Input: A cost-effective alternative is proposed, using genotype information equivalent to typing four SNPs (DR3, DR4-DQB1 * 03: 02, CTLA-4, and INS), which achieved an AUC of 0. 72 in the discovery set and 0. 69 in the validation set. CONCLUSIONSGenotyping data sufficient to tag DR3, DR4-DQB1 * 03: 02, CTLA4, and INS was shown to distinguish between subjects with type 1 diabetes and their unaffected siblings adequately to achieve clinically utility to identify children in multiplex families to be considered for early intervention.


Input: Cuf2 boosts the transcription of APC/C activator Fzr1 to terminate the meiotic division cycle.


Input: The number of nuclear divisions in meiosis is strictly limited to two.


Input: Although the precise mechanism remains unknown, this seems to be achieved by adjusting the anaphase-promoting complex/cyclosome (APC/C) activity to degrade cyclin.


Input: Here, we describe a fission yeast cuf2 mutant that enters into a third nuclear division cycle, represented by ectopic spindle assembly and abnormal chromosome segregation.


Input: Cuf2 is a meiotic transcription factor, and its critical target is fzr1 (+)/mfr1 (+), which encodes a meiotic APC/C activator.


Input: fzr1 Delta also enters a third nuclear division.


Input: Thus, Cuf2 ensures termination of the M-phase cycle by boosting Fzr1 expression to generate functional gametes.


Input: Intracellular trafficking of solid lipid nanoparticles and their distribution between cells through tunneling nanotubes.


Input: The intracellular fate of nanosized drug delivery systems is still not well understood.


Input: Various internalization pathways have been discovered, but knowledge of their intracellular trafficking is still incomplete.


Input: The aim of this study was to examine the internalization, pathways, and positioning taken by solid lipid nanoparticles (SLNs) in cells.


Input: SLNs were fluorescence labeled with a newly synthesized fluorescent probe, 14-DACA.


Input: The probe was strongly incorporated into the nanoparticle core under the influence of its long lipophilic chain, enabling superior visualization of SLNs under complex and dynamic intracellular conditions.


Input: The intracellular distribution of SLNs was studied qualitatively using a co-localization technique and quantitatively using fluorescence intensity profiles.


Input: SLNs were seen inside the cells as distinct bright blue dots that underwent dynamic movement and were finally positioned in the proximity of the nucleus.


Input: A few SLNs were shown to be present in mitochondria and between actin filaments, but none in the cell nucleus or lysosomes.


Input: SLNs are here reported to be present in tunneling nanotubes (TNTs), which could be a new route of SLN transfer between cells.


Input: More TNTs were observed in cells treated with SLNs.


Input: The presence of TNTs was additionally confirmed by atomic force microscopy analysis, which indicated that treated cells were more rough than control cells.


Input: Detailed investigation of the subcellular localization of SLNs and the evidence for their transfer and distribution via TNTs to the cells, which are not in direct contact with the source of SLNs, are important for understanding the mechanism of targeted drug delivery.


Input: Understanding the possible intercellular distribution of SLNs via TNTs can significantly influence approaches to treating organelle-specific diseases.


Input: Ubiquitous trisulfur radical anion: fundamentals and applications in materials science, electrochemistry, analytical chemistry and geochemistry.

trisulfur


Input: The trisulfur radical anion [S3]. (-) is well-known from inorganic chemistry textbooks as the blue chromophore in ultramarine blues in which this highly reactive species is trapped in a zeolitic framework.

trisulfur

[S3]. (-)


Input: Recent findings have revealed that [S3]. (-) has a multi-faceted role in a variety of media, including alkali metal-sulfur batteries, aqueous solutions at high temperatures and pressures, and ionic liquids; it has also been used to detect trace amounts of water in organic solvents.

[S3]. (-)

sulfur


Input: This tutorial review illustrates how various physical techniques are used to identify a reactive species in solution and shows how elucidation of electronic structures can be used to explain spectroscopic and structural properties.


Input: Examples of the function of [S3]. (-) in materials science, electrochemistry, analytical chemistry and geochemistry are used to illustrate the widespread influence of this fundamentally important triatomic sulfur species.

[S3]. (-)

triatomic sulfur


Input: COMPLETE ARTIFICIAL SALIVA ALTERS EXPRESSION OF PROINFLAMMATORY CYTOKINES IN HUMAN DERMAL FIBROBLASTS.


Input: Complete artificial saliva (CAS) is a saliva substitute often used as a vehicle for test articles, including smokeless tobacco products.


Input: In the course of a study employing normal adult human dermal fibroblasts (HDFa) as a model in vitro, we discovered that CAS as a vehicle introduced a significant change in the expression of proinflammatory cytokines.


Input: To determine the effects of CAS on gene expression, real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) gene array analysis was used.


Input: Results indicate that robust changes in the expression of the proinflammatory cytokine interleukin 8 (IL8) and the vascular cell adhesion molecule 1 (VCAM1) occur within 5 hours of exposure to CAS.


Input: To determine whether CAS also alters cytokine release into the culture media, cytometric bead array (CBA) assays for human inflammatory cytokines were performed.


Input: Analysis shows that CAS induced the release of IL8 and interleukin 6 (IL6).


Input: This study focused on determining which components in CAS were responsible for the proinflammatory response in HDFa.


Input: The following components were investigated: alpha-amylase, lysozyme, acid phosphatase, and urea.

urea


Input: Results demonstrated that enzymatically active alpha-amylase induced gene expression for proinflammatory cytokines IL8, IL6, tumor necrosis factor-alpha (TNF alpha), and interleukin 1 alpha (IL1 alpha), and for VCAM1.


Input: Therefore, it is important to carefully evaluate the " vehicle effects " of CAS and its components in in vitro toxicology research.


Input: Simple and Rapid Synthesis of Magnetite/Hydroxyapatite Composites for Hyperthermia Treatments via a Mechanochemical Route.

Magnetite

Hydroxyapatite


Input: This paper presents a simple method for the rapid synthesis of magnetite/hydroxyapatite composite particles.

magnetite

hydroxyapatite


Input: In this method, superparamagnetic magnetite nanoparticles are first synthesized by coprecipitation using ferrous chloride and ferric chloride.

magnetite

ferrous chloride

ferric chloride


Input: Immediately following the synthesis, carbonate-substituted (B-type) hydroxyapatite particles are mechanochemically synthesized by wet milling dicalcium phosphate dihydrate and calcium carbonate in a dispersed suspension of magnetite nanoparticles, during which the magnetite nanoparticles are incorporated into the hydroxyapatite matrix.

carbonate

hydroxyapatite

dicalcium phosphate dihydrate

calcium carbonate

magnetite

magnetite

hydroxyapatite


Input: We observed that the resultant magnetite/hydroxyapatite composites possessed a homogeneous dispersion of magnetite nanoparticles, characterized by an absence of large aggregates.

magnetite

hydroxyapatite

magnetite


Input: When this material was subjected to an alternating magnetic field, the heat generated increased with increasing magnetite concentration.

magnetite


Input: For a magnetite concentration of 30 mass%, a temperature increase greater than 20 K was achieved in less than 50 s.

magnetite


Input: These results suggest that our composites exhibit good hyperthermia properties and are promising candidates for hyperthermia treatments.


Input: A Detailed Experimental and Theoretical Study into the Properties of C60 Dumbbell Junctions.


Input: A combined experimental and theoretical investigation is carried out into the electrical transport across a fullerene dumbbell one-molecule junction.

fullerene


Input: The newly designed molecule comprises two C60 s connected to a fluorene backbone via cyclopropyl groups.

fluorene

cyclopropyl


Input: It is wired between gold electrodes under ambient conditions by pressing the tip of a scanning tunnelling microscope (STM) onto one of the C60 groups.


Input: The STM allows us to identify a single molecule before the junction is formed through imaging, which means unambiguously that only one molecule is wired.


Input: Once lifted, the same molecule could be wired many times as it was strongly fixed to the tip, and a high conductance state close to 10 (-2) G0 is found.


Input: The results also suggest that the relative conductance fluctuations are low as a result of the low mobility of the molecule.


Input: Theoretical analysis indicates that the molecule is connected directly to one electrode through the central fluorene, and that to bind it to the gold fully it has to be pushed through a layer of adsorbates naturally present in the experiment.

fluorene


Input: Extracellular Electron Transfer across Bacterial Cell Membranes via a Cytocompatible Redox-Active Polymer.


Input: A redox-active phospholipid polymer with a phospholipid-mimicking structure (2-methacryloyloxyethyl phosphorylcholine; MPC) was synthesized to construct a biocompatible electron mediator between bacteria and an electrode.

2-methacryloyloxyethyl phosphorylcholine

MPC


Input: In this study, a copolymer of MPC and vinylferrocene [VF; poly (MPC-co-VF)] (PMF) is synthesized.

MPC

vinylferrocene

poly (MPC-co-VF)

PMF


Input: When PMF is added to cultures of the bacterial species Escherichia coli (Gram negative) and Lactobacillus plantarum (Gram positive), which have different cell wall structures, a catalytic current mediated by PMF is observed.

PMF

PMF


Input: In addition, growth curves and live/dead assays indicate that PMF does not decrease metabolic activity or cell viability.

PMF


Input: These results indicate that PMF mediates extracellular electron transfer across bacterial cell membranes without associated cytotoxicity.

PMF


Input: PICK1 Deficiency Impairs Secretory Vesicle Biogenesis and Leads to Growth Retardation and Decreased Glucose Tolerance.

Glucose


Input: Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream.


Input: The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear.


Input: Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs) domain protein PICK1 (protein interacting with C kinase 1) as a key component early in the biogenesis of secretory vesicles in GH-producing cells.


Input: Both PICK1-deficient Drosophila and mice displayed somatic growth retardation.


Input: Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides.


Input: PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary.


Input: Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number.


Input: Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance.

glucose


Input: PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro.


Input: In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression.


Input: In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression.


Input: Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression.


Input: Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones.


Input: The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine cells and support an important role of PICK1/ICA69 in maintenance of metabolic homeostasis.


Input: X-ray structure analysis of a solid solution of milbemycins A3 and A4.

milbemycins A3 and A4


Input: Milbemycins A3 and A4 are pharmaceutically and agriculturally useful macrolides isolated from Streptomyces species.

Milbemycins A3 and A4


Input: The molecular structures of the title compounds were unambiguously established by a single crystal X-ray analysis of the solid solution of both compounds.


Input: The crystals present trigonal system, space group P32 with Z = 3, unit cell dimensions: a = 12. 2211 (4), c = 17. 5372 (7) A; V = 2268. 4 (1) A (3), mu = 0. 082 mm (-1); d = 1. 183 g cm (-3).


Input: An interesting system of intramolecular hydrogen bonds and weak intermolecular CH ... O type hydrogen bond was observed in the solid state.

hydrogen

CH

O

hydrogen


Input: Site-specific and Far-Red Light-Activatable Prodrug of Combretastain A-4 Using Photo-Unclick Chemistry.

Combretastain A-4


Input: Although tissue-penetrable light (red and NIR) has a great potential for spatiotemporally controlled release of therapeutic agents, it has been hampered because of the lack of chemistry translating the photonic energy to a cleavage of a chemical bond.


Input: Recently, we discovered that an aminoacrylate group could be cleaved to release parent drugs after oxidation by SO, and have called this " photo-unclick chemistry ".

aminoacrylate


Input: We demonstrate its application to far-red light-activated prodrugs.


Input: A prodrug of combretastatin A-4 (CA4) was prepared, CMP-L-CA4: CMP (dithiaporphyrin, a photosensitizer) and L (aminoacrylate linker).

combretastatin A-4

CMP

dithiaporphyrin

aminoacrylate


Input: Upon irradiation with 690 nm diode laser, the aminoacrylate linker of the prodrug was cleaved rapidly releasing CA4 (> 80% in 10 min) in CDCl3.

aminoacrylate


Input: In the tissue culture, it showed about a 6-fold increase in its IC50 in MCF-7 after the irradiation, most likely, because of the released CA4.


Input: Most significantly, CMP-L-CA4 had better antitumor efficacy in vivo than its non-cleavable (NC) analog, CMP-NCL-CA4.


Input: This is the first demonstration of the in vivo efficacy of the novel low-energy light-activatable prodrug using the photo-unclick chemistry.


Input: " Strange Kinetics " in the Temperature Dependence of Methionine Ligand Rebinding Dynamics in Cytochrome c.

Methionine


Input: Temperature dependence of methionine ligand dissociation and rebinding dynamics in cytochrome c in aqueous solution has been studied using classical molecular dynamics simulation.

methionine


Input: Results are compared with previous study of rebinding dynamics at 300K in water in order to understand how the change of protein environment and the underlying protein energy landscape influence the dynamics.


Input: Rebinding dynamics at 77K, 180K, and 300K exhibits changes in both timescale and mechanism as the protein and solvent undergo a dynamic " glass transition. " At each temperature, the rebinding dynamics yields a subset of trajectories that undergo fast rebinding as well as a subset of trajectories that undergo slower rebinding.


Input: At 300K in water, both a fast (4. 0 ps) and slow (14. 6 ps) rebinding is observed.


Input: While fast rebinding occurs from a " downward " (heme pointing) substate of the methionine, the slow rebinding involves interconversion between an " upward " substate, from which rebinding cannot occur, and the downward substate.

heme

methionine


Input: At lower temperatures (77K and 180K) the upward dissociated substate was not observed due to the high barrier imposed by the " frozen " protein structure.


Input: However, a slow rebinding phase is observed at both 77K and 180K and is associated with a process of trapping in downward but " binding forbidden " substates with subsequent slow dynamical conversion to " binding competent " substates from which rebinding is relatively rapid.


Input: Distinctive rebinding dynamics at 77K and 180K suggest that different rebinding time scales are predetermined by the protein and solvent structural arrangement prior to photodissociation, which causes either fast rebinding (about 2ps) or slow (> 50ps) rebinding.


Input: Suggestions for future experiments to further probe the role of dynamic heterogeneity in the kinetics of methionine ligand binding in cytochrome c protein are proposed.

methionine


Input: (De) Lithiation Mechanism of Li/SeSx (x = 0-7) Batteries Determined by In-situ Synchrotron X-ray Diffraction and X-ray Absorption Spectroscopy.

Lithiation

SeSx


Input: Electrical energy storage for transportation has going beyond the limit of converntional lithium-ion batteries currently.

lithium


Input: New material or new battery system development is an alternative approach to achieve the goal of new high energy storage system with energy densities five times or more greater.


Input: A series of SeSx-carbon (x = 0-7) composite materials has been prepared and evaluated as the positive electrodes in secondary lithium cells with ether-based electrolyte.

SeSx

carbon

lithium

ether


Input: In-situ synchrotron high energy X-ray diffraction was utilized to investigate the crystalline phase transition during cell cycling.


Input: Complementary, in-situ Se K-edge X-ray absorption near edge structure analysis was used to track the evolution of the Se valence state for both crystalline and non-crystalline phases, including amorphous and electrolyte-dissolved phases in the (de) lithiation process.

Se

Se


Input: On the basis of these reuslts, a mechanism for the (de) lithiation process is proposed, where Se is reduced to the polyselenides, Li2Sen (n >= 4), Li2Se2, and Li2Se sequentially during the lithiation, and Li2Se is oxidized to Se through Li2Sen (n >= 4) during the delithiation.

Se

polyselenides

Se


Input: In addition, X-ray photoelectron spectroscopy and electrochemical impedance spectroscopy demonstrated the reversibility of the Li/Se system in ether-based electrolyte and the presence of side products in the carbonate-based electrolytes.

Li

Se

ether

carbonate


Input: For Li/SeS2 and Li/SeS7 cells, Li2Se and Li2S are the discharged products with the presence of Se only as the crystalline phase in the end of charge.

Li

Li

Se


Input: The Governing Role of Surface Hydration in Ion Specific Adsorption to Silica-an AFM Based Account of the Hofmeister Universality and its Reversal.

Silica


Input: AFM measurements of the force acting between silica surfaces in the presence of varied alkali-chloride salts and pH' s elucidate the origin of the Hofmeister adsorption series and its reversal.

silica

alkali-chloride


Input: At low pH, electrostatics is shown to be insignificant.


Input: The preferential adsorption of Cs + to the silica surface is traced to the weak hydration of neutral silanols and the resulting hydrophobic expulsion of weakly hydrated ions from bulk solution to the interface.

Cs +

silica

silanols


Input: The same interactions keep the strongly hydrated Li + and Na + in solution.

Li +

Na +


Input: As pH is increased, a tightly bound hydration layer forms on deprotonating silanols.

silanols


Input: Cs + is correspondingly expelled from the surface and adsorption of small ions is encouraged.

Cs +


Input: The deduced role of surface hydration is corroborated by hydration repulsion observed at high pH, surface over-charging at low pH, and data in other oxides.

oxides


Input: Fungal ABC Transporter-Associated Activity of Isoflavonoids from the Root Extract of Dalea formosa.

Isoflavonoids


Input: New potential treatments for disseminated fungal infections are needed, especially for infections caused by the commonly drug-resistant pathogens Candida albicans and C. glabrata.


Input: These pathogens cause systemic candidiasis, a significant cause of mortality in immune-compromised patients.


Input: ABC transporters of the pleiotropic drug resistance subfamily, such as Cdr1p of C. albicans, play an important role in antifungal resistance and are potential bioassay targets for antifungal therapies against drug-resistant pathogens.


Input: We observed strong antifungal growth inhibitory activity in the methanol extract of Dalea formosa roots.

methanol


Input: This extract afforded six new isoflavonoids, sedonans A-F (1-6), a new but-2-enolide, 4'-O-methylpuerol A (7), and the new pterocarpan ent-sandwicensin (8).

isoflavonoids

sedonans A-F

4'-O-methylpuerol A

ent-sandwicensin


Input: The structures and absolute configurations of these compounds were assigned using spectroscopic and chiroptical techniques.


Input: The direct antifungal activity of 1 against C. glabrata (MIC = 20 mu M) was higher than that of fluconazole.

fluconazole


Input: Sedonans A-F and ent-sandwicensin were also active against Saccharomyces cerevisiae strains that express differing ABC transporter-associated resistance mechanisms but differed in their susceptibility to Cdr1p-mediated detoxification.

Sedonans A-F

ent-sandwicensin


Input: A sedonan A (1)/ent-sandwicensin (8) combination exhibited synergistic growth inhibition.

sedonan A

ent-sandwicensin


Input: The results demonstrate that multiple crude extract compounds are differentially affected by efflux-mediated resistance and are collectively responsible for the observed bioactivity.


Input: A Chemometric Approach to Distribution of Selenium in Medicinal Plants Cultivated in Poland.

Selenium


Input: Abstract The aim of this study was to evaluate the level of selenium (Se) in common raw plant materials (herbs, leaves, flowers, fruits, and roots) obtained from medicinal plants cultivated in Poland.

selenium

Se


Input: Furthermore, the relationship between the morphological part of a plant and its species was examined, and the concentration of Se in it was measured.

Se


Input: Spectrofluorimetric determination of Se in 148 samples of 44 plant species revealed that the majority of the plants contained Se at a level from several to several tens of mu g/kg dry weight (d. w.).

Se

Se


Input: A relatively high Se concentration, in the order of 50 mu g/kg d. w., was found in Majoranae herba, Crataegi fructus, and Lini semen.

Se


Input: An especially high Se level, > 100 mu g/kg d. w., was found in only three plants-Equiseti herba, Farfarae folium, and Cichorii radix.

Se


Input: Application of a nonparametric Kruskal-Wallis analysis of variance test indicates that the morphological variable influences the level of Se in the studied groups of raw plant materials.

Se


Input: The mean concentration of Se in fruits differs significantly from that found in flowers and roots.

Se


Input: However, there was no statistically significant difference between the Se content in herbs and leaves and its levels in fruits, flowers, and roots.

Se


Input: Cluster analysis and principal component analysis calculations show that it is possible to relate the Se concentration in plant material to the plant species and botanical family of the medicinal plant in only a few cases.

Se


Input: Analysis of average Se levels in the plant species showed that the plants belonging to the Apiaceae and Labiatae are more Se-rich than those belonging to Rosaceae botanical families.

Se

Se


Input: Non-destructive monitoring of creaming of oil-in-water emulsion-based formulations using magnetic resonance imaging.


Input: Abstract A non-destructive method for monitoring creaming of emulsion-based formulations is in great demand because it allows us to understand fully their instability mechanisms.


Input: This study was aimed at demonstrating the usefulness of magnetic resonance (MR) techniques, including MR imaging (MRI) and MR spectroscopy (MRS), for evaluating the physicochemical stability of emulsion-based formulations.


Input: Emulsions that are applicable as the base of practical skin creams were used as test samples.


Input: Substantial creaming was developed by centrifugation, which was then monitored by MRI.


Input: The creaming oil droplet layer and aqueous phase were clearly distinguished by quantitative MRI by measuring T1 and the apparent diffusion coefficient.


Input: Components in a selected volume in the emulsions could be analyzed using MRS.


Input: Then, model emulsions having different hydrophilic-lipophilic balance (HLB) values were tested, and the optimal HLB value for a stable dispersion was determined.


Input: In addition, the MRI examination enables the detection of creaming occurring in a polyethylene tube, which is commonly used for commercial products, without losing any image quality.

polyethylene


Input: These findings strongly indicate that MR techniques are powerful tools to evaluate the physicochemical stability of emulsion-based formulations.


Input: This study will make a great contribution to the development and quality control of emulsion-based formulations.


Input: Spectroscopic Study of the Light-Harvesting CP29 Antenna Complex of Photosystem II-Part I.


Input: Recent structural data revealed that the CP29 protein of higher plant Photosystem II (PSII) contains 13 chlorophylls (Chls) per complex [Pan et al., Nat. Struct. Mol. Biol. 2011, 18, 309], i. e., five Chls more than in the predicted CP29 homology-based structure model [Bassi et al., Proc. Natl. Acad. Sci. USA 1999, 96, 10056].

chlorophylls

Chls


Input: This lack of consensus presents a constraint on the interpretation of CP29 optical spectra and their underlying electronic structure.


Input: To address this problem, we present new low-temperature (5 K) absorption, fluorescence, and hole-burned (HB) spectra for CP29 proteins from spinach, which are compared with the previously reported data.


Input: We focus on excitation energy transfer (EET) and the nature of the lowest-energy state (s).


Input: We argue that CP29 proteins previously studied by HB spectroscopy lacked at least one Chl a molecule (i. e., a615 or a611), which along with Chl a612 contribute to the lowest energy state in more intact CP29, and one Chl b (most likely b607).

Chl a

Chl b


Input: This is why the low-energy state and fluorescence maxima reported by Pieper et al.


Input: [Photochem. Photobiol. 2000, 71, 574] were blueshifted by ~ 1 nm, the low-energy state appeared to be highly localized on a single Chl a molecule, and the position of the low-energy state was independent of burning fluence.

Chl a


Input: In contrast, the position of the nonresonant HB spectrum shifts blue with increasing fluence in intact CP29, as this state is strongly contributed to by several pigments (i. e., a611, a612, a615 and a610).


Input: Zero-phonon hole widths obtained for the Chl b band at 638. 5 nm (5 K) revealed two independent Chl b --> Chl a EET times, i. e., 4 +/- 0. 5 ps and 0. 4 +/- 0. 1 ps.

Chl b

Chl b

Chl a


Input: The latter value is a factor of two faster than previously observed by HB spectroscopy and very similar to the one observed by Gradinaru et al.


Input: [J. Phys. Chem. B 2000, 104, 9330] in pump-probe experiments.


Input: EET time from 650 nm Chl b --> Chl a and downward EET from Chl (s) a state (s) at 665 nm occurs in 4. 9 +/- 0. 7 ps.

Chl b

Chl a


Input: These findings provide important constraints for excitonic calculations that are discussed in the accompanying paper (Part II).


Input: Group B Streptococcus pilus sortase regulation: a single mutation in the lid region induces pilin protein polymerization in vitro.


Input: Gram-positive bacteria build pili on their cell surface via a class C sortase-catalyzed transpeptidation mechanism from pilin protein substrates.


Input: Despite the availability of several crystal structures, pilus-related C sortases remain poorly characterized to date, and their mechanisms of transpeptidation and regulation need to be further investigated.


Input: The available 3-dimensional structures of these enzymes reveal a typical sortase fold, except for the presence of a unique feature represented by an N-terminal highly flexible loop known as the " lid. " This region interacts with the residues composing the catalytic triad and covers the active site, thus maintaining the enzyme in an autoinhibited state and preventing the accessibility to the substrate.

N


Input: It is believed that enzyme activation may occur only after lid displacement from the catalytic domain.


Input: In this work, we provide the first direct evidence of the regulatory role of the lid, demonstrating that it is possible to obtain in vitro an efficient polymerization of pilin subunits using an active C sortase lid mutant carrying a single residue mutation in the lid region.


Input: Moreover, biochemical analyses of this recombinant mutant reveal that the lid confers thermodynamic and proteolytic stability to the enzyme.-Cozzi, R., Zerbini, F., Assfalg, M., D' Onofrio, M., Biagini, M., Martinelli, M., Nuccitelli, A., Norais, N., Telford, J.


Input: L., Maione, D., Rinaudo, C.


Input: D.


Input: Group B Streptococcus pilus sortase regulation: a single mutation in the lid region induces pilin protein polymerization in vitro.


Input: Anti-allergic actions of rottlerin from Mallotus philippinensis in experimental mast cell-mediated anaphylactic models.

rottlerin


Input: Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of the allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation.


Input: Rottlerin is an active molecule isolated from Mallotus philippinensis, a medicinal plant used in Ayurvedic Medicine System for anti-allergic and anti-helminthic treatments.

Rottlerin


Input: The present study investigated potential anti-allergic effects of rottlerin in animal models of IgE-dependent anaphylaxis and the anti-allergic mechanisms of action of rottlerin in mast cells.

rottlerin

rottlerin


Input: Anti-allergic actions of rottlerin were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in anaphylactic contraction of bronchial rings isolated from sensitized guinea pigs.

rottlerin


Input: Direct mast cell-stabilizing effect of rottlerin was examined in RBL-2H3 mast cell line.

rottlerin


Input: Anti-allergic signaling mechanisms of action of rottlerin in mast cells were also examined.

rottlerin


Input: Rottlerin prevented IgE-mediated cutaneous vascular extravasation, hypothermia, elevation in plasma histamine level and tracheal tissue mast cell degranulation in mice in a dose-dependent manner.

Rottlerin

histamine


Input: In addition, rottlerin suppressed ovalbumin-induced guinea pig bronchial smooth muscle contraction.

rottlerin


Input: Furthermore, rottlerin concentration-dependently blocked IgE-mediated immediate release of beta-hexosaminidase from RBL-2H3 mast cells.

rottlerin


Input: Rottlerin was found to inhibit IgE-induced PLC gamma 1 and Akt phosphorylation, production of IP3 and rise in cytosolic Ca (2 +) level in mast cells.

Rottlerin

Ca (2 +)


Input: We report here for the first time that rottlerin possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing rottlerin for the treatment of allergic asthma and other mast cell-mediated allergic disorders.

rottlerin

rottlerin


Input: Clock Gene Expression in the Liver of Streptozotocin-induced and Spontaneous Type 1 Diabetic Rats.

Streptozotocin


Input: Several investigations have shown a relation between diabetes and alterations of the liver circadian clock.


Input: We investigated the diurnal expression of clock genes and clock-controlled genes (CCGs) in 3-hour intervals for a 24-h period in the livers of male streptozotocin (STZ)-treated rats, male spontaneous type 1 diabetic LEW. 1AR1-iddm (Iddm) rats, and Iddm rats treated for 10 days with insulin.

streptozotocin

STZ


Input: Hepatic mRNA was extracted, and the relative expression of clock genes (Per1, Per2, Bmal1, Clock, Cry1), as well as CCGs (Dbp, E4bp4, RevErb alpha, Ror alpha, Ppar gamma), was analyzed by reverse transcription followed by real-time polymerase chain reaction.


Input: Diabetic STZ and Iddm rats, as well as insulin-substituted Iddm rats, exhibited a significant diurnal expression pattern of clock genes as determined by Cosinor analysis; however, the MESOR (midline estimating statistic of rhythm) of Bmal1, Per2, and Clock transcript expression was altered in Iddm and insulin-substituted Iddm rats.

STZ


Input: The hepatic expression of the CCGs Dbp and RevErb alpha revealed a diurnal rhythm in all investigated groups.


Input: Insulin administration to Iddm rats normalized the enhanced MESOR in the expression of Dbp, RevErb alpha, and E4bp4 to the levels of normoglycemic controls.


Input: Cosinor analysis indicated no diurnal rhythm of Ppar gamma expression in the livers of diabetic STZ or Iddm rats or in those of insulin-substituted Iddm rats.

STZ


Input: Also, insulin substitution could not reverse the decreased MESOR of Ppar gamma expression in Iddm rats.


Input: In consequence of the diabetic disease, changes in the expression of clock genes and CCGs suggest alterations in the hepatic peripheral clock mechanism.


Input: Studies on the Himbert Intramolecular Arene/Allene Diels-Alder Cycloaddition.

Arene

Allene


Input: Mechanistic Studies and Expansion of Scope to All-Carbon Tethers.

Carbon


Input: The unusual intramolecular arene/allene cycloaddition described 30 years ago by Himbert permits rapid access to strained polycyclic compounds that offer great potential for the synthesis of complex scaffolds.

arene

allene


Input: To more fully understand the mechanism of this cycloaddition reaction, and to guide efforts to extend its scope to new substrates, quantum mechanical computational methods were employed in concert with laboratory experiments.


Input: These studies indicated that the cycloadditions likely proceed via concerted processes; a stepwise biradical mechanism was shown to be higher in energy in the cases studied.


Input: The original Himbert cycloaddition chemistry is also extended from heterocyclic to carbocyclic systems, with computational guidance used to predict thermodynamically favorable cases.


Input: Complex polycyclic scaffolds result from the combination of the cycloaddition and subsequent ring-rearrangement metathesis reactions.


Input: Reversible Sliding in Networks of Nanowires.


Input: This work demonstrates that metal nanowires in a percolating network can reversibly slide across one another.


Input: Reversible sliding allows networks of metal nanowires to maintain electrical contact while being stretched to strains greater than the fracture strain for individual nanowires.


Input: This phenomenon was demonstrated by using networks of nanowires as compliant electrodes for a dielectric elastomer actuator.


Input: Reversible nanowire sliding enabled actuation to a maximum area strain of 200%, and repetitive cycling of the actuator to an area strain of 25% over 150 times.


Input: During actuation, the transmittance of the network increased 4. 5 times, from 13% to 58%.


Input: Compared to carbon-based compliant electrodes, networks of metal nanowires can actuate across a broader range of optical transmittance.

carbon


Input: The widely tunable transmittance of nanowire-based actuators allows for their use as a light valve.


Input: Piezotronic Effect in Solution-Grown p-Type ZnO Nanowires and Films.

ZnO


Input: Investigating the piezotronic effect in p-type piezoelectric semiconductor is critical for developing a complete piezotronic theory and designing/fabricating novel piezotronic applications with more complex functionality.


Input: Using a low temperature solution method, we were able to produce ultralong (up to 60 mu m in length) Sb doped p-type ZnO nanowires on both rigid and flexible substrates.

Sb

ZnO


Input: For the p-type nanowire field effect transistor, the on/off ratio, threshold voltage, mobility, and carrier concentration of 0. 2% Sb-doped sample are found to be 10 (5), 2. 1 V, 0. 82 cm (2). V (-1). s (-1), and 2. 6 x 10 (17) cm (-3), respectively, and the corresponding values for 1% Sb doped samples are 10 (4), 2. 0 V, 1. 24 cm (2). V (-1). s (-1), and 3. 8 x 10 (17) cm (-3).

Sb

Sb


Input: We further investigated the universality of piezotronic effect in the as-synthesized Sb-doped p-type ZnO NWs and reported for the first time strain-gated piezotronic transistors as well as piezopotential-driven mechanical energy harvesting based on solution-grown p-type ZnO NWs.

Sb

ZnO

ZnO


Input: The results presented here broaden the scope of piezotronics and extend the framework for its potential applications in electronics, optoelectronics, smart MEMS/NEMS, and human-machine interfacing.


Input: Topographically-patterned porous membranes in a microfluidic device as an in vitro model of renal reabsorptive barriers.


Input: Models of reabsorptive barriers require both a means to provide realistic physiologic cues to and quantify transport across a layer of cells forming the barrier.


Input: Here we have topographically-patterned porous membranes with several user-defined pattern types.


Input: To demonstrate the utility of the patterned membranes, we selected one type of pattern and applied it to a membrane to serve as a cell culture support in a microfluidic model of a renal reabsorptive barrier.


Input: The topographic cues in the model resemble physiological cues found in vivo while the porous structure allows quantification of transport across the cell layer.


Input: Sub-micron surface topography generated via hot-embossing onto a track-etched polycarbonate membrane, fully replicated topographical features and preserved porous architecture.

polycarbonate


Input: Pore size and shape were analyzed with SEM and image analysis to determine the effect of hot embossing on pore morphology.


Input: The membrane was assembled into a bilayer microfluidic device and a human kidney proximal tubule epithelial cell line (HK-2) and primary renal proximal tubule epithelial cells (RPTEC) were cultured to confluency on the membrane.


Input: Immunofluorescent staining of both cell types revealed protein expression indicative of the formation of a reabsorptive barrier responsive to mechanical stimulation: ZO-1 (tight junction), paxillin (focal adhesions) and acetylated alpha-tubulin (primary cilia).


Input: HK-2 and RPTEC aligned in the direction of ridge/groove topography of the membrane in the device, evidence that the device has mechanical control over cell response.


Input: This topographically-patterned porous membrane provides an in vitro platform on which to model reabsorptive barriers with meaningful applications for understanding biological transport phenomenon, underlying disease mechanisms, and drug toxicity.


Input: Rapeseed oil-rich diet alters hepatic mitochondrial membrane lipid composition and disrupts bioenergetics.


Input: Diet is directly related with physiological alterations occurring at a cell and subcellular level.


Input: However, the role of diet manipulation on mitochondrial physiology is still largely unexplored.


Input: Aiming at correlating diet with alterations of mitochondrial membrane composition and bioenergetics, Wistar-Han male rats were fed for 11, 22 and 33 days with a rapeseed oil-based diet and mitochondrial bioenergetics, and membrane composition were compared at each time point with a standard diet group.


Input: Considerable differences were noticed in mitochondrial membrane lipid composition, namely in terms of fatty acyl chains and relative proportions of phospholipid classes, the modified diet inducing a decrease in the saturated to unsaturated molar ratio and an increase in the phosphatidylcholine to phosphatidylethanolamine molar ratio.

fatty acyl

phosphatidylcholine

phosphatidylethanolamine


Input: Mass spectrometry lipid analysis showed significant differences in the major species of cardiolipin, with an apparent increased incorporation of oleic acid as a result of exposure to the modified diet.

cardiolipin

oleic acid


Input: Rats fed the modified diet during 22 days showed decreased hepatic mitochondrial state 3 respiration and were more susceptible to Ca (2 +)-induced transition pore opening.

Ca (2 +)


Input: Rapeseed oil-enriched diet also appeared to promote a decrease in hydroperoxide production by the respiratory chain, although a simultaneous decrease in vitamin E content was detected.

hydroperoxide

vitamin E


Input: In conclusion, our data indicate that the rapeseed oil diet causes negative alterations on hepatic mitochondrial bioenergetics, which may result from membrane remodeling.


Input: Such alterations may have an impact not only on energy supply to the cell, but also on drug-induced hepatic mitochondrial liabilities.


Input: Individual multi-locus heterozygosity is associated with lower morning plasma cortisol concentration.

cortisol


Input: OBJECTIVE.


Input: STRESS IS IMPLICATED AS A RISK FACTOR FOR NUMEROUS ILLNESSES IN HUMANS, PUTATIVELY IN PART MEDIATED BY BIOLOGICAL RESPONSES TO STRESS, SUCH AS ELEVATED CORTISOL.

CORTISOL


Input: THE THEORY OF GENETIC HOMEOSTASIS SUGGESTS THAT INDIVIDUAL HETEROZYGOSITY FACILITATES COMPENSATION FOR ENVIRONMENTAL STRESSES.


Input: WE HYPOTHESIZED THAT HETEROZYGOSITY AMELIORATES THE BIOLOGICAL RESPONSE TO A GIVEN LEVEL OF PERCEIVED STRESS, REFLECTED IN LOWER PLASMA CORTISOL CONCENTRATIONS. DESIGN.

CORTISOL


Input: WE EXAMINE THE ROLE OF HETEROZYGOSITY ON THE ASSOCIATION BETWEEN PERCEIVED PSYCHOLOGICAL STRESS AND MORNING CORTISOL CONCENTRATIONS IN 854 INDIVIDUALS FROM THE ISOLATED ISLAND OF VIS, CROATIA. METHODS.

CORTISOL


Input: CORTISOL WAS MEASURED IN MORNING PLASMA SAMPLES.

CORTISOL


Input: 1184 AUTOSOMAL MICROSATELLITE MARKERS WERE GENOTYPED AND INDIVIDUAL MULTI-LOCUS HETEROZYGOSITY WAS CALCULATED AS THE PROPORTION OF HETEROZYGOUS MARKERS.


Input: GENERAL HEALTH QUESTIONNAIRE (GHQ-30) WAS USED TO ASSESS THE DEGREE OF PSYCHOLOGICAL DISTRESS. RESULTS.


Input: MEAN MULTI-LOCUS HETEROZYGOSITY WAS 34. 850. 45% (RANGE: 31. 97-36. 22%).


Input: Psychological distress (GHQ Likert score > 31) was more prevalent in women (37% versus 18% in men, p < 0. 0001), in less educated people (beta =-0. 35 per year in school, p < 0. 001) and in lower socio-economic classes (beta =-3. 59, p < 0. 0001).


Input: Cortisol was positively associated with psychological distress (beta = 2. 20, p = 0. 01).

Cortisol


Input: In a regression model adjusting for age, BMI, education and GHQ-30 score, multi-locus heterozygosity was independently and inversely associated with morning plasma cortisol (p = 0. 005). Conclusion.

cortisol


Input: More heterozygous individuals, as measured by microsatellite markers, had lower morning plasma cortisol concentrations for a given level of perceived psychological stress.

cortisol


Input: This may be important, as higher cortisol concentrations may increase allostatic load and be associated with higher risk of stress-related illness.

cortisol


Input: Efficient Light Harvesting with Micropatterned 3D Pyramidal Photoanodes in Dye-Sensitized Solar Cells.


Input: 3D TiO2 photoanodes in dye-sensitized solar cells (DSCs) are fabricated by the soft lithographic technique for efficient light trapping.


Input: An extended strategy to the construction of randomized pyramid structure is developed by the conventional wet-etching of a silicon wafer for low-cost fabrication.

silicon


Input: Moreover, the futher enhancement of light absorption resulting in photocurrent increase is achieved by combining the 3D photoanode with a conventional scattering layer.


Input: Buckling-Induced Reversible Symmetry Breaking and Amplification of Chirality Using Supported Cellular Structures.


Input: Buckling-induced reversible symmetry breaking and amplification of chirality using macro-and microscale supported cellular structures is described.


Input: Guided by extensive theoretical analysis, cellular structures are rationally designed, in which buckling induces a reversible switching between achiral and chiral configurations.


Input: Additionally, it is demonstrated that the proposed mechanism can be generalized over a wide range of length scales, geometries, materials, and stimuli.


Input: Upgraded Silicon Nanowires by Metal-Assisted Etching of Metallurgical Silicon: A New Route to Nanostructured Solar-Grade Silicon.

Silicon

Silicon

Silicon


Input: Through metal assisted chemical etching (MaCE), superior purification of dirty Si was observed, from 99. 74 to 99. 9884% for metallurgical Si and from 99. 999772 to 99. 999899% for upgraded metallurgical Si.

Si

Si

Si


Input: Meanwhile, large area of silicon nanowires (SiNW) was fabricated.

silicon


Input: The purification effect induced ~ 35% increase in photocurrent for SiNW based photoelectrochemical cell.


Input: High-Performance Vertical Organic Transistors.


Input: Vertical organic thin-film transistors (VOTFTs) are promising devices to overcome the transconductance and cut-off frequency restrictions of horizontal organic thin-film transistors.


Input: The basic physical mechanisms of VOTFT operation, however, are not well understood and VOTFTs often require complex patterning techniques using self-assembly processes which impedes a future large-area production.


Input: In this contribution, high-performance vertical organic transistors comprising pentacene for p-type operation and C60 for n-type operation are presented.

pentacene


Input: The static current-voltage behavior as well as the fundamental scaling laws of such transistors are studied, disclosing a remarkable transistor operation with a behavior limited by injection of charge carriers.


Input: The transistors are manufactured by photolithography, in contrast to other VOTFT concepts using self-assembled source electrodes.


Input: Fluorinated photoresist and solvent compounds allow for photolithographical patterning directly and strongly onto the organic materials, simplifying the fabrication protocol and making VOTFTs a prospective candidate for future high-performance applications of organic transistors.


Input: Protective Role of (RS)-glucoraphanin Bioactivated with Myrosinase in an Experimental Model of Multiple Sclerosis.

(RS)-glucoraphanin


Input: AIM: The discovery of new natural compounds with pharmacological properties is a field of interest widely growing.


Input: Recent literature shows that Brassica vegetables (Cruciferae) possess therapeutic effects particularly ascribed due to their content in glucosinolates, which upon myrosinase hydrolysis release the corresponding isothiocyanates.

glucosinolates

isothiocyanates


Input: This study examines the potential neuroprotective and immunomodulatory effects of (RS)-glucoraphanin from Tuscan black kale (Brassica oleracea L. var. acephala sabellica) bioactivated with myrosinase (bioactive RS-GRA) (10 mg/kg/day intraperitoneally), in an experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis.

(RS)-glucoraphanin

RS-GRA


Input: METHODS: EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG35-55) in mice.


Input: After immunization, mice were observed daily for signs of EAE and weight loss.


Input: Clinical score was evaluated using a standardized scoring system.


Input: RESULTS: By Western blot analysis of spinal cord tissues, we have demonstrated that treatment with bioactive RS-GRA significantly decreased nuclear factor (NF)-kB translocation, pro-inflammatory cytokine production such as interleukin-1 beta (IL-1 beta), and apoptosis (Bax and caspase 3 expression).

RS-GRA


Input: CONCLUSION: Our results clearly demonstrate that bioactive RS-GRA treatment may represent a useful therapeutic perspective in the treatment of this disease.

RS-GRA


Input: Anti-HIV and NO production inhibition activities of epi-aleuritolic acid derivatives.

NO

epi-aleuritolic acid


Input: Fifteen epi-aleuritolic acid derivatives were synthesized and evaluated for anti-HIV activity in 293 T cells and NO production inhibition activity.

epi-aleuritolic acid

NO


Input: Of the derivatives, 1, 2, 3, 4, 11, and 13 showed relatively potent anti-HIV activity with EC50 values ranging from 5. 80 to 13. 30 mu M.


Input: The most potent compound, 3 alpha-2', 2'-dimethylsuccinic acyl epi-aleuritolic acid (11), displayed significant anti-HIV activity with an EC50 value of 5. 80 mu M.

3 alpha-2', 2'-dimethylsuccinic acyl epi-aleuritolic acid


Input: Compounds 1, 3, 4, and 11 showed NO inhibition activity, with IC50 values ranging from 3. 40 to 7. 10 mu M and compound 1 inhibited NO production with an IC50 value of 3. 40 mu M.

NO

NO


Input: Phytochemical investigation on Atriplex halimus L. from Sardinia.


Input: In this study, we reported the phytochemical composition of the aerial parts of Atriplex halimus L. collected from Sardinia.


Input: This species is a halophytic shrub, typical of the Mediterranean Basin.


Input: Four new glycosylated flavonoids were isolated and their structures were elucidated on the basis of 1D, 2D NMR and MS spectra as 3', 5'-dimethoxymyricetin-3-O-beta-d-xylopyranosyl-7-O-fucopyranosyl-(1 --> 3)-beta-d-glucopyranoside (1), 3'-methoxyquercetin-7-O-beta-d-fucopyranosyl-(1 --> 3)-beta-d-glucopyranosyl-3-O-beta-xylopyranosyl-(1 --> 4)-beta-xylopyranoside (2), 3'-methoxyquercetin-7-O-alpha-l-rhamnopyranosyl-3-O-alpha-arabinofuranosyl-(1 --> 6)-beta-d-glucopyranoside (3) and 3', 5'-dimethoxymyricetin-7-O-fucopyranosyl-(1 --> 3)-beta-d-glucopyranoside (4).

glycosylated flavonoids

3', 5'-dimethoxymyricetin-3-O-beta-d-xylopyranosyl-7-O-fucopyranosyl-(1 --> 3)-beta-d-glucopyranoside

3'-methoxyquercetin-7-O-beta-d-fucopyranosyl-(1 --> 3)-beta-d-glucopyranosyl-3-O-beta-xylopyranosyl-(1 --> 4)-beta-xylopyranoside

3'-methoxyquercetin-7-O-alpha-l-rhamnopyranosyl-3-O-alpha-arabinofuranosyl-(1 --> 6)-beta-d-glucopyranoside

3', 5'-dimethoxymyricetin-7-O-fucopyranosyl-(1 --> 3)-beta-d-glucopyranoside


Input: LC-MS (n) analysis on the extract revealed the presence of other myricetin, quercetin, isorhamnetin glycosides, simple phenolic acids and esters.

myricetin

quercetin

isorhamnetin glycosides

phenolic acids

esters


Input: Indanomycin-related antibiotics from marine Streptomyces antibioticus PTZ0016.

Indanomycin


Input: Four indanomycin-related antibiotics 2-5 were isolated from the cultured broth of marine Streptomyces antibioticus strain PTZ0016.

indanomycin


Input: Their structures were characterised as 16-deethylindanomycin (2), iso-16-deethylindanomycin (3), 16-deethylindanomycin methyl ester (4) and iso-16-deethylindanomycin methyl ester (5) on the basis of NMR, HR-ESI-MS and CD evidences.

16-deethylindanomycin methyl ester

iso-16-deethylindanomycin methyl ester


Input: Compounds 3-5 are new additions to the class of indanomycin antibiotics.

indanomycin


Input: All isolated compounds showed in vitro activity against Staphylococcus aureus with minimal inhibitory concentration at 4. 0-8. 0 mu g/ml.


Input: Amelioration of palmitate-induced insulin resistance in C2C12 muscle cells by rooibos (Aspalathus linearis).

palmitate


Input: Increased levels of free fatty acids (FFAs), specifically saturated free fatty acids such as palmitate are associated with insulin resistance of muscle, fat and liver.

free fatty acids

FFAs

saturated free fatty acids

palmitate


Input: Skeletal muscle, responsible for up to 80% of the glucose disposal from the peripheral circulation, is particularly vulnerable to increased levels of saturated FFAs.

glucose

FFAs


Input: Rooibos (Aspalathus linearis) and its unique dihydrochalcone C-glucoside, aspalathin, shown to reduce hyperglycemia in diabetic rats, could play a role in preventing or ameliorating the development of insulin resistance.

dihydrochalcone C-glucoside

aspalathin


Input: This study aims to establish whether rooibos can ameliorate experimentally-induced insulin-resistance in C2C12 skeletal muscle cells.


Input: Palmitate-induced insulin resistant C2C12 cells were treated with an aspalathin-enriched green (unfermented) rooibos extract (GRE), previously shown for its blood glucose lowering effect in vitro and in vivo or an aqueous extract of fermented rooibos (FRE).

Palmitate

aspalathin

glucose


Input: Glucose uptake and mitochondrial activity were measured using 2-deoxy-[(3) H]-d-glucose, MTT and ATP assays, respectively.

Glucose

2-deoxy-[(3) H]-d-glucose

MTT

ATP


Input: Expression of proteins relevant to glucose metabolism was analysed by Western blot.

glucose


Input: GRE contained higher levels of all compounds, except the enolic phenylpyruvic acid-2-O-glucoside and luteolin-7-O-glucoside.

phenylpyruvic acid-2-O-glucoside


Input: Both rooibos extracts increased glucose uptake, mitochondrial activity and ATP production.

glucose

ATP


Input: Compared to FRE, GRE was more effective at increasing glucose uptake and ATP production.

glucose

ATP


Input: At a mechanistic level both extracts down-regulated PKC theta activation, which is associated with palmitate-induced insulin resistance.

palmitate


Input: Furthermore, the extracts increased activation of key regulatory proteins (AKT and AMPK) involved in insulin-dependent and non-insulin regulated signalling pathways.


Input: Protein levels of the glucose transporter (GLUT4) involved in glucose transport via these two pathways were also increased.

glucose

glucose


Input: This in vitro study therefore confirms that rooibos can ameliorate palmitate-induced insulin resistance in C2C12 skeletal muscle cells.

palmitate


Input: Inhibition of PKC theta activation and increased activation of AMPK and AKT offer a plausible mechanistic explanation for this ameliorative effect.


Input: Mikania laevigata: Chemical characterization and selective cytotoxic activity of extracts on tumor cell lines.


Input: Cancer is the second major cause of mortality worldwide, losing only to cardiovascular disease.


Input: Nowadays, around 50% of antineoplastic drugs were discovered and isolated by indications of plants in folk medicine.


Input: In Brazilian flora there are many species of plants which have great therapeutic importance, highlighting the Mikania laevigata (Asteraceae) that has been used for their valuable properties, especially in the respiratory tract.


Input: In the present study, the compounds of M. laevigata extracts were characterized by High Resolution Mass Spectrometry (HRMS) and Gas Chromatography with Mass analysis (GC/MS-EI).


Input: Therefore, the presence of some compounds with promising biological properties as antitumor activity was detected.


Input: Coumarin (1, 2-benzopyrone) was previously reported as responsible for some biological activities of this plant species.

Coumarin

1, 2-benzopyrone


Input: Here, the extracts were evaluated by their cytotoxic activity against tumor (Hep-2, HeLa) and non tumor (MRC-5) cell lines, presenting significant inhibitory activity of cell growth in all extracts analyzed, chloroform, ethyl acetate, hexane, ethanol, which is related to its chemical composition.

chloroform

ethyl acetate

hexane

ethanol


Input: From the four different extracts here tested, two of them, hexane and ethanol, presented a clear selectivity against both tumor cells lines investigated.

hexane

ethanol


Input: This can be explained by variances and increase of phenolic compounds in the ethanol fraction and an association of molecules with coumarin found in the hexane fraction.

phenolic

ethanol

coumarin

hexane


Input: Rokumi-jio-gan-containing prescriptions regulate oxidative stress through improving dyslipidemia in a subtotal nephrectomized rat model.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Rokumi-jio-gan-containing prescriptions, traditional medicine, are widely used to treat renal dysfunction in Japan.


Input: AIM OF THE STUDY: The present study was conducted to examine whether two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) have an ameliorative effect on dyslipidemia in nephrectomized rats.


Input: MATERIALS AND METHODS: Each prescription was orally administered to nephrectomized rats at 150mg/kg body weight per day for 10 weeks, and its effect was compared with vehicle-treated nephrectomized rats.


Input: RESULTS: Rats given Hachimi-jio-gan and Bakumi-jio-gan showed an improvement of renal functional parameters such as serum urea nitrogen, creatinine, creatinine clearance, and urinary protein.

urea nitrogen

creatinine

creatinine


Input: The increased triglyceride, total cholesterol, non-esterified fatty acid, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol/low-density lipoprotein cholesterol levels in serum, and triglyceride and total cholesterol contents in the kidney of nephrectomized rats were significantly decreased by Hachimi-jio-gan and Bakumi-jio-gan administration.

triglyceride

cholesterol

fatty acid

cholesterol

cholesterol

cholesterol

triglyceride

cholesterol


Input: Furthermore, Hachimi-jio-gan acts as a regulator of peroxisome proliferator-activated receptor alpha, sterol regulatory element binding protein (SREBP)-1, and SREBP-2.

sterol


Input: On the contrary, the increased reactive oxygen species and thiobarbituric acid-reactive substance were decreased, while superoxide dismutase and the reduced glutathione/oxidized glutathione ratio were augmented by Hachimi-jio-gan rather than Bakumi-jio-gan.

oxygen

thiobarbituric acid

superoxide

reduced glutathione

oxidized glutathione


Input: The improvement of nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, NF-E2-related factor 2, and heme oxygenase-1 was marked in the group administered Bakumi-jio-gan.

nitric oxide

heme


Input: However, oil red O staining showed that the increased lipid deposition in the kidney of nephrectomized rats improved on Hachimi-jio-gan and Bakumi-jio-gan administration.

oil red O


Input: CONCLUSION: This study provides scientific evidence that two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) improves oxidative stress via dyslipidemia in the remnant kidney of nephrectomized rats.


Input: Cyperi Rhizoma inhibits the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced reduction in nigrostriatal dopaminergenic neurons in estrogen-deprived mice.

1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine

estrogen


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Cyperi Rhizoma has commonly been used for the treatment of gynecological and neuropsychiatric disorders in traditional medicine.


Input: The aim of this study was to evaluate the estrogenic properties and neuroprotective effects of Cyperi Rhizoma under estrogen-deprived condition in female mice.

estrogenic


Input: MATERIALS AND METHODS: To determine the estrogen-like effect of Cyperi Rhizoma extract (CRE), we measured luciferase expression after transfection of a promoter construct containing an estrogen response element (ERE) and treatment of CRE.

estrogen

estrogen


Input: To evaluate the neuroprotective effect of CRE, we measured striatal dopamine, movement ability, tyrosine hydroxylase (TH) immunoreactivity, and apoptosis-related protein expression levels after treatment of CRE either with or without 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in ovariectomized female mice.

dopamine

tyrosine

1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine

MPTP


Input: RESULTS: CRE significantly induced the luciferase expression driven by an ERE in PC12 cells, a dopaminergic cell line, in a dose-dependent manner.


Input: In mice, MPTP significantly decreased the levels of dopamine in the striatum and behavior performance; in contrast, both CRE and 17 beta-estradiol benzoate (EB) recovered these parameters to normal levels.

MPTP

dopamine

17 beta-estradiol benzoate


Input: CRE and EB treatment also recovered TH immunopositive fibers and cells, respectively, from MPTP toxicity.

MPTP


Input: Additionally, MPTP significantly down-regulated Bcl-2 expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in Bax expression, cytochrome C translocation to the cytosol, andcleaved-caspase-3 expression, whereas these were inhibited by CRE or EB treatment.

MPTP


Input: CONCLUSIONS: These findings provide the first evidence that CRE has estrogen-like and neuroprotective effects on dopaminergic neurons in estrogen-deprived mice treated with MPTP-toxin.

estrogen

estrogen

MPTP


Input: Antecedents and consequences of drug abuse in rats selectively bred for high and low response to novelty.


Input: Human genetic and epidemiological studies provide evidence that only a subset of individuals who experiment with potentially addictive drugs become addicts.


Input: What renders some individuals susceptible to addiction remains to be determined, but most would agree that there is no single trait underlying the disorder.


Input: However, there is evidence in humans that addiction liability has a genetic component, and that certain personality characteristics related to temperament (e. g. the sensation-seeking trait) are associated with individual differences in addiction liability.


Input: Consequently, we have used a selective breeding strategy based on locomotor response to a novel environment to generate two lines of rats with distinct behavioral characteristics.


Input: We have found that the resulting phenotypes differ on a number of neurobehavioral dimensions relevant to addiction.


Input: Relative to bred low-responder (bLR) rats, bred high-responder (bHR) rats exhibit increased exploratory behavior, are more impulsive, more aggressive, seek stimuli associated with rewards, and show a greater tendency to relapse.


Input: We therefore utilize this unique animal model to parse the genetic, neural and environmental factors that contribute to addiction liability.


Input: Our work shows that the glucocorticoid receptor (GR), dopaminergic molecules, and members of the fibroblast growth factor family are among the neurotransmitters and neuromodulators that play a role in both the initial susceptibility to addiction as well as the altered neural responses that follow chronic drug exposure.


Input: Moreover, our findings suggest that the hippocampus plays a major role in mediating vulnerability to addiction.


Input: It is hoped that this work will emphasize the importance of personalized treatment strategies and identify novel therapeutic targets for humans suffering from addictive disorders.


Input: This article is part of a Special Issue entitled' NIDA 40th Anniversary Issue'.


Input: Fusidic acid and rifampicin co-loaded PLGA nanofibers for the prevention of orthopedic implant associated infections.

Fusidic acid

rifampicin

PLGA


Input: Implant-associated infections following invasive orthopedic surgery are a major clinical problem, and are one of the primary causes of joint failure following total joint arthroplasty.


Input: Current strategies using perioperative antibiotics have been met with little clinical success and have resulted in various systemic toxicities and the promotion of antibiotic resistant microorganisms.


Input: Here we report the development of a biodegradable localized delivery system using poly (D, L-lactic acid-co-glycolic acid) (PLGA) for the combinatorial release of fusidic acid (FA) (or its sodium salt; SF) and rifampicin (RIF) using electrospinning.

poly (D, L-lactic acid-co-glycolic acid)

PLGA

fusidic acid

sodium

rifampicin

RIF


Input: The drug-loaded formulations showed good antibiotic encapsulation (~ 75%-100%), and a biphasic drug release profile.


Input: All dual-loaded formulations showed direct antimicrobial activity in vitro against Staphylococcus epidermidis, and two strains of methicillin-resistant Staphylococcus aureus (MRSA).

methicillin


Input: Furthermore, lead formulations containing 10% (w/w) FA/SF and 5% (w/w) RIF were able to prevent the adherence of MRSA to a titanium implant in an in vivo rodent model of subcutaneous implant-associated infection.

RIF

titanium


Input: Immune circuits in asthma.


Input: Asthma is an inflammatory disorder of the conducting airways that has traditionally been classified according to severity.


Input: While this has been helpful in guiding treatment with drugs that are currently available such as beta 2-adrenoceptor agonists and corticosteroids, it takes little account of disease heterogeneity and causal pathways.


Input: This review draws attention to subphenotypes of asthma involving different mechanisms and moves the focus away from the adaptive immune response more towards innate immune mechanisms.


Input: This mandates a new view of the disease in which causal pathways linked to biomarkers are found and treatments targeted to these pathways as described in a more personalised approach to medicine.


Input: Synthesis, spectral and antimicrobial evaluation of some novel 1-methyl-3-alkyl-2, 6-diphenylpiperidin-4-one oxime carbonates.

1-methyl-3-alkyl-2, 6-diphenylpiperidin-4-one oxime carbonates


Input: Synthesis of some novel biologically active piperidin-4-one oxime carbonates from 1-methyl-3alkyl-2, 6-diphenylpiperidin-4-one oximes and substituted chloroformates was carried out in the presence of potassium carbonate as base and tetrabutylammonium bromide (TBAB) as catalyst.

piperidin-4-one oxime carbonates

1-methyl-3alkyl-2, 6-diphenylpiperidin-4-one oximes

chloroformates

potassium carbonate

tetrabutylammonium bromide

TBAB


Input: The newly synthesized compounds were characterized by IR, (1) H, (13) C NMR and LC-mass spectra.

(1) H

(13) C


Input: Based on the (1) H NMR analysis, all the compounds were found to adopt normal chair conformation with equatorial orientation of all the substituents.

(1) H


Input: For all the synthesized compounds (5a-5l) antimicrobial activity has been tested against bacterial and fungal strains using Streptomycin and Amphotericin B as standards.

Streptomycin

Amphotericin B


Input: Synthesis of proline analogues as potent and selective cathepsin S inhibitors.

proline


Input: Cathepsin S is a potential target of autoimmune disease.


Input: A series of proline derived compounds were synthesized and evaluated as cathepsin S inhibitors.

proline


Input: We discovered potent cathepsin S inhibitors through structure-activity relationship studies of proline analogues.

proline


Input: In particular, compound 19-(S) showed promising in vitro/vivo pharmacological activities and properties as a selective cathepsin S inhibitor.


Input: The preventive effect of uncarboxylated osteocalcin against free fatty acid-induced endothelial apoptosis through the activation of phosphatidylinositol 3-kinase/Akt signaling pathway: Uncarboxylated osteocalcin and endothelial apoptosis.

free fatty acid

phosphatidylinositol


Input: OBJECTIVE: Increasing evidence suggests that osteocalcin (OC), one of the osteoblast-specific proteins, has been associated with atherosclerosis, but results are conflicting.


Input: The aim of this study was to elucidate the independent effect of uncarboxylated osteocalcin (ucOC), an active form of osteocalcin which has been suggested to have an insulin sensitizing effect, on vascular endothelial cells.


Input: MATERIALS AND METHODS: We used human aortic endothelial cells and treated them with ucOC.


Input: Linoleic acid (LA) was used as a representative free fatty acid.

Linoleic acid

free fatty acid


Input: Apoptosis was evaluated using various methods including a terminal deoxyribonucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling analysis kit and Western blotting for cleaved caspase 3, cleaved poly (ADP-ribose) polymerase and Bcl-xL.

deoxyribonucleotide

deoxyuridine triphosphate

poly (ADP-ribose)


Input: The phosphorylations of Akt and endothelial nitric oxide synthase (eNOS) as well as the level of NO were measured to confirm the effect of ucOC on insulin signaling pathway.

nitric oxide


Input: RESULTS: Pretreatment of ucOC (30ng/ml) prevented LA-induced apoptosis in insulin-stimulated endothelial cells; effects were abolished by pretreatment with the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, wortmannin.

phosphatidylinositol

wortmannin


Input: Treatment of ucOC (ranged from 0. 3 to 30ng/ml) significantly increased the phosphorylation of Akt and eNOS and nitric oxide secretion from endothelial cells in a PI3-kinase dependent manner.

nitric oxide


Input: CONCLUSIONS: Our study is the first to demonstrate the independent effect of ucOC on vascular endothelial cells.


Input: Our results further suggest that ucOC could have beneficial effects on atherosclerosis.


Input: Gene expression profiling and pathway analysis of hepatotoxicity induced by triptolide in Wistar rats.

triptolide


Input: Triptolide (TP), a major component of TWHF, is widely used to treat rheumatoid arthritis, systemic lupus erythematosus, nephritis and leprosy.

Triptolide


Input: However, its clinical use is limited by hepatotoxicity.


Input: To further elucidate the underlying mechanism of its hepatotoxic effects, hepatic gene expression profiles were analyzed.


Input: TP (1000 and 300 mu g/kg) was orally administered to Wistar rats for 14days.


Input: Current study indicated that female rats were more sensitive to TP-induced hepatotoxicity than males.


Input: Genome-wide microarray analyses identified 3329 differentially expressed genes in liver of female rats.


Input: Analyses of these genes identified over-represented functions associated with insulin signaling pathway, glucose metabolism, cell cycle, oxidative stress and apoptosis, which were consistent with the results of significant increase of Caspase-3 activity and reduction of serum glucose, GSH/GSSG ratio, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities, liver glycogen.

glucose

glucose

GSH

GSSG

glucose

phosphoenolpyruvate


Input: In addition, it was observed for the first time that glucocorticoids and IGF1 might get involved in TP-induced hepatotoxicity.


Input: These data suggest that TP treatment could alter the hepatic redox status, reduce serum glucose and induce hepatocyte apoptosis, consistent with the differential expression of genes involved in insulin signaling pathway, glucose metabolism pathway and cell stress pathway, all of which might contribute to the overall TP-induced hepatotoxicity.

glucose

glucose


Input: TCDD induces the expression of insulin-like growth factor binding protein 4 in 5L rat hepatoma cells: a cautionary tale of the use of this cell line in studies on dioxin toxicity.

TCDD

dioxin


Input: Previous quantitative proteomic studies on the actions of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in 5L rat hepatoma cells, a cell model frequently used for investigating the mechanisms of TCDD toxicity, had indicated that dioxin exposure reduced the abundance of numerous proteins which are regulated at the level of protein synthesis initiation.

2, 3, 7, 8-tetrachlorodibenzo-p-dioxin

TCDD

TCDD

dioxin


Input: In the present study, we have analysed the mechanism mediating this inhibition.


Input: TCDD treatment of the cells largely prevented the activation of eukaryotic translation initiation factor 4E-binding protein 1, a regulator of translation initiation and substrate of the mammalian target of rapamycin (mTOR).

TCDD

rapamycin


Input: By " working upwards " from mTOR, we observed that TCDD inhibited endogenous and IGF-I-induced AKT and ERK activation by interfering with tyrosine phosphorylation of insulin receptor substrate 1.

TCDD

tyrosine


Input: This inhibition was mediated by a TCDD-induced secreted factor which was identified as insulin-like growth factor binding protein 4 (IGFBP-4).

TCDD


Input: The induction of IGFBP-4 protein was dependent on a functional aryl hydrocarbon receptor and was preceded by a rapid increase in the level of IGFBP-4 mRNA indicating that IGFBP-4 is a previously unknown transcriptional target of TCDD in 5L cells.

aryl hydrocarbon

TCDD


Input: IGFBP-4 was not induced by TCDD in the parental cell line of 5L cells, Fao, and in various closely related rat hepatoma cell lines as well as in other unrelated cell types.

TCDD


Input: Analysis of 5L cell chromosomes by multicolour spectral karyotyping (SKY) revealed that the cells carry several hitherto uncharacterised chromosomal translocations.


Input: The observations suggest that in 5L cells the Igfbp-4 gene may have got under the control of a promoter containing dioxin responsive element (s) leading to the induction of IGFBP-4 by TCDD.

dioxin

TCDD


Input: These findings emphasise a particular caution when interpreting and extrapolating results on the action mechanisms of TCDD obtained in studies using 5L cells as a model system.

TCDD


Input: Pyrazole derivatives as inhibitors of arachidonic acid-induced platelet aggregation.

Pyrazole

arachidonic acid


Input: Antiplatelet drugs are promising therapeutics to intervene with platelet aggregation in arterial thrombosis, most prominently in myocardial infarction and ischemic stroke.


Input: Here, we describe the synthesis and structure-activity relationships of potent inhibitors of platelet aggregation based on the 1, 5-diarylpyrazol-3-carboxamide scaffold.

1, 5-diarylpyrazol-3-carboxamide


Input: Analogs from this series demonstrated potent anti-aggregatory activities against arachidonic acid-induced platelet aggregation, as measured by turbidimetric method of Born.

arachidonic acid


Input: 1, 5-Diarylpyrazole-3-carboxamides obtained with small-basic amines (7, 8, 50, 51, 61, 62) displayed the strongest activity with IC50 values in low nanomolar range (5. 7-83 nM).

1, 5-Diarylpyrazole-3-carboxamides

amines


Input: On the basis of their high potency in cellular environment, these straightforward pyrazole derivatives may possess potential in the design of more potent compounds for intervention with cardiovascular diseases.

pyrazole


Input: A selective antagonist reveals a potential role of G protein-coupled receptor 55 in platelet and endothelial cell function.


Input: The G protein coupled receptor 55 (GPR55) is a lysophosphatidylinositol (LPI) receptor that is also responsive to certain cannabinoids.

lysophosphatidylinositol

LPI


Input: Although GPR55 has been implicated in several (patho) physiological functions, its role is still enigmatic mainly owing to the lack of selective GPR55 antagonists.


Input: Here we show that the compound CID16020046 ((4-[4-(3-hydroxyphenyl)-3-(4-methylphenyl)-6-oxo-1H, 4H, 5H, 6H-pyrrolo [3, 4-c] pyrazol-5-yl] benzoic acid) is a selective GPR55 antagonist.

(4-[4-(3-hydroxyphenyl)-3-(4-methylphenyl)-6-oxo-1H, 4H, 5H, 6H-pyrrolo [3, 4-c] pyrazol-5-yl] benzoic acid


Input: In yeast cells expressing human GPR55, CID16020046 antagonized agonist-induced receptor activation.


Input: In HEK293 cells stably expressing human GPR55 (HEK-GPR55), the compound behaved as an antagonist on LPI-mediated Ca2 + release and extracellular signal-regulated kinases (ERK1/2) activation, but not in HEK293 cells expressing cannabinoid receptor 1 or 2 (CB1 or CB2).

LPI

Ca2 +


Input: CID16020046 concentration-dependently inhibited LPI-induced activation of nuclear factor of activated T-cells (NFAT), nuclear factor kappa of activated B cells (NF-kappa B) and serum response element (SRE), translocation of NFAT and NF-kappa B, and GPR55 internalization.

LPI


Input: It reduced LPI-induced wound healing in primary human lung microvascular endothelial cells (HMVEC-L) and reversed LPI-inhibited platelet aggregation, suggesting a novel role for GPR55 in platelet and endothelial cell function.

LPI

LPI


Input: CID16020046 is therefore a valuable tool to study GPR55-mediated mechanisms in primary cells and tissues.


Input: Method for quantitative measurements of the elastic modulus of biological cells in AFM indentation experiments.


Input: Here we overview and further develop a quantitative method to measure mechanics of biological cells in indentation experiments, which is based on the use of atomic force microscopy (AFM).


Input: We demonstrate how the elastic modulus of the cell body should be measured when the cellular brush is taken into account.


Input: The brush is an essential inelastic part of the cell, which surrounds all eukaryotic (the brush is mostly microvilli and glycocalyx) and gram-negative prokaryotic cells (the brush is polysaccharides).


Input: The other main feature of the described method is the use of a relatively dull AFM probe to stay in the linear stress-strain regime.


Input: In particular, we show that the elastic modulus (aka the Young' s modulus) of cells is independent of the indentation depth up to 10-20% deformation for the eukaryotic cells studied here.


Input: Besides the elastic modulus, the method presented allows obtaining the parameters of cellular brush, such as the effective length and grafting density of the brush.


Input: Although the method is demonstrated on eukaryotic cells, it is directly applicable for all types of cells, and even non-biological soft materials surrounded by either a brush or any field of long-range forces.


Input: Prostaglandin E2 acts via bone marrow macrophages to block PTH-stimulated osteoblast differentiation in vitro.

Prostaglandin E2


Input: Intermittent PTH is the major anabolic therapy for osteoporosis while continuous PTH causes bone loss.


Input: PTH acts on the osteoblast (OB) lineage to regulate bone resorption and formation.


Input: PTH also induces cyclooxygenase-2 (COX-2), producing prostaglandin E2 (PGE2), that can act on both OBs and osteoclasts (OCs).

prostaglandin E2


Input: Because intermittent PTH is more anabolic in Cox-2 knockout (KO) than wild type (WT) mice, we hypothesized COX-2 might contribute to the effects of continuous PTH by suppressing PTH-stimulated differentiation of mesenchymal stem cells into OBs.


Input: We compared effects of continuous PTH on bone marrow stromal cells (BMSCs) and primary OBs (POBs) from Cox-2 KO mice, mice with deletion of PGE2 receptors (Ptger4 and Ptger2 KO mice), and WT controls.


Input: PTH increased OB differentiation in BMSCs only in the absence of COX-2 expression or activity.


Input: In the absence of COX-2, PTH stimulated differentiation if added during the first week of culture.


Input: In Cox-2 KO BMSCs, PTH-stimulated differentiation was prevented by adding PGE2 to cultures.


Input: Co-culture of POBs with M-CSF-expanded bone marrow macrophages (BMMs) showed that the inhibition of PTH-stimulated OB differentiation required not only COX-2 or PGE2 but also BMMs.


Input: Sufficient PGE2 to mediate the inhibitory effect was made by either WT POBs or WT BMMs.


Input: The inhibitory effect mediated by COX-2/PGE2 was transferred by conditioned media from RANKL-treated BMMs and could be blocked by osteoprotegerin, which interferes with RANKL binding to its receptor on OC lineage cells.


Input: Deletion of Ptger4, but not Ptger2, in BMMs prevented the inhibition of PTH-stimulated OB differentiation.


Input: As expected, PGE2 also stimulated OB differentiation, but when given in combination with PTH, the stimulatory effects of both were abrogated.


Input: These data suggest that PGE2, acting via EP4R on BMMs committed to the OC lineage, stimulated secretion of a factor or factors that acted to suppress PTH-stimulated OB differentiation.


Input: This suppression of OB differentiation could contribute to the bone loss seen with continuous PTH in vivo.


Input: Zno nanoparticle based highly efficient CdS/CdSe quantum dot-sensitized solar cells.

Zno

CdS

CdSe


Input: 20 nm ZnO nanoparticles are used to fabricate the mesoporous photoanode of the CdS/CdSe quantum dot-sensitized solar cells by the simple doctor blade method.

ZnO

CdS

CdSe


Input: A maximum power conversion efficiency of 4. 46% has been achieved, which indicated exciting prospects for ZnO nanoparticle based quantum dot-sensitized solar cells.

ZnO


Input: A randomized, double-blind, placebo-controlled crossover study of alpha 4 beta 2 * nicotinic acetylcholine receptor agonist AZD1446 (TC-6683) in adults with attention-deficit/hyperactivity disorder.

acetylcholine


Input: RATIONALE: Stimulation of nicotinic cholinergic systems has been shown to alleviate ADHD symptoms and to improve cognitive performance.


Input: AZD1446 is a selective alpha 4 beta 2 * nicotinic acetylcholine receptor agonist with potential effect on the symptoms of ADHD.

acetylcholine


Input: OBJECTIVES: The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of AZD1446 in adults with ADHD treated for 2 weeks.


Input: METHOD: This was a randomized, double-blind, placebo-controlled crossover trial.


Input: Participants were 79 adults with ADHD, grouped according to their use of nicotine-containing products.

nicotine


Input: Nicotine non-users received placebo and two of three AZD1446 treatment regimens (80 mg tid, 80 mg qd, 10 mg tid).

Nicotine


Input: Nicotine users received placebo, AZD1446 80 mg tid and 80 mg qd.

Nicotine


Input: Efficacy measures included the Conners' Adult ADHD Rating Scale and cognitive measures of immediate and delayed verbal episodic memory, learning, attention, working memory, executive functioning, and spatial problem solving (CogState computerized test battery).


Input: RESULTS: There was no significant effect of AZD1446 on any of the clinical scores irrespective of dose, schedule, or concomitant use of nicotine products.

nicotine


Input: A statistically significant improvement was seen on the Groton Maze Learning Task, a measure of executive functioning, in nicotine non-users after treatment with AZD1446 80 mg qd.

nicotine


Input: CONCLUSIONS: AZD1446 was well tolerated, but did not significantly improve ADHD symptoms after 2 weeks of treatment compared to placebo.


Input: While the present study does not support the therapeutic utility of AZD1446 in ADHD, its potential pro-cognitive effects remain to be explored in other neuropsychiatric disorders.


Input: Modelling the Cost Effectiveness of Disease-Modifying Treatments for Multiple Sclerosis: Issues to Consider.


Input: Several cost-effectiveness models of disease-modifying treatments (DMTs) for multiple sclerosis (MS) have been developed for different populations and different countries.


Input: Vast differences in the approaches and discrepancies in the results give rise to heated discussions and limit the use of these models.


Input: Our main objective is to discuss the methodological challenges in modelling the cost effectiveness of treatments for MS.


Input: We conducted a review of published models to describe the approaches taken to date, to identify the key parameters that influence the cost effectiveness of DMTs, and to point out major areas of weakness and uncertainty.


Input: Thirty-six published models and analyses were identified.


Input: The greatest source of uncertainty is the absence of head-to-head randomized clinical trials.


Input: Modellers have used various techniques to compensate, including utilizing extension trials.


Input: The use of large observational cohorts in recent studies aids in identifying population-based,' real-world' treatment effects.


Input: Major drivers of results include the time horizon modelled and DMT acquisition costs.


Input: Model endpoints must target either policy makers (using cost-utility analysis) or clinicians (conducting cost-effectiveness analyses).


Input: Lastly, the cost effectiveness of DMTs outside North America and Europe is currently unknown, with the lack of country-specific data as the major limiting factor.


Input: We suggest that limited data should not preclude analyses, as models may be built and updated in the future as data become available.


Input: Disclosure of modelling methods and assumptions could improve the transferability and applicability of models designed to reflect different healthcare systems.


Input: Three Ubiquitination Sites of Organic Anion Transporter-1 Synergistically Mediate Protein Kinase C-dependent Endocytosis of the Transporter.


Input: Organic anion transporter-1 (OAT1) mediates the body disposition of a diverse array of clinically important drugs, including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories.


Input: Therefore, understanding the regulation of OAT1 has profound clinical significance.


Input: We previously established that OAT1 constitutively internalizes from and recycles back to cell surface, and that activation of protein kinase C (PKC) inhibits OAT1 activity by promoting ubiquitination of the transporter, which then leads to an accelerated internalization of the transporter from cell surface to intracellular compartments.


Input: In the current study, we demonstrated that PKC isoform PKC-alpha was responsible for OAT1 ubiquitination.


Input: To directly address the role of OAT1 ubiquitination, we then generated two OAT1 mutants, each having multiple lysines (K) simultaneously mutated to arginine (R).

lysines

arginine


Input: One mutant K163/297/303/315/321R lost sensitivities to PKC-induced inhibition of transport activity, to PKC-induced ubiquitination, and to PKC-induced acceleration of transporter internalization.


Input: Further dissecting each lysine within this mutant, we identified Lys297, Lys303 and Lys315 being the ubiquitin-conjugation sites.

lysine


Input: Interestingly, mutating any one of the three lysines prevented the ubiquitin-conjugation to the other two lysines, suggesting that Lys297, Lys303 and Lys315 may form an optimal structure to interact with ubiquitination machineries.

lysines

lysines


Input: This is the first demonstration that Lys297, Lys303 and Lys315 play synergistic role in PKC-regulated OAT1 ubiquitination, trafficking and transport activity.


Input: Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation.

Progesterone


Input: Steroid receptors were classically described for regulating transcription by binding to target gene promoters.

Steroid


Input: However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions.

steroid


Input: To determine the role of these sites, we examined the effect of progestins on the transcription of the bcl-x gene, where only intragenic progesterone receptor-binding sites (PRbs) were identified.

progesterone


Input: We found that in response to hormone treatment, the PR is recruited to these sites along with two histone acetyltransferases CREB-binding protein (CBP) and GCN5, leading to an increase in histone H3 and H4 acetylation and to the binding of the SWI/SNF complex.


Input: Concomitant, a more relaxed chromatin was detected along bcl-x gene mainly in the regions surrounding the intragenic PRbs.


Input: PR also mediated the recruitment of the positive elongation factor pTEFb, favoring RNA polymerase II (Pol II) elongation activity.


Input: Together these events promoted the re-distribution of the active Pol II toward the 3'-end of the gene and a decrease in the ratio between proximal and distal transcription.


Input: These results suggest a novel mechanism by which PR regulates gene expression by facilitating the proper passage of the polymerase along hormone-dependent genes.


Input: Seawater-driven magnesium based Janus micromotors for environmental remediation.

magnesium


Input: We describe the use of seawater as fuel to propel Janus micromotors.


Input: The new micromotors consist of biodegradable and environmentally friendly magnesium microparticles and a nickel-gold bilayer patch for magnetic guidance and surface modification.

magnesium

nickel


Input: Such seawater-driven micromotors, which utilize macrogalvanic corrosion and chloride pitting corrosion processes, eliminate the need for external fuels to offer efficient and prolonged propulsion towards diverse applications in aquatic environments.

chloride


Input: Electrically driven ultraviolet random lasing from an n-MgZnO/i-ZnO/SiO2/p-Si asymmetric double heterojunction.

MgZnO

ZnO

Si


Input: Electrically pumped lasing action has been realized in ZnO from an n-MgZnO/i-ZnO/SiO2/p-Si asymmetric double heterostructure, an ultralow threshold of 3. 9 mA was obtained.

ZnO

MgZnO

ZnO

Si


Input: The mechanism of the laser is associated with the in-plane random resonator cavities formed in the ZnO films and the elaborate hollow-shaped SiO2 cladding pattern, which prevent the lateral diffusion of injection current and ultimately lower the threshold current of the laser diode.

ZnO


Input: In addition, a waveguide mechanism due to different refractive indices of three epilayers enhances the guided optical field on the ZnO side, resulting in an improved light extraction efficiency.

ZnO


Input: Drug-Induced Macular Edema.


Input: Macular edema constitutes a serious pathologic entity of ophthalmology resulting in vision loss with a remarkable impact on the quality of life of patients.


Input: It is the final common pathway of various systemic diseases and underlying intraocular conditions, with diabetes mellitus being the most frequent cause.


Input: Other causes include venous occlusive disease, intraocular surgery, and inflammatory conditions of the posterior segment of the eye.


Input: Macular edema is a recognized side effect of various systemic and local medications and requires special consideration among ophthalmologists and other clinicians.


Input: Recently, antidiabetic thiazolidinediones have been implicated in the development of macular edema, and a review of the English literature revealed that other systemically administered drugs like fingolimod, recently approved for relapsing forms of multiple sclerosis, the anticancer agents tamoxifen and the taxanes, as well as niacin and interferons have been reported to cause macular edema.

thiazolidinediones

fingolimod

tamoxifen

taxanes

niacin


Input: Ophthalmologic pharmaceutical agents, like prostaglandin analogs, epinephrine, timolol, and ophthalmic preparation preservatives have also been reported to cause macular edema as an adverse event.

prostaglandin

epinephrine

timolol


Input: The purpose of this article is to provide a short, balanced overview of the available evidence in this regard.


Input: The available data and the possible pathophysiologic mechanisms leading to the development of macular edema are discussed.


Input: Possible therapeutic strategies for drug-induced macular edema are also proposed.


Input: A Highly Crystalline Manganese-Doped Iron Oxide Nanocontainer with Predesigned Void Volume and Shape for Theranostic Applications.

Manganese-Doped Iron Oxide


Input: Hollow Mn-doped iron oxide nanocontainers, formed by a novel one-pot synthetic process, fulfill the dual requirements of delivering an effective dose of an anticancer drug to tumor tissue and enabling image-contrast monitoring of the nanocontainer fate through T2-weighted magnetic resonance imaging, thereby determining the optimal balance between diagnostic and therapeutic moieties in an all-in-one theranostic nanoplatform.

Mn-doped iron oxide


Input: Oxygen-functionalized few-layer graphene sheets as active catalysts for oxidative dehydrogenation reactions.

Oxygen

graphene


Input: Invited for this month' s cover is the group from the Center for Nanophase Materials Sciences (CNMS) at the Oak Ridge National Laboratory.


Input: The illustration is of the catalytic activity of the reported oxygen-functionalized few-layer graphenes, whereas the micrograph background image is of the same graphenes recorded by the authors using a new helium-ion microscope at the CNMS.

oxygen

graphenes

graphenes

helium


Input: Read the full text of the article at 10. 1002/cssc. 201200756.


Input: NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS INDUCE A MITOPHAGY-ASSOCIATED ENDOTHELIAL DYSFUNCTION THAT IS REVERSED BY COENZYME Q10 CO-TREATMENT.

NUCLEOSIDE

COENZYME Q10


Input: Cardiovascular complications have been documented in HIV-1 infected populations, and antiretroviral therapy may play a role.


Input: Nucleoside reverse transcriptase inhibitors (NRTI) are antiretrovirals known to induce mitochondrial damage in endothelial cells, culminating in endothelial dysfunction, an initiating event in atherogenesis.

Nucleoside


Input: Though the mechanism for NRTI-induced endothelial toxicity is not yet clear, our prior work suggested that a mitochondrial oxidative stress may be involved.


Input: To further delineate the mechanism of toxicity, endothelial cells were treated with NRTI of varying subclasses, and the level of reactive oxygen species (ROS) and mitochondrial function were assessed.

oxygen


Input: To test whether rescue of mitochondrial electron transport attenuated NRTI-induced endothelial dysfunction, in some cases, cells were co-treated with the electron transport cofactor coenzyme Q10 (Q10).

coenzyme Q10


Input: At 4-6h, NRTI increased levels of ROS but decreased the activities of electron transport chain complexes I-IV, levels of ATP and the NAD/NADH ratio.

ATP

NAD

NADH


Input: Moreover, nitric oxide levels were decreased, while endothelin-1 release was increased.

nitric oxide


Input: Q10 abolished NRTI-induced mitochondria injury and effects on endothelial agonist production.


Input: Interestingly, in cells treated with NRTI only, markers for mitochondrial toxicity returned to baseline levels by 18-24h, suggesting a compensatory mechanism for clearing damaged mitochondria.


Input: Using confocal microscopy, with confirmation utilizing the autophagy and mitophagy markers LC-3 and NIX, respectively, we observed autophagy of mitochondria at 8-10 h after treatment.


Input: Q10 prevented NRTI-mediated increase in LC-3.


Input: These findings suggest that NRTI-induced mitophagy may be involved in NRTI-induced endothelial dysfunction and that this damage likely results from oxidant injury.


Input: Further, Q10 supplementation could potentially prevent NRTI-induced endothelial dysfunction.


Input: X-ray structure analysis and characterization of AFUEI, an elastase inhibitor from Aspergillus fumigatus.


Input: Elastase from Aspergillus sp.


Input: is an important factor for aspergillosis.


Input: AFUEI is an inhibitor of the elastase derived from Aspergillus fumigatus.


Input: AFUEI is a member of the I78 inhibitor family, and has a high inhibitory activity against elastases of Aspergillus fumigatus and Aspergillus flavus, human neutrophil elastase and bovine chymotrypsin, but does not inhibit bovine trypsin.


Input: Here we report the crystal structure of AFUEI in two crystal forms.


Input: AFUEI is a wedge-shaped protein composed of an extended loop and a scaffold protein core.


Input: The structure of AFUEI shows remarkable similarity to serine protease inhibitors of the potato inhibitor I family, although they are classified into different inhibitor families.

serine


Input: A structural comparison with the potato I family inhibitors suggests that the extended loop of AFUEI corresponds to the binding loop of the potato inhibitor I family and AFUEI inhibits its cognate proteases through the same mechanism as the Potato I family inhibitors.


Input: Copolymerization of 2-methylene-1, 3-dioxepane and glycidyl methacrylate, a well-defined and efficient process for achieving functionalized polyesters for covalent binding of bioactive molecules.

2-methylene-1, 3-dioxepane

glycidyl methacrylate

polyesters


Input: The understanding of cell-material interactions is important for creating personalized implants for tissue engineering.


Input: This has resulted in an interest in developing polymers with functional groups with the possibility of controlling the macromolecular surface.


Input: We have in a one-pot reaction synthesized a series of amorphous and degradable polyester-based copolymers with active functional groups by copolymerization of 2-methylene-1, 3-dioxepane and glycidyl methacrylate.

polyester

2-methylene-1, 3-dioxepane

glycidyl methacrylate


Input: The properties of the final polymers were varied by varying the feed ratios of the monomers and it was seen that it was possible to control the amount of active functional groups.


Input: The resulting epoxy-functionalized polyester was further modified by covalent immobilization of heparin.

epoxy-functionalized polyester


Input: The heparinization was done in order, in a future aspect, to enhance the osteogenic differentiation of mesenchymal stem cells.


Input: Heparin binds directly with the growth factor bone morphogenetic protein-2 and helps to retain its activity.


Input: The molecular structure of the copolymers was characterized by nuclear magnetic resonance, size exclusion chromatography, and fourier transform infrared spectroscopy.


Input: Differential scanning calorimetry and tensile testing showed that the monomer feed ratio had a great influence on the properties of the final polymer and that it thus was possible to control the mechanical properties to suit an intended application.


Input: The presence of heparin was verified by toluidine blue staining and all the films tested showed positive signals for heparin.

toluidine blue


Input: Influence of histidine incorporation on buffer capacity and gene transfection efficiency of HPMA-co-oligolysine brush polymers.

histidine

HPMA


Input: One of the major intracellular barriers to non-viral gene delivery is efficient endosomal escape.


Input: The incorporation of histidine residues into polymeric constructs has been found to increase endosomal escape via the proton sponge effect.

histidine


Input: Statistical and diblock copolymers of N-(2-hydroxypropyl) methacrylamide (HPMA), oligolysine, and oligohistidine were synthesized via reversible-addition fragmentation chain transfer (RAFT) polymerization, and tested for in vitro transfection efficiency, buffering ability, and polyplex uptake mechanism via the use of chemical endocytic inhibitors.

N-(2-hydroxypropyl) methacrylamide

HPMA


Input: Interestingly, histidine-containing statistical and diblock polymers exhibited increased buffer capacity in different endosomal pH ranges.

histidine


Input: Statistical copolymers transfected better than block copolymers that contained similar amounts of histidine.

histidine


Input: In addition, only the polymer containing the highest incorporation of oligohistidine residues led to increases in transfection efficiency over the HPMA-oligolysine base polymer.

HPMA