pumice fallout deposits mantle the region and thick pyroclastic flow deposits are found at the coast, 25 km from source. With an estimated magnitude of 7, this event ranks among the largest Holocene explosive eruptions. Radiocarbon dates on charcoal are consistent with a mid-13th century eruption. In addition, glass geochemistry of the associated pumice deposits matches that of shards found in both Arctic and Antarctic ice cores, providing compelling evidence to link the prominent A.D. 1258/1259 ice core sulfate spike to Samalas. We further constrain the timing of the mystery eruption based on tephra dispersal and historical records, suggesting it occurred between May and October A.D. 1257.