No abstract

Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae–Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity.

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ObjectivePre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown.DesignWe performed a case–control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation.ResultsPatients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly Fusobacterium and Veillonella, were enriched, whereas beneficial bacteria, including Faecalibacterium and Akkermansia, were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, Fusobacterium, and inflammatory cytokine levels were significantly increased.ConclusionsThis study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.

Lithosphere delamination is believed to have played a major role in mountain building; however, the mechanism and dynamics of delamination remain poorly understood. Using a 2‐D high‐resolution thermomechanical model, we systematically investigated the conditions for the initiation of lithosphere delamination during orogenesis of continental collision and explored the key factors that control the various modes of delamination. Our results indicate that the negative buoyancy from lithosphere thickening during orogenesis could cause delamination, when the reference density of the lithospheric mantle is not lower than that of the asthenosphere. In these cases, compositional rejuvenation of depleted continental lithosphere by magmatic/metasomatic plume‐ and/or subduction‐induced processes may play crucial roles for subsequent lithosphere delamination. If the reference density of the lithospheric mantle is less than that of the asthenosphere, additional promoting factors, such as lower crust eclogitization, are required for delamination. Our numerical simulations predict three basic modes of lithosphere delamination: pro‐plate delamination, retro‐plate delamination, and a transitional double‐plates (both the pro‐plate and retro‐plate) delamination. Pro‐plate delamination is favored by low convergence rates, high lithospheric density, and relatively strong retro‐plate, whereas retro‐plate delamination requires a weak retro‐plate. The Northern Apennines and Central Northern Tibetan Plateau are possible geological analogs for the pro‐plate and retro‐plate delamination modes, respectively. Our model also shows significant impact of delamination on the topographic evolution of orogens. Large‐scale lithosphere delamination in continental collision zones would lead to wide and flat plateaus, whereas relatively narrow and steep mountain belts are predicted in orogens without major delamination.

[1] The devastating May 2008 Wenchuan earthquake (M w 7.9) resulted from thrust of the Tibet Plateau on the Longmen Shan fault zone, a consequence of the Indo-Asian continental collision. Many have speculated on the role played by the Zipingpu Reservoir, impounded in 2005 near the epicenter, in triggering the earthquake. This study evaluates the stress changes in response to the impoundment of the Zipingpu Reservoir and assesses their impact on the Wenchuan earthquake. We show that the impoundment could have changed the Coulomb stress by À0.01 to 0.05 MPa at locations and depth consistent with reported hypocenter positions. This level of stress change has been shown to be significant in triggering earthquakes on critically stressed faults. Because the loading rate on the Longmen Shan fault is <0.005 MPa/yr, we thus suggest that the Zipingpu Reservoir potentially hastened the occurrence of the Wenchuan earthquake by tens to hundreds of years.

Congenital muscular dystrophy (CMD) 3 is a heterogeneous group of inherited neuromuscular disorders characterized by severe muscle weakness, ocular and neuronal migration abnormalities, and variable mental retardation (1). Within recent years, it has become increasing clear through genetic studies that hypoglycosylation of the protein dystroglycan (DG) is a commonality in many forms of CMD (the so-called dystroglycanopathies). DG is post-translationally cleaved into an extracellular ␣-DG subunit and a transmembrane ␤-DG subunit (2). ␣-DG is a key component of the dystrophin-glycoprotein complex that serves as a link between the cytoskeleton of cells and the extracellular matrix by binding to proteins such as laminin (3). Interaction between ␣-DG and its extracellular ligands requires ␣-DG to be properly post-translationally modified through the addition of O-linked oligosaccharides, specifically O-mannose (4, 5). To date, mutations in six genes that encode determined or predicted glycosyltransferases have been shown to result in varying forms of CMD in which the post-translational processing of ␣-DG is affected (4 -6). The six mutated genes and their original resulting form of CMD are as follows: POMT1 (protein O-mannosyltransferase 1) and POMT2, Walker-Warburg syndrome (7,8); POMGnT1 (protein Olinked mannose ␤1,2-N-acetylglucosaminyltransferase 1), muscle-eye-brain disease (9); fukutin, Fukuyama congenital muscular dystrophy (10); FKRP (fukutin-related protein), congenital muscular dystrophy 1C (11); and LARGE, congenital muscular dystrophy 1D (12). Recent work has demonstrated that selected mutations in some of these genes can cause various forms of CMD that are likely dependent on the severity of the mutation on enzymatic activity and stability (13). Abnormal glycosylation of ␣-DG appears to be a commonality among all of the aforementioned forms of CMD. Although expression of ␣-DG appears not to be grossly affected, the ability of ␣-DG to be recognized by monoclonal antibodies IIH6 and VIA4 1 is eliminated, as is the ability of ␣-DG to properly bind its ligands (14).␣-DG is composed of a central mucin-like region that is extensively heterogeneously glycosylated with glycan chains that are initiated by both O-

UDP-GalNAc:polypeptide ␣-N-Acetylgalactosaminyltransferases (ppGalNAcTs), a family (EC 2.4.1.41) of enzymes that initiate mucin-type O-glycosylation, are structurally composed of a catalytic domain and a lectin domain. Previous studies have suggested that the lectin domain modulates the glycosylation of glycopeptide substrates and may underlie the strict glycopeptide specificity of some isoforms (ppGalNAcT-7 and -10). Using a set of synthetic peptides and glycopeptides based upon the sequence of the mucin, MUC5AC, we have examined the activity and glycosylation site preference of lectin domain deletion and exchange constructs of the peptide/glycopeptide transferase ppGalNAcT-2 (hT2) and the glycopeptide transferase ppGalNAcT-10 (hT10). We demonstrate that the lectin domain of hT2 directs glycosylation site selection for glycopeptide substrates. Pre-steady-state kinetic measurements show that this effect is attributable to two mechanisms, either lectin domain-aided substrate binding or lectin domain-aided product release following glycosylation. We find that glycosylation of peptide substrates by hT10 requires binding of existing GalNAcs on the substrate to either its catalytic or lectin domain, thereby resulting in its apparent strict glycopeptide specificity. These results highlight the existence of two modes of site selection used by these ppGalNAcTs: local sequence recognition by the catalytic domain and the concerted recognition of distal sites of prior glycosylation together with local sequence binding mediated, respectively, by the lectin and catalytic domains. The latter mode may facilitate the glycosylation of serine or threonine residues, which occur in sequence contexts that would not be efficiently glycosylated by the catalytic domain alone. Local sequence recognition by the catalytic domain differs between hT2 and hT10 in that hT10 requires a pre-existing GalNAc residue while hT2 does not.The first committed step in mucin-type O-glycan biosynthesis is the transfer of GalNAc from UDP-GalNAc to Ser/Thr residues of proteins catalyzed by a large family of evolutionarily conserved enzymes, the ppGalNAcTs 2 (1). The collective substrate specificity of the individual family members defines the mucin-type glycome, i.e. the Ser/Thr residues on a protein that acquire mucin-type O-glycans. Despite observations of biases in amino acid composition flanking known sites of O-glycosylation (2-5), no rigid consensus sequence for the prediction of sites has emerged. Consequently, current predictive methods are limited in their accuracy (6 -8). In vitro studies using peptide acceptors have demonstrated that ppGalNAcT isoforms have distinct but overlapping substrate specificities (2, 9 -12). Although a majority of these isoforms can glycosylate both naked peptides and glycopeptides (9 -11), a subset, notably isoforms ppGalNAcT-7 (13) and ppGalNAcT-10 (14), has an apparent strict requirement for prior glycosylation of their substrates to add additional GalNAc.ppGalNAcTs are type II transmembrane proteins with a short cyt...