Structure and Mechanism of Ergothionase from Treponema denticola

Ergothioneine is a sulfur-containing histidine derivative that emerges from microbial biosynthesis and enters the human body through intestinal uptake and regulated distribution into specific tissues. Although the proteins involved in biosynthesis and uptake are well characterized, less is known about the degradative pathways of ergothioneine. This report describes the crystal structure of the active form of ergothionase from the oral pathogen Treponema denticola complexed with the substrate analogue desmethyl-ergothioneine sulfonic acid. This enzyme catalyzes the 1,2-elimination of trimethylamine from ergothioneine and ergothioneine sulfonic acid by using a unique mode of substrate activation combined with acid/base catalysis. This structural and mechanistic investigation revealed four essential catalytic residues, which are strictly conserved in homologous proteins from common gastrointestinal bacteria and numerous pathogenic bacteria, suggesting that bacterial activity may play an important role in determining the availability of ergothioneine in healthy and diseased human tissue

Factors Contributing to Record-Breaking Heat Waves over the Great Plains during the 1930s Dust Bowl

Record-breaking summer heat waves were experienced across the contiguous United States during the decade-long “Dust Bowl” drought in the 1930s. Using high-quality daily temperature observations, the Dust Bowl heat wave characteristics are assessed with metrics that describe variations in heat wave activity and intensity. Despite the sparser station coverage in the early record, there is robust evidence for the emergence of exceptional heat waves across the central Great Plains, the most extreme of which were preconditioned by anomalously dry springs. This is consistent with the entire twentieth-century record: summer heat waves over the Great Plains develop on average ~15–20 days earlier after anomalously dry springs, compared to summers following wet springs. Heat waves following dry springs are also significantly longer and hotter, indicative of the importance of land surface feedbacks in heat wave intensification. A distinctive anomalous continental-wide circulation pattern accompanied exceptional heat waves in the Great Plains, including those of the Dust Bowl decade. An anomalous broad surface pressure ridge straddling an upper-level blocking anticyclone over the western United States forced substantial subsidence and adiabatic warming over the Great Plains, and triggered anomalous southward warm advection over southern regions. This prolonged and amplified the heat waves over the central United States, which in turn gradually spread westward following heat wave emergence. The results imply that exceptional heat waves are preconditioned, triggered, and strengthened across the Great Plains through a combination of spring drought, upper-level continental-wide anticyclonic flow, and warm advection from the north

Northern winter climate change: assessment of uncertainty in CMIP5 projections related to stratosphere-troposphere coupling

Journal ArticlePublished versionFuture changes in the stratospheric circulation could have an important impact on northern winter tropospheric climate change, given that sea level pressure (SLP) responds not only to tropospheric circulation variations but also to vertically coherent variations in troposphere-stratosphere circulation. Here we assess northern winter stratospheric change and its potential to influence surface climate change in the Coupled Model Intercomparison Project-Phase 5 (CMIP5) multimodel ensemble. In the stratosphere at high latitudes, an easterly change in zonally averaged zonal wind is found for the majority of the CMIP5 models, under the Representative Concentration Pathway 8.5 scenario. Comparable results are also found in the 1% CO2 increase per year projections, indicating that the stratospheric easterly change is common feature in future climate projections. This stratospheric wind change, however, shows a signi fi cant spread among the models. By using linear regression, we quantify the impact of tropical upper troposphere warming, polar amplification, and the stratospheric wind change on SLP. We find that the intermodel spread in stratospheric wind change contributes substantially to the intermodel spread in Arctic SLP change. The role of the stratosphere in determining part of the spread in SLP change is supported by the fact that the SLP change lags the stratospheric zonally averaged wind change. Taken together, these findings provide further support for the importance of simulating the coupling between the stratosphere and the troposphere, to narrow the uncertainty in the future projection of tropospheric circulation changes

The Southern Ocean Freshwater Input from Antarctica (SOFIA) Initiative: scientific objectives and experimental design

As the climate warms, the grounded ice sheet and floating ice shelves surrounding Antarctica are melting and releasing additional freshwater into the Southern Ocean. Nonetheless, almost all existing coupled climate models have fixed ice sheets and lack the physics required to represent the dominant sources of Antarctic melt. These missing ice dynamics represent a key uncertainty that is typically unaccounted for in current global climate change projections. Previous modelling studies that have imposed additional Antarctic meltwater have demonstrated regional impacts on Southern Ocean stratification, circulation, and sea ice, as well as remote changes in atmospheric circulation, tropical precipitation, and global temperature. However, these previous studies have used widely varying rates of freshwater forcing, have been conducted using different climate models and configurations, and have reached differing conclusions on the magnitude of meltwater–climate feedbacks. The Southern Ocean Freshwater Input from Antarctica (SOFIA) initiative brings together a team of scientists to quantify the climate system response to Antarctic meltwater input along with key aspects of the uncertainty. In this paper, we summarize the state of knowledge on meltwater discharge from the Antarctic ice sheet and ice shelves to the Southern Ocean and explain the scientific objectives of our initiative. We propose a series of coupled and ocean–sea ice model experiments, including idealized meltwater experiments, historical experiments with observationally consistent meltwater input, and future scenarios driven by meltwater inputs derived from stand-alone ice sheet models. Through coordinating a multi-model ensemble of simulations using a common experimental design, open data archiving, and facilitating scientific collaboration, SOFIA aims to move the community toward better constraining our understanding of the climate system response to Antarctic melt.</p

Saturation Behavior: a general relationship described by a simple second-order differential equation

<p>Abstract</p> <p>Background</p> <p>The numerous natural phenomena that exhibit saturation behavior, <it>e.g</it>., ligand binding and enzyme kinetics, have been approached, to date, via empirical and particular analyses. This paper presents a mechanism-free, and assumption-free, second-order differential equation, designed only to describe a typical relationship between the variables governing these phenomena. It develops a mathematical model for this relation, based solely on the analysis of the typical experimental data plot and its saturation characteristics. Its utility complements the traditional empirical approaches.</p> <p>Results</p> <p>For the general saturation curve, described in terms of its independent (<it>x</it>) and dependent (<it>y</it>) variables, a second-order differential equation is obtained that applies to any saturation phenomena. It shows that the driving factor for the basic saturation behavior is the probability of the interactive site being free, which is described quantitatively. Solving the equation relates the variables in terms of the two empirical constants common to all these phenomena, the initial slope of the data plot and the limiting value at saturation. A first-order differential equation for the slope emerged that led to the concept of the effective binding rate at the active site and its dependence on the calculable probability the interactive site is free. These results are illustrated using specific cases, including ligand binding and enzyme kinetics. This leads to a revised understanding of how to interpret the empirical constants, in terms of the variables pertinent to the phenomenon under study.</p> <p>Conclusions</p> <p>The second-order differential equation revealed the basic underlying relations that describe these saturation phenomena, and the basic mathematical properties of the standard experimental data plot. It was shown how to integrate this differential equation, and define the common basic properties of these phenomena. The results regarding the importance of the slope and the new perspectives on the empirical constants governing the behavior of these phenomena led to an alternative perspective on saturation behavior kinetics. Their essential commonality was revealed by this analysis, based on the second-order differential equation.</p

Fast and slow responses of Southern Ocean sea surface temperature to SAM in coupled climate models

We investigate how sea surface temperatures (SSTs) around Antarctica respond to the Southern An- nular Mode (SAM) on multiple timescales. To that end we examine the relationship between SAM and SST within unperturbed preindustrial control simulations of coupled general circulation models (GCMs) included in the Climate Modeling Intercomparison Project phase 5 (CMIP5). We develop a technique to extract the re- sponse of the Southern Ocean SST (55◦S−70◦S) to a hypothetical step increase in the SAM index. We demonstrate that in many GCMs, the expected SST step re- sponse function is nonmonotonic in time. Following a shift to a positive SAM anomaly, an initial cooling regime can transition into surface warming around Antarctica. However, there are large differences across the CMIP5 ensemble. In some models the step response function never changes sign and cooling persists, while in other GCMs the SST anomaly crosses over from negative to positive values only three years after a step increase in the SAM. This intermodel diversity can be related to differences in the models’ climatological thermal ocean stratification in the region of seasonal sea ice around Antarctica. Exploiting this relationship, we use obser- vational data for the time-mean meridional and vertical temperature gradients to constrain the real Southern Ocean response to SAM on fast and slow timescales

Natural hazards in Australia: heatwaves

As part of a special issue on natural hazards, this paper reviews the current state of scientific knowledge of Australian heatwaves. Over recent years, progress has been made in understanding both the causes of and changes to heatwaves. Relationships between atmospheric heatwaves and large-scale and synoptic variability have been identified, with increasing trends in heatwave intensity, frequency and duration projected to continue throughout the 21st century. However, more research is required to further our understanding of the dynamical interactions of atmospheric heatwaves, particularly with the land surface. Research into marine heatwaves is still in its infancy, with little known about driving mechanisms, and observed and future changes. In order to address these knowledge gaps, recommendations include: focusing on a comprehensive assessment of atmospheric heatwave dynamics; understanding links with droughts; working towards a unified measurement framework; and investigating observed and future trends in marine heatwaves. Such work requires comprehensive and long-term collaboration activities. However, benefits will extend to the international community, thus addressing global grand challenges surrounding these extreme events

Subcellular Localization of Hexokinases I and II Directs the Metabolic Fate of Glucose

The first step in glucose metabolism is conversion of glucose to glucose 6-phosphate (G-6-P) by hexokinases (HKs), a family with 4 isoforms. The two most common isoforms, HKI and HKII, have overlapping tissue expression, but different subcellular distributions, with HKI associated mainly with mitochondria and HKII associated with both mitochondrial and cytoplasmic compartments. Here we tested the hypothesis that these different subcellular distributions are associated with different metabolic roles, with mitochondrially-bound HK's channeling G-6-P towards glycolysis (catabolic use), and cytoplasmic HKII regulating glycogen formation (anabolic use).To study subcellular translocation of HKs in living cells, we expressed HKI and HKII linked to YFP in CHO cells. We concomitantly recorded the effects on glucose handling using the FRET based intracellular glucose biosensor, FLIPglu-600 mM, and glycogen formation using a glycogen-associated protein, PTG, tagged with GFP. Our results demonstrate that HKI remains strongly bound to mitochondria, whereas HKII translocates between mitochondria and the cytosol in response to glucose, G-6-P and Akt, but not ATP. Metabolic measurements suggest that HKI exclusively promotes glycolysis, whereas HKII has a more complex role, promoting glycolysis when bound to mitochondria and glycogen synthesis when located in the cytosol. Glycogen breakdown upon glucose removal leads to HKII inhibition and dissociation from mitochondria, probably mediated by increases in glycogen-derived G-6-P.These findings show that the catabolic versus anabolic fate of glucose is dynamically regulated by extracellular glucose via signaling molecules such as intracellular glucose, G-6-P and Akt through regulation and subcellular translocation of HKII. In contrast, HKI, which activity and regulation is much less sensitive to these factors, is mainly committed to glycolysis. This may be an important mechanism by which HK's allow cells to adapt to changing metabolic conditions to maintain energy balance and avoid injury

Holocene dynamics of the Southern Hemisphere westerly winds and possible links to CO2 outgassing

The Southern Hemisphere westerly winds (SHW) play an important role in regulating the capacity of the Southern Ocean carbon sink. They modulate upwelling of carbon-rich deep water and, with sea ice, determine the ocean surface area available for air–sea gas exchange. Some models indicate that the current strengthening and poleward shift of these winds will weaken the carbon sink. If correct, centennial- to millennial-scale reconstructions of the SHW intensity should be linked with past changes in atmospheric CO2, temperature and sea ice. Here we present a 12,300-year reconstruction of wind strength based on three independent proxies that track inputs of sea-salt aerosols and minerogenic particles accumulating in lake sediments on sub-Antarctic Macquarie Island. Between about 12.1 thousand years ago (ka) and 11.2 ka, and since about 7 ka, the wind intensities were above their long-term mean and corresponded with increasing atmospheric CO2. Conversely, from about 11.2 to 7.2 ka, the wind intensities were below their long-term mean and corresponded with decreasing atmospheric CO2. These observations are consistent with model inferences of enhanced SHW contributing to the long-term outgassing of CO2 from the Southern Ocean