Ten Myths around Open Scholarly Publishing

The changing world of scholarly communication and the emergence of ‘Open Science’ or ‘Open Research’ has brought to light a number of controversial and hotly-debated topics. Yet, evidence-based rational debate is regularly drowned out by misinformed or exaggerated rhetoric, which does not benefit the evolving system of scholarly communication. The aim of this article is to provide a baseline evidence framework for ten of the most contested topics, in order to help frame and move forward discussions, practices and policies. We address preprints and scooping, the practice of copyright transfer, the function of peer review, and the legitimacy of ‘global’ databases. The presented facts and data will be a powerful tool against misinformation across wider academic research, policy and practice, and may be used to inform changes within the rapidly evolving scholarly publishing system

A measure of bending in nucleic acids structures applied to A-tract DNA

A method is proposed to measure global bending in DNA and RNA structures. It relies on a properly defined averaging of base-fixed coordinate frames, computes mean frames of suitably chosen groups of bases and uses these mean frames to evaluate bending. The method is applied to DNA A-tracts, known to induce considerable bend to the double helix. We performed atomistic molecular dynamics simulations of sequences containing the A4T4 and T4A4 tracts, in a single copy and in two copies phased with the helical repeat. Various temperature and salt conditions were investigated. Our simulations indicate bending by roughly 10° per A4T4 tract into the minor groove, and an essentially straight structure containing T4A4, in agreement with electrophoretic mobility data. In contrast, we show that the published NMR structures of analogous sequences containing A4T4 and T4A4 tracts are significantly bent into the minor groove for both sequences, although bending is less pronounced for the T4A4 containing sequence. The bending magnitudes obtained by frame averaging are confirmed by the analysis of superhelices composed of repeated tract monomers

Ten Hot Topics around Scholarly Publishing

The changing world of scholarly communication and the emergence of a new wave of 'Open Science' or 'Open Research' has brought to light a number of controversial and hotly-debated topics. Yet, evidence-based rational debate is regularly drowned out by misinformed or exaggerated rhetoric, which does not benefit the evolving system of scholarly communication. The aim of this article is to provide a baseline evidence framework for ten of the most contested topics, in order to help frame and move forward discussions, practices and policies. We address issues around preprints and scooping, the practice of copyright transfer, the function of peer review, predatory publishers, and the legitimacy of 'global' databases. The presented facts, arguments and data will be a powerful tool against misinformation across wider academic research, policy and practice, and may be used to inform changes within the rapidly evolving scholarly publishing system

Structure-Based Rational Design of a Toll-like Receptor 4 (TLR4) Decoy Receptor with High Binding Affinity for a Target Protein

Repeat proteins are increasingly attracting much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural features. Nonetheless, engineering interaction interface and understanding molecular basis for affinity maturation of repeat proteins still remain a challenge. Here, we present a structure-based rational design of a repeat protein with high binding affinity for a target protein. As a model repeat protein, a Toll-like receptor4 (TLR4) decoy receptor composed of leucine-rich repeat (LRR) modules was used, and its interaction interface was rationally engineered to increase the binding affinity for myeloid differentiation protein 2 (MD2). Based on the complex crystal structure of the decoy receptor with MD2, we first designed single amino acid substitutions in the decoy receptor, and obtained three variants showing a binding affinity (KD) one-order of magnitude higher than the wild-type decoy receptor. The interacting modes and contributions of individual residues were elucidated by analyzing the crystal structures of the single variants. To further increase the binding affinity, single positive mutations were combined, and two double mutants were shown to have about 3000- and 565-fold higher binding affinities than the wild-type decoy receptor. Molecular dynamics simulations and energetic analysis indicate that an additive effect by two mutations occurring at nearby modules was the major contributor to the remarkable increase in the binding affinities

Patterns of Selection in Anti-Malarial Immune Genes in Malaria Vectors: Evidence for Adaptive Evolution in LRIM1 in Anopheles arabiensis

Co-evolution between Plasmodium species and its vectors may result in adaptive changes in genes that are crucial components of the vector's defense against the pathogen. By analyzing which genes show evidence of positive selection in malaria vectors, but not in closely related non-vectors, we can identify genes that are crucial for the mosquito's resistance against Plasmodium.We investigated genetic variation of three anti-malarial genes; CEC1, GNBP-B1 and LRIM1, in both vector and non-vector species of the Anopheles gambiae complex. Whereas little protein differentiation was observed between species in CEC1 and GNBP-B1, McDonald-Kreitman and maximum likelihood tests of positive selection show that LRIM1 underwent adaptive evolution in a primary malaria vector; An. arabiensis. In particular, two adjacent codons show clear signs of adaptation by having accumulated three out of four replacement substitutions. Furthermore, our data indicate that this LRIM1 allele has introgressed from An. arabiensis into the other main malaria vector An. gambiae.Although no evidence exists to link the adaptation of LRIM1 to P. falciparum infection, an adaptive response of a known anti-malarial gene in a primary malaria vector is intriguing, and may suggest that this gene could play a role in Plasmodium resistance in An. arabiensis. If so, our data also predicts that LRIM1 alleles in An. gambiae vary in their level of resistance against P. falciparum

Ten Myths around Open Scholarly Publishing

The changing world of scholarly communication and the emergence of ‘Open Science’ or ‘Open Research’ has brought to light a number of controversial and hotly-debated topics. Yet, evidence-based rational debate is regularly drowned out by misinformed or exaggerated rhetoric, which does not benefit the evolving system of scholarly communication. The aim of this article is to provide a baseline evidence framework for ten of the most contested topics, in order to help frame and move forward discussions, practices and policies. We address preprints and scooping, the practice of copyright transfer, the function of peer review, and the legitimacy of ‘global’ databases. The presented facts and data will be a powerful tool against misinformation across wider academic research, policy and practice, and may be used to inform changes within the rapidly evolving scholarly publishing system

Statistical shape methodology for the analysis of helices

Consider a helix in three-dimensional space along which a sequence of equally spaced points is observed, subject to statistical noise. For data coming from a single helix, a two-stage algorithm based on a profile likelihood is developed to compute the maximum likelihood estimate of the helix parameters. Statistical properties of the estimator are studied and comparisons are made to other estimators found in the literature. Next a likelihood ratio test is developed to test if there is a change point in the helix, splitting the data into two sub-helices. The shapes of protein α-helices are used to illustrate the methodology