Insights into the lifestyle of uncultured bacterial natural product factories associated with marine sponges.

The as-yet uncultured filamentous bacteria "Candidatus Entotheonella factor" and "Candidatus Entotheonella gemina" live associated with the marine sponge Theonella swinhoei Y, the source of numerous unusual bioactive natural products. Belonging to the proposed candidate phylum "Tectomicrobia," Candidatus Entotheonella members are only distantly related to any cultivated organism. The Ca E.

Zwitterionic Iron Oxide (γ-Fe O ) Nanoparticles Based on P(2VP-grad-AA) Copolymers.

This study presents the synthesis and characterization of zwitterionic core-shell hybrid nanoparticles consisting of a core of iron oxide multicore nanoparticles (MCNPs, γ-Fe O ) and a shell of sultonated poly(2-vinylpyridine-grad-acrylic acid) copolymers. The gradient copolymers are prepared by reversible addition fragmentation chain transfer polymerization of 2-vinylpyridine (2VP), followed by the addition of tert-butyl acrylate and subsequent hydrolysis. Grafting of P(2VP-grad-AA) onto MCNP results in P(2VP-grad-AA)@MCNP, followed by quaternization using 1,3-propanesultone-leading to P(2VP -grad-AA)@MCNP with a zwitterionic shell.

A systems study reveals concurrent activation of AMPK and mTOR by amino acids.

Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational-experimental approach with text mining-enhanced quantitative proteomics.

Bioactivity of topologically confined gramicidin A dimers.

The d-/l-peptide gramicidin A (gA) is well known as a pivotal ion channel model and shows a broad spectrum of bioactivities such as antibiosis, antimalarial activity, as well as hemolysis. We applied inter-chain disulfide bonds to constrain the conformational freedom of gA into parallel and antiparallel dimeric topologies. Albeit the constructs were not found to be monoconformational, CD- and IR-spectroscopic studies suggested that this strategy indeed restricted the conformational space of the d-/l-peptide construct, and that β-helical secondary structures prevail.

Class I histone deacetylases regulate p53/NF-κB crosstalk in cancer cells.

The transcription factors NF-κB and p53 as well as their crosstalk determine the fate of tumor cells upon therapeutic interventions. Replicative stress and cytokines promote signaling cascades that lead to the co-regulation of p53 and NF-κB. Consequently, nuclear p53/NF-κB signaling complexes activate NF-κB-dependent survival genes.

Mechanical strain stimulates vasculogenesis and expression of angiogenesis guidance molecules of embryonic stem cells through elevation of intracellular calcium, reactive oxygen species and nitric oxide generation.

Objectives: Differentiation of embryonic stem (ES) cells may be regulated by mechanical strain. Herein, signaling molecules underlying mechanical stimulation of vasculogenesis and expression of angiogenesis guidance cues were investigated in ES cell-derived embryoid bodies.

Methods And Results: Treatment of embryoid bodies with 10% static mechanical strain using a Flexercell strain system significantly increased CD31-positive vascular structures and the angiogenesis guidance molecules plexinB1, ephrin B2, neuropilin1 (NRP1), semaphorin 4D (sem4D) and robo4 as well as vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-BB (PDGF-BB) as evaluated by Western blot and real time RT-PCR.

Developmental Control and Plasticity of Fruit and Seed Dimorphism in Aethionema arabicum.

Understanding how plants cope with changing habitats is a timely and important topic in plant research. Phenotypic plasticity describes the capability of a genotype to produce different phenotypes when exposed to different environmental conditions. In contrast, the constant production of a set of distinct phenotypes by one genotype mediates bet hedging, a strategy that reduces the temporal variance in fitness at the expense of a lowered arithmetic mean fitness.

Effects of a commonly used glyphosate-based herbicide formulation on early developmental stages of two anuran species.

Environmental contamination, especially due to the increasing use of pesticides, is suggested to be one out of six main reasons for the global amphibian decline. Adverse effects of glyphosate-based herbicides on amphibians have been already discussed in several studies with different conclusions, especially regarding sublethal effects at environmentally relevant concentrations. Therefore, we studied the acute toxic effects (mortality, growth, and morphological changes) of the commonly used glyphosate-based herbicide formulation Roundup® UltraMax on early aquatic developmental stages of two anuran species with different larval types (obligate vs.

Biomimetic Thioesters as Probes for Enzymatic Assembly Lines: Synthesis, Applications, and Challenges.

Thioesters play essential roles in many biosynthetic pathways to fatty acids, esters, polyketides, and non-ribosomal peptides. Coenzyme A (CoA) and related phosphopantetheine thioesters are typically employed as activated acyl units for diverse C-C, C-O, and C-N coupling reactions. To study and control these enzymatic assembly lines in vitro and in vivo structurally simplified analogs such as N-acetylcysteamine (NAC) thioesters have been developed.

Assessment of HDACi-Induced Cytotoxicity.

The chromatin contains the genetic and the epigenetic information of a eukaryotic organism. Posttranslational modifications of histones, such as acetylation and methylation, regulate their structure and control gene expression. Histone acetyltransferases (HATs) acetylate lysine residues in histones while histone deacetylases (HDACs) remove this modification.

Crossing the blood-brain barrier: Glutathione-conjugated poly(ethylene imine) for gene delivery.

The targeted drug delivery to the central nervous system represents one of the major challenges in pharmaceutical formulations since it is strictly limited through the highly selective blood-brain barrier (BBB). l-Glutathione (GSH), a tripeptide and well-known antioxidant, has been studied in the last years as potential candidate to facilitate the receptor-mediated transcytosis of nanocarriers. We thus tested whether GSH decoration of a positively charged polymer, poly(ethylene imine), with this vector enables the transport of genetic material and, simultaneously, the passage through the BBB.

Plants are less negatively affected by flooding when growing in species-rich plant communities.

Flooding is expected to increase in frequency and severity in the future. The ecological consequences of flooding are the combined result of species-specific plant traits and ecological context. However, the majority of past flooding research has focused on individual model species under highly controlled conditions.

Highly purified calf hemodialysate (Actovegin®) may improve endothelial function by activation of proteasomes: A hypothesis explaining the possible mechanisms of action.

Highly purified calf hemodialysate (HPCH) known as Actovegin® or Solcoseryl® is one of the most controversial drugs currently marketed worldwide. It is not registered as drug in some countries and therefore its medical use there is illegal, while in others it is often among the top 10 of the best-selling medications. It could be also found in the list of the "most useless drugs" and was banned for short time by World Anti-Doping Agency as performance enhancer.

Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study.

Background: In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding.

BRP-187: A potent inhibitor of leukotriene biosynthesis that acts through impeding the dynamic 5-lipoxygenase/5-lipoxygenase-activating protein (FLAP) complex assembly.

The pro-inflammatory leukotrienes (LTs) are formed from arachidonic acid (AA) in activated leukocytes, where 5-lipoxygenase (5-LO) translocates to the nuclear envelope to assemble a functional complex with the integral nuclear membrane protein 5-LO-activating protein (FLAP). FLAP, a MAPEG family member, facilitates AA transfer to 5-LO for efficient conversion, and LT biosynthesis critically depends on FLAP. Here we show that the novel LT biosynthesis inhibitor BRP-187 prevents the 5-LO/FLAP interaction at the nuclear envelope of human leukocytes without blocking 5-LO nuclear redistribution.

Development of smart cell-free and cell-based assay systems for investigation of leukotriene C synthase activity and evaluation of inhibitors.

Cysteinyl leukotrienes (cys-LTs) cause bronchoconstriction in anaphylaxis and asthma. They are formed by 5-lipoxygenase (5-LOX) from arachidonic acid (AA) yielding the unstable leukotriene A (LTA) that is subsequently conjugated with glutathione (GSH) by LTC synthase (LTCS). Cys-LT receptor antagonists and LTCS inhibitors have been developed, but only the former have reached the market.

Allometric equations for integrating remote sensing imagery into forest monitoring programmes.

Remote sensing is revolutionizing the way we study forests, and recent technological advances mean we are now able - for the first time - to identify and measure the crown dimensions of individual trees from airborne imagery. Yet to make full use of these data for quantifying forest carbon stocks and dynamics, a new generation of allometric tools which have tree height and crown size at their centre are needed. Here, we compile a global database of 108753 trees for which stem diameter, height and crown diameter have all been measured, including 2395 trees harvested to measure aboveground biomass.

Lecithin and PLGA-based self-assembled nanocomposite, Lecithmer: preparation, characterization, and pharmacokinetic/pharmacodynamic evaluation.

The present study investigates the drug delivery potential of polymer lipid hybrid nanocomposites (Lecithmer®) composed of poly(D,L-lactide-co-glycolide (PLGA) and soya lecithin. Core-shell structure of Lecithmer was evident from cryo-TEM images. Daunorubicin (DNR) and lornoxicam (LNX)-incorporated Lecithmer nanocomposites were evaluated for anticancer and anti-inflammatory activity.

Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats.

A Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague-Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks.

Stress promotes Arabidopsis - Piriformospora indica interaction.

The endophytic fungus Piriformospora indica colonizes Arabidopsis thaliana roots and promotes plant performance, growth and resistance/tolerance against abiotic and biotic stress. Here we demonstrate that the benefits for the plant increase when the two partners are co-cultivated under stress (limited access to nutrient, exposure to heavy metals and salt, light and osmotic stress, pathogen infection). Moreover, physical contact between P.

Oxygen-Dependent Photocatalytic Water Reduction with a Ruthenium(imidazolium) Chromophore and a Cobaloxime Catalyst.

Detailed investigations of a photocatalytic system capable of producing hydrogen under pre-catalytic aerobic conditions are reported. This system consists of the NHC precursor chromophore [Ru(tbbpy)2 (RR'ip)][PF6 ]3 (abbreviated as Ru(RR'ip)[PF6 ]3 ; tbbpy=4,4'-di-tert-butyl-2,2'-bipyridine, RR'ip=1,3-disubstituted-1H-imidazo[4,5-f][1,10]phenanthrolinium), the reduction catalyst Co(dmgH)2 (dmgH=dimethylglyoximato), and the electron donor ascorbic acid (AA). Screening studies with respect to solvent, cobaloxime catalyst, electron donor, pH, and concentrations of the individual components yielded optimized photocatalytic conditions.

Plant diversity effects on grassland productivity are robust to both nutrient enrichment and drought.

Global change drivers are rapidly altering resource availability and biodiversity. While there is consensus that greater biodiversity increases the functioning of ecosystems, the extent to which biodiversity buffers ecosystem productivity in response to changes in resource availability remains unclear. We use data from 16 grassland experiments across North America and Europe that manipulated plant species richness and one of two essential resources-soil nutrients or water-to assess the direction and strength of the interaction between plant diversity and resource alteration on above-ground productivity and net biodiversity, complementarity, and selection effects.

Single cell analysis in native tissue: Quantification of the retinoid content of hepatic stellate cells.

Hepatic stellate cells (HSCs) are retinoid storing cells in the liver: The retinoid content of those cells changes depending on nutrition and stress level. There are also differences with regard to a HSC's anatomical position in the liver. Up to now, retinoid levels were only accessible from bulk measurements of tissue homogenates or cell extracts.

The hypoxia-induced dehydrogenase HorA is required for coenzyme Q10 biosynthesis, azole sensitivity and virulence of Aspergillus fumigatus.

Aspergillus fumigatus is the predominant airborne pathogenic fungus causing invasive aspergillosis in immunocompromised patients. During infection A. fumigatus has to adapt to oxygen-limiting conditions in inflammatory or necrotic tissue.

Research Resource: Real-Time Analysis of Somatostatin and Dopamine Receptor Signaling in Pituitary Cells Using a Fluorescence-Based Membrane Potential Assay.

Stable somatostatin analogues and dopamine receptor agonists are the mainstay for the pharmacological treatment of functional pituitary adenomas; however, only a few cellular assays have been developed to detect receptor activation of novel compounds without disrupting cells to obtain the second messenger content. Here, we adapted a novel fluorescence-based membrane potential assay to characterize receptor signaling in a time-dependent manner. This minimally invasive technique provides a robust and reliable read-out for ligand-induced receptor activation in permanent and primary pituitary cells.