Winter snow and spring temperature have differential effects on vegetation phenology and productivity across Arctic plant communities.

Tundra dominates two-thirds of the unglaciated, terrestrial Arctic. Although this region has experienced rapid and widespread changes in vegetation phenology and productivity over the last several decades, the specific climatic drivers responsible for this change remain poorly understood. Here we quantified the effect of winter snowpack and early spring temperature conditions on growing season vegetation phenology (timing of the start, peak, and end of the growing season) and productivity of the dominant tundra vegetation communities of Arctic Alaska. We used daily remotely sensed normalized difference vegetation index (NDVI), and daily snowpack and temperature variables produced by SnowModel and MicroMet, coupled physically based snow and meteorological modeling tools, to (1) determine the most important snowpack and thermal controls on tundra vegetation phenology and productivity and (2) describe the direction of these relationships within each vegetation community. Our results show that soil temperature under the snowpack, snowmelt timing, and air temperature following snowmelt are the most important drivers of growing season timing and productivity among Arctic vegetation communities. Air temperature after snowmelt was the most important control on timing of season start and end, with warmer conditions contributing to earlier phenology in all vegetation communities. In contrast, the controls on the timing of peak season and productivity also included snowmelt timing and soil temperature under the snowpack, dictated in part by the snow insulating capacity. The results of this novel analysis suggest that while future warming effects on phenology may be consistent across communities of the tundra biome, warming may result in divergent, community-specific productivity responses if coupled with reduced snow insulating capacity lowers winter soil temperature and potential nutrient cycling in the soil.

Differential stoichiometric homeostasis and growth in two native and two invasive C3 grasses.

Global changes interact with plant invasions by differentially impacting native and invasive species. For example, invasive plants often benefit from eutrophication to a greater degree than native plants. While this is well-documented, a broad, trait-based explanation for this phenomenon is lacking. Recent research shows that stoichiometric homeostasis predicts plant species responses to eutrophication and drought, but this research has not been extended into an invasion ecology paradigm. We tested the hypotheses that stoichiometric homeostasis would differ between native and invasive plants, that expressed levels of stoichiometric homeostasis would respond to water availability, and that differences in stoichiometric homeostasis would match differences in growth. In a nutrient and water manipulation study, we found that stoichiometric homeostasis differed between native grasses (Elymus canadensis and Pascopyrum smithii) and invasive grasses (Agropyron cristatum and Bromus inermis), that differences in stoichiometric homeostasis matched differences in growth in well-watered grasses, and that expressed levels of stoichiometric homeostasis were stable across the water supply treatments. These results suggest that invasive plants maintain growth advantages over native plants in eutrophic conditions because of differential homeostatic requirements. We argue that stoichiometric homeostasis is therefore a useful functional trait to explain and predict differential native and invasive plant responses to global change.

The Missing Angle: Ecosystem Consequences of Phenological Mismatch.

Climate change leads to unequal shifts in the phenology of interacting species, such as consumers and their resources, leading to potential phenological mismatches. While studies have investigated how phenological mismatch affects wild populations, we still lack studies and a framework for investigating how phenological mismatch affects ecosystems, particularly nutrient cycling.

Migratory goose arrival time plays a larger role in influencing forage quality than advancing springs in an Arctic coastal wetland.

With warmer springs, herbivores migrating to Arctic breeding grounds may experience phenological mismatches between their energy demands and the availability of high quality forage. Yet, how the timing of the start of the season and herbivore arrival influences forage quality is often unknown. In coastal western Alaska, approximately one million migratory geese arrive each spring to breed, where foliar %N and C:N ratios are linked to gosling survival and population growth. We conducted a three-year experiment where we manipulated the start of the growing season using warming chambers and grazing times using captive Pacific black brant (Branta bernicla nigricans) to examine how the timing of these events influences the quality of an important forage species. Our results suggest that grazing timing plays a much greater role than an advanced growing season in determining forage quality. All top models included grazing timing, and suggested that compared to typical grazing timing, early grazing significantly reduced foliar %C by 6% and C:N ratios by 16%, while late goose grazing significantly reduced foliar %N by 15% and increased foliar C:N ratios by 21%. While second-ranking top models included the effect of season, the advanced growing season effect was not significant and only reduced %N by 4%, increased %C by <1%, and increased C:N ratios by 5% compared to an ambient growing season. In summary, in years where geese arrive early, they will consume higher quality forage when they arrive and throughout the season, while in years that geese arrive late they will consume lower quality forage when they arrive and for the remainder of the season. When the growing season starts has only a minor influence on this pattern. Our findings suggest that cues determining migration and arrival times to breeding areas are important factors influencing forage quality for geese in western Alaska.

[Catheterization of the subclavian vein and the risk of pneumothorax : Mechanical ventilation increases the risk of pneumothorax during infraclavicular landmark-guided subclavian vein puncture: a prospective randomized study]. / Vena-subclavia-Katheter und Pneumothoraxrisiko : Maschinelle Beatmung erhöht das Pneumothoraxrisiko während infraklavikulärer landmarkengestützter V.­subclavia-Punktion: eine prospektive randomisierte Studie.

BACKGROUND: Infraclavicular subclavian vein (SCV) catheterization is a standard procedure in anesthesia and intensive care. There is a lack of evidence on how mechanical ventilation during venipuncture of the SCV influences pneumothorax rates. OBJECTIVE: Primary hypothesis: non-inferiority of continuing vs. discontinuing mechanical ventilation during infraclavicular puncture of the SCV with respect to the pneumothorax rate. MATERIAL AND METHODS: This prospective, randomized and single-blinded study was approved by the local ethics committee. A total of 1021 eligible patients who underwent cranial neurosurgery in 2 different university hospitals were assessed between August 2014 and October 2017. Patients were randomly assigned to two groups directly before induction of anesthesia. Intervention groups for venipuncture of the SCV were mechanical ventilation: tidal volume 7 ml/kg ideal body weight, positive end expiratory pressure (PEEP) ideal body weight/10, n = 535, or apnea: manual/spontaneous, APL valve 0 mbar, n = 486. Patients and the physicians who assessed pneumothorax rates were blinded to the intervention group. Venipuncture was carried out by both inexperienced and experienced physicians. RESULTS: The pneumothorax rate was significantly higher in the mechanical ventilation group (2.2% vs. 0.4%; p = 0.012) with an odds ratio (OR) of 5.63 (95% confidence interval, CI: 1.17-27.2; p = 0.031). A lower body mass index (BMI) was associated with a higher pneumothorax rate, OR 0.89 (95% CI: 0.70-0.96; p = 0.013). CONCLUSION: In this study landmark-guided infraclavicular SCV catheterization was associated with a significantly higher rate of pneumothorax when venipuncture was performed during mechanical ventilation and not in apnea. If a short phase of apnea is justifiable in the patient, mechanical ventilation should be discontinued during the venipuncture procedure.

Delayed herbivory by migratory geese increases summer-long CO2 uptake in coastal western Alaska.

The advancement of spring and the differential ability of organisms to respond to changes in plant phenology may lead to "phenological mismatches" as a result of climate change. One potential for considerable mismatch is between migratory birds and food availability in northern breeding ranges, and these mismatches may have consequences for ecosystem function. We conducted a three-year experiment to examine the consequences for CO2 exchange of advanced spring green-up and altered timing of grazing by migratory Pacific black brant in a coastal wetland in western Alaska. Experimental treatments represent the variation in green-up and timing of peak grazing intensity that currently exists in the system. Delayed grazing resulted in greater net ecosystem exchange (NEE) and gross primary productivity (GPP), while early grazing reduced CO2 uptake with the potential of causing net ecosystem carbon (C) loss in late spring and early summer. Conversely, advancing the growing season only influenced ecosystem respiration (ER), resulting in a small increase in ER with no concomitant impact on GPP or NEE. The experimental treatment that represents the most likely future, with green-up advancing more rapidly than arrival of migratory geese, results in NEE changing by 1.2 µmol m-2  s-1 toward a greater CO2 sink in spring and summer. Increased sink strength, however, may be mitigated by early arrival of migratory geese, which would reduce CO2 uptake. Importantly, while the direct effect of climate warming on phenology of green-up has a minimal influence on NEE, the indirect effect of climate warming manifest through changes in the timing of peak grazing can have a significant impact on C balance in northern coastal wetlands. Furthermore, processes influencing the timing of goose migration in the winter range can significantly influence ecosystem function in summer habitats.

Arctic plant ecophysiology and water source utilization in response to altered snow: isotopic (δ18O and δ2H) evidence for meltwater subsidies to deciduous shrubs.

Warming-linked woody shrub expansion in the Arctic has critical consequences for ecosystem processes and climate feedbacks. The snow-shrub interaction model has been widely implicated in observed Arctic shrub increases, yet equivocal experimental results regarding nutrient-related components of this model have highlighted the need for a consideration of the increased meltwater predicted in expanding shrub stands. We used a 22-year snow manipulation experiment to simultaneously address the unexplored role of snow meltwater in arctic plant ecophysiology and nutrient-related components of the snow-shrub hypothesis. We coupled measurements of leaf-level gas exchange and leaf tissue chemistry (%N and δ13C) with an analysis of stable isotopes (δ18O and δ2H) in soil water, precipitation, and stem water. In deeper snow areas photosynthesis, conductance, and leaf N increased and δ13C values decreased in the deciduous shrubs, Betula nana and Salix pulchra, and the graminoid, Eriophorum vaginatum, with the strongest treatment effects observed in deciduous shrubs, consistent with predictions of the snow-shrub hypothesis. We also found that deciduous shrubs, especially S. pulchra, obtained much of their water from snow melt early in the growing season (40-50%), more than either E. vaginatum or the evergreen shrub, Rhododendron tomentosum (Ledum palustre). This result provides the basis for adding a meltwater-focused feedback loop to the snow-shrub interaction model of shrub expansion in the Arctic. Our results highlight the critical role of winter snow in the ecophysiology of Arctic plants, particularly deciduous shrubs, and underline the importance of understanding how global warming will affect the Arctic winter snowpack.

[Antipyretics in intensive care patients]. / Antipyretika bei Intensivpatienten.

BACKGROUND: Antipyretics are among the most widely prescribed drugs in German hospitals. Despite this widespread use, their role for treatment of critically ill patients still remains unclear. In particular, the questionable positive effects of reducing fever are discussed. OBJECTIVES: In this review we aimed to summarize and discuss current study results covering the use of antipyretics in critically ill patients. Suspected effects with regard to fever reduction and lethality should be considered. MATERIALS AND METHODS: A selective literature search was carried out in the PubMed database. We reviewed the bibliographies of all work considered relevant. RESULTS: There are only a few studies on the use of antipyretics in intensive care patients, which are difficult to compare systematically due to different designs, protocols and endpoints. All in all, the decrease in temperature was very low (0.3 °C) and showed even adverse effects on 28-days mortality in sepsis. In patients with sepsis and ASS medication, a decreased mortality has been shown in retrospective analysis. CONCLUSIONS: The benefit of fever control using antipyretics in intensive care patients with regard to endpoints like lethality remains unclear. Randomized controlled trials with suitable protocols and endpoints are needed to provide a solid base for development of guidelines.

[Pain and analgesia : Mutations of voltage-gated sodium channels]. / Schmerz und Schmerzlosigkeit : Mutationen spannungsabhängiger Natriumkanäle.

Voltage-gated sodium channels (Navs) are crucial for the generation and propagation of action potentials in all excitable cells, and therefore for the function of sensory neurons as well. Preclinical research over the past 20 years identified three Nav-isoforms in sensory neurons, namely Nav1.7, Nav1.8 and Nav1.9. A specific role for the function of nociceptive neurons was postulated for each. Whereas no selective sodium channel inhibitors have been established in the clinic so far, the relevance of all three isoforms regarding the pain sensitivity in humans is currently undergoing a remarkable verification through the translation of preclinical data into clinically manifest pictures. For the last ten years, Nav1.7 has been the main focus of clinical interest, as a large number of hereditary mutants were identified. The so-called "gain-of-function" mutations of Nav1.7 cause the pain syndromes hereditary erythromelalgia and paroxysmal extreme pain disorder. In addition, several Nav1.7 mutants were shown to be associated with small-fiber neuropathies. On the contrary, "loss-of-function" Nav1.7 mutants lead to a congenital insensitivity to pain. Recently, several gain-of-function mutations in Nav1.8 and Nav1.9 have been identified in patients suffering from painful peripheral neuropathies. However, another gain-of-function Nav1.9 mutation is associated with congenital insensitivity to pain. This review offers an overview of published work on painful Nav mutations with clinical relevance, and proposes possible consequences for the therapy of different pain symptoms resulting from these findings.

Tetrodotoxin-sensitive α-subunits of voltage-gated sodium channels are relevant for inhibition of cardiac sodium currents by local anesthetics.

The sodium channel α-subunit (Nav) Nav1.5 is regarded as the most prevalent cardiac sodium channel required for generation of action potentials in cardiomyocytes. Accordingly, Nav1.5 seems to be the main target molecule for local anesthetic (LA)-induced cardiotoxicity. However, recent reports demonstrated functional expression of several "neuronal" Nav's in cardiomyocytes being involved in cardiac contractility and rhythmogenesis. In this study, we examined the relevance of neuronal tetrodotoxin (TTX)-sensitive Nav's for inhibition of cardiac sodium channels by the cardiotoxic LAs ropivacaine and bupivacaine. Effects of LAs on recombinant Nav1.2, 1.3, 1.4, and 1.5 expressed in human embryonic kidney cell line 293 (HEK-293) cells, and on sodium currents in murine, cardiomyocytes were investigated by whole-cell patch clamp recordings. Expression analyses were performed by reverse transcription PCR (RT-PCR). Cultured cardiomyocytes from neonatal mice express messenger RNA (mRNA) for Nav1.2, 1.3, 1.5, 1.8, and 1.9 and generate TTX-sensitive sodium currents. Tonic and use-dependent block of sodium currents in cardiomyocytes by ropivacaine and bupivacaine were enhanced by 200 nM TTX. Inhibition of recombinant Nav1.5 channels was similar to that of TTX-resistant currents in cardiomyocytes but stronger as compared to inhibition of total sodium current in cardiomyocytes. Recombinant Nav1.2, 1.3, 1.4, and 1.5 channels displayed significant differences in regard to use-dependent block by ropivacaine. Finally, bupivacaine blocked sodium currents in cardiomyocytes as well as recombinant Nav1.5 currents significantly stronger in comparison to ropivacaine. Our data demonstrate for the first time that cardiac TTX-sensitive sodium channels are relevant for inhibition of cardiac sodium currents by LAs.

Coupled long-term summer warming and deeper snow alters species composition and stimulates gross primary productivity in tussock tundra.

Climate change is expected to increase summer temperature and winter precipitation throughout the Arctic. The long-term implications of these changes for plant species composition, plant function, and ecosystem processes are difficult to predict. We report on the influence of enhanced snow depth and warmer summer temperature following 20 years of an ITEX experimental manipulation at Toolik Lake, Alaska. Winter snow depth was increased using snow fences and warming was accomplished during summer using passive open-top chambers. One of the most important consequences of these experimental treatments was an increase in active layer depth and rate of thaw, which has led to deeper drainage and lower soil moisture content. Vegetation concomitantly shifted from a relatively wet system with high cover of the sedge Eriophorum vaginatum to a drier system, dominated by deciduous shrubs including Betula nana and Salix pulchra. At the individual plant level, we observed higher leaf nitrogen concentration associated with warmer temperatures and increased snow in S. pulchra and B. nana, but high leaf nitrogen concentration did not lead to higher rates of net photosynthesis. At the ecosystem level, we observed higher GPP and NEE in response to summer warming. Our results suggest that deeper snow has a cascading set of biophysical consequences that include a deeper active layer that leads to altered species composition, greater leaf nitrogen concentration, and higher ecosystem-level carbon uptake.

Arctic cyclone water vapor isotopes support past sea ice retreat recorded in Greenland ice.

Rapid Arctic warming is associated with important water cycle changes: sea ice loss, increasing atmospheric humidity, permafrost thaw, and water-induced ecosystem changes. Understanding these complex modern processes is critical to interpreting past hydrologic changes preserved in paleoclimate records and predicting future Arctic changes. Cyclones are a prevalent Arctic feature and water vapor isotope ratios during these events provide insights into modern hydrologic processes that help explain past changes to the Arctic water cycle. Here we present continuous measurements of water vapor isotope ratios (δ(18)O, δ(2)H, d-excess) in Arctic Alaska from a 2013 cyclone. This cyclone resulted in a sharp d-excess decrease and disproportional δ(18)O enrichment, indicative of a higher humidity open Arctic Ocean water vapor source. Past transitions to warmer climates inferred from Greenland ice core records also reveal sharp decreases in d-excess, hypothesized to represent reduced sea ice extent and an increase in oceanic moisture source to Greenland Ice Sheet precipitation. Thus, measurements of water vapor isotope ratios during an Arctic cyclone provide a critical processed-based explanation, and the first direct confirmation, of relationships previously assumed to govern water isotope ratios during sea ice retreat and increased input of northern ocean moisture into the Arctic water cycle.

Methadone is a local anaesthetic-like inhibitor of neuronal Na+ channels and blocks excitability of mouse peripheral nerves.

BACKGROUND: Opioids enhance and prolong analgesia when applied as adjuvants to local anaesthetics (LAs). A possible molecular mechanism for this property is a direct inhibition of voltage-gated Na(+) channels which was reported for some opioids. Methadone is an effective adjuvant to LA and was recently reported to inhibit cardiac Na(+) channels. Here, we explore and compare LA properties of methadone and bupivacaine on neuronal Na(+) channels, excitability of peripheral nerves, and cell viability. METHODS: Effects of methadone were explored on compound action potentials (CAP) of isolated mouse saphenous nerves. Patch clamp recordings were performed on Na(+) channels in ND7/23 cells, the α-subunits Nav1.2, Nav1.3, Nav1.7, and Nav1.8, and the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2). Cytotoxicity was determined using flow cytometry. RESULTS: Methadone (IC50 86-119 µM) is a state-dependent and unselective blocker on Nav1.2, Nav1.3, Nav1.7, and Nav1.8 with a potency comparable with that of bupivacaine (IC50 177 µM). Both bupivacaine and methadone also inhibit C- and A-fibre CAPs in saphenous nerves in a concentration-dependent manner. Tonic block of Nav1.7 revealed a discrete stereo-selectivity with a higher potency for levomethadone than for dextromethadone. Methadone is also a weak blocker of HCN2 channels. Both methadone and bupivacaine induce a pronounced cytotoxicity at concentrations required for LA effects. CONCLUSIONS: Methadone induces typical LA effects by inhibiting Na(+) channels with a potency similar to that of bupivacaine. This hitherto unknown property of methadone might contribute to its high efficacy when applied as an adjuvant to LA.

[Update on the pharmacology and effects of local anesthetics]. / Update zu Pharmakologie und Wirkung von Lokalanästhetika.

Local anesthetics (LA) are broadly used in all disciplines and it could be considered that relatively little is reflected on the mechanisms of action of this old substance group. However, several molecular mechanisms of LAs mediating wanted and unwanted effects remain to be explored. Furthermore, the number of indications for application of LAs seems to be expanding. The local anesthetic effect of LAs is primarily mediated by a potent inhibition of voltage-gated sodium channels. However, this effect is due to much more than the interaction of LAs with one single molecule. Most recent studies indicated that the development of selective local anesthetics might be possible and LAs also interact with several other membrane molecules. Although the relevance of these effects is still unclear, they might play a role in systemic analgesia, tissue protection and anti-inflammatory effects of LA. The therapeutic index of systemically applied LA is very narrow. Systemic application is formally not permitted because the impending systemic toxicity is still a life-threatening complication. Although the cardiac and central nervous toxicity at least partly result from an unselective block of neuronal and cardiac sodium channels, preclinical studies suggest the involvement of several mechanisms. A local LA toxicity is less clinically impressive; however, all LAs induce a significant tissue toxicity for which the underlying mechanisms have been partly identified. This review reports on recent findings on mechanisms and on the clinical relevance of some LA-induced effects which are of relevance for anesthesiological activities.

A new perspective on trait differences between native and invasive exotic plants.

Functional differences between native and exotic species potentially constitute one factor responsible for plant invasion. Differences in trait values between native and exotic invasive species, however, should not be considered fixed and may depend on the context of the comparison. Furthermore, the magnitude of difference between native and exotic species necessary to trigger invasion is unknown. We propose a criterion that differences in trait values between a native and exotic invasive species must be greater than differences between co-occurring natives for this difference to be ecologically meaningful and a contributing factor to plant invasion. We used a meta-analysis to quantify the difference between native and exotic invasive species for various traits examined in previous studies and compared this value to differences among native species reported in the same studies. The effect size between native and exotic invasive species was similar to the effect size between co-occurring natives except for studies conducted in the field; in most instances, our criterion was not met although overall differences between native and exotic invasive species were slightly larger than differences between natives. Consequently, trait differences may be important in certain contexts, but other mechanisms of invasion are likely more important in most cases. We suggest that using trait values as predictors of invasion will be challenging.

The opioid methadone induces a local anaesthetic-like inhibition of the cardiac Na⁺ channel, Na(v)1.5.

BACKGROUND AND PURPOSE: Treatment with methadone is associated with severe cardiac arrhythmias, a side effect that seems to result from an inhibition of cardiac hERG K⁺ channels. However, several other opioids are inhibitors of voltage-gated Na⁺ channels. Considering the common assumption that an inhibition of the cardiac Na⁺ channel Na(v)1.5, is the primary mechanism for local anaesthetic (LA)-induced cardiotoxicity, we hypothesized that methadone has LA-like properties leading to a modulation of Na(v)1.5 channels. EXPERIMENTAL APPROACH: The whole-cell patch clamp technique was applied to investigate the effects of methadone on wild-type and mutant human Na(v)1.5 channels expressed in HEK293 cells. A homology model of human Na(v)1.5 channels was used to perform automated ligand-docking studies. KEY RESULTS: Methadone inhibited Na(v)1.5 channels in a state-dependent manner, that is, tonic block was stronger with inactivated channels than with resting channels and a use-dependent block at 10 Hz. Methadone induced a concentration-dependent shift of the voltage dependency of both fast and slow inactivation towards more hyperpolarized potentials, and impaired recovery from fast and slow inactivation. The LA-insensitive mutants N406K and F1760A exhibited reduced tonic and use-dependent block by methadone, and docking predictions positioned methadone in a cavity that was delimited by the residue F1760. Dextromethadone and levomethadone induced discrete stereo-selective effects on Na(v)1.5 channels. CONCLUSIONS AND IMPLICATIONS: Methadone interacted with the LA-binding site to inhibit Na(v)1.5 channels. Our data suggest that these channels are a hitherto unrecognized molecular component contributing to cardiac arrhythmias induced by methadone.

The influence of intensity and duration of a painful conditioning stimulation on conditioned pain modulation in volunteers.

BACKGROUND AND METHOD: The aim was to investigate influence from variations in intensity of a painful conditioning stimulation (CS) on early (0-6 min) and prolonged (6-12 min) conditioned pain modulation (CPM) in volunteers during concurrent exposure to test stimuli (TS). CS was applied to either forearm using painful heat with an intensity of 2/10 and 5/10, respectively, rated on a 0-10 numerical pain rating scale. At a second session, CS with an intensity of 7/10 was applied to the arm using a tourniquet. Threshold and suprathreshold painful heat and pressure as well as painful repeated monofilament pricking (RMP) were assessed as TS. RESULTS: Regardless of TS, there was no significant difference in the magnitude of CPM within the same stimulus modality during the various intensities and phases of the CS. Significant modulation of heat pain thresholds (HPTs) was found during the early phase at 5/10 and 7/10, but not at 2/10. Only at 5/10 the prolonged CS resulted in a significant additional increase in HPT. During the early CS phase, CPM of suprathreshold heat pain was found at 2/10 and 5/10. The prolonged CS resulted in a significant additional temperature increase at 5/10. Only during the early phase significant CPM of pressure pain thresholds were found for all three pain intensities in conjunction with a significant CPM of suprathreshold pressure pain at 5/10. There was no CPM of RMP. CONCLUSION: The CS intensity and the duration of CPM modulated pain sensitivity differentially across TS modalities.