The Role of the Lipid Bilayer in Tau Aggregation

Tau is a microtubule associated protein whose aggregation is implicated in a number of neurodegenerative diseases. We investigate the mechanism by which anionic lipid vesicles induce aggregation of tau in vitro using K18, a fragment of tau corresponding to the four repeats of the microtubule binding domain. Our results show that aggregation occurs when the amount of K18 bound to the lipid bilayer exceeds a critical surface density. The ratio of protein/lipid at the critical aggregation concentration is pH-dependent, as is the binding affinity. At low pH, where the protein binds with high affinity, the critical surface density is independent both of total lipid concentration as well as the fraction of anionic lipid present in the bilayer. Furthermore, the aggregates consist of both protein and vesicles and bind the β-sheet specific dye, Thioflavin T, in the manner characteristic of pathological aggregates. Our results suggest that the lipid bilayer facilitates protein-protein interactions both by screening charges on the protein and by increasing the local protein concentration, resulting in rapid aggregation. Because anionic lipids are abundant in cellular membranes, these findings contribute to understanding tau-lipid bilayer interactions that may be relevant to disease pathology.     

绝经后女性血清瘦素、骨密度及血骨特异性碱性磷酸酶和Ⅰ型胶原交联氨基末端肽的测定及意义

目的:测定绝经后女性血清瘦素(leptin)与骨密度及及血清骨特异性碱性磷酸酶(BAP)和Ⅰ型胶原交联氨基末端肽(NTx)并探讨其关系。方法:用酶联免疫吸附试验测定287名40-80岁健康绝经后女性血清leptin以及血清骨特异性碱性磷酸酶(BAP)和Ⅰ型胶原交联氨基末端肽(NTx);用双能X线骨密度扫描仪测定总体、腰椎正位、总髋部骨密度以及体脂、瘦体重;分析它们之间的关系。结果:Leptin与髋部总体BMD呈正相关(r=0.162,P<0.05),校正年龄和体脂后,Leptin与髋部总体BMD相关性消失,Leptin与BAP相关无统计学意义;与NTX呈负相关(r=-0.119,P<0.05),校正年龄和体脂后,相关无统计学意义。BAP与总体骨密度、腰椎骨密度、髋部总体骨密度均呈负相关(r=-0.210,r=-0.236,r=-0.223,P<0.05),校正年龄和体质指数后,相关性都依然存在(r=-0.168,r=-0.187,r=-0.169,P<0.05)。NTx与总体骨密度、腰椎骨密度、髋部总体骨密度均呈负相关(r=-0.238,r=-0.232,r=-0.239,P<0.05),校正年龄和体质指数后...     

Rhh: an R extension for estimating multilocus heterozygosity and heterozygosity-heterozygosity correlation

Individual multilocus heterozygosity estimates based on a limited number of loci are expected to correlate only weakly with the inbreeding level of an individual. Before using multilocus heterozygosity estimates in studies of inbreeding, their ability to capture information on inbreeding in the given setting should be tested. A convenient method for this is to compute the heterozygosity-heterozygosity correlation, i.e. the mean correlation between multilocus heterozygosity estimates calculated from random samples of loci, which should be positive if multilocus heterozygosity carries a signature of inbreeding. Rhh is an extension package for the statistical software r that estimates this correlation and calculates three measures of individual multilocus heterozygosity: homozygosity by loci, internal relatedness and standardized heterozygosity. The extension package is available through the CRAN (http://cran.r-project.org) and has a homepage at http://www.helsinki.fi/biosci/egru/research/software.     

Testing Reliability of Body Size Measurements Using Hind Foot Length in Roe Deer

Abstract: We quantified the repeatability of >900 individual measures of hind foot length from 2 French populations of roe deer (Capreolus capreolus) monitored by capture-recapture. We found a high repeatability (i.e., high intra-class correlation, 0.76, 95% CI = 0.72–0.83 and 0.92, 95% CI = 0.91–0.95) in both populations. We also found that inexperienced observers reached a high level of intra- (1.00, 95% CI = 0.96–1.00) and inter-observer repeatability (0.99, 95% CI = 0.98–1.00) when measuring hind foot length of harvested animals with a tool specifically designed for this task. Managers should pay particular attention to limit measurement errors because unreliable measurements require an increased sample size to assess individual variation and can mask biological patterns.     

Merits of Modelling Multivariate Survival Data Using Random Effects Proportional Odds Model

Recently, there has been a great deal of interest in the analysis of multivariate survival data. In most epidemiological studies, survival times of the same cluster are related because of some unobserved risk factors such as the environmental or genetic factors. Therefore, modelling of dependence between events of correlated individuals is required to ensure a correct inference on the effects of treatments or covariates on the survival times. In the past decades, extension of proportional hazards model has been widely considered for modelling multivariate survival data by incorporating a random effect which acts multiplicatively on the hazard function. In this article, we consider the proportional odds model, which is an alternative to the proportional hazards model at which the hazard ratio between individuals converges to unity eventually. This is a reasonable property particularly when the treatment effect fades out gradually and the homogeneity of the population increases over time. The objective of this paper is to assess the influence of the random effect on the within‐subject correlation and the population heterogeneity. We are particularly interested in the properties of the proportional odds model with univariate random effect and correlated random effect. The correlations between survival times are derived explicitly for both choices of mixing distributions and are shown to be independent of the covariates. The time path of the odds function among the survivors are also examined to study the effect of the choice of mixing distribution. Modelling multivariate survival data using a univariate mixing distribution may be inadequate as the random effect not only characterises the dependence of the survival times, but also the conditional heterogeneity among the survivors. A robust estimate for the correlation of the logarithm of the survival times within a cluster is obtained disregarding the choice of the mixing distributions. The sensitivity of the estimate of the regression parameter under a misspecification of the mixing distribution is studied through simulation. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Making the right connections: biological networks in the light of evolution

Our understanding of how evolution acts on biological networks remains patchy, as is our knowledge of how that action is best identified, modelled and understood. Starting with network structure and the evolution of protein–protein interaction networks, we briefly survey the ways in which network evolution is being addressed in the fields of systems biology, development and ecology. The approaches highlighted demonstrate a movement away from a focus on network topology towards a more integrated view, placing biological properties centre‐stage. We argue that there remains great potential in a closer synergy between evolutionary biology and biological network analysis, although that may require the development of novel approaches and even different analogies for biological networks themselves.     

Interaction among Non-toxic Phytoplankton,Toxic Phytoplankton and Zooplankton: Inferences from Field Observations

We explore the mutual dependencies and interactions among different groups of species of the plankton population, based on an analysis of the long-term field observations carried out by our group in the North–West coast of the Bay of Bengal. The plankton community is structured into three groups of species, namely, non-toxic phytoplankton (NTP), toxic phytoplankton (TPP) and zooplankton. To find the pair-wise dependencies among the three groups of plankton, Pearson and partial correlation coefficients are calculated. To explore the simultaneous interaction among all the three groups, a time series analysis is performed. Following an Expectation Maximization (E-M) algorithm, those data points which are missing due to irregularities in sampling are estimated, and with the completed data set a Vector Auto-Regressive (VAR) model is analyzed. The overall analysis demonstrates that toxin-producing phytoplankton play two distinct roles: the inhibition on consumption of toxic substances reduces the abundance of zooplankton, and the toxic materials released by TPP significantly compensate for the competitive disadvantages among phytoplankton species. Our study suggests that the presence of TPP might be a possible cause for the generation of a complex interaction among the large number of phytoplankton and zooplankton species that might be responsible for the prolonged coexistence of the plankton species in a fluctuating biomass.     

Spatial Patterns of Prisoner’s Dilemma Game in Metapopulations

Because to defect is the evolutionary stable strategy in the prisoner’s dilemma game (PDG), understanding the mechanism generating and maintaining cooperation in PDG, i.e. the paradox of cooperation, has intrinsic significance for understanding social altruism behaviors. Spatial structure serves as the key to this dilemma. Here, we build the model of spatial PDG under a metapopulation framework: the sub-populations of cooperators and defectors obey the rules in spatial PDG as well as the colonization–extinction process of metapopulations. Using the mean-field approximation and the pair approximation, we obtain the differential equations for the dynamics of occupancy and spatial correlation. Cellular automaton is also built to simulate the spatiotemporal dynamics of the spatial PDG in metapopulations. Join-count statistics are used to measure the spatial correlation as well as the spatial association of the metapopulation. Simulation results show that the distribution is self-organized and that it converges to a static boundary due to the boycotting of cooperators to defectors. Metapopulations can survive even when the colonization rate is lower than the extinction rate due to the compensation of cooperation rewards for extinction debt. With a change of parameters in the model, a metapopulation can consist of pure cooperators, pure defectors, or cooperator–defector coexistence. The necessary condition of cooperation evolution is the local colonization of a metapopulation. The spatial correlation between the cooperators tends to be weaker with the increase in the temptation to defect and the habitat connectivity; yet the spatial correlation between defectors becomes stronger. The relationship between spatial structure and the colonization rate is complicated, especially for cooperators. The metapopulation may undergo a temporary period of prosperity just before the extinction, even while the colonization rate is declining. An erratum to this article can be found at     

Solution structure of DNA/RNA hybrid duplex with C8-propynyl 2′-deoxyadenosine modifications: Implication of RNase H and DNA/RNA duplex interaction

Solution structures of DNA/RNA hybrid duplexes, d(GCGCA*AA*ACGCG): r(cgcguuuugcg)d(C) (designated PP57), containing two C8-propynyl 2′-deoxyadenosines (A*) and unmodified hybrid (designated U4A4) are solved. The C8-propynyl groups on 2′-deoxyadenosine perturb the local structure of the hybrid duplex, but overall the structure is similar to that of canonical DNA/RNA hybrid duplex except that Hoogsteen hydrogen bondings between A* and U result in lower thermal stability. RNase H is known to cleave RNA only in DNA/RNA hybrid duplexes. Minor groove widths of hybrid duplexes, sugar puckerings of DNA are reported to be responsible for RNase H mediated cleavage, but structural requirements for RNase H mediated cleavage still remain elusive. Despite the presence of bulky propynyl groups of PP57 in the minor groove and greater flexibility, the PP57 is an RNase H substrate. To provide an insight on the interactions between RNase H and substrates we have modeled Bacillus halodurans RNase H-PP57 complex, our NMR structure and modeling study suggest that the residue Gly(15) and Asn(16) of the loop residues between first β sheet and second β sheet of RNase HI of Escherichia coli might participate in substrate binding.     

New radiolarian species from the Upper Cretaceous-Lower Paleogene of the eastern slope of the northern Ural Mountains

Five new radiolarian species, Dictyophimus? orbiculiporosus sp. nov., Spongomelissa imperceptusa sp. nov., Theocoronium puncticulatum sp. nov., Pterocyrtidium porrectum sp. nov., and Tripodiscinus corona sp. nov., from the Campanian-Danian diatomites of the Leplinskaya Formation of the northern Ural Mountains are described. They are useful for stratification and correlation of the Upper Cretaceous and Lower Paleogene beds of the Ural Region of Western Siberia.