Input: The soman-labeled tyrosines in these proteins are surrounded by different amino acid sequences, suggesting that the polyclonal recognizes soman-tyrosine independent of the amino acid sequence.

soman

tyrosines

amino acid

soman

tyrosine

amino acid


Input: Antiserum obtained after 4 antigen injections over a period of 18 weeks was tested in a competition ELISA where it had an IC50 of 10 (-11) M.


Input: The limit of detection on Western blots was 0. 01 mu g (15 picomoles) of soman-labeled albumin.

soman


Input: In conclusion, a high-affinity, polyclonal antibody that specifically recognizes soman adducts on tyrosine in a variety of proteins has been produced.

soman

tyrosine


Input: Such an antibody could be useful for identifying secondary targets of soman toxicity.

soman


Input: NTproBNP: An Important Biomarker in Cardiac Diseases.


Input: Natriuretic neuropeptides (ANP, BNP, CNP) are produced primarily in the cardiac atria under normal conditions.


Input: The main stimulus for ANP and BNP peptide synthesis and secretion is cardiac wall stress.


Input: Cardiac ventricular myocytes constitute the major source of BNP-related peptides.


Input: Ventricular NT-proBNP production is upregulated in cardiac failure and locally in the area surrounding a myocardial infarct.


Input: NT-proBNP is cleared passively by organs with high rate of blood flow (muscle, liver, kidney).


Input: It has a longer half life than BNP and higher plasma concentration.


Input: BNP and NTproBNP tend to be higher in women and lower in obese individuals.


Input: They are also higher in elderly, in left ventricular tachycardia, right ventricular overload, myocardial ischemia, hypoxaemia, renal dysfunction, liver cirrhosis, sepsis and infection.


Input: NT-proBNP is useful both in the diagnosis and prognosis of heart failure and is considered to be a gold standard biomarker in heart failure similar to BNP.


Input: A cut-off point 300 pg/ml has 99% sensitivity, 60% specificity and NPV 98% for exclusion of acute heart failure.


Input: NT proBNP has also a strong prognostic value of death in acute and chronic heart failure and also predicts short and long term mortality in patient with suspected or confirmed unstable CVD.


Input: Natriuretic peptides are also prognostic markers for the RV (Right Ventricular) Dysfunction.


Input: Their release is due to myocardial stretch from right ventricular pressure overload. Finally, there are data supporting that NT-proBNP might be useful to put a time frame on atrial fibrillation of unknown onset.


Input: Biocompatible, functional spheres based on oxidative coupling assembly of green tea polyphenols.

polyphenols


Input: Green luminescent, monodisperse, smooth, porous and hollow spheres were simply prepared by Cu (2 +) and temperature mediated oxidative coupling assembly of green tea polyphenols in water.

Cu (2 +)

polyphenols


Input: These polymeric tea polyphenol spheres are GSH responsive, acid resistant but alkali-responsive, ideally used as platform for controlled delivery of functional guests.

polyphenol

GSH


Input: Crystalline growth of rubrene film enhanced by vertical ordering in cadmium arachidate multilayer substrate.

rubrene

cadmium arachidate


Input: The growth of highly crystalline rubrene thin films for organic field effect transistor (OFET) application remains a challenge.

rubrene


Input: Here, we report on the vapor-deposited growth of rubrene films on the substrates made of cadmium arachidate (CdA) multilayers deposited onto SiO2/Si (100) via the Langmuir-Blodgett technique.

rubrene

cadmium arachidate

CdA

Si


Input: The CdA films, containing 2n + 1 layers, with integer n ranging from 0 to 4, are surface-terminated identically by the methyl group but exhibit the thickness-dependent morphology.

CdA

methyl


Input: The morphology and structure of both CdA and rubrene films are characterized by X-ray reflectivity (XRR), X-ray diffraction (XRD), near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, and atomic force microscopy (AFM).

CdA

rubrene


Input: Crystalline rubrene films, evidenced by XRD and marked by platelet features in AFM images, become observable when grown onto the CdA layer thicker than 5L.

rubrene

CdA


Input: XRD data show that vertical ordering, that is, ordering along surface normal, of CdA multilayer substrates exerts a strong influence in promoting the crystalline growth of rubrene films.

CdA

rubrene


Input: This promoted growth is not due to the surface energy of CdA layer but derived from the additional interaction localized between rubrene and CdA island sidewall and presumably strengthened by a close dimensional match between the a-axis of rubrene lattice and the layer spacing of CdA multilayer.

CdA

rubrene

CdA

rubrene

CdA


Input: The best OFET mobility is recorded for 9L CdA substrate and reaches 6. 7 x 10 (-2) cm (2) V (-1) s (-1), presumably limited by the roughness of the interface between CdA and rubrene films.

CdA

CdA

rubrene


Input: Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii.

Calcium


Input: Toxoplasma gondii is sensitive to bulky pyrazolo [3, 4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1).

pyrazolo [3, 4-d] pyrimidine

Gly

calcium


Input: Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1).


Input: The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low mu M EC50 values) were highly correlated and occurred in a CDPK1-specific manner.


Input: Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity.


Input: Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model.


Input: Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.


Input: A newly synthesized sinapic Acid derivative inhibits endothelial activation in vitro and in vivo.

sinapic Acid


Input: Inhibition of oxidative stress and inflammation in vascular endothelial cells (ECs) may represent a new therapeutic strategy against endothelial activation.


Input: Sinapic acid (SA), a phenylpropanoid compound, is found in natural herbs and high-bran cereals and has moderate antioxidant activity.

Sinapic acid

phenylpropanoid


Input: We aimed to develop new SA agents with the properties of antioxidation and blocking EC activation for possible therapy of cardiovascular disease.


Input: We designed and synthesized 10 SA derivatives according to their chemical structures.


Input: Preliminary screening of the compounds involved scavenging hydroxyl radicals and 2, 2-diphenyl-1-picrylhydrazyl (DPPH (.)), croton oil-induced ear edema in mice, and analysis of the mRNA expression of adhesion molecules in ECs.

hydroxyl

2, 2-diphenyl-1-picrylhydrazyl

DPPH (.)


Input: 1-Acetyl-sinapic acyl-4-(3'-chlorine-) benzylpiperazine (SA9) had the strongest antioxidant and anti-inflammatory activities both in vitro and in vivo.

1-Acetyl-sinapic acyl-4-(3'-chlorine-) benzylpiperazine


Input: Thus, the effect of SA9 was further studied.


Input: SA9 inhibited tumor necrosis factor alpha-induced upregulation of adhesion molecules in ECs at both mRNA and protein levels, as well as the consequent monocyte adhesion to ECs.


Input: In vivo, result of face-to-face immunostaining showed that SA9 reduced lipopolysaccharide-induced expression of intercellular adhesion molecule-1 in mouse aortic intima.


Input: To study the molecular mechanism, results from luciferase assay, nuclear translocation of NF-kappa B, and Western blot indicated that the mechanism of the anti-inflammatory effects of SA9 might be suppression of intracellular generation of ROS and inhibition of NF-kappa B activation in ECs.


Input: SA9 is a prototype of a novel class of antioxidant with anti-inflammatory effects in ECs.


Input: It may represent a new therapeutic approach for preventing endothelial activation in cardiovascular disorders.


Input: Measurement of Transport Activities of 3 beta-Hydroxy-Delta (5)-bile Acids in Bile Salt Export Pump and Multidrug Resistance-Associated Proteins Using LC-MS/MS.

3 beta-Hydroxy-Delta (5)-bile Acids

Bile Salt


Input: A method has been developed for the measurement of transport activities in membrane vesicles obtained from Sf9 cells for 3 beta-hydroxy-Delta (5)-bile acids by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

3 beta-hydroxy-Delta (5)-bile acids


Input: Calibration curves for the bile acids were linear over the range of 10 to 2000 pmol/mL, and the detection limit was less than 1 pmol/mL for 3 beta-hydroxy-Delta (5)-bile acids using selected reaction monitoring analysis.

bile acids

3 beta-hydroxy-Delta (5)-bile acids


Input: The analytical method was applied to measurements of transport activities in membrane vesicles obtained from human multidrug resistance-associated protein 2-, 3-, and human bile salt export pump-expressing Sf9 cells for conjugated 3 beta-hydroxy-Delta (5)-bile acids.

bile salt

3 beta-hydroxy-Delta (5)-bile acids


Input: The present study demonstrated that human multidrug resistance-associated protein 3 vesicles accepted conjugated 3 beta-hydroxy-Delta (5)-bile acids along with common bile acids such as glycocholic acid and taurolithocholic acid 3-sulfate.

3 beta-hydroxy-Delta (5)-bile acids

bile acids

glycocholic acid

taurolithocholic acid 3-sulfate


Input: Investigation of the effects of chest physiotherapy in different positions on the heart and the respiratory system after coronary artery bypass surgery.


Input: This trial was conducted to investigate the effect of chest physiotherapy in different positions on the heart and the respiratory system after coronary artery bypass surgery.


Input: Patients are divided into two groups of 30 patients each in the study.


Input: To the patients in the first group (30 patients), percussion-vibration was performed in the 45 degrees supine position, while slightly laterally lying and endotracheal aspiration was performed in the supine position.


Input: To the patients in the second group (30 patients), percussion-vibration was performed in the 0 degrees supine position, while slightly laterally lying and endotracheal aspiration was performed in the supine position.


Input: The procedures are repeated two times for all patients and their means were taken.


Input: The pre-and postapplication values of patients were measured from central venous and arterial catheters and the values of patient monitors were recorded.


Input: Comparison of the two groups in terms of respiratory values did not reveal a significant difference, but chest physiotherapy with the head of the bed at 0 degrees was determined to improve cardiac functions.


Input: Evaluation of the groups in terms of pre-and postphysiotherapy applications showed a significant increase in mixed venous oxygen saturation in both groups.

oxygen


Input: Chest physiotherapy with the head of the bed elevated to 45 degrees may be recommended in patients who carry a risk of pulmonary complications and who are candidates for chest physiotherapy at an early stage.


Input: A new anti-inflammatory triterpene saponin isolated from Anabasis setifera.

triterpene saponin


Input: A bio-guided fractionation of Anabasis setifera Moq.


Input: (Chenopodiaceae) for anti-inflammatory activity was carried out using carrageenin rat paw edema model in rats.


Input: On the basis of percent edema inhibition after 3 h of carrageenin injection, n-butanol fraction showed promising activity through a significant (p < 0. 05) decrease in paw volume by 85. 6% from control using indomethacin as reference standard.

n-butanol

indomethacin


Input: Moreover, the n-butanol fraction significantly (p < 0. 05) decreased PGE2 and TNF-alpha in the exudates of rat paw edema.

n-butanol


Input: Chemical investigation of n-butanol fraction afforded alpha-amyrin 3-O-glucopyranoside (1), patuletin 7-O-glucopyranoside (2), myricitrin (3) and a new oleanane triterpene saponin derivative (4), sophradiol 3-O-alpha-L-(1) C4-rhamnopyranosyl-(1''' --> 4'')-O-beta-D-(4) C1-galactopyranosyl (1'' --> 6')-O-beta-D-(4) C1-glucopyranoside.

n-butanol

alpha-amyrin 3-O-glucopyranoside

patuletin 7-O-glucopyranoside

myricitrin

oleanane triterpene saponin

sophradiol 3-O-alpha-L-(1) C4-rhamnopyranosyl-(1''' --> 4'')-O-beta-D-(4) C1-galactopyranosyl (1'' --> 6')-O-beta-D-(4) C1-glucopyranoside


Input: The structure of the new compound was determined by comprehensive analyses of their 1D and 2D NMR, mass spectral data and comparison with previously known analogs.


Input: Only compound 4 revealed a significant (p < 0. 05) inhibition of cyclooxygenase 1 and 2 (COX) activities.


Input: Bladder Polypoid Cystitis-Derived A20 Associates with Tumorigenesis.


Input: Bladder chronic inflammation is associated with the pathogenesis of bladder cancer; the underlying mechanism is unclear.


Input: The PT53 gene is an important anticancer gene in the body, which is suppressed in cancer.


Input: The ubiquitin E3 ligase A20 (A20) plays a role in regulating the activities of epithelial cells.


Input: This study was designed to investigate the correlation between A20 and the pathogenesis of bladder cancer.


Input: The biopsy tissues of human bladder cancer, bladder polypoid cystitis, and chronic inflammation were collected; the levels of A20 and p53 were analyzed by quantitative real-time RT-PCR, Western blotting, and immune precipitation.


Input: HEK293 cells were employed to test the role of overexpression of A20 in the suppression of the p53 gene in the cells.


Input: Fifty-six patients with bladder cancer, 48 patients with bladder polypoid cystitis, and 16 patients with bladder chronic inflammation were recruited into this study.


Input: Human bladder cancer tissue and the polypoid tissue showed high levels of A20, which had a positive correlation with the tumorigenesis in the bladder; 12 out of 46 (26. 1%) patients with bladder polypoid cystitis were diagnosed as bladder cancer.


Input: A20 bound to p53 to form complexes in bladder cancer tissue and bladder polypoid tissue.


Input: The overexpression of A20 suppresses p53 protein levels in HEK293 cells.


Input: A20 has a positive correlation in the tumorigenesis of bladder polypoid disorders.


Input: Acute Myocardial Infarction During Regadenoson Myocardial Perfusion Imaging.

Regadenoson


Input: Pharmacologic stress testing uses vasodilators to provide objective evidence of myocardial ischemia.


Input: Adenosine and dipyridamole are nonselective adenosine receptor agonists that have been associated with myocardial infarction (MI) during intravenous infusion.

Adenosine

dipyridamole

adenosine


Input: Mechanisms postulated for this effect include coronary steal, transmural steal, global hypotension, and direct vasoconstriction.


Input: Regadenoson, a direct A2A agonist, was approved for use in stress testing in 2008.

Regadenoson


Input: We describe a 68-year-old man who presented to our institution with typical angina, relieved by nitroglycerin.

nitroglycerin


Input: He did not have electrocardiogram (ECG) changes suggestive of myocardial pathology, and laboratory testing did not reveal a significant rise in troponin-I levels.


Input: To further assess the etiology of his symptoms, he underwent a pharmacologic stress test with regadenoson followed by technetium 99 m sestamibi.

regadenoson

technetium 99 m sestamibi


Input: Six minutes after regadenoson infusion, the patient developed severe retrosternal chest pain accompanied by ST elevations on ECG.

regadenoson


Input: Sublingual nitroglycerin was administered that resolved both the pain and ECG changes.

nitroglycerin


Input: The patient subsequently underwent urgent coronary angiography and was found to have a 95% critical stenosis involving the left anterior descending artery.


Input: We conclude this case represents a MI secondary to coronary steal phenomenon induced by regadenoson infusion.

regadenoson


Input: Clinicians should be aware this adverse effect can occur despite the improved side-effect profile of regadenoson.

regadenoson


Input: Continuous monitoring of vital signs and the ECG with regular assessment of symptoms is imperative to identify this rare but potentially devastating adverse event.


Input: The Efficiency of the Metal Catalysts in the Nucleophilic Substitution of Alcohols is Dependent on the Nucleophile and Not on the Electrophile.

Alcohols


Input: In this study, we investigate the effect of the electrophiles and the nucleophiles for eight catalysts in the catalytic SN 1 type substitution of alcohols with different degree of activation by sulfur-, carbon-, oxygen-, and nitrogen-centered nucleophiles.

alcohols

sulfur

carbon

oxygen

nitrogen


Input: The catalysts do not show any general variance in efficiency or selectivity with respect to the alcohols and follow the trend of alcohol reactivity.

alcohols

alcohol


Input: However, when it comes to the nucleophile, the eight catalysts show general and specific variances in the efficiency and selectivity to perform the desired substitution.


Input: Interestingly, the selectivity of the alcohols to produce the desired substitution products was found to be independent of the electrophilicity of the generated carbocations but highly dependent on the ease of formation of the cation.

alcohols


Input: Catalysts based on iron (III), bismuth (III), and gold (III) show higher conversions for S-, C-, and N-centered nucleophiles, and Bi (III) was the most efficient catalyst in all combinations.

iron (III)

bismuth (III)

gold (III)

S

C

N

Bi (III)


Input: Catalysts based on rhenium (I) or rhenium (VII), palladium (II), and lanthanum (III) were the most efficient in performing the nucleophilic substitution on the various alcohols with the O-centered nucleophiles.

rhenium (I)

rhenium (VII)

palladium (II)

lanthanum (III)

alcohols

O


Input: These catalysts generate the symmetrical ether as a by-product from the reactions of S-, C-, and N-centered nucleophiles as well, resulting in lower chemoselectivity.

S

C

N


Input: Energies and Spin States of FeS (0/-), FeS2 (0/-), Fe2 S2 (0/-), Fe3 S4 (0/-), and Fe4 S4 (0/-) Clusters.

FeS

Fe2 S2

Fe3 S4

Fe4 S4


Input: The structures and energies of the electronic ground states of the FeS (0/-), FeS2 (0/-), Fe2 S2 (0/-), Fe3 S4 (0/-), and Fe4 S4 (0/-) neutral and anionic clusters have been computed systematically with nine computational methods in combination with seven basis sets.

FeS

Fe2 S2

Fe3 S4

Fe4 S4


Input: The computed adiabatic electronic affinities (AEA) have been compared with available experimental data.


Input: Most reasonable agreements between theory and experiment have been found for both hybrid B3LYP and B3PW91 functionals in conjugation with 6-311 + G * and QZVP basis sets.


Input: Detailed comparisons between the available experimental and computed AEA data at the B3LYP/6-311 + G * level identified the electronic ground state of (5) Delta for FeS, (4) Delta for FeS (-), (5) B2 for FeS2, (6) A1 for FeS2 (-), (1) A1 for Fe2 S2, (8) A' for Fe2 S2 (-), (5) A'' for Fe3 S4, (6) A'' for Fe3 S4 (-), (1) A1 for Fe4 S4, and (1) A2 for Fe4 S4 (-).

FeS

FeS (-)

FeS2 (-)

Fe2 S2

Fe2 S2 (-)

Fe3 S4

Fe3 S4 (-)

Fe4 S4

Fe4 S4 (-)


Input: In addition, Fe2 S2, Fe3 S4, Fe3 S4 (-), Fe4 S4, and Fe4 S4 (-) are antiferromagnetic at the B3LYP/6-311 + G * level.

Fe2 S2

Fe3 S4

Fe3 S4 (-)

Fe4 S4

Fe4 S4 (-)


Input: The magnetic properties are discussed on the basis of natural bond orbital analysis.


Input: Ras/cAMP-dependent Protein Kinase (PKA) Regulates Multiple Aspects of Cellular Events by Phosphorylating the Whi3 Cell Cycle Regulator in Budding Yeast.

cAMP


Input: The Start/G1 phase in the cell cycle is an important period during which cells determine their developmental fate, onset of mitotic progression, or the switch to developmental stages in response to both external and internal signals.


Input: In the budding yeast Saccharomyces cerevisiae, Whi3, a negative regulator of the G1 cyclins, has been identified as a positive regulator of cell size control and is involved in the regulation of Start.


Input: However, the regulatory pathway of Whi3 governing the response to multiple signals remains largely unknown.


Input: Here, we show that Whi3 is phosphorylated by the Ras/cAMP-dependent protein kinase (PKA) and that phosphorylation of Ser-568 in Whi3 by PKA plays an inhibitory role in Whi3 function.

cAMP

Ser


Input: Phosphorylation of Whi3 by PKA led to its decreased interaction with CLN3 G1 cyclin mRNA and was required for the promotion of G1/S progression.


Input: Furthermore, we demonstrate that the phosphomimetic S568D mutation of Whi3 prevented the developmental fate switch to sporulation or invasive growth.


Input: Thus, PKA modulated the function of Whi3 by phosphorylation, thus implicating PKA-mediated modulation of Whi3 in multiple cellular events.


Input: Nanoparticles Adsorbed at the Water/Oil Interface: Coverage and Composition Effects on Structure and Diffusion.


Input: Dissipative particle dynamics simulations are performed to study the structural and dynamical properties of various systems of nanoparticles accumulated at the water/oil interface.


Input: Homogeneous and Janus nanoparticles with different surface compositions are studied.


Input: For all nanoparticles, as the surface density increases, a transition from a liquidlike to a solidlike state is observed, as expected.


Input: At a high density of nanoparticles, hexagonal structures emerge and the nanoparticles' self-diffusion coefficient decreases because of caging effects.


Input: Similar results are observed for nanoparticles with different surface chemistry.


Input: Because different nanoparticles have different contact angles at the water/oil interface, the results obtained for systems containing mixed nanoparticles are more interesting.


Input: For example, our results show that the self-diffusion coefficient is not a monotonic function of the system composition, caused by the complex relation between hydrodynamic interactions and effective nanoparticle-nanoparticle interactions.


Input: Presence of hydrophobic groups may modify the specific ion effect in aqueous polyelectrolyte solutions.


Input: Enthalpies of dilution of aqueous solutions of aliphatic 6, 12-and 12, 12-ionene bromides and fluorides and enthalpies of mixing with low molecular-weight salts, such as sodium fluoride and bromide, are determined.

aliphatic 6, 12-and 12, 12-ionene bromides and fluorides

sodium fluoride and bromide


Input: In the second part of the study, the various x, y-ionenes (x, y are numbers of methylene groups between the adjacent charges) with fluoride, bromide, and iodide counterions are mixed with aqueous sodium sulfate solution.

methylene

fluoride

bromide

iodide

sodium sulfate


Input: The polyelectrolytes examined in this part of the work are 3, 3-, 6, 9-, 6, 12-, and 12, 12-ionenes.

3, 3-, 6, 9-, 6, 12-, and 12, 12-ionenes


Input: A comparison with theoretical results, based on the Poisson-Boltzmann cell model, is presented.


Input: The theory predicts for the enthalpy of dilution to be exothermic and the enthalpy of mixing endothermic, while experiments show that signs of the heat effects depend on the nature of the counterion of the added salt, as also on the hydrophobicity (numbers x, y of methylene groups) of the ionene.

methylene


Input: We show that the salts when ordered by heat effects produced by mixing of NaF and NaBr with 3, 3-, 6, 9-, or 6, 12-ionene fluorides and bromides follow the opposite ordering than in the case when the same alkali halide salts are mixed with more hydrophobic 12, 12-ionene salts.

NaF

NaBr

3, 3-, 6, 9-, or 6, 12-ionene fluorides and bromides

alkali halide

12, 12-ionene


Input: The results for the enthalpy of mixing of ionenes under study with Na2SO4 follow the same order as obtained for monovalent salts.


Input: Do the physical properties of water in mixed reverse micelles follow a synergistic effect: a spectroscopic investigation.


Input: In this contribution we have tried to investigate whether the mechanical properties of the reverse micellar (RM) interface dictate the physical properties of entrapped water molecules in the RM waterpool.


Input: We choose AOT/Igepal-520/cyclohexane (Cy) mixed RM as a model system which exhibits synergistic water solubilization behavior as a function of interfacial stoichiometry.

AOT

cyclohexane


Input: Such a phenomenon associates systematic modification of the interface curvature.


Input: Dynamic light scattering (DLS) studies reveal linear increase in the droplet size and aggregation number of the RMs with increasing XIgepal (mole fraction of Igepal in the surfactant mixture).


Input: FTIR study in the 3000-3800 cm (-1) region identifies that the relative population of the surface-bound water molecules is higher in AOT RM compared to that in Igepal RM, and in mixed systems it also follows a linear trend with XIgepal.

AOT

Igepal


Input: Water relaxation dynamics as probed by time-resolved fluorescence spectroscopy using Coumarin-500 also reveals an overall linear trend with no characteristic feature around the solubilization inflation point.


Input: Our study clearly identifies that the physical properties of water in RM are mostly governed by the interfacial stoichiometry and water content, and merely bares any dependence on the mechanical properties of the interface.


Input: Discovery of (R)-2-amino-6-borono-2-(2-(piperidin-1-yl) ethyl) hexanoic acid and congeners as highly potent inhibitors of human arginases I and II for treatment of myocardial reperfusion injury.

(R)-2-amino-6-borono-2-(2-(piperidin-1-yl) ethyl) hexanoic acid


Input: Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in the discovery of a novel series of highly potent alpha, alpha-disubstituted amino acid-based arginase inhibitors.

alpha, alpha-disubstituted amino acid


Input: The lead candidate, (R)-2-amino-6-borono-2-(2-(piperidin-1-yl) ethyl) hexanoic acid, compound 9, inhibits human arginases I and II with IC50s of 223 and 509 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells).

(R)-2-amino-6-borono-2-(2-(piperidin-1-yl) ethyl) hexanoic acid


Input: It is 28% orally bioavailable and significantly reduces the infarct size in a rat model of myocardial ischemia/reperfusion injury.


Input: Herein, we report the design, synthesis, and structure-activity relationships (SAR) for this novel series of inhibitors along with pharmacokinetic and in vivo efficacy data for compound 9 and X-ray crystallography data for selected lead compounds cocrystallized with arginases I and II.


Input: Xenobiotics and the human gut microbiome: metatranscriptomics reveal the active players.


Input: The human gut microbiome plays an important role in the metabolism of xenobiotics.


Input: In a recent issue of Cell, Maurice et al.


Input: (2013) identify the active members of the gut microbiome and show how gene-expression profiles change within the gut microbial community in response to antibiotics and host-targeted xenobiotics.


Input: Design, Synthesis, and Biological Evaluation of a Series of Benzo [de] [1, 7] naphthyridin-7 (8H)-ones Bearing a Functionalized Longer Chain Appendage as Novel PARP1 Inhibitors.

Benzo [de] [1, 7] naphthyridin-7 (8H)-ones


Input: A series of benzo [de] [1, 7] naphthyridin-7 (8H)-ones possessing a functionalized long-chain appendage have been designed and evaluated as novel PARP1 inhibitors.

benzo [de] [1, 7] naphthyridin-7 (8H)-ones


Input: The initial effort led to the first-generation PARP1 inhibitor 26 bearing a terminal phthalazin-1 (2H)-one framework and showing remarkably high PARP1 inhibitory activity (0. 31 nM) but only moderate potency in the cell.

phthalazin-1 (2H)-one


Input: Further effort generated the second-generation lead 41, showing high potency against both the PARP1 enzyme and BRCA-deficient cells, especially for the BRCA1-deficient MDA-MB-436 cells (CC50 < 0. 26 nM).


Input: Mechanistic studies revealed that the new PARP1 inhibitors significantly inhibited H2O2-triggered PARylation in SKOV3 cells, induced cellular accumulation of DNA double-strand breaks, and impaired cell-cycle progression in BRCA2-deficient cells.


Input: Significant potentiation on the cytotoxicity of Temozolomide was also observed.

Temozolomide


Input: The unique structural character and exceptionally high potency of 41 made it stand out as a promising drug candidate worthy for further evaluation.


Input: Engineered Magnetic Shape Anisotropy in BiFeO3-CoFe2O4 Self-Assembled Thin Films.


Input: We report growth of various phase architectures of self-assembled BiFeO3-CoFe2O4 (BFO-CFO) thin films on differently oriented SrTiO3 (STO) substrates.

BFO

CFO

STO


Input: CFO forms segregated square, stripe, and triangular nanopillars embedded in a coherent BFO matrix on (001)-, (110)-, and (111)-oriented STO substrates, respectively.

CFO

BFO

STO


Input: Nanostructures with an aspect ratio of up to 5: 1 with a prominent magnetic anisotropy were obtained on both (001) and (110) STO along out-of-plane and in-plane directions.

STO


Input: Magnetic easy axis rotation from in-plane to out-of-plane directions was realized through aspect ratio control.


Input: An intractable in-plane anisotropy was fixed in CFO on (111) STO due to the triangular shape of the ferromagnetic phase nanopillars.

CFO

STO


Input: These studies established a detailed relationship of magnetic anisotropy with specific shape and dimensions of ordered magnetic arrays.


Input: The results suggest a way to effectively control the magnetic anisotropy in patterned ferromagnetic oxide arrays with tunable shape, aspect ratio, and elastic strain conditions of the nanostructures.

oxide


Input: Biodistribution of different sized nanoparticles assessed by positron emission tomography: a general strategy for direct activation of metal oxide particles.

metal oxide


Input: The extraordinary small size of NPs makes them difficult to detect and quantify once distributed in a material or biological system.


Input: We present a simple and straightforward method for the direct proton beam activation of synthetic or commercially available aluminum oxide NPs (Al2O3 NPs) via the (16) O (p, alpha) (13) N nuclear reaction in order to assess their biological fate using positron emission tomography (PET).

aluminum oxide

(16) O

(13) N


Input: The radiolabeling of the NPs does not alter their surface or structural properties as demonstrated by TEM, DLS, and zeta-potential measurements.


Input: The incorporation of radioactive (13) N atoms in the Al2O3 NPs allowed the study of the biodistribution of the metal oxide NPs in rats after intravenous administration via PET.

(13) N

metal oxide


Input: Despite the short half-life of (13) N (9. 97 min), the accumulation of NPs in different organs could be measured during the first 68 min after administration.

(13) N


Input: The percentage amount of radioactivity per organ was calculated to evaluate the relative amount of NPs per organ.


Input: This simple and robust activation strategy can be applied to any synthetic or commercially available metal oxide particle.

metal oxide


Input: Sonochemical synthesis and characterization of nano-sized lead (II) 3D coordination polymer: Precursor for the synthesis of lead (II) oxybromide nanoparticles.

lead (II)

lead (II) oxybromide


Input: Nanoparticles of a three-dimensional coordination polymer, [Pb (L) (mu 2-Br) (H2O)] n (1), (L (-) = 1H-1, 2, 4-triazole-3-carboxylate), have been synthesized by an ultrasonic method and characterized by scanning electron microscopy, X-ray powder diffraction, IR spectroscopy and elemental analyses.

[Pb (L) (mu 2-Br) (H2O)] n

1H-1, 2, 4-triazole-3-carboxylate


Input: The thermal stability of compound 1 both its bulk and nano-size has been studied by thermal gravimetric (TG) and differential thermal (DTA) analyses and compared each other.


Input: Concentration of initial reagents effects and the role of power ultrasound irradiation on size and morphology of nano-structured compound 1, have been studied.


Input: Calcination of the compound 1 at 500 degrees C under air atmosphere yields Pb3O2Br2 nanoparticles.


Input: Co-ordination of base excision repair and genome stability.


Input: Base excision repair (BER) is a major DNA repair pathway employed in mammalian cells that is required to maintain genome stability, thus preventing several human diseases, such as ageing, neurodegenerative diseases and cancer.


Input: This is achieved through the repair of damaged DNA bases, sites of base loss and single strand breaks of varying complexity that are continuously induced endogenously or via exogenous mutagens.


Input: Whilst the enzymes involved in BER are now well known and characterised, the role of the co-ordination of BER enzymatic activities in the cellular response to DNA damage and the mechanisms regulating this process are only now being revealed.


Input: Post-translational modifications of BER proteins, including ubiquitylation and phosphorylation, are increasingly being identified as key processes that regulate BER.


Input: In this review we will summarise recent evidence discovering novel mechanisms that are involved in maintaining genome stability by regulation of the key BER proteins in response to DNA damage.


Input: Melanoma targeting property of a Lu-177-labeled lactam bridge-cyclized alpha-MSH peptide.

lactam


Input: The purpose of this study was to determine the melanoma targeting property of (177) Lu-DOTA-GGNle-CycMSHhex in B16/F1 melanoma-bearing C57 mice.

(177) Lu-DOTA-GGNle-CycMSHhex


Input: (177) Lu-DOTA-GGNle-CycMSHhex exhibited high receptor-mediated melanoma uptake and fast urinary clearance.

(177) Lu-DOTA-GGNle-CycMSHhex


Input: The tumor uptake of (177) Lu-DOTA-GGNle-CycMSHhex was 20. 25 +/- 4. 59 and 21. 63 +/- 6. 27% ID/g at 0. 5 and 2h post-injection, respectively.

(177) Lu-DOTA-GGNle-CycMSHhex


Input: Approximately 83% of injected dose cleared out the body via urinary system at 2h post-injection.


Input: (177) Lu-DOTA-GGNle-CycMSHhex showed high tumor to normal organ uptake ratios except for the kidneys.

(177) Lu-DOTA-GGNle-CycMSHhex


Input: The tumor/kidney uptake ratios of (177) Lu-DOTA-GGNle-CycMSHhex were 2. 76 and 1. 74 at 2 and 24h post-injection.

(177) Lu-DOTA-GGNle-CycMSHhex


Input: The melanoma lesions were clearly visualized by SPECT/CT using (177) Lu-DOTA-GGNle-CycMSHhex as an imaging probe at 2h post-injection.

(177) Lu-DOTA-GGNle-CycMSHhex


Input: Overall, high melanoma uptake coupled with fast urinary clearance of (177) Lu-DOTA-GGNle-CycMSHhex underscored its potential for melanoma treatment in the future.

(177) Lu-DOTA-GGNle-CycMSHhex


Input: BCR-ABL tyrosine kinase inhibitor pharmacophore model derived from a series of phenylaminopyrimidine-based (PAP) derivatives.

tyrosine

phenylaminopyrimidine

PAP


Input: To reveal novel insights into the inhibition of BCR-ABL tyrosine kinase, pharmacophore mapping studies were performed for a series of phenylaminopyrimidine-based (PAP) derivatives, including imatinib (Gleevec).

tyrosine

phenylaminopyrimidine

PAP

imatinib


Input: A seven-point pharmacophore model with one hydrophobic group (H), two hydrogen bond donors (D) and four aromatic rings (R) was developed using phase (pharmacophore alignment & scoring engine).

hydrogen


Input: The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of 0. 886 and a survival score of 4. 97 for training set molecules.


Input: The model showed excellent predictive power, with a correlation coefficient of Q (2) = 0. 768 for an external test set of ten molecules.


Input: The results obtained from our studies provide a valuable tool for designing new lead molecules with potent activity.


Input: Time-dependent effects of corticosterone on reward-based decision-making in a rodent model of the Iowa Gambling Task.

corticosterone


Input: Corticosteroid hormones, released after stress, are known to change neuronal activity in two time-domains: within minutes via non-genomic pathways and with a delay of > 1 h through pathways involving transcriptional regulation.


Input: Recent evidence in rodents and humans indicates that these two modes of corticosteroid action differently affect cognitive tasks.


Input: Here, we investigated whether reward-based decision-making, in a rat model of the Iowa Gambling Task (rIGT), is also differently altered by rapid versus delayed actions of corticosterone.

corticosterone


Input: We targeted the rapid and delayed time domain by injecting corticosterone (CORT, 1 mg/kg, s. c.) at 30 min (rapid) or 180 min (delayed) respectively prior to behavioural testing, during the final 3 days of the behavioural paradigm.

corticosterone

CORT


Input: In saline treated rats, the number of visits to the disadvantageous arm decreased over trial blocks, whilst this was attenuated when CORT was administered 30 min before testing.

CORT


Input: This attenuation was associated with a significantly increased c-Fos expression in the lateral orbitofrontal cortex and insular cortex, and a trend for an increase in the infralimbic cortex.


Input: The rapid corticosteroid effect contrasted with treatment 180 min before testing, where the number of visits to the disadvantageous arm as well as c-Fos labelling was not affected.


Input: These findings indicate that rapid corticosteroid actions impair reward-based decision-making.


Input: Bioinspired peptides as versatile nucleic acid delivery platforms.


Input: Non-viral gene therapy approaches have strongly established the utility of peptides as integral constituents of delivery platforms devised for efficient transfer of therapeutic molecules into cells.


Input: Among these, cell-penetrating peptides (CPPs), encompassing a family of short peptide sequences and their chimeric derivatives, have gained versatility through the addition of de novo peptide ligands primarily to facilitate cell-specific nucleic acid delivery in vitro and in vivo.


Input: The review illustrates the structural requirements of a noteworthy peptide TAT-PTD and other derivatives chiefly to exemplify their implication in gene therapy.


Input: An overview of the emerging concept and recent explorations will be presented through unique examples which form a facet in nanotechnology-based cancer therapy.


Input: Finally the basis for the utility of CPPs in plants will be discussed in view of its biotechnological potential.


Input: Discovery of the Antibiotic Phosacetamycin via a New Mass Spectrometry-Based Method for Phosphonic Acid Detection.

Phosacetamycin

Phosphonic Acid


Input: Naturally occurring phosphonates such as phosphinothricin (Glufosinate, a commercially used herbicide) and fosfomycin (Monurol, a clinically used antibiotic) have proved to be potent and useful biocides.

phosphonates

phosphinothricin

Glufosinate

fosfomycin

Monurol


Input: Yet this class of natural products is still an under explored family of secondary metabolites.


Input: Discovery of the biosynthetic pathways responsible for the production of these compounds has been simplified by using gene based screening approaches, but detection and identification of the natural products the genes produce have been hampered by a lack of high-throughput methods for screening potential producers under various culture conditions.


Input: Here, we present an efficient mass-spectrometric method for the selective detection of natural products containing phosphonate and phosphinate functional groups.

phosphonate

phosphinate


Input: We have used this method to identify a new phosphonate metabolite, phosacetamycin, whose structure, biological activity, and biosynthetic gene cluster are reported.

phosphonate

phosacetamycin


Input: Anti-tuberculosis neolignans from Piper regnellii.


Input: The present study determined the anti-Mycobacterium tuberculosis activities of supercritical CO2 extracts, neolignans eupomatenoid-5 (1), conocarpan (4) and eupomatenoid-3 (7) and their derivatives (2, 3, 5, 6, and 8) from Piper regnellii, as well as their cytotoxicities.

neolignans eupomatenoid-5

conocarpan


Input: The supercritical CO2 extract from leaves was purified by chromatographic methods, yielding compounds (1), (4) and (7), which were identified by (1) H NMR and comparison with literature data.

(1) H


Input: Anti-M. tuberculosis activity (H37Rv and clinical isolates) was evaluated using a resazurin microtiter assay plate (REMA) to determine the MIC.


Input: The cytotoxicity assay was carried out in macrophages J774G. 8 by sulforhodamine B colorimetric assay.

sulforhodamine B


Input: The supercritical CO2 extracts from leaves and stems, and compound (4) showed activity against M. tuberculosis (MIC 15. 6 mu g/ml).


Input: Compound (1) showed the best activity (MIC 1. 9 mu g/ml), with good SI.


Input: Compounds (7) and (8) showed low activity against M. tuberculosis H37Rv.


Input: The derivative compounds did not show increased anti-M. tuberculosis activity.


Input: This is the first report, to our knowledge, to describe neolignans from P. regnellii with activity against M. tuberculosis, and compound (1) is a potential candidate for future antituberculosis drugs.

neolignans


Input: The crucial role of the MyD88 adaptor protein in the inflammatory response induced by Bothrops atrox venom.


Input: Most snake accidents in North Brazil are attributed to Bothrops atrox, a snake species of the Viperidae family whose venom simultaneously induces local and systemic effects in the victims.


Input: The former are clinically more important than the latter, as they cause severe tissue lesions associated with strong inflammatory responses.


Input: Although several studies have shown that inflammatory mediators are produced in response to B. atrox venom (BaV), there is little information concerning the molecular pathways involved in innate immune system signaling.


Input: Myeloid differentiation factor 88 (MyD88) is an adaptor molecule responsible for transmitting intracellular signals from most toll-like receptors (TLRs) after they interact with pathogen-associated molecular patterns (PAMPs) or other stimuli such as endogenous damage-associated molecular patterns (DAMPs).


Input: The MyD88-dependent pathway leads to activation of transcription factors, which in turn induce synthesis of inflammatory mediators such as eicosanoids, cytokines and chemokines.


Input: The aim of this study was to investigate the involvement of MyD88 on the acute inflammatory response induced by BaV.


Input: Wild-type (WT) C57BL/6 mice and MyD88 knockout (MyD88 (-/-)) mice were intraperitoneally injected with BaV.


Input: Compared to WT mice, MyD88 (-/-) animals showed an impaired inflammatory response to BaV, with lower influx of polymorphonuclear and mononuclear cells to the peritoneal cavity.


Input: Furthermore, peritoneal leukocytes from BaV-injected MyD88 (-/-) mice did not induce COX-2 or LTB4 protein expression and released low concentrations of PGE2.


Input: These mice also failed to produce Th1 and Th17 cytokines and CCL-2, but IL-10 levels were similar to those of BaV-injected WT mice.


Input: Our results indicate that MyD88 signaling is required for activation of the inflammatory response elicited by BaV, raising the possibility of developing new therapeutic targets to treat Bothrops sp. poisoning.


Input: Prilling of fatty acids as a continuous process for the development of controlled release multiparticulate dosage forms.

fatty acids


Input: In this study, prilling was evaluated as a technique for the development of multiparticulate dosage forms using the fatty acids, stearic acid, and behenic acid as potential matrix formers to control the release of metoprolol tartrate (MPT), a highly water soluble drug.

fatty acids

stearic acid

behenic acid

metoprolol tartrate

MPT


Input: The in vitro drug release was dependent on the drug load, type of fatty acid, and pH of the dissolution medium.

fatty acid


Input: Higher drug loads resulted in faster release with behenic acid releasing drug over longer periods relative to stearic acid.

behenic acid

stearic acid


Input: The in vitro drug release was pH-dependent at low drug load with the release being slower at lower pH.


Input: Due to ionization of the fatty acid at pH 7. 4, drug release was susceptible to the ionic strength at this pH value.

fatty acid


Input: Solid state characterization indicated that the crystalline state of the fatty acids was not affected by thermal processing via prilling, while the crystallinity of MPT was decreased.

fatty acids

MPT


Input: During storage, the amorphous MPT fraction recrystallized in the entire matrix.

MPT


Input: Drug release from behenic acid matrices was increased during storage at 40 degrees C; however, no polymorphism of behenic acid was detected.

behenic acid

behenic acid


Input: The bioavailability of MPT, after oral administration to dogs as prills containing 30% and 40% MPT using behenic acid as matrix former, was not significantly different from a commercial sustained release reference formulation, although the 40% MPT prills showed a burst release.

MPT

MPT

behenic acid

MPT


Input: Synthesis and evaluation of 3-(benzylthio)-5-(1H-indol-3-yl)-1, 2, 4-triazol-4-amines as Bcl-2 inhibitory anticancer agents.

3-(benzylthio)-5-(1H-indol-3-yl)-1, 2, 4-triazol-4-amines


Input: A series of substituted 3-(benzylthio)-5-(1H-indol-3-yl)-4H-1, 2, 4-triazol-4-amines has been synthesised and tested in vitro as potential pro-apoptotic Bcl-2-inhibitory anticancer agents.

3-(benzylthio)-5-(1H-indol-3-yl)-4H-1, 2, 4-triazol-4-amines


Input: Synthesis of the target compounds was readily accomplished in good yields through a cyclisation reaction between indole-3-carboxylic acid hydrazide and carbon disulfide under basic conditions, followed by S-benzylation.

indole-3-carboxylic acid hydrazide

carbon disulfide

S


Input: Active compounds, such as the nitrobenzyl analogue 6c, were found to exhibit sub-micromolar IC50 values in Bcl-2 expressing human cancer cell lines.

nitrobenzyl


Input: Molecular modelling and ELISA studies further implicated anti-apoptotic Bcl-2 as a candidate molecular target underpinning anticancer activity.


Input: Sulfur-nitrogen co-doped three-dimensional carbon foams with hierarchical pore structures as efficient metal-free electrocatalysts for oxygen reduction reactions.

Sulfur

nitrogen

carbon

oxygen


Input: Despite the good progress in developing doped carbon catalysts for oxygen-reduction reaction (ORR), the current metal-free carbon catalysts are still far from satisfactory for large-scale applications of fuel cell.

oxygen

carbon


Input: Developing new metal free doped carbon materials with abundance active sites as well as excellent electron transfer and reactant transport rate towards ORR may be a potential solution.

carbon


Input: Herein, we develop a novel three-dimensional (3D) sulfur-nitrogen co-doped carbon foams (S-N-CF) with hierarchical pore structures, using a convenient, economical, and scalable method.

sulfur-nitrogen co-doped carbon

S

N


Input: The experimental results have demonstrated that the obtained 3D S-N-CF exhibited better catalytic activity, longer-term stability and higher methanol tolerance than a commercial Pt/C catalyst.

S

N

methanol

Pt

C


Input: Such excellent performances may be attributed to the synergistic effect, which includes high catalytic sites for ORR provided by high S-N heteroatom loading, excellent reactant transport caused by hierarchical pore structures and high electron transfer rate provided by 3D continuous networks.

Such

N


Input: Our results not only develop a new type of catalysts with excellent electrocatalytic performance by a commercially valid route, but also provide useful information for further clarification of the relationship between the microstructures of metal-free carbon materials and catalyst properties for ORR.

carbon


Input: More importantly, the idea to design hierarchical pore structures could be applied to other catalytic materials and serve as a general strategy for improving the activity of various ORR catalysts.


Input: Aortic Distensibility in Type 1 Diabetes.


Input: OBJECTIVESTo evaluate the relationship between long-term glycemia, traditional cardiovascular disease (CVD) risk factors, and ascending aortic stiffness in type 1 diabetes. RESEARCH DESIGN AND METHODSEight hundred seventy-nine subjects in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study were evaluated.


Input: The stiffness/distensibility of the ascending thoracic aorta (AA) was measured with magnetic resonance imaging.


Input: Associations of AA distensibility and CVD risk factors, mean HbA1c, and cardiovascular complications including macroalbuminuria were assessed using multivariate linear regression models. RESULTSThe mean age of the subjects was 50 +/- 7 years (47% women, mean diabetes duration of 28 years).


Input: Over 22 years of follow-up, 27% of participants had cardiovascular complications.


Input: After adjusting for gender and cohort, AA distensibility was lower with increasing age, mean systolic blood pressure, LDL, and HbA1c measured over an average of 22 years (-26. 3% per 10 years,-11. 0% per 10 mmHg SBP,-1. 8% per 10 mg/dL of LDL, and-9. 3% per unit mean HbA1c [%], respectively).


Input: Patients with macroalbuminuria had 25% lower AA distensibility compared with those without (P < 0. 0001).


Input: Lower AA distensibility also was associated with greater ratio of left ventricular mass to volume (-3. 4% per 0. 1 g/mL; P < 0. 0001). CONCLUSIONSOur findings indicate strong adverse effects of hypertension, chronic hyperglycemia and macroalbuminuria on AA stiffness in type 1 diabetes in the DCCT/EDIC cohort.


Input: Biotransformation of Two beta-Secretase Inhibitors Including Ring Opening and Contraction of a Pyrimidine Ring.

Pyrimidine


Input: Recently, the discovery of the aminoisoindoles as potent and selective inhibitors of beta-secretase was reported, including the close structural analogs compound (S)-1-pyridin-4-yl-4-fluoro-1-(3-(pyrimidin-5-yl) phenyl)-1H-isoindol-3-amine [(S)-25] and (S)-1-(2-(difluoromethyl) pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl) phenyl)-1H-isoindol-3-amine hemifumarate (AZD3839), the latter being recently progressed to the clinic.

aminoisoindoles

(S)-1-pyridin-4-yl-4-fluoro-1-(3-(pyrimidin-5-yl) phenyl)-1H-isoindol-3-amine

(S)-1-(2-(difluoromethyl) pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl) phenyl)-1H-isoindol-3-amine hemifumarate


Input: The biotransformation of (S)-25 was investigated in vitro and in vivo in rat, rabbit, and human and compared with AZD3839 to further understand the metabolic fate of these compounds.


Input: In vitro, CYP3A4 was the major responsible enzyme and metabolized both compounds to a large extent in the commonly shared pyridine and pyrimidine rings.

pyridine

pyrimidine


Input: The main proposed metabolic pathways in various in vitro systems were N-oxidation of the pyridine and/or pyrimidine ring and conversion to 4-pyrimidone and pyrimidine-2, 4-dione.

N

pyridine

pyrimidine

pyrimidine-2, 4-dione


Input: Both compounds were extensively metabolized, and more than 90% was excreted in feces after intravenous administration of radiolabeled compound to the rat.


Input: Here, the main pathways were N-oxidation of the pyridine and/or pyrimidine ring and a ring contraction of the pyrimidine ring into an imidazole ring.

N

pyridine

pyrimidine

pyrimidine

imidazole


Input: Ring-contracted metabolites accounted for 25% of the total metabolism in the rat for (S)-25, whereas the contribution was much smaller for AZD3839.


Input: This metabolic pathway was not foreseen on the basis of the obtained in vitro data.


Input: In conclusion, we discovered an unusual metabolic pathway of aryl-pyrimidine-containing compounds by a ring-opening reaction followed by elimination of a carbon atom and a ring closure to form an imidazole ring.

aryl-pyrimidine

carbon

imidazole


Input: Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers.


Input: Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer.


Input: Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms.


Input: Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair.


Input: As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel.


Input: Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms. Oncogene advance online publication, 11 March 2013; doi: 10. 1038/onc. 2013. 48.


Input: Impact of the virus purification protocol on aggregation and electrokinetics of MS2 phages and corresponding virus-like particles.


Input: Previous experimental and theoretical studies have established that electrokinetic and aggregation properties of soft MS2 phages are not only governed by the physico-chemical features of their proteinaceous outer surface but are also significantly impacted by those of their inner RNA component (Dika et al. Appl. Environ. Microbiol., 2011, 14, 4939-4948).


Input: These conclusions contradict the recent findings of Nguyen et al.


Input: (Soft Matter, 2011, 7, 10449-10456) who reported identical electrokinetic and aggregation characteristics for MS2 and corresponding virus like particles (VLPs) that lack the internal RNA component.


Input: We demonstrate here that this contradiction originates from the different purification methods adopted prior to measurements.


Input: More generally, we show that stability and electrohydrodynamics of viruses differ according to purification by (i) dialysis, (ii) isopycnic centrifugation in the cesium chloride gradient, and (iii) precipitation using polyethylene glycol (PEG).

cesium chloride

polyethylene glycol

PEG


Input: Methods (i) and (iii) lead to aggregation of MS2 phages at pH <= 4 and pH <= 6 in 1-100 mM NaNO3 solutions, respectively, while under such conditions aggregation is not observed for MS2 and VLP suspensions prepared according to (ii).


Input: In addition, VLPs prepared following methods (i) and (iii) aggregate only at the isoelectric point (pH ~ 3-4) in 1 mM NaNO3 solution.


Input: Electrophoretic mobility data of stable MS2 and VLP particles were further examined using a recent formalism for electrokinetics of soft multilayered colloids.


Input: The analysis qualitatively shows how the purification protocol may affect either the outer particle surface properties and/or the inner particle content.


Input: Finally, the non-DLVO aggregation behavior of MS2 and VLPs purified via the above protocols is discussed in terms of the possible change in corresponding interparticular interactions.


Input: The antipsychotic-like effects of the mGlu group III orthosteric agonist, LSP1-2111, involves 5-HT1A signalling.


Input: RATIONALE: Several studies have suggested that modulation of the glutamatergic system via metabotropic glutamate receptors (mGlu) could be a new way to achieve antipsychotic-like activity.

glutamatergic


Input: LSP1-2111, the group III mGlu receptor orthosteric agonist, with a high affinity towards mGlu4 receptors, was previously shown to exhibit antipsychotic-like action in animal models displaying positive symptoms of schizophrenia.


Input: OBJECTIVES: Here, we decided to investigate the possible role of LSP1-2111 in models of negative (social interaction) and cognitive (NOR) symptoms of psychosis.


Input: We also investigated the involvement of 5-HT1A receptors in the LSP1-2111-induced antipsychotic effects.


Input: Apart from the above-mentioned models of negative and cognitive symptoms, MK-801 and amphetamine-induced hyperactivity tests, plus the DOI-induced head twitches in mice as models for positive symptoms of psychosis, were used in this part of the investigations.

amphetamine

DOI


Input: RESULTS: LSP1-2111 (0. 5, 2, and 5 mg/kg) dose-dependently inhibited MK-801-induced deficits in social interaction and NOR tests.


Input: The effects of the drug were antagonized by 5-HT1A antagonist, WAY100635 (0. 1 mg/kg).


Input: A similar inhibition of LSP1-2111-induced effects was observed in models of positive symptoms of schizophrenia.


Input: Moreover, the concomitant administration of subeffective doses of LSP1-2111 (0. 3-0. 5 mg/kg) with a subeffective dose of 5-HT1A agonist, (R)-(+)-8-Hydroxy-DPAT (0. 01 mg/kg), induced a clear antipsychotic-like effect in all of the procedures used.


Input: CONCLUSIONS: Altogether, we propose that the activation of group III mGlu receptors may be a promising target for the development of novel antipsychotic drugs, towards not only positive but also negative and cognitive symptoms.


Input: The action of the compound is 5-HT1A-dependent.


Input: Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha antagonist lead compound.

chromene

retinoic acid


Input: Retinoic acid receptor alpha (RAR alpha) selective compounds may guide the design of drugs that can be used in conjunction with hormonal adjuvant therapy in the treatment of breast cancer.

Retinoic acid


Input: Herein we report a modified synthesis of a known RAR alpha antagonist, 2-fluoro-4-[[[8-bromo-2, 2-dimethyl-4-(4-methylphenyl) chroman-6-yl] carbonyl] amino] benzoic acid and a synthesis of its unknown, desfluoro analog, 4-[[[8-bromo-2, 2-dimethyl-4-(4-methylphenyl) chroman-6-yl] carbonyl] amino] benzoic acid.

2-fluoro-4-[[[8-bromo-2, 2-dimethyl-4-(4-methylphenyl) chroman-6-yl] carbonyl] amino] benzoic acid

4-[[[8-bromo-2, 2-dimethyl-4-(4-methylphenyl) chroman-6-yl] carbonyl] amino] benzoic acid


Input: The modified route allows for facile reaction workups, increased yields, lower cost and incorporates a green alternative step.


Input: Structure-activity relationship studies determined through functional cell-based assays, demonstrated antagonism to RAR alpha for both compounds.


Input: Molecular modeling within the RAR alpha binding pocket was used to compare binding interactions of the desfluoro analog to a known RAR antagonist.


Input: Synthesis of decacationic [60] fullerene decaiodides giving photoinduced production of superoxide radicals and effective PDT-mediation on antimicrobial photoinactivation.

decacationic [60] fullerene decaiodides

superoxide


Input: We report a novel class of highly water-soluble decacationic methano [60] fullerene decaiodides C60 [> M (C3N6 (+) C3) 2]-(I (-)) 10 [1-(I (-)) 10] capable of co-producing singlet oxygen (Type-II) and highly reactive hydroxyl radicals, formed from superoxide radicals in Type-I photosensitizing reactions, upon illumination at both UVA and white light wavelengths.

decacationic methano [60] fullerene decaiodides C60 [> M (C3N6 (+) C3) 2]-(I (-)) 10

(I (-)) 10

oxygen

hydroxyl

superoxide


Input: The O2 (-).-production efficiency of 1-(I (-)) 10 was confirmed by using an O2 (-).-reactive bis (2, 4-dinitrobenzenesulfonyl) tetrafluorofluorescein probe and correlated to the photoinduced electron-transfer event going from iodide anions to (3) C60 * [> M (C3N6 (+) C3) 2] leading to C60 (-). [> M (C3N6 (+) C3) 2].

O2 (-).

(I (-)) 10

O2 (-).

bis (2, 4-dinitrobenzenesulfonyl) tetrafluorofluorescein

iodide

(3) C60 * [> M (C3N6 (+) C3) 2]

C60 (-). [> M (C3N6 (+) C3) 2]


Input: Incorporation of a defined number (ten) of quaternary ammonium cationic charges per C60 in 1 was aimed to enhance its ability to target pathogenic Gram-positive and Gram-negative bacterial cells.

quaternary ammonium


Input: We used the well-characterized malonato [60] fullerene diester monoadduct C60 [> M (t-Bu) 2] as the starting fullerene derivative to provide a better synthetic route to C60 [> M (C3N6 (+) C3) 2] via transesterification reaction under trifluoroacetic acid catalyzed conditions.

malonato [60] fullerene diester

C60 [> M (t-Bu) 2]

fullerene

C60 [> M (C3N6 (+) C3) 2]

trifluoroacetic acid


Input: These compounds may be used as effective photosensitizers and nano-PDT drugs for photoinactivation of pathogens.


Input: Synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of fused [1, 3, 4] thiadiazoles.

[1, 3, 4] thiadiazoles


Input: New series of [1, 3, 4] thiadiazolo [3, 2-a] pyrimidines, benzo [h] [1, 3, 4] thiadiazolo [2, 3-b] quinazolines, benzothiadiazolotriazocine, and imidazo [2, 1-b] [1, 3, 4] thiadiazoles have been synthesized and characterized by analytical and spectrometrical methods (IR, MS, (1) H and (13) C NMR).

[1, 3, 4] thiadiazolo [3, 2-a] pyrimidines

benzo [h] [1, 3, 4] thiadiazolo [2, 3-b] quinazolines

benzothiadiazolotriazocine

imidazo [2, 1-b] [1, 3, 4] thiadiazoles

(1) H

(13) C


Input: Twenty of the synthesized compounds were screened for antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus cereus.


Input: They were found to be either moderately active, slightly active or inactive against the tested microorganisms.


Input: The antifungal activity of these compounds were also tested against Candida albicans, Aspergillus fumigatus 293 and Aspergillus flavus 3375.


Input: Compounds 3g, h showed potent antifungal activity against C. albicans.


Input: In addition, the same compounds were tested for antiquorum-sensing activity against Chromobacterium violacium ATCC 12472, where compounds 3b, c, 3f-h, 6b-d, 9, 10 and 12 demonstrated acceptable activity.


Input: Compounds 3d, 9 and 10 were screened for antitumor activity at National Cancer Institute, USA.


Input: The in vitro cytotoxic activity of eighteen of the synthesized compounds was studied by brine shrimp lethality bioassay, and results indicated that compounds 6c, 13, 3h, 6d and 3d have the highest cytotoxic activity.


Input: Synthesis using microwave irradiation and antibacterial evaluation of new N, O-acetals and N, S-acetals derived from 2-amino-1, 4-naphthoquinones.

N, O-acetals

N, S-acetals

2-amino-1, 4-naphthoquinones


Input: This paper describes a novel series of N, O-acetals and N, S-acetals (7a-o) derived from 2-amino-1, 4-naphthoquinones that were synthesized and evaluated as potential antimicrobial agents.

N, O-acetals

N, S-acetals

2-amino-1, 4-naphthoquinones


Input: These compounds were obtained in good yields using microwave irradiation, and several of them showed promising antibacterial profiles.


Input: Three of our biologically active 2-amino-1, 4-naphthoquinone N, O-acetals and N, S-acetals tested against hospital bacterial strains were identified as potential lead compounds.

2-amino-1, 4-naphthoquinone N, O-acetals

N, S-acetals


Input: Characterization of all compounds was performed using one-dimensional NMR techniques ((1) H, (13) C-APT), IR spectra, elemental analyses and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS).

(1) H

(13) C


Input: Exact time-dependent density functional theory for impurity models.


Input: We employ the density matrix renormalization group to construct the exact time-dependent exchange-correlation potential for an impurity model with an applied transport voltage.


Input: Even for short-ranged interaction we find an infinitely long-ranged exchange-correlation potential which is built up instantly after switching on the voltage.


Input: Our result demonstrates the fundamental difficulties of transport calculations based on time-dependent density functional theory.


Input: While formally the approach works, important information can be missing in the ground-state functionals and may be hidden in the usually unknown non-equilibrium functionals.


Input: Isoflavone supplementation influenced levels of triglyceride and luteunizing hormone in Korean postmenopausal women.

Isoflavone

triglyceride


Input: We conducted a double-blind, randomized, placebo-controlled trial to evaluate the effects of soy-derived isoflavone on blood glucose, lipid profiles, and sex hormones related to cardiovascular disease in Korean postmenopausal women.

isoflavone

glucose


Input: One hundred thirteen postmenopausal women were recruited from the Seoul metropolitan area.


Input: To confirm postmenopausal and gynecologic status, the subjects were clinically examined by a gynecologist using ultra sound and X-ray.


Input: Finally, 85 postmenopausal women whose follicle-stimulating hormone (FSH) levels were higher than 40 IU/ml were enrolled.


Input: Subjects received either 70 mg isoflavone or placebo capsules daily for 12 weeks.

isoflavone


Input: As a result, the values of fasting glucose, insulin and HOMA-IR, as well as those of TC, LDL-C, HDL-C and FFA, were not different between the groups after supplementation.

glucose


Input: However, triglyceride (TG) levels in the treatment group decreased significantly compared with those of the placebo group (p = 0. 0215).

triglyceride


Input: The levels of luteinizing hormone (LH) significantly decreased in the treatment group (p = 0. 027); however, the levels of FSH, estrone and estradiol were not changed after intervention.

estrone

estradiol


Input: In conclusion, isoflavone supplement of 70 mg/day for 12 weeks decreased blood levels of TG and LH in Korean postmenopausal women.

isoflavone


Input: Arsenic speciation and spatial and interspecies differences of metal concentrations in mollusks and crustaceans from a South China estuary.

Arsenic


Input: Arsenic speciation and concentrations were determined in mollusks and crustaceans in the intertidal zone from twelve locations in Zhanjiang estuary, South China.

Arsenic


Input: Metal concentrations (Ag, As, Cd, Cu, Hg, Ni, Pb, and Zn) were also concurrently determined in these species.

Ag

As

Cd

Cu

Hg

Ni

Pb

Zn


Input: Arsenic speciation analysis showed that the less-toxic arsenobetaine (AsB) constituted 80. 6-98. 8% of all As compounds, and dimethylarsinic acid (DMA) constituted 0. 47-3. 44%.

Arsenic

arsenobetaine

AsB

dimethylarsinic acid

DMA


Input: Monomethylarsonic acid (MMA) and As (V) were only detected in the whelk Drupa fiscella and the crab Heteropilumnus ciliatus, respectively.

Monomethylarsonic acid

MMA

As (V)


Input: Arsenite [As (III)] was not detected in any of the sampled specimens, but there were also unidentified other As species.

Arsenite

As (III)

As


Input: A strong spatial variation of metals in the oyster Saccostrea cucullata was found in the estuary, confirming that oysters can be used as a good biomonitor of metal contamination in the studied area.


Input: The concentrations of eight metals in the studied mollusks and crustaceans clearly revealed that these invertebrates accumulated different metals to different degrees.


Input: Furthermore, As, Cd, Cu, Hg, and Pb contents in mollusks and crustacean samples were below the Food and Agricultural Organization (FAO) safe concentrations, thus there was no obvious health risk from the intake of the metals through marine mollusks and crustaceans consumption.

As

Cd

Cu

Hg

Pb


Input: Pharmacological inhibition of Eph receptors enhances glucose-stimulated insulin secretion from mouse and human pancreatic islets.

glucose


Input: AIMS/HYPOTHESIS: Type 2 diabetes is characterised by impaired glucose-stimulated insulin secretion (GSIS) from pancreatic islets.

glucose


Input: Since erythropoietin-producing hepatoma (Eph)-ephrin bidirectional signalling fine-tunes GSIS from pancreatic beta cells, we investigated Eph receptor tyrosine kinases (RTK) as potential drug targets for selectively increasing GSIS.

tyrosine


Input: METHODS: Insulin secretion assays were carried out using mouse and human pancreatic islets as well as mouse insulinoma (MIN6) cells in the presence or absence of two Eph RTK inhibitors.


Input: Furthermore, the most potent inhibitor was injected into mice to evaluate its effects on glucose tolerance and plasma insulin levels.

glucose


Input: RESULTS: We showed that the Eph RTK inhibitors selectively increased GSIS from MIN6 cells as well as mouse and human islets.


Input: Our results also showed that the insulin secretory effects of these compounds required Eph-ephrin signalling.


Input: Finally, pharmacological inhibition of Eph receptor signalling improved glucose tolerance in mice.

glucose


Input: CONCLUSIONS/INTERPRETATION: We showed for the first time that Eph RTKs represent targets for small molecules to selectively increase GSIS and improve glucose tolerance.

glucose


Input: Effects of Strontium on Collagen Content and Expression of Related Genes in Rat Chondrocytes Cultured In Vitro.

Strontium


Input: Strontium stimulates cartilage matrix formation in vitro.

Strontium


Input: However, the mechanisms governing these effects have not yet been extensively reported.


Input: In this study, chondrocytes were isolated from rat articular cartilage by enzymatic digestion and cultured for 24-72 h with 1-5 mM strontium.

strontium


Input: We investigated the effects of different concentrations of strontium on collagen content, type II collagen, insulin-like growth factor (IGF-1) and matrix metalloproteinase (MMP)-13 expression in rat cultured articular chondrocytes in vitro.

strontium


Input: The collagen content of the chondrocytes, determined as hydroxyproline, was measured by a colorimetry method.

hydroxyproline


Input: Type II collagen, IGF-1, and MMP-13 mRNA abundance and protein expression levels were determined by real-time polymerase chain reaction (real-time PCR) and western blot, respectively.


Input: The results showed that collagen content from the chondrocytes extracellular matrix increased with increasing strontium concentration.

strontium


Input: Moreover, 3 and 5 mM strontium strongly stimulated protein expression and mRNA levels of type II collagen and IGF-1.

strontium


Input: Conversely, MMP-13 expression in chondrocytes decreased dose-dependently with increasing strontium concentration.

strontium


Input: These results should provide insight into the ability of strontium to promote chondrocyte extracellular matrix synthesis.

strontium


Input: Strontium could promote collagen synthesis and suppress collagen degradation via the repression of MMP-13 expression.

Strontium


Input: Effect of nicotine pretreatment on arsenic-induced oxidative stress in male Wistar rats.

nicotine

arsenic


Input: Humans are commonly exposed to nicotine, one of the most important lifestyle chemicals.

nicotine


Input: The occurrence of high levels of arsenic in the groundwater of the southeast region of Asia has received much attention in the past decade and has become a global health concern.

arsenic


Input: Predominant occurrence of both these chemicals and ease of their human exposure led us to investigate the effect of nicotine, a major tobacco alkaloid, on arsenic toxicity.

nicotine

arsenic


Input: Adult male rats were pre-exposed to two different doses of nicotine (0. 75 and 3 mg/kg, intraperitoneally) for 7 days followed by 30 days of arsenic exposure (50 ppm sodium arsenite in drinking water).

nicotine

arsenic

sodium arsenite


Input: Nicotine pre-exposure resulted in an increased brain arsenic accumulation and a decreased liver arsenic concentration.

Nicotine

arsenic

arsenic


Input: Arsenic also caused a significant oxidative stress in the blood, brain and liver of the exposed rats.

Arsenic


Input: Glutathione-S-transferase, a phase II enzyme, was inhibited by both arsenic and nicotine but no such inhibition was noted in arsenic-treated animals pre-exposed to nicotine.

Glutathione

S

arsenic

nicotine

arsenic

nicotine


Input: Upon nicotine pre-exposure, brain acetylcholinesterase increased, while monoamine oxidase (MAO) decreased.

nicotine


Input: The toxic effects of MAO significantly attenuated with nicotine pre-exposure.

nicotine


Input: The present study suggests that nicotine may not be the major contributing factor for the previously reported synergistic toxic interaction between tobacco and arsenic.

nicotine

arsenic


Input: Nicotine pre-exposure in arsenic-exposed animals revealed interesting toxicokinetics and oxidative stress modulating interactions in the brain and liver of rats, which requires further exploration.

Nicotine

arsenic


Input: Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition: II.


Input: Computational Modeling.


Input: Endocrine-disrupting chemicals can affect reproduction and development in humans and wildlife.


Input: We developed a computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (DRTC) behaviors for endocrine effects of the aromatase inhibitor, fadrozole (FAD).

fadrozole

FAD


Input: The model describes adaptive responses to endocrine stress involving regulated secretion of a generic gonadotropin (LH/FSH) from the hypothalamic-pituitary complex.


Input: For model development, we used plasma 17 beta-estradiol (E2) concentrations and ovarian cytochrome P450 (CYP) 19A aromatase mRNA data from two time-course experiments, each of which included both an exposure and a depuration phase, and plasma E2 data from a third 4-day study.

17 beta-estradiol


Input: Model parameters were estimated using E2 concentrations for 0, 0. 5, and 3 micro g/l FAD exposure concentrations, and good fits to these data were obtained.

FAD


Input: The model accurately predicted CYP19A mRNA fold changes for controls and three FAD doses (0, 0. 5, and 3 micro g/l) and plasma E2 dose response from the 4-day study.

FAD


Input: Comparing the model-predicted DRTC with experimental data provided insight into how the feedback control mechanisms in the HPG axis mediate these changes: specifically, adaptive changes in plasma E2 levels occurring during exposure and " overshoot " occurring postexposure.


Input: This study demonstrates the value of mechanistic modeling to examine and predict dynamic behaviors in perturbed systems.


Input: As this work progresses, we will obtain a refined understanding of how adaptive responses within the vertebrate HPG axis affect DRTC behaviors for aromatase inhibitors and other types of endocrine-active chemicals and apply that knowledge in support of risk assessments.


Input: A novel nontoxic inhibitor of the activation of NADPH oxidase reduces reactive oxygen species production in mouse lung.

NADPH

oxygen


Input: 1-Hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33) is a fluorinated phospholipid analog that inhibits the phospholipase A2 (PLA2) activity of peroxiredoxin 6 (Prdx6).

1-Hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol


Input: Prdx6 PLA2 activity is required for activation of NADPH oxidase 2 and subsequent generation of reactive oxygen species (ROS).

NADPH

oxygen


Input: In vitro, MJ33 inhibited agonist-stimulated production of ROS by the isolated perfused mouse lung, lung microvascular endothelial cells, and polymorphonuclear leukocytes.


Input: MJ33 (0. 02-0. 5 micro mol MJ33/kg body weight) in mixed unilamellar liposomes was administered to C57BL/6 mice by either intratracheal (i. t.) or i. v. routes.


Input: Lung MJ33 content, measured by liquid chromatography/mass spectroscopy, showed uptake of 67-87% of the injected dose for i. t. and 23-42% for i. v. administration at 4 hours postinjection.


Input: PLA2 activity of lung homogenates was markedly inhibited (> 85%) at 4 hours postadministration.


Input: Both MJ33 content and PLA2 activity gradually returned to near control levels over the subsequent 24-72 hours.


Input: Mice treated with MJ33 at 12. 5-25 micro mol/kg did not show changes (compared with control) in clinical symptomatology, body weight, hematocrit, and histology of lung, liver, and kidney during a 30-to 50-day observation period.


Input: Thus, the toxic dose of MJ33 was > 25 micro mol/kg, whereas the PLA2 inhibitory dose was approximately 0. 02 micro mol/kg, indicating a high margin of safety.


Input: MJ33 administered to mice prior to lung isolation markedly reduced ROS production and tissue lipid and protein oxidation during ischemia followed by reperfusion.


Input: Thus, MJ33 could be useful as a therapeutic agent to prevent ROS-mediated tissue injury associated with lung inflammation or in harvested lungs prior to transplantation.


Input: When bugs reveal biodiversity.


Input: One of the fundamental challenges of conservation biology is gathering data on species distribution and abundance.


Input: And unless conservationists know where a species is found and in which numbers, it is very difficult to apply effective conservation efforts.


Input: In today' s age of increasingly powerful monitoring tools, instant communication and online databases, one might be forgiven for thinking that such knowledge is easy to come by.


Input: However, of the approximately 5, 400 terrestrial mammals on the IUCN Red List, no fewer than 789 (ca. 14%) are listed as' Data Deficient' (IUCN 2012)-IUCN' s term for' haven' t got a clue'.


Input: Until recently, the only way to gather information of numbers and distribution of terrestrial mammals (and many other vertebrates) was through observational-based approaches such as visual records, the presence of tracks or spoor or even identification from bushmeat or hunters' trophies pinned to the walls in local villages.


Input: While recent technological developments have considerably improved the efficacy of such approaches, for example, using remote-sensing devices such as audio-or camera-traps or even remote drones (Koh & Wich 2012), there has been a growing realization of the power of molecular methods that identify mammals based on trace evidence.


Input: Suitable substrates include the obvious, such as faecal and hair samples (e. g. Vigilant et al. 2009), to the less obvious, including environmental DNA extracted from sediments, soil or water samples (e. g. Taberlet et al. 2012), and as recently demonstrated, the dietary content of blood-sucking invertebrates (Gariepy et al. 2012; Schnell et al. 2012).


Input: In this issue of Molecular Ecology, Calvignac-Spencer et al.


Input: (2013) present a potentially powerful development in this regard; diet analysis of carrion flies.


Input: With their near global distribution, and as most field biologists know, irritatingly high frequency in most terrestrial areas of conservation concern (which directly translates into ease of sampling them), the authors present extremely encouraging results that indicate how carnivorous flies may soon represent a strong weapon in the conservation arsenal.


Input: Modeling ring/chain equilibrium in nanoconfined sulfur.

sulfur


Input: The effect of nanoconfinement on the thermodynamics of free radical polymerization of sulfur is examined.

sulfur


Input: We extend Tobolsky and Eisenberg' s model of bulk sulfur polymerization to nanopores accounting for the confinement entropy of the chains and ring using scaling reported in literature.

sulfur


Input: The model quantitatively captures literature data from Yannopoulos and co-workers for the extent of polymerization versus temperature for bulk sulfur polymerization and for polymerization in 20, 7. 5, and 2. 5 nm diameter Gelsil nanopores, assuming that the change of entropy of nanoconfined chains scales with molecular size to the second power and with nanopore diameter to either the-3. 0 or-3. 8 power, the former of which fits slightly better.

sulfur

Gelsil


Input: The scaling, which is valid for strong confinement in spherical pores, predicts that the propagation equilibrium constant will depend on both nanopore size and chain length, such that the average chain length decreases significantly upon confinement.


Input: Mechanisms of vesicle spreading on surfaces: coarse-grained simulations.


Input: Exposition of unilamellar vesicles to attractive surfaces is a frequently used way to create supported lipid bilayers.


Input: Although this approach is known to produce continuous supported bilayer coatings, the mechanism of their formation and its dependence on factors like surface interaction and roughness or membrane tension as well as the interplay between neighboring vesicles or the involvement of preadsorbed bilayer patches are not well understood.


Input: Using dissipative particle dynamics simulations, we assess different mechanisms of vesicle spreading on attractive surfaces, placing special emphasis on the orientation of the resulting bilayer.


Input: Making use of the universality of collective phenomena in lipid membranes, we employed a solvent-free coarse-grained model, enabling us to cover the relatively large system sizes and time scales required.


Input: Our results indicate that one can control the mechanism of vesicle spreading by tuning the strength and range of the interactions with the substrate as well as the surface' s roughness, resulting in a switch from a predominant inside-up to an outside-up orientation of the created supported bilayer.


Input: Secondary Metabolites of Capsicum Species and Their Importance in the Human Diet.


Input: The genus Capsicum (pepper) comprises a large number of wild and cultivated species.


Input: The plants are grown all over the world, primarily in tropical and subtropical countries.


Input: The fruits are an excellent source of health-related compounds, such as ascorbic acid (vitamin C), carotenoids (provitamin A), tocopherols (vitamin E), flavonoids, and capsaicinoids.

ascorbic acid

vitamin C

tocopherols

vitamin E

flavonoids

capsaicinoids


Input: Pepper fruits have been used for fresh and cooked consumption, as well as for medicinal purposes, such as treatment of asthma, coughs, sore throats, and toothache.


Input: Depending on its uses, there are several main characters important for product quality; pungency, bright attractive colors, highly concentrated extracts, and a small number of seeds are the main characters on which quality is based and priced.


Input: Herein, a general overview of biochemical composition, medical properties of these compounds, and characteristics of quality attributes of pepper fruits is presented.


Input: Thermorheological complexity and fragility in plasticized lignocellulose.


Input: It is demonstrated that plasticized lignocellulose fails to satisfy classic criteria normally required to validate time/temperature superposition (TTS) in dynamic mechanical analysis (DMA).


Input: However, insightful relaxation behavior is available and dismissing it would be a mistake.


Input: TTS was applied to Liriodendron tulipifera wood using parallel plate compressive-torsion DMA with specimens immersed in different organic liquids, ranging from weak to strong swelling power.


Input: While all storage moduli shifted smoothly, thermorheological complexity was detected in loss modulus shift failures, which themselves must reflect unknown structural features.


Input: Storage modulus shift factors clearly distinguished solvent specific relaxation behavior and interpretations through the WLF model or through fragility (cooperativity) analysis are useful.


Input: However, it is demonstrated that fragility analysis is preferred and solvents of different swelling power are compared.


Input: Coupled with other methods, TTS and fragility analysis warrant further development as a means to improve the understanding of structure/property relationships in plasticized lignocellulose.


Input: DNA Adducts in Aldehyde Dehydrogenase-Positive Lung Stem Cells of A/J Mice Treated with the Tobacco Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

Aldehyde

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone

NNK


Input: Lung cancer is the leading cause of cancer death in the world.


Input: Evidence suggests that lung cancer could originate from mutations accumulating in a subpopulation of self-renewing cells, lung stem cells.


Input: Aldehyde dehydrogenase (ALDH) is a marker of stem cells.

Aldehyde


Input: To investigate the presence of DNA modifications in these cells, we isolated ALDH-positive lung cells from A/J mice exposed to the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone


Input: Using LC-NSI-HRMS/MS-PRM, O (6)-methyl-G, 7-POB-G, and O (2)-POB-dT were positively identified in ALDH-positive cell DNA.

O (6)-methyl-G

O (2)-POB-dT


Input: This is the first example of detection of carcinogen-DNA adducts in lung stem cells, supporting the hypothesis of their role in lung carcinogenesis.


Input: Safety and efficacy of polycalcium for improving biomarkers of bone metabolism: a 4-week open-label clinical study.

polycalcium


Input: Polycalcium is a mixture of Polycan and calcium lactate-gluconate 1: 9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies.

Polycalcium

calcium lactate-gluconate


Input: These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety.

Polycalcium


Input: In total, 30 healthy women (range 40-60 years) were administered 400 mg of Polycalcium for 4 weeks.

Polycalcium


Input: The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium.

deoxypyridinoline

DPYR

N

calcium

Ca

phosphorus

P

Polycalcium


Input: After 4 weeks of Polycalcium administration, 27 subjects completed the test plan.

Polycalcium


Input: Three subjects withdrew their consent to participate.


Input: The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by-28. 44%, 14. 37%, 6. 11%, and 1. 42%, respectively.

Ca

P


Input: Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by-13. 40%, 6. 67%,-5. 13%,-22. 43%, and-3. 04%, respectively.

DPYR

Ca

P


Input: Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400 mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe.

Polycalcium


Input: Polycalcium was apparently safe and efficacious.

Polycalcium


Input: Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor.


Input: A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design.


Input: An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation.


Input: Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model.


Input: A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket.

Asp

Lys


Input: Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4.

amino-acid


Input: Autophagy is an evolutionarily conserved catabolic mechanism that targets intracellular molecules and damaged organelles to lysosomes.


Input: Autophagy is achieved by a series of membrane trafficking events, but their regulatory mechanisms are poorly understood.


Input: Here, we report small GTPase Rab12 as a new type of autophagic regulator that controls the degradation of an amino-acid transporter.

amino-acid


Input: Knockdown of Rab12 results in inhibition of autophagy and in increased activity of mTORC1 (mammalian/mechanistic target of rapamycin complex 1), an upstream regulator of autophagy.

rapamycin


Input: We also found that Rab12 promotes constitutive degradation of PAT4 (proton-coupled amino-acid transporter 4), whose accumulation in Rab12-knockdown cells modulates mTORC1 activity and autophagy.

amino-acid


Input: Our findings reveal a new mechanism of regulation of mTORC1 signalling and autophagy, that is, quality control of PAT4 by Rab12.


Input: Chondroitin sulfate, hyaluronic Acid and chitin/chitosan production using marine waste sources: characteristics, applications and eco-friendly processes: a review.


Input: In the last decade, an increasing number of glycosaminoglycans (GAGs), chitin and chitosan applications have been reported.


Input: Their commercial demands have been extended to different markets, such as cosmetics, medicine, biotechnology, food and textiles.


Input: Marine wastes from fisheries and aquaculture are susceptible sources for polymers but optimized processes for their recovery and production must be developed to satisfy such necessities.


Input: In the present work, we have reviewed different alternatives reported in the literature to produce and purify chondroitin sulfate (CS), hyaluronic acid (HA) and chitin/chitosan (CH/CHs) with the aim of proposing environmentally friendly processes by combination of various microbial, chemical, enzymatic and membranes strategies and technologies.


Input: Benzoquinone Reveals a Cysteine-Dependent Desensitization Mechanism of TRPA1.

Benzoquinone

Cysteine


Input: The transient receptor potential ankyrin 1 (TRPA1) nonselective cation channel has a conserved function as a noxious chemical sensor throughout much of Metazoa.


Input: Electrophilic chemicals activate both insect and vertebrate TRPA1 via covalent modification of cysteine residues in the amino-terminal region.

cysteine

amino


Input: Although naturally occurring electrophilic plant compounds, such as mustard oil and cinnamaldehyde, are TRPA1 agonists, it is unknown whether arthropod-produced electrophiles activate mammalian TRPA1.

cinnamaldehyde


Input: We characterized the effects of the electrophilic arthropod defensive compound para-benzoquinone (pBQN) on the human TRPA1 channel.

para-benzoquinone

pBQN


Input: We used whole-cell recordings of human embryonic kidney cells heterologously expressing either wild-type TRPA1 or TRPA1 with three serine-substituted cysteines crucial for electrophile activation (C621S, C641S, C665S).

serine

cysteines


Input: We found that pBQN activates TRPA1 starting at 10 nM and peaking at 300 nM; higher concentrations caused rapid activation followed by a fast decline.

pBQN


Input: Activation by pBQN required reactivity with cysteine residues, but ones that are distinct from those previously reported to be the key targets of electrophiles.

pBQN

cysteine


Input: The current reduction we found at higher pBQN concentrations was a cysteine-dependent desensitization of TRPA1, and did not require prior activation.

pBQN


Input: The cysteines required for desensitization are not accessible to all electrophiles as iodoacetamide and internally applied 2-(trimethylammonium) ethyl methanesulfonate failed to cause desensitization (despite large activation).

cysteines

iodoacetamide

2-(trimethylammonium) ethyl methanesulfonate


Input: Interestingly, following pBQN desensitization, wild-type TRPA1 had dramatically reduced response to the nonelectrophile agonist carvacrol, whereas the triple cysteine mutant TRPA1 retained its full response.

pBQN

carvacrol

cysteine


Input: Our results suggest that modification of multiple cysteine residues by electrophilic compounds can generate both activation and desensitization of the TRPA1 channel.

cysteine


Input: Multiplex analysis of enzyme kinetics and inhibition by droplet microfluidics using picoinjectors.


Input: Enzyme kinetics and inhibition is important for a wide range of disciplines including pharmacology, medicine and industrial bioprocess technology.


Input: We present a novel microdroplet-based device for extensive characterization of the reaction kinetics of enzyme substrate inhibitor systems in a single experiment utilizing an integrated droplet picoinjector for bioanalysis.


Input: This device enables the scanning of multiple fluorescently-barcoded inhibitor concentrations and substrate conditions in a single, highly time-resolved experiment yielding the Michaelis constant (Km), the turnover number (kcat) and the enzyme inhibitor dissociation constants (ki, ki').


Input: Using this device we determine Km and kcat for beta-galactosidase and the fluorogenic substrate Resorufin beta-d-galactopyranoside (RBG) to be 442 mu M and 1070 s (-1), respectively.

Resorufin beta-d-galactopyranoside

RBG


Input: Furthermore, we examine the inhibitory effects of isopropyl-beta-d-thiogalactopyranoside (IPTG) on beta-galactosidase.

isopropyl-beta-d-thiogalactopyranoside

IPTG


Input: This system has a number of potential applications, for example it could be used to screen inhibitors to pharmaceutically relevant enzymes and to characterize engineered enzyme variants for biofuels production, in both cases acquiring detailed information about the enzyme catalysis and enzyme inhibitor interaction at high throughput and low cost.


Input: A study of parabens and bisphenol A in surface water and fish brain tissue from the Greater Pittsburgh Area.

parabens

bisphenol A


Input: Pollution from xenoestrogens has been discovered in the aquatic environment of the Greater Pittsburgh Area and is suspected to be caused by the failing sewer system.

xenoestrogens


Input: Personal care products and plasticizers have the potential to enter the water supply though treated and untreated sewage.


Input: Many of these compounds are suspected xenoestrogens.

xenoestrogens


Input: Paraben detection in surface waters was as follows: methyl paraben ranged between 2. 2 to 17. 3 ppt; ethyl paraben was not detectable; propyl paraben was detected at 9. 2 and 12. 0 ppt; butyl paraben was detected at 0. 2 ppt.

Paraben

methyl paraben

ethyl paraben

propyl paraben

butyl paraben


Input: BPA was detected between 0. 6 and 15. 4 ppt.

BPA


Input: Estrogenic potential of extracts from fish brain tissue was tested via Bromodeoxyuridine MCF-7 analysis and paired with HPLC-MS to investigate the presence of xenoestrogens.

Bromodeoxyuridine

xenoestrogens


Input: All samples were non-detectable for parabens.


Input: BPA was detected in 44 of the 58 samples, with a range from non-detectable to 120 pg/g.

BPA


Input: BCFs were calculated.


Input: Results were statistically significant for location of capture (p < 0. 05) and correlation existed between estrogenicity and BPA.

BPA


Input: Sulfide induces apoptosis and Rho kinase-dependent cell blebbing in Jurkat cells.

Sulfide


Input: Hydrogen sulfide (H2S) is a toxic gaseous substance, and accidental exposure to high concentrations of H2S has been reported to be lethal to humans.

Hydrogen sulfide


Input: Inhaled and absorbed H2S is partially dissolved within the circulation and causes toxic effects on lymphocytes.


Input: However, the mechanisms involved in H2S toxicity have not been well documented.


Input: In this study, we examined the cellular uptake and injury of sulfide-exposed human T lymphocytes (Jurkat).

sulfide


Input: Cells were exposed to a H2S donor, sodium hydroxysulfide (NaHS), at pH 6. 0, 7. 0, or 8. 0 for 1 h at 37 degrees C in a sealed conical tube to avoid the loss of dissolved H2S gas.

sodium hydroxysulfide

NaHS


Input: Cytotoxicity and cellular sulfide concentrations increased dramatically as the pH of the NaHS solution decreased.

sulfide

NaHS


Input: Sulfide enhanced the cleavage of caspase-3 and poly (ADP-ribose) polymerase and induced early cellular apoptosis.

Sulfide

poly (ADP-ribose)


Input: A pan-caspase inhibitor reduced sulfide-induced apoptosis.

sulfide


Input: These results indicate that sulfide induces pH-dependent and caspase-dependent apoptosis.

sulfide


Input: We also found that blebbing of the plasma membrane occurred in sulfide-exposed cells.

sulfide


Input: Both ROCK-1 and ROCK-2 (Rho kinases) were activated by sulfide, and sulfide-induced cell blebbing was suppressed by a ROCK inhibitor, suggesting that a Rho pathway is involved in sulfide-induced blebbing in lymphocytes.

sulfide

sulfide

sulfide


Input: Association Between Lipids, Lipoproteins Composition of HDL Particles and Triglyceride-Rich Lipoproteins, and LCAT and CETP Activity in Post-renal Transplant Patients.

Triglyceride


Input: High-density lipoprotein (HDL) remodeling within the plasma compartment and the association between lecithin-cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) activity, and lipid, lipoprotein concentrations and composition were investigated.

cholesterol

cholesterol ester


Input: The aim was to examine the high sensitivity of C-reactive protein (hsCRP), lipid, apolipoprotein B (apoB), apoAI, total apoAII, apoAIInonB, apoB-containing apoAII (apoB: AII), total apoCIII, apoCIIInonB, apoB-containing apoCIII (apoB: CIII) concentration and LCAT and CETP activity to gain an insight into the association between them and LCAT and CETP, 57 post-renal transplant (Tx) patients with and without statin therapy and in 15 healthy subjects.


Input: Tx patients had moderate hypertriglyceridemia, hypercholesterolemia, and dyslipoproteinemia, disturbed triglyceride-rich lipoproteins (TRLs) and HDL composition, decreased LCAT, and slightly increased hsCRP but no CETP activity.


Input: Spearman' s correlation test showed the association between lipids and lipoproteins and LCAT or CETP, and multiple ridge stepwise forward regression showed that immunosuppressive therapy in Tx patients can disturb HDL and TRLs composition.


Input: The results suggest that inhibition or activation of LCAT is due, in part, to HDL-associated lipoprotein.