低温下水稻幼苗形态生理应变研究

低温下水稻幼苗形态生理应变研究李太贵王磊（中国水稻研究所，杭州３１０００６）ＳｔｕｄｙｏｆＭｏｒｐｈｏＰｈｙｓｉｏｌｏｇｉｃａｌＳｔｒａｉｎｏｆＲｉｃｅＳｅｅｄｌｉｎｇＵｎｄｅｒＬｏｗＴｅｍｐｅｒａｔｕｒｅ．ＬｉＴａｉｇｕｉ，ＷａｎｇＬｅｉ（Ｃｈｉ...     

The Effects of Organic Solvent on the Ribosyl Transfer Reaction by Thermostable Purine Nucleoside Phosphorylase and Pyrimidine Nucleoside Phosphorylase from Bacillus stearothermophilus JTS 859

The effects of organic solvents on the reaction rate and equilibrium of the ribosyl transfer reaction catalyzed by thermostable purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus JTS 859 were examined at 60°C. The reaction rate in the presence of 10% acetone was 1.6 times higher than that of the control. Acetone was the best organic solvent among those tested for accelerating the reaction rate without denaturing the enzymes. On the other hand, the reaction rate in the presence of 5% ethyl acetate was 1.5 times higher than that of the control. However the enzymes were denatured completely after 1 h incubation. Consequently, the acceleration was not attributed to the stabilization of the enzymes. The equilibrium constants of the reaction were not influenced by the presence of acetone, methyl or ethyl alcohols.     

π–π Stacking mediated drug–drug interactions in human CYP2E1

Because of having many low molecular mass substrates, CYP2E1 is of particular interests to the pharmaceutical industry. Many evidences showed that this enzyme can adopt multiple substrates to significantly reduce the oxidation rate of the substrates. The detailed mechanism for this observation is still unclear. In the current study, we employed GPU‐accelerated molecular dynamics simulations to study the multiple‐binding mode of human CYP2E1, with an aim of offering a mechanistic explanation for the unexplained multiple‐substrate binding. Our results showed that Thr303 and Phe478 were key factors for the substrate recognition and multiple‐substrate binding. The former can form a significant hydrogen bond to recognize and position the substrate in the productive binding orientation in the active site. The latter acted as a mediator for the substrate communications via π–π stacking interactions. In the multiple‐binding mode, the aforementioned π–π stacking interactions formed by the aromatic rings of both substrates and Phe478 drove the first substrate far away from the catalytic center, orienting in an additional binding position and going against the substrate metabolism. All these findings could give atomic insights into the detailed mechanism for the multiple‐substrate binding in human CYP2E1, providing useful information for the drug metabolism mechanism and personalized use of clinical drugs. Proteins 2013; © 2012 Wiley Periodicals, Inc.     

Rapid and accurate structure-based therapeutic peptide design using GPU accelerated thermodynamic integration

Peptide-based therapeutics are an alternative to small molecule drugs as they offer superior specificity, lower toxicity, and easy synthesis. Here we present an approach that leverages the dramatic performance increase afforded by the recent arrival of GPU accelerated thermodynamic integration (TI). GPU TI facilitates very fast, highly accurate binding affinity optimization of peptides against therapeutic targets. We benchmarked TI predictions using published peptide binding optimization studies. Prediction of mutations involving charged side-chains was found to be less accurate than for non-charged, and use of a more complex 3-step TI protocol was found to boost accuracy in these cases. Using the 3-step protocol for non-charged side-chains either had no effect or was detrimental. We use the benchmarked pipeline to optimize a peptide binding to our recently discovered cancer target: EME1. TI calculations predict beneficial mutations using both canonical and non-canonical amino acids. We validate these predictions using fluorescence polarization and confirm that binding affinity is increased. We further demonstrate that this increase translates to a significant reduction in pancreatic cancer cell viability.     

Lower-limb muscle function during sidestep cutting

To investigate lower-limb muscle function during sidestep cutting, prior studies have analysed electromyography (EMG) data together with three dimensional motion analysis. Such an approach does not directly quantify the biomechanical role of individual lower-limb muscles during a sidestep cut. This study recorded three dimensional motion analysis, ground reaction force (GRF) and EMG data for eight healthy males executing an unanticipated sidestep cut. Using a musculoskeletal modelling approach, muscle function was determined by computing the muscle contributions to the GRFs and lower-limb joint moments. We found that bodyweight support (vertical GRF) was primarily provided by the vasti, gluteus maximus, soleus and gastrocnemius. These same muscles, along with the hamstrings, were also primarily responsible for modulating braking and propulsion (anteroposterior GRF). The vasti, gluteus maximus and gluteus medius were the key muscles for accelerating the centre-of-mass towards the desired cutting direction by generating a medially-directed GRF. Our findings have implications for designing retraining programs to improve sidestep cutting technique.     

Estimating the energy expenditure of free‐ranging polar bears using tri‐axial accelerometers: A validation with doubly labeled water

Measures of energy expenditure can be used to inform animal conservation and management, but methods for measuring the energy expenditure of free‐ranging animals have a variety of limitations. Advancements in biologging technologies have enabled the use of dynamic body acceleration derived from accelerometers as a proxy for energy expenditure. Although dynamic body acceleration has been shown to strongly correlate with oxygen consumption in captive animals, it has been validated in only a few studies on free‐ranging animals. Here, we use relationships between oxygen consumption and overall dynamic body acceleration in resting and walking polar bears Ursus maritimus and published values for the costs of swimming in polar bears to estimate the total energy expenditure of 6 free‐ranging polar bears that were primarily using the sea ice of the Beaufort Sea. Energetic models based on accelerometry were compared to models of energy expenditure on the same individuals derived from doubly labeled water methods. Accelerometer‐based estimates of energy expenditure on average predicted total energy expenditure to be 30% less than estimates derived from doubly labeled water. Nevertheless, accelerometer‐based measures of energy expenditure strongly correlated (r² = 0.70) with measures derived from doubly labeled water. Our findings highlight the strengths and limitations in dynamic body acceleration as a measure of total energy expenditure while also further supporting its use as a proxy for instantaneous, detailed energy expenditure in free‐ranging animals.     

The nature and dynamics of world religions: a life-history approach

In contrast with tribal and archaic religions, world religions are characterized by a unique emphasis on extended prosociality, restricted sociosexuality, delayed gratification and the belief that these specific behaviours are sanctioned by some kind of supernatural justice. Here, we draw on recent advances in life history theory to explain this pattern of seemingly unrelated features. Life history theory examines how organisms adaptively allocate resources in the face of trade-offs between different life-goals (e.g. growth versus reproduction, exploitation versus exploration). In particular, recent studies have shown that individuals, including humans, adjust their life strategy to the environment through phenotypic plasticity: in a harsh environment, organisms tend to adopt a ‘fast'' strategy, pursuing smaller but more certain benefits, while in more affluent environments, organisms tend to develop a ‘slow'' strategy, aiming for larger but less certain benefits. Reviewing a range of recent research, we show that world religions are associated with a form of ‘slow'' strategy. This framework explains both the promotion of ‘slow'' behaviours such as altruism, self-regulation and monogamy in modern world religions, and the condemnation of ‘fast'' behaviours such as selfishness, conspicuous sexuality and materialism. This ecological approach also explains the diffusion pattern of world religions: why they emerged late in human history (500–300 BCE), why they are currently in decline in the most affluent societies and why they persist in some places despite this overall decline.     

On Dioxygen and Substrate Access to Soluble Methane Monooxygenases: An all‐Atom Molecular Dynamics Investigation in Water Solution

In a preliminary exploration of the dummy model for diiron proteins, random‐acceleration molecular dynamics (RAMD) revealed that a pure four‐helix bundle structure, like hemerythrin, constitutes an efficient cage for dioxygen (O₂), which can only leave from defined, albeit very broad, gates. However, this well ordered structure does not constitute an archetype on which to compare O₂ permeation of other diiron proteins, like the complex of soluble methane monooxygenase hydroxylase with the regulatory protein (sMMOH‐MMOB). The reason is that with this complex, unlike hemerythrin, the four helices of the four‐helix bundle are heavily bent, and RAMD showed that most traps for O₂ lie outside them. It was also observed that, in spite of a nearly identical van der Waals radius for O₂ and the natural substrate CH₄, the latter behaves under RAMD as a bulkier molecule than O₂, requiring a higher external force to be brought out of sMMOH‐MMOB along trajectories of viable length. All that determined with sMMOH‐MMOB multiple gates and multiple pathways to each of them through several binding pockets, for both O₂ and CH₄. Of the two equally preferred pathways for O₂, at right angle with one another, one proved to be in accordance with the Xe‐atom mapping for sMMOH. In contrast, none of the pathways identified for CH₄ proved to be in accordance with such mapping, CH₄ looking for more open avenues instead.     

Gait and posture discrimination in sheep using a tri-axial accelerometer

Temporo-spatial observation of the leg could provide important information about the general condition of an animal, especially for those such as sheep and other free-ranging farm animals that can be difficult to access. Tri-axial accelerometers are capable of collecting vast amounts of data for locomotion and posture observations; however, interpretation and optimization of these data records remain a challenge. The aim of the present study was to introduce an optimized method for gait (walking, trotting and galloping) and posture (standing and lying) discrimination, using the acceleration values recorded by a tri-axial accelerometer mounted on the hind leg of sheep. The acceleration values recorded on the vertical and horizontal axes, as well as the total acceleration values were categorized. The relative frequencies of the acceleration categories (RFACs) were calculated in 3-s epochs. Reliable RFACs for gait and posture discrimination were identified with discriminant function and canonical analyses. Post hoc predictions for the two axes and total acceleration were conducted, using classification functions and classification scores for each epoch. Mahalanobis distances were used to determine the level of accuracy of the method. The highest discriminatory power for gait discrimination yielded four RFACs on the vertical axis, and five RFACs each on the horizontal axis and total acceleration vector. Classification functions showed the highest accuracy for walking and galloping. The highest total accuracy on the vertical and horizontal axes were 90% and 91%, respectively. Regarding posture discrimination, the vertical axis exhibited the highest discriminatory power, with values of RFAC (0, 1]=99.95% for standing; and RFAC (−1, 0]=99.50% for lying. The horizontal axis showed strong discrimination for the lying side of the animal, as values were in the acceleration category of (0, 1] for lying on the left side and (−1, 0] on the right side. The algorithm developed by the method employed in the present study facilitates differentiation of the various types of gait and posture in animals from fewer data records, and produces the most reliable acceleration values from only one axis within a short time frame. The present study introduces an optimized method by which the tri-axial accelerometer can be used in gait and posture discrimination in sheep as an animal model.