Microsecond Dynamics During the Binding-induced Folding of an Intrinsically Disordered Protein

Tau is an intrinsically disordered protein implicated in many neurodegenerative diseases. The repeat domain fragment of tau, tau-K18, is known to undergo a disorder to order transition in the presence of lipid micelles and vesicles, in which helices form in each of the repeat domains. Here, the mechanism of helical structure formation, induced by a phospholipid mimetic, sodium dodecyl sulfate (SDS) at sub-micellar concentrations, has been studied using multiple biophysical probes. A study of the conformational dynamics of the disordered state, using photoinduced electron transfer coupled to fluorescence correlation spectroscopy (PET-FCS) has indicated the presence of an intermediate state, I, in equilibrium with the unfolded state, U. The cooperative binding of the ligand (L), SDS, to I has been shown to induce the formation of a compact, helical intermediate (IL₅) within the dead time (∼37 µs) of a continuous flow mixer. Quantitative analysis of the PET-FCS data and the ensemble microsecond kinetic data, suggests that the mechanism of induction of helical structure can be described by a U ↔ I ↔ IL₅ ↔ FL₅ mechanism, in which the final helical state, FL₅, forms from IL₅ with a time constant of 50–200 µs. Finally, it has been shown that the helical conformation is an aggregation-competent state that can directly form amyloid fibrils.     

Dispersion population models discrete in time and continuous in space

We analyze a discrete-time model of populations that grow and disperse in separate phases. The growth phase is a nonlinear process that allows for the effects of local crowding. The dispersion phase is a linear process that distributes the population throughout its spatial habitat. Our study quantifies the issues of survival and extinction, the existence and stability of nontrivial steady states, and the comparison of various dispersion strategies. Our results show that all of these issues are tied to the global nature of various model parameters. The extreme strategies of staying-in place and going-everywhere-uniformly are compared numerically to diffusion strategies in various contexts. We approach the mathematical analysis of our model from a functional analysis and an operator theory point of view. We use recent results from the theory of positive operators in Banach lattices.     

Phosphorus efficiency of plants

Föhse et al. (1988) have shown that P influx per unit root length in seven plant species growing in a low-P soil varied from 0.6×10^-14 to 4.8×10^-14 mol cm^-1s^-1. The objective of this work was to investigate the reasons for these differences. No correlation was found between P influx and root radius, root hairs, cation-anion balance and Ca uptake. However, when root hairs were included in mathematical model calculations, the differences of P influx could be accounted for. These calculations have shown that in soils low in available P, contribution to P uptake by root hairs was up to 90% of total uptake. The large contribution of root hairs to P uptake was partly due to their surface area, which was similar to that of the root cylinder. However, the main reason for the high P uptake efficiency of root hairs was their small radius (approx. 5×10^-4 cm) and their perpendicular growth into the soil from the root axis. Because of the small radius compared to root axes, P concentration at root hair surfaces decreased at a slower pace and therefore P influx remained higher. Under these conditions higher I_max (maximum influx) or smaller K_m values (Michaelis constant) increased P influx. The main reasons for differences found in P influx among species were the size of I_max and the number and length of root hairs. In a soil low in available P, plant species having more root hairs were able to satisfy a higher proportion of their P demand required for maximum growth.     

具有节点偏置的高阶神经网络模型

在汪涛文献基础上提出了一个具有节点偏置的高阶神经网络模型、给出了模型的哈密顿量和学习算法,证明了学习算法的收敛性,该模型能对每一神经元自动引入一个节点偏置使得网络能够存储所有学习图样包括相关图样,其存储容量远高于Hebb—rule—like学习算法下的高阶神经网络模型.对由30个神经元组成的二阶神经网络进行了计算机仿真,结果证实了上述结论.此外,对初始突触强度对学习效果的影响和不同存储图样数目下的平均吸引半径进行了仿真计算并分析了所得结果.新模型的特点使其具有良好的应用前景     

对分子置换法中积分半径选取方法的探讨

通过对晶胞中帕特逊向量的统计分布的研究,从理论上阐述了根据模型结构单元的线度确定旋转函数的积分半径这种作法的合理性,并且指出了估算积分半径取值范围的具体方法,以及自身旋转函数与交叉旋转函数的积分半径取值范围的区别。经过我们将此方法应用于酚胰岛素Ｂ链羰端六肽胰岛素的旋转函数求解,计算结果证实了这种积分半径的估算方法的可靠性。     

Evaluation of the role ofMicrovelia douglasi atrolineata (Bergroth) (Heteroptera: Veliidae) as predator of the brown planthopperNilaparvata lugens (Stål) (Homoptera: Delphacidae)

The biology of the veliid bug M. d. atrolineata, its predatory behavior, and the effects of plural hunting were studied to evaluate its role as a predator of the brown planthopper Nilaparvata lugens in the Philippines. The probability of planthoppers falling onto the water surface and provision of habitat continuity was measured by a sticky trap placed at the base of rice hills in a greenhouse and in paddy fields. The developmental period of immature stages combined was 21 days. If given prey, females laid 25 eggs on the average during an adult life span of 18 days. Starved adults could survive for only 3–5 days. The functional response to prey density was sigmoid, and the maximum number of prey killed was 7 per day. Prey feeding was completed in 12–36 min. The percentage of successful prey attacks averaged 5–8%, decreasing with higher (and larger) developmental. stages of prey, but adult prey were found the soonest. Plural hunting increased the probability of capturing prey by as much as 2.5 times that by individual hunting. Late-instar nymphs, which may be more active, fell from rice hills in a greenhouse more than early-instar nymphs, and the number falling increased with density. In the field the percentage of planthoppers falling to the water in 1 day varied considerably, from 1% for nymphs in one field to 67% for adults in another field. On the basis of work described above and given the high density of veliid predators in flooded paddy fields of tropical Asia, M. d. atrolineata is considered one of the most important natural enemies of the brown planthopper.     

Author index

Using dynamic light scattering we have been able to determine precisely the hydrodynamic radius of l-α-dimyristoylphosphatidylcholine (DMPC) vesicles as a function of temperature. We have detected a sharp, thermally reversible change in the vesicle radius at a phase transition temperature 24°C, corresponding to an approximate 11% increase in surface are. In the range 10–20°C, the change in radius is less than 1%.     

Dynamic structure of metallothionein

Molecular sieve chromatography of rabbit liver metallothionein at different electrolyte concentrations revealed that this protein undergoes an increase in Stokes radius from 1.50 to 1.78 nm when the ionic strength is lowered from 0.5 to 0.015 indicating a change in molecular shape and/or hydration. The variation in ionic strength also affects the far-UV circular dichroism of metallothionein reflecting a conformational transition in the protein. The effects are attributed to changes in intramolecular repulsion between the strongly negatively charged metal-thiolate clusters of the protein. It is suggested that metallothionein exists in at least two interchangeable conformational states which differ in hydrodynamic properties and whose equilibrium concentrations are determined by the electrostatic free energy of the system.     

Assessing the effectiveness of foraging radius models for seabird distributions using biotelemetry and survey data

Relatively simple foraging radius models have the potential to generate predictive distributions for a large number of species rapidly, thus providing a cost-effective alternative to large-scale surveys or complex modelling approaches. Their effectiveness, however, remains largely untested. Here we compare foraging radius distribution models for all breeding seabirds in Ireland, to distributions of empirical data collected from tracking studies and aerial surveys. At the local/colony level, we compared foraging radius distributions to GPS tracking data from seabirds with short (Atlantic puffin Fratercula arctica, and razorbill Alca torda) and long (Manx shearwater Puffinus puffinus, and European storm-petrel Hydrobates pelagicus) foraging ranges. At the regional/national level, we compared foraging radius distributions to extensive aerial surveys conducted over a two-year period. Foraging radius distributions were significantly positively correlated with tracking data for all species except Manx shearwater. Correlations between foraging radius distributions and aerial survey data were also significant, but generally weaker than those for tracking data. Correlations between foraging radius distributions and aerial survey data were benchmarked against generalised additive models (GAMs) of the aerial survey data that included a range of environmental covariates. While GAM distributions had slightly higher correlations with aerial survey data, the results highlight that the foraging radius approach can be a useful and pragmatic approach for assessing breeding distributions for many seabird species. The approach is likely to have acceptable utility in complex, temporally variable ecosystems and when logistic and financial resources are limited.     

When size does matter: organelle size influences the properties of transport mediated by molecular motors

Background

Organelle transport is driven by the action of molecular motors. In this work, we studied the dynamics of organelles of different sizes with the aim of understanding the complex relation between organelle motion and microenvironment.

Methods

We used single particle tracking to obtain trajectories of melanosomes (pigmented organelles in Xenopus laevis melanophores). In response to certain hormones, melanosomes disperse in the cytoplasm or aggregate in the perinuclear region by the combined action of microtubule and actin motors.

Results and conclusions

Melanosome trajectories followed an anomalous diffusion model in which the anomalous diffusion exponent (α) provided information regarding the trajectories' topography and thus of the processes causing it. During aggregation, the directionality of big organelles was higher than that of small organelles and did not depend on the presence of either actin or intermediate filaments (IF). Depolymerization of IF significantly reduced α values of small organelles during aggregation but slightly affect their directionality during dispersion.

General significance

Our results could be interpreted considering that the number of copies of active motors increases with organelle size. Transport of big organelles was not influenced by actin or IF during aggregation showing that these organelles are moved processively by the collective action of dynein motors. Also, we found that intermediate filaments enhance the directionality of small organelles suggesting that this network keeps organelles close to the tracks allowing their efficient reattachment. The higher directionality of small organelles during dispersion could be explained considering the better performance of kinesin-2 vs. dynein at the single molecule level.