Gene flow and an anomaly zone complicate phylogenomic inference in a rapidly radiated avian family (Prunellidae).

BACKGROUND: Resolving the phylogeny of rapidly radiating lineages presents a challenge when building the Tree of Life. An Old World avian family Prunellidae (Accentors) comprises twelve species that rapidly diversified at the Pliocene-Pleistocene boundary. RESULTS: Here we investigate the phylogenetic relationships of all species of Prunellidae using a chromosome-level de novo assembly of Prunella strophiata and 36 high-coverage resequenced genomes. We use homologous alignments of thousands of exonic and intronic loci to build the coalescent and concatenated phylogenies and recover four different species trees. Topology tests show a large degree of gene tree-species tree discordance but only 40-54% of intronic gene trees and 36-75% of exonic genic trees can be explained by incomplete lineage sorting and gene tree estimation errors. Estimated branch lengths for three successive internal branches in the inferred species trees suggest the existence of an empirical anomaly zone. The most common topology recovered for species in this anomaly zone was not similar to any coalescent or concatenated inference phylogenies, suggesting presence of anomalous gene trees. However, this interpretation is complicated by the presence of gene flow because extensive introgression was detected among these species. When exploring tree topology distributions, introgression, and regional variation in recombination rate, we find that many autosomal regions contain signatures of introgression and thus may mislead phylogenetic inference. Conversely, the phylogenetic signal is concentrated to regions with low-recombination rate, such as the Z chromosome, which are also more resistant to interspecific introgression. CONCLUSIONS: Collectively, our results suggest that phylogenomic inference should consider the underlying genomic architecture to maximize the consistency of phylogenomic signal.

Oral Delivery of Gemcitabine-Loaded Glycocholic Acid-Modified Micelles for Cancer Therapy.

The clinical utility of gemcitabine, an antimetabolite antineoplastic agent applied in various chemotherapy treatments, is limited due to the required intravenous injection. Although chemical structure modifications of gemcitabine result in enhanced oral bioavailability, these modifications compromise complex synthetic routes and cause unexpected side effects. In this study, gemcitabine-loaded glycocholic acid-modified micelles (Gem-PPG) were prepared for enhanced oral chemotherapy. The in vitro transport pathway experiments revealed that intact Gem-PPG were transported across the intestinal epithelial monolayer via an apical sodium-dependent bile acid transporter (ASBT)-mediated pathway. In mice, the pharmacokinetic analyses demonstrated that the oral bioavailability of Gem-PPG approached 81%, compared to less than 20% for unmodified micelles. In addition, the antitumor activity of oral Gem-PPG (30 mg/kg, BIW) was superior to that of free drug injection (60 mg/kg, BIW) in the xenograft model. Moreover, the assessments of hematology, blood chemistry, and histology all indicated the hypotoxicity profile of the drug-loaded micelles.

Gold-Catalyzed Conversion of Highly Strained Compounds.

The past decade has witnessed the golden age of homogeneous gold-catalyzed reactions, especially those that involve the transformation of highly strained molecules into complex molecular architectures. Gold catalysts, with unique electronic properties and catalytic abilities, have elevated versatile reaction modes through π-interaction induced activation. On the basis of increasing research interest in this topic, together with the significant development of various ligands, including phosphine ligands and azacyclic or noncyclic carbene ligands, the understanding of the catalytic function of gold catalysts has become much deeper and more comprehensive. Different reaction needs thus could be adapted by a novel gold catalyst with a diversified ligand selection. Furthermore, the whole evolution of the gold catalysis on synthetic methodologies has realized and expanded its application into natural product synthesis as well as the potentiality of drug discovery, which endows this ancient metal with a magnificent renaissance. The reactivity of strained small ring molecules with high tension has always been an important research topic in organic chemistry. When the highly strained small ring is linked with a π-electron rich moiety or contains a heteroatom, the gold activation of the π-system or coordination with the heteroatom can initiate a cascade reaction, usually followed by ring opening or expansion. These processes can result in the rapid construction of complex and distinct molecular structures, many of which feature in biologically important molecules. In this review, we will mainly summarize the advances on diverse reaction types and molecular constructions accomplished by homogeneous gold catalysis using highly strained substrates, including methylenecyclopropanes (MCPs), vinylidenecyclopropanes (VDCPs), cyclopropenes as well as aziridine- and epoxide-containing molecules, focusing on the last 10 years. For functionalized alkynyl cyclopropanes, several early inspiring and elegant examples will be described in this review for systematically understanding these transformations.

Divergent Construction of Fully Substituted Pyrroles and Cyclopentadiene Derivatives by Ynamide Annulations: 1,2-Cyclopropyl Migration versus Proton Transfer.

A switchable cyclopropyl ynamide cyclization to construct fully substituted pyrroles and cyclopentadiene derivatives in the presence of a gold catalyst was developed. In this version of pyrrole generation, a novel method to furnish gold vinylidenes through [1,2]-cyclopropyl migration was described. On the contrary, the production of cyclopentadienes proceeded through a proton-transfer step. These intriguing mechanisms were proposed based on the structure identification of the alkynyl enamine intermediate and a crossover experiment. The feasibility of cyclobutyl ynamides to specifically construct cyclopentadienes through ring expansion was also investigated.

A highly efficient method for the construction of cyclopropane-containing dihydroindole derivatives from indolemethylenecyclopropanes with DIAD and DEAD.

A highly efficient method for the construction of cyclopropane-containing dihydroindole derivatives from indolemethylenecyclopropanes with DIAD and DEAD has been disclosed. The transformation could occur under catalyst-free conditions at ambient temperature to afford dihyroindole derivatives in good yields. It has been proved that the strained moiety of methylenecyclopropane in the substrate of indolemethylenecyclopropane is critical and DFT calculations reveal that the reaction proceeds through a two-step pathway.

Gold(i)-catalyzed cascade cyclization of O-tethered 1,7-enynes bearing a cyclopropane moiety: construction of multi-substituted furans.

A gold-catalyzed cascade cyclization of O-tethered 1,7-enynes bearing a cyclopropane moiety has been reported in this communication, affording multi-substituted furans in moderate to good yields. The reaction proceeded through an intramolecular O-nucleophilic addition and 3,3-sigmatropic rearrangement followed by ring-opening of the cyclopropane unit along with the further reaction with electrophiles. The C-C bond cleavage of a strained cyclopropane moiety in the presence of a gold catalyst and the aromatization provided the driving force for this cascade cyclization. The practical transformations of the obtained diiodinated furan have also been indicated.

Gold(I)-catalyzed Benzylation of (Hetero)aryl Boronic Acids with (Hetero)benzyl Bromides by the Strategy of a SN 2-type Reaction.

Herein, the first example of gold-catalyzed benzylation of (hetero)aryl boronic acids with (hetero)benzyl bromides to give the corresponding cross-coupling products in moderate to good yields is reported. The reaction proceeds through a possible intermolecular SN 2-type reaction pathway to give a wide variety of di(hetero)arylmethanes as the desired products. An intriguing reaction mechanism has been proposed on the basis of control experiments, 31 P-NMR spectroscopic detection and DFT calculations.