BackgroundLeucine-rich repeat receptor-like protein kinases (LRR-RLKs) are the largest group of receptor-like kinases in plants and play crucial roles in development and stress responses. The evolutionary relationships among LRR-RLK genes have been investigated in flowering plants; however, no comprehensive studies have been performed for these genes in more ancestral groups. The subfamily classification of LRR-RLK genes in plants, the evolutionary history and driving force for the evolution of each LRR-RLK subfamily remain to be understood.ResultsWe identified 119 LRR-RLK genes in the Physcomitrella patens moss genome, 67 LRR-RLK genes in the Selaginella moellendorffii lycophyte genome, and no LRR-RLK genes in five green algae genomes. Furthermore, these LRR-RLK sequences, along with previously reported LRR-RLK sequences from Arabidopsis thaliana and Oryza sativa, were subjected to evolutionary analyses. Phylogenetic analyses revealed that plant LRR-RLKs belong to 19 subfamilies, eighteen of which were established in early land plants, and one of which evolved in flowering plants. More importantly, we found that the basic structures of LRR-RLK genes for most subfamilies are established in early land plants and conserved within subfamilies and across different plant lineages, but divergent among subfamilies. In addition, most members of the same subfamily had common protein motif compositions, whereas members of different subfamilies showed variations in protein motif compositions. The unique gene structure and protein motif compositions of each subfamily differentiate the subfamily classifications and, more importantly, provide evidence for functional divergence among LRR-RLK subfamilies. Maximum likelihood analyses showed that some sites within four subfamilies were under positive selection.ConclusionsMuch of the diversity of plant LRR-RLK genes was established in early land plants. Positive selection contributed to the evolution of a few LRR-RLK subfamilies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-017-0891-5) contains supplementary material, which is available to authorized users.

An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3-cyclopentylacrylaldehyde (23) using diarylprolinol silyl ether as the catalyst was developed. Michael adducts (R)-24 and (R)-27 were isolated in good yield and high ee and were readily converted to INCB018424.

Ecological speciation is a common mechanism by which new species arise. Despite great efforts, the role of gene expression in ecological divergence and speciation is poorly understood. Here, we conducted a genome-wide gene expression investigation of two Oryza species that are evolutionarily young and distinct in ecology and morphology. Using digital gene expression technology and the paired-end RNA sequencing method, we obtained 21,415 expressed genes across three reproduction-related tissues. Of them, approximately 8% (1,717) differed significantly in expression levels between the two species and these differentially expressed genes are randomly distributed across the genome. Moreover, 62% (1,064) of the differentially expressed genes exhibited a signature of directional selection in at least one species. Importantly, the genes with differential expression between species evolved more rapidly at the 5' flanking sequences than the genes without differential expression relative to coding sequences, suggesting that cis-regulatory changes are likely adaptive and play an important role in the ecological divergence of the two species. Finally, we showed evidence of significant differentiation between species in phenotype traits and observed that genes with differential expression were overrepresented with functional terms involving phenotypic and ecological differentiation between the two species, including reproduction- and stress-related characteristics. Our findings demonstrate that ecological speciation is associated with widespread and adaptive alterations in genome-wide gene expression and provide new insights into the importance of regulatory evolution in ecological speciation in plants.

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Background: Emerging evidence has suggested that dysbiosis of the lung microbiota may be associated with the development of lung diseases. However, the interplay between the lung microbiome and lung cancer remains unclear. The aim of the present study was to evaluate and compare differences in taxonomic and derived functional profiles in the lung microbiota between lung cancer and benign pulmonary diseases.Methods: Bronchoalveolar lavage fluid (BALF) samples were collected from 32 patients with lung cancer and 22 patients with benign pulmonary diseases, and further analyzed by 16S rRNA amplicon sequencing.The obtained sequence data were deeply analyzed by bioinformatics methods.Results: A significant differentiation trend was observed between the lung cancer and control groups based on principal coordinate analysis (PCoA), while richness and evenness in the lung microbiome of lung cancer patients generally resembled those of patients with benign pulmonary diseases. Phylum TM7 and six genera (c:TM7-3, Capnocytophaga, Sediminibacterium, Gemmiger, Blautia and Oscillospira) were enriched in the lung cancer group compared with the control group (adjust P<0.05). The area under the curve (AUC) combining the microbiome with clinical tumor markers to predict lung cancer was 84.52% (95% CI: 74.06-94.97%).In addition, predicted KEGG pathways showed that the functional differences in metabolic pathways of microbiome varied with groups. Conclusions:The results indicated that differences existed in the lung microbiome of patients with lung cancer and those with benign pulmonary diseases, and some certain bacteria may have potential to predict lung cancer, though future larger-sample studies are required to validate this supposition.

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Lectin receptor-like kinases (LecRLKs) play important roles in plant development and stress responses. Although genome-wide studies of LecRLKs have been performed in several species, a comprehensive analysis including evolutionary, structural and functional analysis has not been carried out in soybean (Glycine max). In this study, we identified 185 putative LecRLK genes in the soybean genome, including 123 G-type, 60 L-type and 2 C-type LecRLK genes. Tandem duplication and segmental duplication appear to be the main mechanisms of gene expansion in the soybean LecRLK (GmLecRLK) gene family. According to our phylogenetic analysis, G-type and L-type GmLecRLK genes can be organized into fourteen and eight subfamilies, respectively. The subfamilies within the G-type GmLecRLKs differ from each other in gene structure and/or protein domains and motifs, which indicates that the subfamilies have diverged. The evolution of L-type GmLecRLKs has been more conservative: most genes retain the same gene structures and nearly the same protein domain and motif architectures. Furthermore, the expression profiles of G-type and L-type GmLecRLK genes show evidence of functional redundancy and divergence within each group. Our results contribute to a better understanding of the evolution and function of soybean LecRLKs and provide a framework for further functional investigation of them.

Early process development and salt selection for AMG 837, a novel GPR40 receptor agonist, is described. The synthetic route to AMG 837 involved the convergent synthesis and coupling of two key fragments, (S)-3-(4-hydroxyphenyl)hex-4-ynoic acid (1) and 3-(bromomethyl)-4 0 -(trifluoromethyl)biphenyl (2). The chiral β-alkynyl acid 1 was prepared in 35% overall yield via classical resolution of the corresponding racemic acid (()-1. An efficient and scalable synthesis of (()-1 was achieved via a telescoped sequence of reactions including the conjugate alkynylation of an in situ protected Meldrum's acid derived acceptor prepared from 3. The biaryl bromide 2 was prepared in 86% yield via a 2-step SuzukiÀMiyaura couplingÀbromination sequence. Chemoselective phenol alkylation mediated by tetrabutylphosphonium hydroxide allowed direct coupling of 1 and 2 to afford AMG 837. Due to the poor physiochemical stability of the free acid form of the drug substance, a sodium salt form was selected for early development, and a more stable, crystalline hemicalcium salt dihydrate form was subsequently developed. Overall, the original 12-step synthesis of AMG 837 was replaced by a robust 9-step route affording the target in 25% yield.