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

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

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

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

Challenges and opportunities for improved understanding of regional climate dynamics

Dynamical processes in the atmosphere and ocean are central to determining the large-scale drivers of regional climate change, yet their predictive understanding is poor. Here, we identify three frontline challenges in climate dynamics where significant progress can be made to inform adaptation: response of storms, blocks and jet streams to external forcing; basin-to-basin and tropical–extratropical teleconnections; and the development of non-linear predictive theory. We highlight opportunities and techniques for making immediate progress in these areas, which critically involve the development of high-resolution coupled model simulations, partial coupling or pacemaker experiments, as well as the development and use of dynamical metrics and exploitation of hierarchies of models

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries