The novel herbicide icafolin-methyl is a plant-specific inhibitor of tubulin polymerization.

Background: Without controlling weeds, it is estimated that about one third of global crop yields would be lost. Herbicides remain the most effective solution for weed control, but they face multiple challenges, such as the emergence and growth of resistant weed populations. Consequently, there is an urgent need for either herbicides with new modes of action or at least novel chemistries within established modes of action, with outstanding efficacy but without showing cross-resistance to the herbicides present in the prospective markets.

A Study in Scaffold Hopping: Discovery and Optimization of Thiazolopyridines as Potent Herbicides That Inhibit Acyl-ACP Thioesterase.

In the search for new chemical entities that can control resistant weeds by addressing novel modes of action (MoAs), we were interested in further exploring a compound class that contained a 1,8-naphthyridine core. By leveraging scaffold hopping methodologies, we were able to discover the new thiazolopyridine compound class that act as potent herbicidal molecules. Further biochemical investigations allowed us to identify that the thiazolopyridines inhibit acyl-acyl carrier protein (ACP) thioesterase (FAT), with this being further confirmed via an X-ray cocrystal structure.

Effects of huoxin formula on the arterial functions of patients with coronary heart disease.

Huoxin formula is a Traditional Chinese Medicine for coronary heart disease (CHD) treatment. To explore the therapeutic mechanism of the Huoxin formula on arterial functions in CHD patients. Fifty-eight CHD patients receiving cardiovascular drugs including β-receptor blocker, statins, and antiplatelet medications or others were randomized into intervention [additionally 13.

Int6/eIF3e Silencing Promotes Placenta Angiogenesis in a Rat Model of Pre-eclampsia.

We investigated whether stable eukaryotic translation initiation factor 3e/inter 6 (eIF-3e/Int6) RNA-silencing (siRNA-Int6) can ameliorate pre-eclampsia (PE) by promoting angiogenesis in an N-nitro-L-arginine methyl ester (L-NAME)-induced rat pre-eclampsia (PE) model. Twenty-four pregnant female Sprague-Dawley rats were allocated into 4 groups, including controls (Con) without any treatment, and 18 from gestational day (GD) 7 to GD17 L-NAME-treated rats, which were divided into stable siRNA-Int6 transfected (siRNA-Int6), negative vector control siRNA (NC-siRNA) and PE control (PE-Con) groups. All adenovirus siRNA transfections were performed on GD7 via intravenous tail injection.

Extreme and superextreme events in a loss-modulated CO_{2} laser: Nonlinear resonance route and precursors.

We investigate the occurrence of extreme and rare events, i.e., giant and rare light pulses, in a periodically modulated CO_{2} laser model.

The cellulose synthase companion proteins act non-redundantly with CELLULOSE SYNTHASE INTERACTING1/POM2 and CELLULOSE SYNTHASE 6.

Cellulose is a cell wall constituent that is essential for plant growth and development, and an important raw material for a range of industrial applications. Cellulose is synthesized at the plasma membrane by massive cellulose synthase (CesA) complexes that track along cortical microtubules in elongating cells of Arabidopsis through the activity of the protein CELLULOSE SYNTHASE INTERACTING1 (CSI1). In a recent study we identified another family of proteins that also are associated with the CesA complex and microtubules, and that we named COMPANIONS OF CELLULOSE SYNTHASE (CC).

A Mechanism for Sustained Cellulose Synthesis during Salt Stress.

Abiotic stress, such as salinity, drought, and cold, causes detrimental yield losses for all major plant crop species. Understanding mechanisms that improve plants' ability to produce biomass, which largely is constituted by the plant cell wall, is therefore of upmost importance for agricultural activities. Cellulose is a principal component of the cell wall and is synthesized by microtubule-guided cellulose synthase enzymes at the plasma membrane.

Silencing of eIF3e promotes blood perfusion recovery after limb ischemia through stabilization of hypoxia-inducible factor 2α activity.

Objective: We previously observed that silencing of eukaryotic translation initiation factor 3 subunit e (eIF3e), a hypoxia-independent downregulator of hypoxia-inducible factor 2α (HIF-2α), led to neoangiogenesis by promoting HIF-2α activity under normoxic conditions. In the current study, we investigated whether temporary silencing of eIF3e in muscles affects blood flow recovery in a mouse ischemic limb model.

Methods: eIF3e silencing was performed using small interfering RNA (siRNA), and changes in gene transcription and protein expression were analyzed in vitro using murine primary skeletal muscle myoblast and human primary skeletal muscle myoblast cell cultures.

Coactivator recruitment of AhR/ARNT1.

A common feature of nuclear receptors (NRs) is the transformation of external cell signals into specific transcriptions of the signal molecule. Signal molecules function as ligands for NRs and, after their uptake, activated NRs form homo- or heterodimers at promoter recognition sequences of the specific genes in the nucleus. Another common feature of NRs is their dependence on coactivators, which bridge the basic transcriptional machinery and other cofactors to the target genes, in order to initiate transcription and to unwind histone-bound DNA for exposing additional promoter recognition sites via their histone acetyltransferase (HAT) function.

Arabidopsis ABCG14 is essential for the root-to-shoot translocation of cytokinin.

Cytokinins are phytohormones that induce cytokinesis and are essential for diverse developmental and physiological processes in plants. Cytokinins of the trans-zeatin type are mainly synthesized in root vasculature and transported to the shoot, where they regulate shoot growth. However, the mechanism of long-distance transport of cytokinin was hitherto unknown.

Stochastic perturbations in open chaotic systems: random versus noisy maps.

We investigate the effects of random perturbations on fully chaotic open systems. Perturbations can be applied to each trajectory independently (white noise) or simultaneously to all trajectories (random map). We compare these two scenarios by generalizing the theory of open chaotic systems and introducing a time-dependent conditionally-map-invariant measure.

Int6/eIF3e silenced HIF2α stabilization enhances migration and tube formation of HUVECs via IL-6 and IL-8 signaling.

We previously identified the tumor suppressor INT6/eIF3e as a novel down regulator of HIF2α. Small interfering RNA targeting Int6 (siRNA-Int6) in HeLa cells led to normoxic stabilization of HIF2α, with concomitant transcription of angiogenic factors, including angiopoietin, basic fibroblast growth factor, and vascular endothelial growth factor. Here we used HIF2α normoxic up-regulation via Int6 silencing to investigate the role of HIF2α in endothelial cells.

Cardioankle vascular index evaluations revealed that cotreatment of ARB Antihypertension medication with traditional Chinese medicine improved arterial functionality.

Qian Yang He Ji (QYHJ) is a traditional Chinese medicine composed of Digitalis purpurea, Uncaria gambir, Fructus tribuli terrestris, and Ligustrum lucidum. Here, we explored whether combining an antihypertensive angiotensin II receptor blocker (ARB) therapy with QYHJ can improve the arterial functionality of hypertensive patients. One hundred and eight hypertensive patients were randomized into 2 groups; 1 group (n = 53) was treated with ARB and the other group (n = 55) was treated with ARB combined with QYHJ.

Adiabatic-nonadiabatic transition in warm long-range interacting systems: the transport of intense inhomogeneous beams.

We investigate the role of the temperature in the onset of singularities and the consequent breakdown in a macroscopic fluid model for long-range interacting systems. In particular, we consider an adiabatic fluid description for the transport of intense inhomogeneous charged particle beams. We find that there exists a critical temperature below which the fluid model always develops a singularity and breaks down as the system evolves.

Regulation of ABCB1/PGP1-catalysed auxin transport by linker phosphorylation.

Polar transport of the plant hormone auxin is controlled by PIN- and ABCB/PGP-efflux catalysts. PIN polarity is regulated by the AGC protein kinase, PINOID (PID), while ABCB activity was shown to be dependent on interaction with the FKBP42, TWISTED DWARF1 (TWD1). Using co-immunoprecipitation (co-IP) and shotgun LC-MS/MS analysis, we identified PID as a valid partner in the interaction with TWD1.

Binding of the ERα and ARNT1 AF2 domains to exon 21 of the SRC1 isoform SRC1e is essential for estrogen- and dioxin-related transcription.

Steroid receptor co-activator 1 (SRC1) is a transcriptional co-activator of numerous transcription factors involving nuclear receptors. Aryl hydrocarbon receptor nuclear translocator 1 (ARNT1) is an obligatory transcriptional partner of the aryl hydrocarbon receptor (AhR) and hypoxia inducible factor-1α (HIF-1α), as well as a co-activator of estrogen receptors (ERs). To initiate transcription, the activation function 2 (AF2) domains of estrogen-activated ERs interact with LxxLL motifs in the nuclear receptor interaction domain (NID) of SRC1.

Use of phosphoproteomics to study posttranslational protein modifications in Arabidopsis chloroplasts.

The posttranslational modification of proteins is important for the regulation of enzymatic activity, protein half-life, and interaction with other molecules. One of the best understood posttranslational modifications is the reversible phosphorylation of proteins at serine, threonine, or tyrosine residues. These phosphoamino acids are relatively stable in acidic solutions, and their comprehensive identification by mass spectrometry is, therefore, feasible.

Comparative phosphoproteome profiling reveals a function of the STN8 kinase in fine-tuning of cyclic electron flow (CEF).

Important aspects of photosynthetic electron transport efficiency in chloroplasts are controlled by protein phosphorylation. Two thylakoid-associated kinases, STN7 and STN8, have distinct roles in short- and long-term photosynthetic acclimation to changes in light quality and quantity. Although some substrates of STN7 and STN8 are known, the complexity of this regulatory kinase system implies that currently unknown substrates connect photosynthetic performance with the regulation of metabolic and regulatory functions.

Cellulose synthases and synthesis in Arabidopsis.

Plant cell walls are complex structures composed of high-molecular-weight polysaccharides, proteins, and lignins. Among the wall polysaccharides, cellulose, a hydrogen-bonded β-1,4-linked glucan microfibril, is the main load-bearing wall component and a key precursor for industrial applications. Cellulose is synthesized by large multi-meric cellulose synthase (CesA) complexes, tracking along cortical microtubules at the plasma membrane.

Noise-enhanced trapping in chaotic scattering.

We show that noise enhances the trapping of trajectories in scattering systems. In fully chaotic systems, the decay rate can decrease with increasing noise due to a generic mismatch between the noiseless escape rate and the value predicted by the Liouville measure of the exit set. In Hamiltonian systems with mixed phase space we show that noise leads to a slower algebraic decay due to trajectories performing a random walk inside Kolmogorov-Arnold-Moser islands.

Int6/eIF3e silencing promotes functional blood vessel outgrowth and enhances wound healing by upregulating hypoxia-induced factor 2alpha expression.

Background: We previously identified INT6/eIF3e as a novel regulator of hypoxia-inducible factor 2alpha (HIF2alpha) activity. Small interfering RNA (siRNA)-Int6 adequately stabilized HIF2alpha, even under normoxic conditions, and thereby enhanced the expression of several angiogenic factors in vitro, suggesting that siRNA-Int6 may induce angiogenesis in vivo.

Methods And Results: We demonstrated a 6- to 8-fold enhanced formation of normal arteries and veins in the subcutaneous regions of adult mice 5 days after a single siRNA-Int6 application.

AtALMT12 represents an R-type anion channel required for stomatal movement in Arabidopsis guard cells.

Stomatal pores formed by a pair of guard cells in the leaf epidermis control gas exchange and transpirational water loss. Stomatal closure is mediated by the release of potassium and anions from guard cells. Anion efflux from guard cells involves slow (S-type) and rapid (R-type) anion channels.

Hypoxia and angiogenesis: regulation of hypoxia-inducible factors via novel binding factors.

The mechanisms that regulate angiogenesis in hypoxia or hypoxic microenvironment are modulated by several pro- and antiangiogenic factors. Hypoxia-inducible factors (HIFs) have been established as the basic and major inducers of angiogenesis, but understanding the role of interacting proteins is becoming increasingly important to elucidate the angiogenic processes of a hypoxic response. In particular, with regard to wound healing and the novel therapies for vascular disorders such as ischemic brain and heart attack, it is essential to gain insights in the formation and regulation of HIF transcriptional machineries related to angiogenesis.

Large-scale Arabidopsis phosphoproteome profiling reveals novel chloroplast kinase substrates and phosphorylation networks.

We have characterized the phosphoproteome of Arabidopsis (Arabidopsis thaliana) seedlings using high-accuracy mass spectrometry and report the identification of 1,429 phosphoproteins and 3,029 unique phosphopeptides. Among these, 174 proteins were chloroplast phosphoproteins. Motif-X (motif extractor) analysis of the phosphorylation sites in chloroplast proteins identified four significantly enriched kinase motifs, which include casein kinase II (CKII) and proline-directed kinase motifs, as well as two new motifs at the carboxyl terminus of ribosomal proteins.