Bayesian Inference of the Evolution of a Phenotype Distribution on a Phylogenetic Tree

The distribution of a phenotype on a phylogenetic tree is often a quantity of interest. Many phenotypes have imperfect heritability, so that a measurement of the phenotype for an individual can be thought of as a single realization from the phenotype distribution of that individual. If all individuals in a phylogeny had the same phenotype distribution, measured phenotypes would be randomly distributed on the tree leaves. This is, however, often not the case, implying that the phenotype distribution evolves over time. Here we propose a new model based on this principle of evolving phenotype distribution on the branches of a phylogeny, which is different from ancestral state reconstruction where the phenotype itself is assumed to evolve. We develop an efficient Bayesian inference method to estimate the parameters of our model and to test the evidence for changes in the phenotype distribution. We use multiple simulated data sets to show that our algorithm has good sensitivity and specificity properties. Since our method identifies branches on the tree on which the phenotype distribution has changed, it is able to break down a tree into components for which this distribution is unique and constant. We present two applications of our method, one investigating the association between HIV genetic variation and human leukocyte antigen and the other studying host range distribution in a lineage of Salmonella enterica, and we discuss many other potential applications.     

Docking of tryptophanyl [corrected tryptophan] analogs to trytophanyl-tRNA synthetase: implications for non-canonical amino acid incorporations

Abstract Non-canonical amino acids (N(AA)), as building blocks for peptides and proteins during ribosomal translation, represent a nearly infinite supply of novel functions. The specific selection, activation and tRNA-charging of amino acids by aminoacyl-tRNA synthetases (AARS) in the aminoacylation reaction are essential steps. In most cases, aminoacylation of N(AA) is a good indication that the related amino acid will participate in ribosomal translation as well. However, testing the translational capacity of amino acid analogs has technical limitations. Therefore, a rapid and reliable in silico test for N(AA) recognition by AARS would be advantageous in experimental design. We chose tryptophanyl-tRNA synthetase from Escherichia coli as a model system for docking studies with various tryptophan analogs using the FlexX-Pharm strategy. We were able to calculate relative binding energies for Trp analogs in TrpRS that correlate well with their translational activities in E. coli. In particular, FlexX-Pharm predicted the binding sites of fluoro-, amino-, hydroxyl- and aza-containing Trp analogs within 1.5 A of Trp in the homology model of E. coli TrpRS. Therefore, the use of ligand docking prior to N(AA) incorporation experiments might provide a straightforward means for determining N(AA) that can be efficiently incorporated into a protein.     

Predictions of co-contraction depend critically on degrees-of-freedom in the musculoskeletal model

In biomechanics, the calculation of individual muscle forces during movements is based on a model of the musculoskeletal system and a method for extracting a unique set of muscle forces. To obtain a unique set of muscle forces, non-linear, static optimisation is commonly used. However, the optimal solution is dependent on the musculoskeletal geometry, and single joints may be represented using one, two or three degrees-of-freedom. Frequently, a system with multiple degrees-of-freedom is replaced with a system that contains a subset of all the possible degrees-of-freedom. For example, the cat ankle joint is typically modelled as a planar joint with its primary degree-of-freedom (plantar-dorsiflexion), whereas, the actual joint has three rotational degrees-of-freedom. Typically, such simplifications are justified by the idea that the reduced case is contained as a specific solution of the more general case. However, here we demonstrate that the force-sharing solution space of a general, three degrees-of-freedom musculoskeletal system does not necessarily contain the solutions from the corresponding one or two degrees-of-freedom systems. Therefore, solutions of a reduced system, in general, are not sub-set solutions of the actual three degrees-of-freedom system, but are independent solutions that are often incompatible with solutions of the actual system. This result shows that representing a three degrees-of-freedom system as a one or two degrees-of-freedom system gives force-sharing solutions that cannot be extrapolated to the actual system, and vice-versa. These results imply that general solutions cannot be extracted from models with fewer degrees-of-freedom than the actual system. They further emphasise the need for precise geometric representation of the musculoskeletal system, if general force-sharing rules are to be derived.     

Two new myrmecophilous species of the genus Scutacarus (Acari: Prostigmata: Scutacaridae) with world keys to related species groups

In a survey on heterostigmatic mites (Acari: Prostigmata: Heterostigmata) associated with insects including ants in northwestern Iran, two new species of myrmecophilous mites of the genus Scutacarus (Acari: Scutacaridae) were found. They are S. shajariani sp. nov. phoretic on Tetramorium sp. (Hymenoptera: Formicidae) and S. ebermanni sp. nov. phoretic on Messor sp. The mentioned new species belong to groups of species with reduced setae e and h₂, and no setae 4b, respectively. These two new species are described and illustrated, and world keys are provided for respective species groups.     

Stepwise morphological changes and cytoskeletal reorganization of human mesenchymal stem cells treated by short-time cyclic uniaxial stretch

This study aimed to investigate stepwise remodeling of human mesenchymal stem cells (hMSCs) in response to cyclic stretch through rearrangement and alignment of cells and cytoskeleton regulation toward smooth muscle cell (SMC) fate in different time spans. Image analysis techniques were utilized to calculate morphological parameters. Cytoskeletal reorganization was observed by investigating F-actin filaments using immunofluorescence staining, and expression level of contractile SMC markers was followed by a quantitative polymerase chain reaction method. Applying cyclic uniaxial stretch on cultured hMSCs, utilizing a costume-made device, led to alteration in fractal dimension (FD) and cytoskeleton structure toward continuous alignment and elongation of cells by elevation of strain duration. Actin filaments became more aligned perpendicular to the axis of mechanical stretch by increasing uniaxial loading duration. At first, FD met a significant decrease in 4 h loading duration then increased significantly by further loading up to 16 h, followed by another decrease up to 1 d of uniaxial stretching. HMSCs subjected to 24 h cyclic uniaxial stretching significantly expressed early and intermediate contractile SM markers. It was hypothesized that the increase in FD after 4 h while cells continuously became more aligned and elongated was due to initiation of change in phenotype that influenced arrangement of cells. At this point, change in cell phenotype started leading to change in morphology while mechanical loading still caused cell alignment and rearrangement. Results can be helpful when optimized engineered cells are needed based on mechanical condition for functional engineered tissue and cell therapy.     

Growth and nutrient removal of three macrophytes in response to concentrations and ratios of N and P

Wastewater from different sources shows great differences in concentrations and ratios of N and P. In order to choose suitable plant species to remove excess N and/or P from polluted waters, it is important to know the performances of these plants under different N and P concentrations. In this study, we investigated the growth and N and P removal rate of three macrophytes, Coix lacryma-jobi, Iris wilsonii, and Arundo donax under six N and P combination treatments. C. lacryma-jobi preferred higher N and P concentrations (16 mg N L^?1 and 3.2 mg P L^?1), and increasing N supply could increase its P removal rate. I. wilsonii exhibited a growth preference at a combination of moderate N and P concentrations (8 mg N L^?1 and 0.8 mg P L^?1). A. donax could grow well at all combinations of N and P and had significantly higher relative growth rate and N and P removal rates than the other two species. These results showed A. donax is a promising species to treat various polluted waters and the other two species can be used specifically to treat certain types of wastewater.