Partner-specific prediction of RNA-binding residues in proteins: A critical assessment

RNA-protein interactions play essential roles in regulating gene expression. While some RNA-protein interactions are “specific”, that is, the RNA-binding proteins preferentially bind to particular RNA sequence or structural motifs, others are “non-RNA specific.” Deciphering the protein-RNA recognition code is essential for comprehending the functional implications of these interactions and for developing new therapies for many diseases. Because of the high cost of experimental determination of protein-RNA interfaces, there is a need for computational methods to identify RNA-binding residues in proteins. While most of the existing computational methods for predicting RNA-binding residues in RNA-binding proteins are oblivious to the characteristics of the partner RNA, there is growing interest in methods for partner-specific prediction of RNA binding sites in proteins. In this work, we assess the performance of two recently published partner-specific protein-RNA interface prediction tools, PS-PRIP, and PRIdictor, along with our own new tools. Specifically, we introduce a novel metric, RNA-specificity metric (RSM), for quantifying the RNA-specificity of the RNA binding residues predicted by such tools. Our results show that the RNA-binding residues predicted by previously published methods are oblivious to the characteristics of the putative RNA binding partner. Moreover, when evaluated using partner-agnostic metrics, RNA partner-specific methods are outperformed by the state-of-the-art partner-agnostic methods. We conjecture that either (a) the protein-RNA complexes in PDB are not representative of the protein-RNA interactions in nature, or (b) the current methods for partner-specific prediction of RNA-binding residues in proteins fail to account for the differences in RNA partner-specific versus partner-agnostic protein-RNA interactions, or both.     

Inter‐individual variation in colour patterns in noctuid moths characterizes long‐distance dispersers and agricultural pests

A high capacity for long‐distance dispersal is a key to success for species confronted with environmental heterogeneity, habitat modification, fragmentation and loss. However, dispersal capacity is difficult to quantify and therefore poorly known in most taxa. Here, we report on a test for an association of variation in dispersal capacity with variable colouration of noctuid moths. First, using data from 12 experienced lepidopterologists, we showed that despite variation among experts in average assessments, different species are consistently classified as having non‐variable, variable or highly variable colour patterns when assessed by different experts. We then compared the incidence of non‐resident species with high inter‐individual variation in colour patterns recorded on the isolated island Utklippan (n = 47), with that in a species pool of potential long‐distance dispersers from the nearest mainland (n = 295). Species with high inter‐individual colour pattern variation were over‐represented on the island compared with species having non‐variable colouration. This finding constitutes rare evidence from the wild of long‐distance dispersal, measured on a spatial scale relevant for moths when tracking habitats in fragmented and changing landscapes or when keeping pace with environmental challenges associated with climate change. Finally, we showed that Swedish noctuid moths classified as agricultural pests (n = 28) had more variable colour patterns compared with non‐pests (n = 368). The majority of agricultural pests were also recorded on the isolated island, an outcome that is indicative of pest species having high dispersal capacity. Data on colour pattern variation may thus offer a simple and cost‐effective proxy to estimate dispersal capacity and can also help identify potential pest species. Our findings are potentially useful when modelling and predicting population and range dynamics of species in spatiotemporally heterogeneous environments, with direct implications for conservation biology and pest management.     

N-(4-(2-chloro-4-(trifluoromethyl)phenoxy)phenyl)picolinamide as a new inhibitor of mitochondrial complex III: Synthesis,biological evaluation and computational simulations

Mitochondrial complex III is one of the most promising targets for a number of pharmaceuticals and fungicides. Due to the wide-spread use of complex III-inhibiting fungicides, a considerable increase of resistance has occurred worldwide. Therefore, inhibitors with novel scaffolds and potent activity against complex III are still in great demand. In this article, a new series of amide compounds bearing the diaryl ether scaffold were designed and prepared, followed by the biological evaluation. Gratifyingly, several compounds demonstrated potent activity against succinate-cytochrome c reductase (SCR, a mixture of mitochondrial complex II and complex III), with compound 3w possessing the best inhibitory activity (IC₅₀ = 0.91 ± 0.09 μmol/L). Additional studies verified that 3w was a new inhibitor of complex III. Moreover, computational simulations elucidated that 3w should bind to the Q_o site of complex III. We believe this work will be valuable for the preparation and discovery of more complex III inhibitors.     

Sampling Plan Optimization: A Data Review and Sampling Frequency Evaluation Process

Lawrence Livermore National Laboratory (LLNL) uses a cost-effective sampling (CES) methodology to evaluate and review ground water contaminant data and optimize the site's ground water monitoring plan. The CES methodology is part of LLNL's regulatory approved compliance monitoring plan (Lamarre et al., 1996 Lamarre, A. L., Nichols, E. M., Berg, L. L., Dresen, M. D., Gelinas, R. J., Bainer, R. W. and Folsom, E. N. 1996. Compliance monitoring plan for the Lawrence Livermore National Laboratory Livermore Site UCRL-AR-120936 [Google Scholar]). It allows LLNL to adjust the ground water sampling plan every quarter in response to changing conditions at the site. Since the use of the CES methodology has been approved by the appropriate regulatory agencies, such adjustments do not need additional regulatory approval. This permits LLNL to respond more quickly to changing conditions. The CES methodology bases the sampling frequency for each location on trend, variability, and magnitude statistics describing the contaminants at that location, and on the input of the technical staff (hydrologists, chemists, statisticians, and project leaders). After initial setup is complete, each application of CES takes only a few days for as many as 400 wells. Effective use of the CES methodology requires sufficient data, an understanding of contaminant transport at the site, and an adequate number of monitoring wells downgradient of the contamination. The initial implementation of CES at LLNL in 1992 produced a 40% reduction in the required number of annual routine ground water samples at LLNL. This has saved LLNL $390,000 annually in sampling, analysis, and data management costs.     

A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs

Fatty acids, which are essential nutritional components, are also involved in cardiovascular and metabolic diseases. Here we report a human cell surface receptor that we name free fatty acid receptor (FFAR), because it is specifically activated by medium to long-chain free fatty acids. The receptor belongs to the class of seven-transmembrane, G-protein coupled receptors (GPCRs) and also mediates responses to antidiabetic drugs of the thiazolidinedione type. It is expressed in skeletal muscle, heart, liver, and pancreatic beta-cells. Stimulation of FFAR increases the intracellular calcium concentration in cells expressing the receptor in a native (pancreatic beta-cell line) or in a recombinant form. In view of the nature of the activating substances, their physiological role in the body, and the tissue distribution of FFAR we suggest the term "nutrient sensing receptor" for receptors acting at the interface between dietary components and signalling molecules.     

Bequest: The framework and directory of assessment methods

This paper has outlined the areas of the Environment and Climate Programme (Economic and Social Aspects of Human Settlement) the BEQUEST project addresses. It has also examined the framework for analysis the project sets out for a common understanding of SUD and the assessment methods currently made use of by planners, architects, engineers and surveyors to build environmental capacity. The paper has done this by:

Bollworm responses to release of genetically modified Helicoverpa armigera nucleopolyhedroviruses in cotton

Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus (HaSNPV) has been developed as a commercial biopesticide to control the cotton bollworm, H. armigera, in China. The major limitation to a broader application of this virus has been the relative long time to incapacitate the target insect. Two HaSNPV recombinants with improved insecticidal properties were released in bollworm-infested cotton. One recombinant (HaCXW1) lacked the ecdysteroid UDP-glucosyltransferase (egt) gene and in another recombinant (HaCXW2), an insect-selective scorpion toxin (AaIT) gene replaced the egt gene. In a cotton field situation H. armigera larvae treated with either HaCXW1 or HaCXW2 were killed faster than larvae in HaSNPV-wt treated plots. Second instar H. armigera larvae, which were collected from HaCXW1 and HaCXW2 treated plots and further reared on artificial diet, showed reduced ST(50) values of 15.3 and 26.3%, respectively, as compared to larvae collected from HaSNPV-wt treated plots. The reduction in consumed leaf area of field collected larvae infected with HaCXW1 and HaCXW2 was approximated 50 and 63%, respectively, as compared to HaSNPV-wt infected larvae at 108 h after treatment. These results suggest that in a cotton field situation the recombinants will be more effective control agents of the cotton bollworm than wild-type HaSNPV.     

The Effect of Recombination on the Accuracy of Phylogeny Estimation

Phylogenetic studies based on DNA sequences typically ignore the potential occurrence of recombination, which may produce different alignment regions with different evolutionary histories. Traditional phylogenetic methods assume that a single history underlies the data. If recombination is present, can we expect the inferred phylogeny to represent any of the underlying evolutionary histories? We examined this question by applying traditional phylogenetic reconstruction methods to simulated recombinant sequence alignments. The effect of recombination on phylogeny estimation depended on the relatedness of the sequences involved in the recombinational event and on the extent of the different regions with different phylogenetic histories. Given the topologies examined here, when the recombinational event was ancient, or when recombination occurred between closely related taxa, one of the two phylogenies underlying the data was generally inferred. In this scenario, the evolutionary history corresponding to the majority of the positions in the alignment was generally recovered. Very different results were obtained when recombination occurred recently among divergent taxa. In this case, when the recombinational breakpoint divided the alignment in two regions of similar length, a phylogeny that was different from any of the true phylogenies underlying the data was inferred.     

A new archaeobotanical database program

The available quantity of archaeobotanical data derived from the identification of macroremains has expanded considerably over the last few decades. In order to obtain a supraregional or even regional overview for a particular period of time, or of the distribution of a single species, a database is needed. At the Archaeobotanical Department of the Institute of the "Kommission für Arch?ologische Landesforschung in Hessen e.V." (KAL) such a database has been developed in the last few years. It is suitable for the handling of large quantities of archaeobotanical results, including a whole range of background information comprising archaeological, ecological and other related data, and offers various possibilities for the evaluation of these data. Received January 8, 2001 / Accepted April 9, 2002