Characterization of a Phanerochaete chrysosporium Glutathione Transferase Reveals a Novel Structural and Functional Class with Ligandin Properties

Glutathione S-transferases (GSTs) form a superfamily of multifunctional proteins with essential roles in cellular detoxification processes. A new fungal specific class of GST has been highlighted by genomic approaches. The biochemical and structural characterization of one isoform of this class in Phanerochaete chrysosporium revealed original properties. The three-dimensional structure showed a new dimerization mode and specific features by comparison with the canonical GST structure. An additional β-hairpin motif in the N-terminal domain prevents the formation of the regular GST dimer and acts as a lid, which closes upon glutathione binding. Moreover, this isoform is the first described GST that contains all secondary structural elements, including helix α4′ in the C-terminal domain, of the presumed common ancestor of cytosolic GSTs (i.e. glutaredoxin 2). A sulfate binding site has been identified close to the glutathione binding site and allows the binding of 8-anilino-1-naphtalene sulfonic acid. Competition experiments between 8-anilino-1-naphtalene sulfonic acid, which has fluorescent properties, and various molecules showed that this GST binds glutathionylated and sulfated compounds but also wood extractive molecules, such as vanillin, chloronitrobenzoic acid, hydroxyacetophenone, catechins, and aldehydes, in the glutathione pocket. This enzyme could thus function as a classical GST through the addition of glutathione mainly to phenethyl isothiocyanate, but alternatively and in a competitive way, it could also act as a ligandin of wood extractive compounds. These new structural and functional properties lead us to propose that this GST belongs to a new class that we name GSTFuA, for fungal specific GST class A.     

The Effect of Disease-Induced Mortality on Structural Network Properties

As the understanding of the importance of social contact networks in the spread of infectious diseases has increased, so has the interest in understanding the feedback process of the disease altering the social network. While many studies have explored the influence of individual epidemiological parameters and/or underlying network topologies on the resulting disease dynamics, we here provide a systematic overview of the interactions between these two influences on population-level disease outcomes. We show that the sensitivity of the population-level disease outcomes to the combination of epidemiological parameters that describe the disease are critically dependent on the topological structure of the population’s contact network. We introduce a new metric for assessing disease-driven structural damage to a network as a population-level outcome. Lastly, we discuss how the expected individual-level disease burden is influenced by the complete suite of epidemiological characteristics for the circulating disease and the ongoing process of network compromise. Our results have broad implications for prediction and mitigation of outbreaks in both natural and human populations.     

Structural Differentiation of Graphs Using Hosoya-Based Indices

In this paper, we introduce the Hosoya-Spectral indices and the Hosoya information content of a graph. The first measure combines structural information captured by partial Hosoya polynomials and graph spectra. The latter is a graph entropy measure which is based on blocks consisting of vertices with the same partial Hosoya polynomial. We evaluate the discrimination power of these quantities by interpreting numerical results.     

Beyond Bar and Line Graphs: Time for a New Data Presentation Paradigm

Figures in scientific publications are critically important because they often show the data supporting key findings. Our systematic review of research articles published in top physiology journals (n = 703) suggests that, as scientists, we urgently need to change our practices for presenting continuous data in small sample size studies. Papers rarely included scatterplots, box plots, and histograms that allow readers to critically evaluate continuous data. Most papers presented continuous data in bar and line graphs. This is problematic, as many different data distributions can lead to the same bar or line graph. The full data may suggest different conclusions from the summary statistics. We recommend training investigators in data presentation, encouraging a more complete presentation of data, and changing journal editorial policies. Investigators can quickly make univariate scatterplots for small sample size studies using our Excel templates.     

Information Properties of Naturally-Occurring Proteins: Fourier Analysis and Complexity Phase Plots

In previous work from this lab, the information in natural proteins was investigated with Ribonuclease A (RNase A) serving as the source. The signature traits were investigated at three structure levels: primary through tertiary. The present paper travels further by charting the primary structure information of about half a million molecules. This was feasible given abundant sequence archives for both living and viral systems. Notably, a method is presented for evaluating primary structure information, based on Fourier analysis and spectral complexity. Significantly, the results show certain complexity traits to be universal for living sources. Viruses, by contrast, encode protein collections which are case-specific and complexity-divergent. The results have ramifications for discriminating collections on the basis of sequence information. This discrimination offers new strategies for selecting drug targets.     

Association of Structural Global Brain Network Properties with Intelligence in Normal Aging

Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60–85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R) and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient) were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.     

IMDB Network Revisited: Unveiling Fractal and Modular Properties from a Typical Small-World Network

We study a subset of the movie collaboration network, http://www.imdb.com, where only adult movies are included. We show that there are many benefits in using such a network, which can serve as a prototype for studying social interactions. We find that the strength of links, i.e., how many times two actors have collaborated with each other, is an important factor that can significantly influence the network topology. We see that when we link all actors in the same movie with each other, the network becomes small-world, lacking a proper modular structure. On the other hand, by imposing a threshold on the minimum number of links two actors should have to be in our studied subset, the network topology becomes naturally fractal. This occurs due to a large number of meaningless links, namely, links connecting actors that did not actually interact. We focus our analysis on the fractal and modular properties of this resulting network, and show that the renormalization group analysis can characterize the self-similar structure of these networks.     

R~3中的一类拟齐次向量场的性质

利用三维拟齐次向量场和三维齐次向量场之间的等价关系并借鉴对齐次向量场的研究方法,把齐次向量场的一些结论推广到拟齐次向量场.并运用这些理论分析了具有不同增长率的三种群竞争模型的动力学性质和生物意义,得到增长率最大的种群在此竞争系统中占优,增长率最小的种群在此竞争系统中灭绝的结论.     

Plant Coilin: Structural Characteristics and RNA-Binding Properties

Cajal bodies (CBs) are dynamic subnuclear compartments involved in the biogenesis of ribonucleoproteins. Coilin is a major structural scaffolding protein necessary for CB formation, composition and activity. The predicted secondary structure of Arabidopsis thaliana coilin (Atcoilin) suggests that the protein is composed of three main domains. Analysis of the physical properties of deletion mutants indicates that Atcoilin might consist of an N-terminal globular domain, a central highly disordered domain and a C-terminal domain containing a presumable Tudor-like structure adjacent to a disordered C terminus. Despite the low homology in amino acid sequences, a similar type of domain organization is likely shared by human and animal coilin proteins and coilin-like proteins of various plant species. Atcoilin is able to bind RNA effectively and in a non-specific manner. This activity is provided by three RNA-binding sites: two sets of basic amino acids in the N-terminal domain and one set in the central domain. Interaction with RNA induces the multimerization of the Atcoilin molecule, a consequence of the structural alterations in the N-terminal domain. The interaction with RNA and subsequent multimerization may facilitate coilin’s function as a scaffolding protein. A model of the N-terminal domain is also proposed.     

Structural and Dynamical Properties of a Full-length HIV-1 Integrase: Molecular Dynamics Simulations

Abstract

The structural and dynamical properties of the complete full-length structure of HIV-1 integrase were investigated using Molecular Dynamics approach. Simulations were carried out for the three systems, core domain only (CORE), full-length structure without (FULL) and with a Mg²⁺ (FULL+ION) in its active site, aimed to investigate the difference in the molecular properties of the full-length models due to their different construction procedures as well as the effects of the two ends, C- and N-terminal, on those properties in the core domain. The full-length structure was prepared from the two experimental structures of two-domain fragment. The following properties were observed to differ significantly from the previous reports: (i) relative topology formed by an angle between the three domains; (ii) the cavity size defined by the catalytic triad, Asp64, Asp116, and Glul52; (iii) distances and solvation of the Mg²⁺; and (iv) conformation of the catalytic residues. In addition, the presence of the two terminal domains decreases the mobility of the central core domain significantly.     

Functional and Structural Properties of Ovomucin

Relationships between the structural (hydrophobicity and viscosity) and functional (foaming and emulsifying) properties of proteins were investigated by using a polymeric form of ovomucin (soluble type), and dissociated ovomucins which were treated with sonication (sonicated type) and reduction (reduced type). The soluble, sonicated and reduced ovomucins were ascertained to have excellent foaming and emulsifying properties. The foaming properties of the ovomucins decreased in proportion to decreases in the viscosity as the dissociation proceeded, in the order of the soluble, sonicated and reduced types. On the other hand, the emulsifying properties of ovomucins increased in proportion to increases in the surface hydrophobicity as the dissociation proceeded.

Thus, it was suggested that the foaming properties of ovomucins were dependent upon viscosity, and that the emulsifying properties of ovomucins were dependent upon surface hydrophobicity.     

Structural Properties of Gene Regulatory Networks: Definitions and Connections

The study of gene regulatory networks is a significant problem in systems biology. Of particular interest is the problem of determining the unknown or hidden higher level regulatory signals by using gene expression data from DNA microarray experiments. Several studies in this area have demonstrated the critical aspect of the network structure in tackling the network modelling problem. Structural analysis of systems has proved useful in a number of contexts, viz., observability, controllability, fault diagnosis, sparse matrix computations etc. In this contribution, we formally define structural properties that are relevant to Gene Regulatory Networks. We explore the structural implications of certain quantitative methods and explain completely the connections between the identifiability conditions and structural criteria of observability and distinguishability. We illustrate these concepts in case studies using representative biologically motivated network examples. The present work bridges the quantitative modelling methods with those based on the structural analysis.     

Sleep-Inducing Properties of DSIP Analogs: Structural and Functional Relationships

The sleep-inducing activity of Delta Sleep-Inducing Peptide (DSIP) and its 13 synthetic analogs has been studied on rabbits with preliminary implanted electrodes. The peptides were injected into the lateral ventricle of cerebrum. Polygraphic computer monitoring of sleep–wake states was carried out at daytime for 7–12 h. DSIP and most analogs had no statistically significant effect on sleep compared to the control administration of saline to the same animals. [NMeAla²]DSIP and [Pro²]DSIP had a pronounced sleep-inducing effect and reliably increased the proportion of slow-wave sleep by 10–15% on average compared to the control. Several other analogs had a week sleep-inducing effect, increasing the proportion of slow-wave sleep during specific recording time only. [-Ala²]DSIP significantly suppressed sleep. In addition, this analog, as well as parent DSIP and four proline-containing nonapeptides, slightly increased the body temperature. The revealed differences may be due to both conformation properties and proteolytic resistance of the studied molecules, and it may reflect their indirect involvement in the control sleep–wake hormonal processes.