Exploring uncertainty in the calibration of the molecular clock

Calibration is a critical step in every molecular clock analysis but it has been the least considered. Bayesian approaches to divergence time estimation make it possible to incorporate the uncertainty in the degree to which fossil evidence approximates the true time of divergence. We explored the impact of different approaches in expressing this relationship, using arthropod phylogeny as an example for which we established novel calibrations. We demonstrate that the parameters distinguishing calibration densities have a major impact upon the prior and posterior of the divergence times, and it is critically important that users evaluate the joint prior distribution of divergence times used by their dating programmes. We illustrate a procedure for deriving calibration densities in Bayesian divergence dating through the use of soft maximum constraints.     

Fas ligand enhances malignant behavior of tumor cells through interaction with Met, hepatocyte growth factor receptor, in lipid rafts

Many late-stage cancer cells express Fas ligand (FasL) and show high malignancy with metastatic potential. We report here a novel signaling mechanism for FasL that hijacks the Met signal pathway to promote tumor metastasis. FasL-expressing human tumor cells express a significant amount of phosphorylated Met. The down-regulation of FasL in these cells led to decreased Met activity and reduced cell motility. Ectopic expression of human FasL in NIH3T3 cells significantly stimulated their migration and invasion. The inhibition of Met and Stat3 activities reverted the FasL-associated phenotype. Notably, FasL variants activated the Met pathway, even though most of their intracellular domain or Fas binding sites were deleted. FasL interacted with Met through the FasL(105-130) extracellular region in lipid rafts, which consequently led to Met activation. Knocking down Met gene expression by RNAi technology reverted the FasL-associated motility to basal levels. Furthermore, treatment with synthetic peptides corresponding to FasL(117-126) significantly reduced the FasL/Met interaction, Met phosphorylation, and cell motility of FasL(+) transfectants and tumor cells. Finally, the transfectants of truncated FasL showed strong anchorage-independent growth and lung metastasis potential in null mice. Collectively, our results establish the FasL-Met-Stat3 signaling pathway and explains the metastatic phenotype of FasL-expressing tumors.     

Chemical synthesis,microbial transformation and biological evaluation of tetrahydroprotoberberines as dopamine D1/D2 receptor ligands

Dopamine D1/D2 receptors are important targets for drug discovery in the treatment of central nervous system diseases. To discover new and potential D1/D2 ligands, 17 derivatives of tetrahydroprotoberberine (THPB) with various substituents were prepared by chemical synthesis or microbial transformation using Streptomyces griseus ATCC 13273. Their functional activities on D1 and D2 receptors were determined by cAMP assay and calcium flux assay. Seven compounds showed high activity on D1/D2 receptor with low IC₅₀ values less than 1?µM. Especially, top compound 5 showed strong antagonistic activity on both D1 and D2 receptor with an IC₅₀ of 0.391 and 0.0757?µM, respectively. Five compounds displayed selective antagonistic activity on D1 and D2 receptor. The SAR studies revealed that (1) the hydroxyl group at C-9 position plays an important role in keeping a good activity and small or fewer substituents on ring D of THPBs may also stimulate their effects, (2) the absence of substituents at C-9 position tends to be more selective for D2 receptor, and (3) hydroxyl substitution at C-2 position and the substitution at C-9 position may facilitate the conversion of D1 receptor from antagonist to agonist. Molecular docking simulations found that Asp 103/Asp 114, Ser 107/Cys 118, and Trp 285/ Trp 386 of D1/ D2 receptors are the key residues, which have strong interactions with the active D1/D2 compounds and may influence their functional profiles.     

步行友好的绿道评价研究——以南京环紫金山绿道为例

绿道步行友好性评价丰富了绿道的研究内容,评价结果可为绿道的规划建设提供科学依据。以南京环紫金山绿道为例,在梳理步行友好的绿道概念的基础上,通过层次分析法评价了各段绿道的步行友好程度。结果表明：环紫金山绿道整体步行友好程度虽然较高,但各区段之间差异较大。另外,在绿道建设质量较高的前提下,步行爱好者更关注绿道的可达性、线路的安全性、清晰的标识系统、舒适宜人的服务设施以及绿道沿线高质量的视觉景观等几方面,而对绿道本身功能性要素并不是太在意。因此,规划建设城市休闲绿道时,在满足步行功能的前提下,应将行人的步行感受放在首位,而不是过度注重绿道本身的形式美。     

Feasible D1–A–D2–A Random Copolymers for Simultaneous High‐Performance Fullerene and Nonfullerene Solar Cells

A series of PBDB‐TTn random donor copolymers is synthesized, consisting of an electron‐deficient benzo[1,2‐c:4,5‐c′]dithiophene‐4,8‐dione (BDD) unit and different ratios of two electron‐rich benzo[1,2‐b:4,5‐b′]dithiophene (BDT) and thieno[3,2‐b]thiophene (TT) units, with intention to modulate the intrachain and/or interchain interactions and ultimately bulk‐heterojunction morphology evolution. A comparative study using 4 × 2 polymer solar cell (PSC) performance maps and each of the [6,6]‐phenyl‐C₇₁‐butyric acid methyl ester (PC₇₁BM) and the fused‐aromatic‐ring‐based molecule (m‐ITIC) acceptors are carried out. Given the similarities in their absorption ranges and energy levels, the PBDB‐TTn copolymers clearly reveal a change in the absorption coefficients upon optimization of the BDT to TT ratio in the backbone. Among the given acceptor combination sets, superior performances are observed in the case of PBDB‐TT5 blended with PC₇₁BM (8.34 ± 0.10%) or m‐ITIC (11.10 ± 0.08%), and the dominant factors causing power conversion efficiency differences in them are found to be distinctly different. For example, the performances of PC₇₁BM‐based PSCs are governed by size and population of face‐on crystallites, while intermixed morphology without the formation of large phase‐separated aggregates is the key factor for achieving high‐performance m‐ITIC‐based PSCs. This study presents a new sketch of structure–morphology–performance relationships for fullerene‐ versus nonfullerene‐based PSCs.     

Orientation Regulation of Phenylethylammonium Cation Based 2D Perovskite Solar Cell with Efficiency Higher Than 11%

Increasing the power conversion efficiency (PCE) of the two‐dimensional (2D) perovskite‐based solar cells (PVSCs) is really a challenge. Vertical orientation of the 2D perovskite film is an efficient strategy to elevate the PCE. In this work, vertically orientated highly crystalline 2D (PEA)₂(MA)_n–1Pb_nI_3n+1 (PEA= phenylethylammonium, MA = methylammonium, n = 3, 4, 5) films are fabricated with the assistance of an ammonium thiocyanate (NH₄SCN) additive by a one‐step spin‐coating method. Planar‐structured PVSCs with the device structure of indium tin oxide (ITO)/poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate)/(PEA)₂(MA)_n–1Pb_nI_3n+1/[6,6]‐phenyl‐C61‐butyric acid methyl ester/bahocuproine/Ag are fabricated. The PCE of the PVSCs is boosted from the original 0.56% (without NH₄SCN) to 11.01% with the optimized NH₄SCN addition at n = 5, which is among the highest PCE values for the low‐n (n < 10) 2D perovskite‐based PVSCs. The improved performance is attributed to the vertically orientated highly crystalline 2D perovskite thin films as well as the balanced electron/hole transportation. The humidity stability of this oriented 2D perovskite thin film is also confirmed by the almost unchanged X‐ray diffraction patterns after 28 d exposed to the moisture in a humidity‐controlled cabinet (H_r = 55 ± 5%). The unsealed device retains 78.5% of its original PCE after 160 h storage in air atmosphere with humidity of 55 ± 5%. The results provide an effective approach toward a highly efficient and stable PVSC for future commercialization.     

Ethers Illume Sodium‐Based Battery Chemistry: Uniqueness,Surprise, and Challenges

Sodium‐ion batteries (SIBs) have the potential to be practically applied in large‐scale energy storage markets. The rapid progress of SIBs research is primarily focused on electrodes, while electrolytes attract less attention. Indeed, the improvement of electrode performance is arguably correlated with the electrolyte optimization. In conventional lithium‐ion batteries (LIBs), ether‐based electrolytes are historically less practical owing to the insufficient passivation of both anodes and cathodes. As an important class of aprotic electrolytes, ethers have revived with the emerging lithium‐sulfur and lithium‐oxygen batteries in recent years, and are even booming in the wave of SIBs. Ether‐based electrolytes are unique to enabling these new battery chemistries in terms of producing stable ternary graphite intercalation compounds, modifying anode solid electrolyte interphases, reducing the solubility of intermediates, and decreasing polarization. Better still, ether‐based electrolytes are compatible with specific inorganic cathodes and could catalyze the assembly of full SIBs prototypes. This Research News article aims to summarize the recent critical reports on ether‐based electrolytes in sodium‐based batteries, to unveil the uniqueness of ether‐based electrolytes to advancing diverse electrode materials, and to shed light on the viability and challenges of ether‐based electrolytes in future sodium‐based battery chemistries.     

Peptide MSI-1 inhibited MCR-1 and regulated outer membrane vesicles to combat immune evasion of Escherichia coli

Polymyxin resistance is conferred by MCR-1 (mobile colistin resistance 1)-induced lipopolysaccharide (LPS) modification of G⁻ bacteria. However, the peptide MSI-1 exerts potent antimicrobial activity against mcr-1-carrying bacteria. To further investigate the potential role of MCR-1 in improving bacterial virulence and facilitating immune evasion, and the immunomodulatory effect of peptide MSI-1, we first explored outer membrane vesicle (OMV) alterations of mcr-1-carrying bacteria in the presence and absence of sub-MIC MSI-1, and host immune activation during bacterial infection and OMV stimulation. Our results demonstrated that LPS remodelling induced by MCR-1 negatively affected OMV formation and protein cargo by E. coli. In addition, MCR-1 diminished LPS-stimulated pyroptosis but facilitated mitochondrial dysfunction, further aggravating apoptosis in macrophages induced by OMVs of E. coli. Similarly, TLR4-mediated NF-κB activation was markedly alleviated once LPS was modified by MCR-1. However, peptide MSI-1 at the sub-MIC level inhibited the expression of MCR-1, further partly rescuing OMV alteration and attenuation of immune responses in the presence of MCR-1 during both infection and OMV stimulation, which can be exploited for anti-infective therapy.     

Identification of MiRNA from Eggplant (Solanum melongena L.) by Small RNA Deep Sequencing and Their Response to Verticillium dahliae Infection

MiRNAs are a class of non-coding small RNAs that play important roles in the regulation of gene expression. Although plant miRNAs have been extensively studied in model systems, less is known in other plants with limited genome sequence data, including eggplant (Solanum melongena L.). To identify miRNAs in eggplant and their response to Verticillium dahliae infection, a fungal pathogen for which clear understanding of infection mechanisms and effective cure methods are currently lacking, we deep-sequenced two small RNA (sRNA) libraries prepared from mock-infected and infected seedlings of eggplants. Specifically, 30,830,792 reads produced 7,716,328 unique miRNAs representing 99 known miRNA families that have been identified in other plant species. Two novel putative miRNAs were predicted with eggplant ESTs. The potential targets of the identified known and novel miRNAs were also predicted based on sequence homology search. It was observed that the length distribution of obtained sRNAs and the expression of 6 miRNA families were obviously different between the two libraries. These results provide a framework for further analysis of miRNAs and their role in regulating plant response to fungal infection and Verticillium wilt in particular.