Heat stress-induced transposon activation correlates with 3D chromatin organization rearrangement in Arabidopsis.

In higher eukaryotes, heterochromatin is mainly composed of transposable elements (TEs) silenced by epigenetic mechanisms. But, the silencing of certain heterochromatin-associated TEs is disrupted by heat stress. By comparing genome-wide high-resolution chromatin packing patterns under normal or heat conditions obtained through Hi-C analysis, we show here that heat stress causes global rearrangement of the 3D genome in Arabidopsis thaliana.

Asymmetric Total Synthesis of (-)-Spirochensilide A.

An asymmetric total synthesis of (-)-spirochensilide A has been achieved for the first time. The synthesis features a semipinacol rearrangement reaction to stereoselectively construct the two-vicinal quaternary chiral centers at C8 and C10, a tungsten-mediated cyclopropene-based Pauson-Khand reaction to install the C13 quaternary chiral center, and a furan-based oxidative cyclization to stereoselectively form the spiroketal motif.

An Arabidopsis Secondary Metabolite Directly Targets Expression of the Bacterial Type III Secretion System to Inhibit Bacterial Virulence.

Plants deploy a variety of secondary metabolites to fend off pathogen attack. Although defense compounds are generally considered toxic to microbes, the exact mechanisms are often unknown. Here, we show that the Arabidopsis defense compound sulforaphane (SFN) functions primarily by inhibiting Pseudomonas syringae type III secretion system (TTSS) genes, which are essential for pathogenesis.

Computation-Guided Development of the "Click" -Quinone Methide Cycloaddition with Improved Kinetics.

We report here a deep mechanistic study of the "click" -quinone methide (QM) cycloaddition between -quinolinone quinone methide (QQM) and thio-vinyl ether (TV), named as TQ-ligation. DFT calculations revealed the unexpected fact that dehydration of QQM precursors is the rate-determining step of this transformation, and two highly reactive QQM precursors were predicted. Guided by the calculations, a new "click" QM cycloaddition which shows significantly improved kinetics and remarkable efficiency on protein labeling was developed.

Asymmetric Total Synthesis of (+)-Waihoensene.

The asymmetric total synthesis of (+)-waihoensene, which has a -fused [6,5,5,5] tetracyclic core bearing an angular triquinane, a -fused six-membered ring, and four contiguous quaternary carbon atoms, was achieved through a sequence of chemical reactions in a stereochemically well-defined manner. The total synthesis features the following: (1) Cu-catalyzed asymmetric conjugated 1,4-addition; (2) diastereoselective Conia-ene type reaction; (3) diastereoselective intramolecular Pauson-Khand reaction; (4) Ni-catalyzed diastereoselective conjugated 1,4-addition; and (5) radical-initiated intramolecular hydrogen atom transfer (HAT). Control experiments and density functional theory calculations support the proposed HAT process.

The replisome guides nucleosome assembly during DNA replication.

Nucleosome assembly during DNA replication is tightly coupled to ongoing DNA synthesis. This process, termed DNA replication-coupled (RC) nucleosome assembly, is essential for chromatin replication and has a great impact on both genome stability maintenance and epigenetic inheritance. This review discusses a set of recent findings regarding the role of replisome components contributing to RC nucleosome assembly.

Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring.

Directed differentiation methods allow acquisition of high-purity cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs); however, their immaturity characteristic limits their application for drug screening and regenerative therapy. The rapid electrical pacing of cardiomyocytes has been used for efficiently promoting the maturation of cardiomyocytes, here we describe a simple device in modified culture plate on which hiPSC-derived cardiomyocytes can form three-dimensional self-organized tissue rings (SOTRs). Using calcium imaging, we show that within the ring, reentrant waves (ReWs) of action potential spontaneously originated and ran robustly at a frequency up to 4 Hz.

A microfluidic approach for experimentally modelling the intercellular coupling system of a mammalian circadian clock at single-cell level.

In mammals, it is believed that the intercellular coupling mechanism between neurons in the suprachiasmatic nucleus (SCN) confers robustness and distinguishes the central clock from peripheral circadian oscillators. Current in vitro culturing methods used in Petri dishes to study intercellular coupling by exogenous factors invariably cause perturbations, such as simple media changes. Here, we design a microfluidic device to quantitatively study the intercellular coupling mechanism of circadian clock at the single cell level, and demonstrate that vasoactive intestinal peptide (VIP) induced coupling in clock mutant Cry1-/- mouse adult fibroblasts engineered to express the VIP receptor, VPAC2, is sufficient to synchronize and maintain robust circadian oscillations.

Protecting-Group-Free Total Syntheses of (±)-Norascyronones A and B.

Protecting-group-free total syntheses of natural products norascyronone A and norascyronone B were accomplished in eight steps from the commercially available starting material 1-bromo-4-methoxy-2-methylbenzene. The key step was a Mn/Cu-mediated oxidative cascade annulation reaction that formed the tetracyclic core of the target molecules bearing vicinal bridge-head all-carbon quaternary chiral centers. Our investigation indicated that the C5 stereogenic center of norascyronone C plays a critical role in the proposed biomimetic oxidative reaction for B-ring formation.

Evaluation of chemical cross-linkers for in-depth structural analysis of G protein-coupled receptors through cross-linking mass spectrometry.

Chemical cross-linking would conceivably cause structural disruption of a protein, but few cross-linkers have been fully evaluated in this aspect. Furthermore, integral membrane proteins may differ from soluble proteins in the selection of suitable cross-linkers, which has never been investigated. In this study, we systematically evaluated the impact of five conventional cross-linkers targeting Lys, Asp and Glu, and two Arg-reactive cross-linkers on the structural and functional integrity of two G protein-coupled receptors (GPCRs).

The evolutionary arms race between transposable elements and piRNAs in Drosophila melanogaster.

Background: The piwi-interacting RNAs (piRNAs) are small non-coding RNAs that specifically repress transposable elements (TEs) in the germline of Drosophila. Despite our expanding understanding of TE:piRNA interaction, whether there is an evolutionary arms race between TEs and piRNAs was unclear.

Results: Here, we studied the population genomics of TEs and piRNAs in the worldwide strains of D.

Biomimetic Synthesis of Rhytidenone A and Mode of Action of Cytotoxic Rhytidenone F.

The rhytidenone family comprises spirobisnaphthalene natural products isolated from the mangrove endophytic fungus Rhytidhysteron rufulum AS21B. The biomimetic synthesis of rhytidenone A was achieved by a Michael reaction/aldol/lactonization cascade in a single step from the proposed biosynthetic precursor rhytidenone F. Moreover, the mode of action of the highly cytotoxic rhytidenone F was investigated.

Concise gram-scale synthesis of Euphorikanin A skeleton through a domino ring-closing metathesis strategy.

Euphorikanin A is a diterpenoid possessing a highly congested and unprecedented 5/6/7/3-fused tetracyclic ring skeleton. To access the challenging chemical structure of Euphorikanins, an efficient total synthetic approach is described. The stereoselective synthesis of the core structure of Euphorikanin A has been achieved from a simple dienyne building block, and a domino ring-closing metathesis (RCM) strategy was used for the gram-scale synthesis of the highly strained Euphorikanin A core.

Validation of new classification criteria of rheumatoid arthritis in an international multicentre study.

Objectives: Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study.

Methods: A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India.

A method for recording the two phases of dopamine release in mammalian brain striatum slices.

Striatal dopamine (DA) release plays an essential role in many physiological functions including motor and non-motor behaviors (such as reward, motivation, and cognition). We have previously reported that, following a single electrical field stimulation, the amperometric recording of DA release from presynaptic terminals in striatal slices (both ventral and dorsal) contains two temporally separated phases. The first phase (direct DA transmission, direct DT) arises from DA terminal release following autologous action potentials (APs), while the second phase (cholinergic transmission-induced DA transmission, CTDT) arises from delayed DA release triggered by the activation of cholinergic interneurons to DA terminals (axon-axon transmission).

Asymmetric Total Synthesis of Pre-schisanartanin C.

Pre-schisanartanin C belongs to the family of nortriterpenoids with potent antihepatitis, antitumor, and anti-HIV activities. This paper presents the enantioselective total synthesis of pre-schisanartanin C (). An important step in the total synthesis of is gold-catalyzed intramolecular cyclopropanation of a 1,8-enyne substrate bearing a secondary ester group at the propargylic position to prepare a bicyclo[6.

A phenotype-directed chemical screen identifies ponalrestat as an inhibitor of the plant flavin monooxygenase YUCCA in auxin biosynthesis.

Plant development is regulated by both synergistic and antagonistic interactions of different phytohormones, including a complex crosstalk between ethylene and auxin. For instance, auxin and ethylene synergistically control primary root elongation and root hair formation. However, a lack of chemical agents that specifically modulate ethylene or auxin production has precluded precise delineation of the contribution of each hormone to root development.

Synchronized replication of genes encoding the same protein complex in fast-proliferating cells.

DNA replication perturbs the dosage balance among genes; at mid-S phase, early-replicating genes have doubled their copies while late-replicating ones have not. Dosage imbalance among genes, especially within members of a protein complex, is toxic to cells. However, the molecular mechanisms that cells use to deal with such imbalance remain not fully understood.

Cell Cycle Inhibitor Whi5 Records Environmental Information to Coordinate Growth and Division in Yeast.

Proliferating cells need to evaluate the environment to determine the optimal timing for cell cycle entry. However, how this is achieved is not well understood. Here, we show that, in budding yeast, the G1 inhibitor Whi5 is a key environmental indicator and plays a crucial role in coordinating cell growth and division.

Reading Chemical Modifications in the Transcriptome.

Diverse chemical modifications have been identified in the transcriptome, leading to the emerging field of epitranscriptomics. In eukaryotic mRNA, the 5' cap and 3' poly(A) tail play important roles in regulation, and multiple internal modifications have also been revealed to participate in RNA metabolism. In this review, we focus on internal modifications in eukaryotic mRNA, including modifications to A/U/C/G bases and to ribose as well.

Staphylopine and pseudopaline dehydrogenase from bacterial pathogens catalyze reversible reactions and produce stereospecific metallophores.

Pseudopaline and staphylopine are opine metallophores biosynthesized by and , respectively. The final step in opine metallophore biosynthesis is the condensation of the product of a nicotianamine (NA) synthase reaction ( l-HisNA for pseudopaline and d-HisNA for staphylopine) with an α-keto acid (α-ketoglutarate for pseudopaline and pyruvate for staphylopine), which is performed by an opine dehydrogenase. We hypothesized that the opine dehydrogenase reaction would be reversible only for the opine metallophore product with ()-stereochemistry at carbon C2 of the α-keto acid (prochiral prior to catalysis).

Impaired D2 receptor-dependent dopaminergic transmission in prefrontal cortex of awake mouse model of Parkinson's disease.

The loss-of-function mutation in PARK7/DJ-1 is one of the most common causes of autosomal recessive Parkinson's disease, and patients carrying PARK7 mutations often exhibit both a progressive movement disorder and emotional impairment, such as anxiety. However, the causes of the emotional symptom accompanying PARK7-associated and other forms of Parkinson's disease remain largely unexplored. Using two-photon microscopic Ca2+ imaging in awake PARK7-/- and PARK7+/+ mice, we found that (i) PARK7-/- neurons in the frontal association cortex showed substantially higher circuit activity recorded as spontaneous somatic Ca2+ signals; (ii) both basal and evoked dopamine release remained intact, as determined by both electrochemical dopamine recordings and high performance liquid chromatography in vivo; (iii) D2 receptor expression was significantly decreased in postsynaptic frontal association cortical neurons, and the hyper-neuronal activity were rescued by D2 receptor intervention using either local pharmacology or viral D2 receptor over-expression; and (iv) PARK7-/- mice showed anxiety-like behaviours that were rescued by either local D2 receptor pharmacology or overexpression.