Motif patterns in 2D

Motif patterns consisting of sequences of intermixed solid and don’t-care characters have been introduced and studied in connection with pattern discovery problems of computational biology and other domains. In order to alleviate the exponential growth of such motifs, notions of maximal saturation and irredundancy have been formulated, whereby more or less compact subsets of the set of all motifs can be extracted, that are capable of expressing all others by suitable combinations. In this paper, we introduce the notion of maximal irredundant motifs in a two-dimensional array and develop initial properties and a combinatorial argument that poses a linear bound on the total number of such motifs. The remainder of the paper presents approaches to the discovery of irredundant motifs both by offline and incremental algorithms.     

Parallel discovery of network motifs

Many natural structures can be naturally represented by complex networks. Discovering network motifs, which are overrepresented patterns of inter-connections, is a computationally hard task related to graph isomorphism. Sequential methods are hindered by an exponential execution time growth when we increase the size of motifs and networks. In this article we study the opportunities for parallelism in existing methods and propose new parallel strategies that adapt and extend one of the most efficient serial methods known from the Fanmod tool. We propose both a master–worker strategy and one with distributed control, in which we employ a randomized receiver initiated methodology capable of providing dynamic load balancing during the whole computation process. Our strategies are capable of dealing both with exact and approximate network motif discovery. We implement and apply our algorithms to a set of representative networks and examine their scalability up to 128 processing cores. We obtain almost linear speedups, showcasing the efficiency of our proposed approach and are able to reach motif sizes that were not previously achievable using conventional serial algorithms.     

Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A–class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg^2.39, His^2.43 and Glu^3.46, which makes a polar lock with T^6.37. These alignments and models provide useful tools for understanding class B GPCR function.     

Purification and characterisation of a novel protease from Cordyceps sinensis and determination of the cleavage site motifs using oriented peptide library mixtures

A novel protease, from the edible fungus Cordyceps sinensis, was purified and characterised. Its cleavage site motifs were determined by oriented peptide library mixtures and validated by synthetic peptides and natural proteins.     

CpG序列及阳离子脂质体对猪带绦虫抗原基因免疫应答的影响

本实验将猪带绦虫抗原基因VTS76分别与pUC18质粒，重组pUC18-CpG质粒联合及阳离子脂质体包装后免疫小鼠，结果表明：pUC18和pUC18-CpG能显著提高免疫小鼠总IgG和特异性抗体水平，增加小鼠免疫细胞数量，增强淋巴细胞增殖活性及白细胞介素－2的诱生活性，其中，pUC18-CpG的免疫增强效果更显著，阳离子脂质体包裹具有减少质粒用量，提高免疫应答水平的作用。     

Improved Bioactivity of Antimicrobial Peptides by Addition of Amino‐Terminal Copper and Nickel (ATCUN) Binding Motifs

Antimicrobial peptides (AMPs) are promising candidates to help circumvent antibiotic resistance, which is an increasing clinical problem. Amino‐terminal copper and nickel (ATCUN) binding motifs are known to actively form reactive oxygen species (ROS) upon metal binding. The combination of these two peptidic constructs could lead to a novel class of dual‐acting antimicrobial agents. To test this hypothesis, a set of ATCUN binding motifs were screened for their ability to induce ROS formation, and the most potent were then used to modify AMPs with different modes of action. ATCUN binding motif‐containing derivatives of anoplin (GLLKRIKTLL‐NH₂), pro‐apoptotic peptide (PAP; KLAKLAKKLAKLAK‐NH₂), and sh‐buforin (RAGLQFPVGRVHRLLRK‐NH₂) were synthesized and found to be more active than the parent AMPs against a panel of clinically relevant bacteria. The lower minimum inhibitory concentration (MIC) values for the ATCUN–anoplin peptides are attributed to the higher pore‐forming activity along with their ability to cause ROS‐induced membrane damage. The addition of the ATCUN motifs to PAP also increases its ability to disrupt membranes. DNA damage is the major contributor to the activity of the ATCUN–sh‐buforin peptides. Our findings indicate that the addition of ATCUN motifs to AMPs is a simple strategy that leads to AMPs with higher antibacterial activity and possibly to more potent, usable antibacterial agents.     

中日传统家具装饰五金的图案与题材

传统家具五金配件作为古典家具结构与装饰艺术中的一个重要组成部分,是体现其风格特征的重要特点之一。它们种类繁多,工艺考究,用处很广,造型也很丰富,为传统家具增添了不少光彩。中国与日本的传统家具五金配饰,各有其精致之美,本文对二者丰富的图案题材进行了浅析。     

Role of RNA Motifs in RNA Interaction with Membrane Lipid Rafts: Implications for Therapeutic Applications of Exosomal RNAs

RNA motifs may promote interactions with exosomes (EXO-motifs) and lipid rafts (RAFT-motifs) that are enriched in exosomal membranes. These interactions can promote selective RNA loading into exosomes. We quantified the affinity between RNA aptamers containing various EXO- and RAFT-motifs and membrane lipid rafts in a liposome model of exosomes by determining the dissociation constants. Analysis of the secondary structure of RNA molecules provided data about the possible location of EXO- and RAFT-motifs within the RNA structure. The affinity of RNAs containing RAFT-motifs (UUGU, UCCC, CUCC, CCCU) and some EXO-motifs (CCCU, UCCU) to rafted liposomes is higher in comparison to aptamers without these motifs, suggesting direct RNA-exosome interaction. We have confirmed these results through the determination of the dissociation constant values of exosome-RNA aptamer complexes. RNAs containing EXO-motifs GGAG or UGAG have substantially lower affinity to lipid rafts, suggesting indirect RNA-exosome interaction via RNA binding proteins. Bioinformatics analysis revealed RNA aptamers containing both raft- and miRNA-binding motifs and involvement of raft-binding motifs UCCCU and CUCCC. A strategy is proposed for using functional RNA aptamers (fRNAa) containing both RAFT-motif and a therapeutic motif (e.g., miRNA inhibitor) to selectively introduce RNAs into exosomes for fRNAa delivery to target cells for personalized therapy.