NATURE GEOSCIENCE | ADVANCE ONLINE PUBLICATION | www.nature.com/naturegeoscience 1 T he Arctic cryosphere is an integral part of Earth's climate system and has undergone unprecedented changes within the past few decades. Rapid warming and sea-ice loss has had significant impacts locally, particularly in late summer and early autumn. September sea ice has declined at a rate of 12.4% per decade since 1979 (ref. 1), so that by summer 2012, nearly half of the areal coverage had disappeared. This decrease in ice extent has been accompanied by an approximately 1.8 m (40%) decrease in mean winter ice thickness since 1980 (ref.2) and a 75-80% loss in volume 3 . Though sea-ice loss has received most of the research and media attention, snow cover in spring and summer has decreased at an even greater rate than sea ice. June snow cover alone has decreased at nearly double the rate of September sea ice 4 . The decrease in spring snow cover has contributed to both the rise in warm season surface temperatures over the Northern Hemisphere extratropical landmasses and the decrease in summer Arctic sea ice 5 . The combined rapid loss of sea ice and snow cover in the spring and summer has played a role in amplifying Arctic warming. However, snow cover and sea-ice trends diverge in the autumn and winter with sea ice decreasing in all months while snow cover has exhibited a neutral to positive trend in autumn and winter 6 . Climate change and Arctic amplificationWhile the global-mean surface temperature has unequivocally risen over the instrumental record 7 , spatial heterogeneity of this warming plays an important role in the resulting climate impacts. In particular, the near-surface of the Northern Hemisphere high latitudes are warming at rates double that of lower latitudes [8][9][10] . This observed The Arctic region has warmed more than twice as fast as the global average -a phenomenon known as Arctic amplification. The rapid Arctic warming has contributed to dramatic melting of Arctic sea ice and spring snow cover, at a pace greater than that simulated by climate models. These profound changes to the Arctic system have coincided with a period of ostensibly more frequent extreme weather events across the Northern Hemisphere mid-latitudes, including severe winters. The possibility of a link between Arctic change and mid-latitude weather has spurred research activities that reveal three potential dynamical pathways linking Arctic amplification to mid-latitude weather: changes in storm tracks, the jet stream, and planetary waves and their associated energy propagation. Through changes in these key atmospheric features, it is possible, in principle, for sea ice and snow cover to jointly influence mid-latitude weather. However, because of incomplete knowledge of how high-latitude climate change influences these phenomena, combined with sparse and short data records, and imperfect models, large uncertainties regarding the magnitude of such an influence remain. We conclude that improved process understanding, sustained and additional...

Inflammatory bowel diseases (IBDs), mainly Crohn's disease and ulcerative colitis, are dynamic, chronic inflammatory conditions that are associated with an increased colon cancer risk. Inflammatory cell apoptosis is a key mechanism for regulating IBD. Peptidylarginine deiminases (PADs) catalyze the posttranslational conversion of peptidylarginine to peptidylcitrulline in a calcium-dependent, irreversible reaction and mediate the effects of proinflammatory cytokines. Because PAD levels are elevated in mouse and human colitis, we hypothesized that a novel small-molecule inhibitor of the PADs, i.e., chloramidine (Cl-amidine), could suppress colitis in a dextran sulfate sodium mouse model. Results are consistent with this hypothesis, as demonstrated by the finding that Cl-amidine treatment, both prophylactic and after the onset of disease, reduced the clinical signs and symptoms of colitis, without any indication of toxic side effects. Interestingly, Cl-amidine drives apoptosis of inflammatory cells in vitro and in vivo, providing a mechanism by which Cl-amidine suppresses colitis. In total, these data help validate the PADs as therapeutic targets for the treatment of IBD and further suggest Cl-amidine as a candidate therapy for this disease.

Protein citrullination has been shown to regulate numerous physiological pathways (e.g., the innate immune response and gene transcription), and is, when dysregulated, known to be associated with numerous human diseases, including cancer, rheumatoid arthritis, and multiple sclerosis. This modification, also termed deimination, is catalyzed by a group of enzymes called the Protein Arginine Deiminases (PADs). In mammals, there are five PAD family members (i.e., PADs 1, 2, 3, 4, and 6) that exhibit tissue specific expression patterns, and vary in their subcellular localization. The kinetic characterization of PAD4 was recently reported, and these efforts guided the development of the two most potent PAD4 inhibitors (i.e., F- and Cl-amidine) known to date. In addition to being potent PAD4 inhibitors, we show here that Cl-amidine also exhibits a strong inhibitory effect against PADs 1 and 3, thus indicating its utility as a pan PAD inhibitor. Given the increasing number of diseases in which dysregulated PAD activity has been implicated, the development of PAD-selective inhibitors is of paramount importance. To aid that goal, we characterized the catalytic mechanism and substrate specificity of PADs 1 and 3. Herein, we report the results of these studies, which suggest that, like PAD4, PADs 1 and 3 employ a reverse protonation mechanism. Additionally, the substrate specificity studies provided critical information that aided the identification of PAD3-selective inhibitors. These compounds, denoted F4- and Cl4-amidine, are the most potent PAD3 inhibitors ever described.

[1] Winter 2009-2010 made headlines for extreme cold and snow in most of the major population centers of the industrialized countries of the Northern Hemisphere (NH). The major teleconnection patterns of the Northern Hemisphere, El Niño/Southern Oscillation (ENSO) and the Arctic Oscillation (AO) were of moderate to strong amplitude, making both potentially key players during the winter of 2009-2010. The dominant NH winter circulation pattern can be shown to have originated with a two-way stratosphere-troposphere interaction forced by Eurasian land surface and lower tropospheric atmospheric conditions during autumn. This cycle occurred twice in relatively quick succession contributing to the record low values of the AO observed. Using a skillful winter temperature forecast, it is shown that the AO explained a greater variance of the observed temperature pattern across the extratropical landmasses of the NH than did ENSO.

Many tropospheric Arctic Oscillation (AO) events are preceded by stratospheric AO events and even earlier in time by anomalous upward energy flux associated with Rossby waves in the troposphere. This study identifies lower-tropospheric circulation anomalies that precede large AO events in both the troposphere and stratosphere and the anomalous upward energy flux. Compositing analysis of stratospheric warming events identifies regional tropospheric precursors, which precede stratospheric warmings. The tropospheric precursor is found to vary when compositing over polar vortex displacements and splits separately. Prior to vortex displacements the main anomaly sea level pressure center of the tropospheric precursor is located across northwest Eurasia and is associated with the Siberian high. Prior to vortex splits a similar anomaly center is identified in the tropospheric precursor but is weaker and appears to be more strongly related to a shift in the storm tracks. Differences in the sea level pressure anomalies in the North Atlantic and the North Pacific are also observed when comparing the precursors prior to vortex displacements and splits. Identification of a unique tropospheric precursor to stratospheric warming and subsequent tropospheric AO events can help to improve understanding troposphere–stratosphere coupling. Furthermore, the observational evidence presented here can be compared with model simulations of winter climate variability and lead to potential model improvements.

We analyzed rain‐on‐snow (ROS) events in two reanalysis products. ROS events are a relatively rare phenomenon outside of a few regional maxima including western Eurasia, the higher elevations of western North America, the northeastern United States, and southeastern Canada. ROS events occur at the high latitudes, especially away from the continental interior, and no robust trends were found in the frequency of ROS events. We also explored the variability of ROS events with dominant large climate modes. The most robust relationship was found with the Arctic Oscillation or North Atlantic Oscillation (AO/NAO). The most notable variability associated with the AO/NAO was a northeast/southwest dipole feature across western Eurasia. More ROS events were found for northeastern Europe for the positive phase of the AO/NAO due to the increased frequency of rainfall. However, more ROS events were found for Central Europe for the negative phase of the AO/NAO due to the increased frequency of snow cover.

[1] Seasonal climate prediction remains a challenge. During Northern Hemisphere (NH) winter the large-scale teleconnection pattern the Arctic Oscillation (AO) explains the largest fraction of temperature variance of any other known climate mode. However the Arctic Oscillation is considered to be a result of intrinsic atmospheric dynamics or chaotic behavior and therefore is unpredictable. Here we develop a snow advance index (SAI) derived from antecedent observed snow cover that explains a large fraction of the variance of the winter AO. The high correlati on bet ween the SAI and t he wi nt er AO demonstrates that the AO is most likely predictable and that this index can be exploited for skillful seasonal climate predictions. Citation: Cohen, J., and J. Jones (2011),A new index for more accurate winter predictions, Geophys. Res. Lett., 38, L21701,

Previous research has linked wintertime Arctic Oscillation (AO) variability to indices of Siberian snow cover and upward wave activity flux in the preceding fall season. Here, daily data are used to examine the surface and tropospheric processes that occur as the link between snow cover and upward forcing into the stratosphere develops. October Eurasian mean snow cover is found to be significantly related to sea level pressure (SLP) and to lower-stratosphere (100 hPa) meridional heat flux. Analysis of daily SLP and 100-hPa heat flux shows that in years with high October snow, the SLP is significantly higher from approximately 1 November to 15 December, and the 100-hPa heat flux is significantly increased with a two-week lag, from approximately 15 November to 31 December. During November–December, there are periods with upward wave activity flux extending coherently from the surface to the stratosphere, and these events occur nearly twice as often in high snow years compared to low snow years. The vertical structure of these events is a westward-tilting pattern of high eddy heights, with the largest normalized anomalies near the surface in the same region as the snow and SLP changes. These results suggest that high SLP develops in response to the snow cover and this higher pressure, in turn, provides part of the structure of a surface-to-stratosphere wave activity flux event, thus making full events more likely. Implications for improved winter forecasts exist through recognition of these precursor signals.