Two new compounds, named eudesm-4(15),7-diene-3α,9β,11-triol (1) and eudesm-4(15),7-diene-1β,3α,9β,11-tetraol (2) together with three known sesquiterpene lactones (1S,5R,7R,10R)-secoatractylolactone ...(3), (1S,5R,7R,10R)-secoatractylolactone-11-O-β-D-glucopyranoside (4) atractylenolide III (5) were isolated from the rhizomes of Atractylodes macrocephala. Their structures were elucidated by using one-dimensional (1D) and 2D-NMR spectra and high resolution electrospray ionization (HR-ESI)-MS data. Compound 5 exhibited the most active anti-inflammatory activity with IC50 values of 27.5 µM in inhibiting of nitric oxide production. Compounds 1, 2, and 3 showed moderate effects while compound 4 was inactive.
Abstract
Using time-reversible Markov models is a very common practice in phylogenetic analysis, because although we expect many of their assumptions to be violated by empirical data, they provide ...high computational efficiency. However, these models lack the ability to infer the root placement of the estimated phylogeny. In order to compensate for the inability of these models to root the tree, many researchers use external information such as using outgroup taxa or additional assumptions such as molecular clocks. In this study, we investigate the utility of nonreversible models to root empirical phylogenies and introduce a new bootstrap measure, the rootstrap, which provides information on the statistical support for any given root position. Bootstrap; nonreversible models; phylogenetic inference; root estimation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In phylogenetic inference, we commonly use models of substitution which assume that sequence evolution is stationary, reversible, and homogeneous (SRH). Although the use of such models is often ...criticized, the extent of SRH violations and their effects on phylogenetic inference of tree topologies and edge lengths are not well understood. Here, we introduce and apply the maximal matched-pairs tests of homogeneity to assess the scale and impact of SRH model violations on 3,572 partitions from 35 published phylogenetic data sets. We show that roughly one-quarter of all the partitions we analyzed (23.5%) reject the SRH assumptions, and that for 25% of data sets, tree topologies inferred from all partitions differ significantly from topologies inferred using the subset of partitions that do not reject the SRH assumptions. This proportion increases when comparing trees inferred using the subset of partitions that rejects the SRH assumptions, to those inferred from partitions that do not reject the SRH assumptions. These results suggest that the extent and effects of model violation in phylogenetics may be substantial. They highlight the importance of testing for model violations and possibly excluding partitions that violate models prior to tree reconstruction. Our results also suggest that further effort in developing models that do not require SRH assumptions could lead to large improvements in the accuracy of phylogenomic inference. The scripts necessary to perform the analysis are available in https://github.com/roblanf/SRHtests, and the new tests we describe are available as a new option in IQ-TREE (http://www.iqtree.org).
Abstract
Motivation
Sequence simulation plays a vital role in phylogenetics with many applications, such as evaluating phylogenetic methods, testing hypotheses, and generating training data for ...machine-learning applications. We recently introduced a new simulator for multiple sequence alignments called AliSim, which outperformed existing tools. However, with the increasing demands of simulating large data sets, AliSim is still slow due to its sequential implementation; for example, to simulate millions of sequence alignments, AliSim took several days or weeks. Parallelization has been used for many phylogenetic inference methods but not yet for sequence simulation.
Results
This paper introduces AliSim-HPC, which, for the first time, employs high-performance computing for phylogenetic simulations. AliSim-HPC parallelizes the simulation process at both multi-core and multi-CPU levels using the OpenMP and message passing interface (MPI) libraries, respectively. AliSim-HPC is highly efficient and scalable, which reduces the runtime to simulate 100 large gap-free alignments (30 000 sequences of one million sites) from over one day to 11 min using 256 CPU cores from a cluster with six computing nodes, a 153-fold speedup. While the OpenMP version can only simulate gap-free alignments, the MPI version supports insertion–deletion models like the sequential AliSim.
Availability and implementation
AliSim-HPC is open-source and available as part of the new IQ-TREE version v2.2.3 at https://github.com/iqtree/iqtree2/releases with a user manual at http://www.iqtree.org/doc/AliSim.
Abstract
Amino acid substitution models are a key component in phylogenetic analyses of protein sequences. All commonly used amino acid models available to date are time-reversible, an assumption ...designed for computational convenience but not for biological reality. Another significant downside to time-reversible models is that they do not allow inference of rooted trees without outgroups. In this article, we introduce a maximum likelihood approach nQMaker, an extension of the recently published QMaker method, that allows the estimation of time nonreversible amino acid substitution models and rooted phylogenetic trees from a set of protein sequence alignments. We show that the nonreversible models estimated with nQMaker are a much better fit to empirical alignments than pre-existing reversible models, across a wide range of data sets including mammals, birds, plants, fungi, and other taxa, and that the improvements in model fit scale with the size of the data set. Notably, for the recently published plant and bird trees, these nonreversible models correctly recovered the commonly estimated root placements with very high-statistical support without the need to use an outgroup. We provide nQMaker as an easy-to-use feature in the IQ-TREE software (http://www.iqtree.org), allowing users to estimate nonreversible models and rooted phylogenies from their own protein data sets. The data sets and scripts used in this article are available at https://doi.org/10.5061/dryad.3tx95x6hx. amino acid sequence analyses; amino acid substitution models; maximum likelihood model estimation; nonreversible models; phylogenetic inference; reversible models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Phytochemical investigation of the whole plants of Vernonia gratiosa Hance. led in the isolation and identification of two new stigmastane-type steroidal glucosides (1-2), namely vernogratiosides A ...(1), and B (2). Their chemical structures were fully elucidated based on 1 D/2D NMR spectroscopic, HR-ESI-MS data analyses, and by producing derivatives by chemical reactions. The binding potential of the isolated compounds to replicase protein − main protease of SARS-CoV-2 were examined using the molecular docking simulations. Our results show that the isolated steroidal glucosides (1-2) bind to the substrate-binding site of SARS-CoV-2 main protease with binding affinities of −7.2 and −7.6 kcal/mol, respectively, as well as binding abilities equivalent to N3 inhibitor that has already been reported (-7.5 kcal/mol).
Inductively coupled plasma mass spectrometry (ICP-MS) analytical method was used to determine the content of 40 elements in 38 soybean samples (Glycine Max) from 4 countries. Multivariate statistical ...methods, such as principal components analysis (PCA), were performed to analyze the obtained data to establish the provenance of the soybeans. Although soybean is widely marketed in many countries, no universal method is used to discriminate the origin of these cereals. Our study introduced the initial step to the identification of the geographical origin of commercial soybean marketed in Vietnam. The analysis pointed out that there are significant differences in the mean of 33 of the 40 analyzed elements among 4 countries’ soybean samples, namely, 11B, 27Al, 44Ca, 45Sc, 47Ti, 55Mn, 56Fe, 59Co, 60Ni, 63Cu, 66Zn, 69Ga, 75As, 78Se, 85Rb, 88Sr, 89Y, 90Zr, 93Nb, 95Mo, 103Rh, 137Ba, 163Dy, 165Ho, 175Lu, 178Hf, 181Ta, 182W, 185Re, 197Au, 202Hg, 205Tl, and 208Pb. The PCA analysis showed that the soybean samples can be classified correctly according to their original locations. This research can be used as a prerequisite for future studies of using the combination of elemental composition analysis with statistical classification methods for an accurate provenance establishment of soybean, which determined a variation of key markers for the original discrimination of soybean.
Abstract
Serine protease inhibitors (serpins) are found in all kingdoms of life and play essential roles in multiple physiological processes. Owing to the diversity of the superfamily, phylogenetic ...analysis is challenging and prokaryotic serpins have been speculated to have been acquired from Metazoa through horizontal gene transfer due to their unexpectedly high homology. Here, we have leveraged a structural alignment of diverse serpins to generate a comprehensive 6,000-sequence phylogeny that encompasses serpins from all kingdoms of life. We show that in addition to a central “hub” of highly conserved serpins, there has been extensive diversification of the superfamily into many novel functional clades. Our analysis indicates that the hub proteins are ancient and are similar because of convergent evolution, rather than the alternative hypothesis of horizontal gene transfer. This work clarifies longstanding questions in the evolution of serpins and provides new directions for research in the field of serpin biology.
In this work, pH-responsive polypeptide-based nanogels are reported as potential drug delivery systems. By the formation of pH-sensitive benzoic imine bonds, pH-responsive nanogels are constructed ...using hydrophilic methoxy poly(ethylene glycol)-b-polyN-N-(2-aminoethyl)-2-aminoethyl-l-glutamate (MPEG-b-PNLG) and hydrophobic terephthalaldehyde (TPA) as a cross-linker. At pH 7.4, MPEG-b-PNLG nanogels exhibit high stabilities with hydrophobic inner cores, which allow encapsulation of hydrophobic therapeutic agents. Under tumoral acidic environments (pH ∼6.4), the cleavage of benzoic imine bonds induces the destruction of MPEG-b-PNLG nanogels and leads to rapid release of their payloads. The formation and pH sensitivity of the nanogels are investigated by dynamic light scattering. These nanogels exhibit excellent stabilities in the presence of salt or against dilution. The globular morphologies of the nanogels are confirmed using transmission electron microscopy. Doxorubicin is used as a model drug to evaluate drug encapsulation and release. Finally, the anticancer activities of the drug-encapsulated nanogels are assessed in vitro.
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