Input: The 50% protective etomidate concentration (PC50) is 14 mu M in inactive receptors and 1. 1 to 2. 2 mu M during GABA-activation, experimentally demonstrating that activated receptors bind etomidate more avidly than inactive receptors.

etomidate

GABA

etomidate


Input: The experimental PC50 values are remarkably close to, and therefore validate MWC model predictions for etomidate dissociation constants in both inactive and active receptors.

etomidate


Input: Our results support MWC models as valid frameworks for understanding agonism, co-agonism, and modulation of ligand-gated ion channels.


Input: The nuclear receptors COUP-TF: a long-lasting experience in forebrain assembly.


Input: Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are nuclear receptors belonging to the superfamily of the steroid/thyroid hormone receptors.

steroid


Input: Members of this family are internalized to the nucleus both in a ligand-dependent or-independent manner and act as strong transcriptional regulators by binding to the DNA of their target genes.


Input: COUP-TFs are defined as orphan receptors, since ligands regulating their activity have not so far been identified.


Input: From the very beginning of metazoan evolution, these molecules have been involved in various key events during embryonic development and organogenesis.


Input: In this review, we will mainly focus on their function during development and maturation of the central nervous system, which has been well characterized in various animal classes ranging from ctenophores to mammals.


Input: We will start by introducing the current knowledge on COUP-TF mechanisms of action and then focus our discussion on the crucial processes underlying forebrain ontogenesis, with special emphasis on mammalian development.


Input: Finally, the conserved roles of COUP-TFs along phylogenesis will be highlighted, and some hypotheses, worth exploring in future years to gain more insight into the mechanisms controlled by these factors, will be proposed.


Input: Cavitation during tensile deformation of isothermally crystallized polypropylene and high-density polyethylene.

polypropylene

polyethylene


Input: The cavitation phenomenon was studied in isothermally and non-isothermally crystallized polypropylene and high-density polyethylene.

polypropylene

polyethylene


Input: It was found that nano-voids were not present in the crystallized samples, but were formed during their tensile deformation.


Input: The process of cavitation was initiated before reaching the yield point.


Input: The ellipsoidal voids were initially elongated perpendicularly to the deformation direction, but if the polymer (i. e., high-density polyethylene) was able to deform beyond the yield, then the reorientation of voids into the deformation direction was observed at local strains of 100-200%.

polyethylene


Input: This behavior was similar to that observed previously in the samples crystallized without an exact control of solidification conditions.


Input: The calculations of Guinier' s radius showed that voids in deformed polypropylene samples were characterized by the gyration radii of 28-50 nm.

polypropylene


Input: Smaller voids were observed in polyethylene.

polyethylene


Input: The scale of cavitation during deformation, studied on the example of polyethylene, depended on the preceding crystallization process and was most intensive for the specimens crystallized at the highest temperature of 125 degrees C.

polyethylene


Input: Combinatorial Design of Hydrolytically Degradable, Bone-like Biocomposites Based on PHEMA and Hydroxyapatite.

PHEMA

Hydroxyapatite


Input: With advantages such as design flexibility in modifying degradation, surface chemistry, and topography, synthetic bone-graft substitutes are increasingly demanded in orthopedic tissue engineering to meet various requirements in the growing numbers of cases of skeletal impairment worldwide.


Input: Using a combinatorial approach, we developed a series of biocompatible, hydrolytically degradable, elastomeric, bone-like biocomposites, comprising 60 wt% poly (2-hydroxyethyl methacrylate-co-methacrylic acid), poly (HEMA-co-MA), and 40 wt% bioceramic hydroxyapatite (HA).

poly (2-hydroxyethyl methacrylate-co-methacrylic acid)

poly (HEMA-co-MA)

hydroxyapatite


Input: Hydrolytic degradation of the biocomposites is rendered by a degradable macromer/crosslinker, dimethacrylated poly (lactide-b-ethylene glycol-b-lactide), which first degrades to break up 3-D hydrogel networks, followed by dissolution of linear pHEMA macromolecules and bioceramic particles.

dimethacrylated poly (lactide-b-ethylene glycol-b-lactide)

pHEMA


Input: Swelling and degradation were examined at Hank' s balanced salt solution at 37 degrees C in a 12-week period of time.


Input: The degradation is strongly modulated by altering the concentration of the co-monomer of methacrylic acid and of the macromer, and chain length/molecular weight of the macromer.

methacrylic acid


Input: 95% weight loss in mass is achieved after degradation for 12 weeks in a composition consisting of HEMA/MA/Macromer = 0/60/40, while 90% weight loss is seen after degradation only for 4 weeks in a composition composed of HEMA/MA/Macromer = 27/13/60 using a longer chain macromer.

HEMA

HEMA


Input: For compositions without a co-monomer, only about 14% is achieved in weight loss after 12-week degradation.


Input: These novel biomaterials offer numerous possibilities as drug delivery carriers and bone grafts particularly for low and medium load-bearing applications.


Input: Chemical genetic analyses of quantitative changes in Cdk1 activity during the human cell cycle.


Input: Cyclin-dependent kinase 1 (Cdk1) controls cell proliferation and is inhibited by promising anticancer agents, but its mode of action and the consequences of its inhibition are incompletely understood.


Input: Cdk1 promotes S-and M-phases during the cell-cycle but also suppresses endoreduplication, which is associated with polyploidy and genome instability.


Input: The complexity of Cdk1 regulation has made it difficult to determine whether these different roles require different thresholds of kinase activity and whether the surge of activity as inhibitory phosphates are removed at mitotic onset is essential for cell proliferation.

phosphates


Input: Here, we have used chemical genetics in a human cell line to address these issues.


Input: We rescued cells lethally depleted of endogenous Cdk1 with an exogenous Cdk1 conferring sensitivity to one ATP analogue inhibitor (1NMPP1) and resistance to another (RO3306).

ATP


Input: At no 1NMPP1 concentration was mitosis in rescued clones prevented without also inducing endoreduplication, suggesting that these two key roles for Cdk1 are not simply controlled by different Cdk1 activity thresholds.


Input: We also rescued RO3306-resistant clones using exogenous Cdk1 without inhibitory phosphorylation sites, indicating that the mitotic surge of Cdk1 activity is dispensable for cell proliferation.


Input: These results suggest that the basic mammalian cycle requires at least some qualitative changes in Cdk1 activity and that quantitative increases in activity need not be rapid.


Input: Furthermore, the viability of cells that are unable to undergo rapid Cdk1 activation, and the strong association between endoreduplication and impaired proliferation, may place restrictions on the therapeutic use of a Cdk1 inhibitors.


Input: Serum trace elements levels in preeclampsia and eclampsia: correlation with the pregnancy disorder.


Input: Preeclampsia and eclampsia are fatal medical complications of pregnancy accounting for 20-80% of increased maternal death in developing countries.


Input: Their aetiologies are still under investigation.


Input: Serum trace elements have been suggested to be involved in the pathogenesis of preeclampsia.


Input: Aim of this study was to address the correlation of serum trace elements with preeclampsia and eclampsia.


Input: It was a comparative cross-sectional study conducted on conveniently recruited 44 preeclampsia, 33 eclampsia and 27 normotensive pregnant patients.


Input: Atomic absorption spectrometry was employed to analyse serum concentrations of Ca, Mg, Cu, Zn and Fe.

Ca

Mg

Cu

Zn

Fe


Input: Data were analysed by Student' s t test, one-way analysis of variance and multinomial logistic and binary regression analyses.


Input: p < 0. 05 was considered as a level of significance.


Input: In preeclampsia, the serum Ca and Mg were significantly lower than those in eclampsia, while Cu and Zn values were higher.

Ca

Mg

Cu

Zn


Input: Significant changes of Ca, Mg and Cu were noted among preeclampsia, eclampsia and pregnant control.

Ca

Mg

Cu


Input: Serum Ca and Mg indicated a positive association, and Cu gave a negative association in preeclampsia.

Ca

Mg

Cu


Input: Cu/Fe ratio was high in eclampsia.

Cu

Fe


Input: Significant correlations of Mg with Zn in eclampsia and Mg with Fe in preeclampsia and eclampsia were predicted.

Mg

Zn

Mg

Fe


Input: Significant changes in serum trace element levels were present in preeclampsia and eclampsia that may have a link with the pathogenesis of pregnancy disorder.


Input: Blood Flow of the Acral Finger Arterioles in Patients With Type 2 Diabetes by Quality Doppler Profiles.


Input: Patients with diabetes mellitus exhibit peripheral arterioles lesions that is associated with reduced blood flow.


Input: Here, we intended to assess the acral arterioles lesion in patients with type 2 diabetes based on the rate of blood flow by multigate spectral Doppler ultrasonography.


Input: Fifty-two patients with type 2 DM were divided into two groups.


Input: Group 1 included 13 men and 12 women with an average age of 60. 60 +/- 14. 03 years and a duration of type 2 diabetes for 2. 44 +/- 1. 50 years.


Input: Group 2 included 17 men and 11 women with an average age of 64. 25 +/- 10. 84 years and type 2 diabetes for 12. 57 +/- 6. 26 years.


Input: Age-matched control subjects (n = 52) were recruited (30 men and 22 woman, mean age of 61. 19 +/- 10. 38 years).


Input: A multigate spectral Doppler algorithm was applied to the acral finger of the thumb of the right hand to test the arteriole diameter and hemodynamic parameters, including diameter of the acral finger arterioles (D), area of the blood flow profile of the acral finger arterioles (A max) and hemodynamic parameters.


Input: Patients with diabetes exhibited a significant reduction in the arteriole diameter (1. 63 +/- 0. 18 and 1. 57 +/- 0. 22 mm, respectively, P < 0. 001 for both) compared to control subjects (2. 09 +/- 0. 17 mm).


Input: A max were significantly reduced in patients with diabetes (61. 35 +/- 10. 66 mm (2)/s for group 1 and 46. 50 +/- 6. 59 mm (2)/s for group 2, P < 0. 001 for both) compared to that in control subjects (77. 93 +/- 12. 37 mm (2)/s).


Input: Furthermore, a significant difference in Amax was found between group 1 and group 2 (P < 0. 001).


Input: The vascular resistance index (RI) was significantly higher in both patient groups 0. 58 +/- 0. 06 for group 1 (P < 0. 001) and 0. 64 +/- 0. 07 for group 2 (P < 0. 001) than that in control subjects (0. 48 +/- 0. 04).


Input: The RI value of the acral finger arterioles differed significantly between group 1 and group 2 (P < 0. 01).


Input: Diabetic patients exhibited a weak blood flow in the acral finger arterioles.


Input: The multigate spectral Doppler technology can be used to test blood flow in the acral finger arterioles and provide hemodynamic data for systematic analyses of the peripheral arteriole lesions in diabetes.


Input: Alkaloids from Lycoris caldwellii and their particular cytotoxicities against the astrocytoma and glioma cell lines.


Input: Phytochemical investigation of the ethanol extract of the bulbs of Lycoris caldwellii afforded four new alkaloids, (+)-N-methoxylcarbonyl-nandigerine (1), (+)-N-methoxycarbonyl-lindcarpine (2), (+)-10-O-methylhernovine N-oxide (3), and (+)-3-hydroxy-anhydrolycorine N-oxide (4).

ethanol

(+)-N-methoxylcarbonyl-nandigerine

(+)-N-methoxycarbonyl-lindcarpine

(+)-10-O-methylhernovine N-oxide

(+)-3-hydroxy-anhydrolycorine N-oxide


Input: Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D ((1) H-(1) H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry.

(1) H

(1) H


Input: All the alkaloids were in vitro evaluated for their cytotoxic activities against eight tumor cell lines (BEN-MEN-1, CCF-STTG1, CHG-5, SHG-44, U251, BGC-823, HepG2, and SK-OV-3).


Input: Alkaloids 1 and 2 exhibited particular cytotoxic activities against astrocytoma and glioma cell lines with IC50 of 9. 2-11. 3 mu M and 10. 4-12. 2 mu M respectively.


Input: Discovery of a Series of Thiazole Derivatives as Novel Inhibitors of Metastatic Cancer Cell Migration and Invasion.

Thiazole


Input: Effective inhibitors of cancer cell migration and invasion can potentially lead to clinical applications as therapy to block tumor metastasis, the primary cause of death in cancer patients.


Input: To this end we have designed and synthesized a series of thiazole derivatives that showed potent efficacy against cell migration and invasion in metastatic cancer cells.

thiazole


Input: The most effective compound, 5k, was found to have an IC50 value of 176 nM in the dose-dependent transwell migration assays in MDA-MB-231cells.


Input: At the dose of 10 mu M, 5k also blocked about 80% of migration in HeLa and A549 cells and 60% of invasion of MDA-MB-231 cells.


Input: Importantly, the majority of the derivatives exhibited no apparent cytotoxicity in the clonogenic assays.


Input: The low to negligible inhibition of cell proliferation is a desirable property of these anti-migration derivatives because they hold promise of low toxicity to healthy cells as potential therapeutic agents.


Input: Mechanistic studies analyzing the actin cytoskeleton by microscopy demonstrate that compound 5k substantially reduced cellular f-actin, and prevented localization of fascin to actin-rich membrane protrusions.


Input: These results suggest that the anti-migration activity may result from impaired actin structures in protrusions that are necessary to drive migration.


Input: Recent Advances in Metal-Organic Framework-Based Mixed Matrix Membranes.


Input: Mixed matrix membranes (MMMs) combine easy processability and low cost of polymers with the high selectivity of nanoporous filler particles.


Input: These membranes represent an important avenue for enhancing the performance of polymeric membranes in gas separations.


Input: Recently, a new group of nanoporous materials called metal-organic frameworks (MOFs) have been used as filler particles in MMM applications, and significant improvements in gas selectivity and permeability have been reported for these MOF-based membranes.


Input: We discuss the recent developments in MOF-based MMMs by reviewing both the experimental studies and computational modeling methods that can accelerate selection of MOF/polymer combinations for high-performance gas separations.


Input: Acute Kidney Injury During Vancomycin Therapy in Critically Ill Children.

Vancomycin


Input: STUDY OBJECTIVE: To determine the rate, risk factors, and outcome of vancomycin-associated acute kidney injury (AKI) in critically ill children.

vancomycin


Input: DESIGN: Retrospective cohort study.


Input: SETTING: Tertiary care children' s hospital.


Input: PATIENTS: We reviewed the charts of children admitted to the pediatric intensive care unit during a 2-year period who were treated with vancomycin.

vancomycin


Input: Courses of vancomycin interrupted by 3 days or more were counted separately.

vancomycin


Input: Patients were excluded if they received vancomycin treatment for fewer than 3 days, had preexisting renal failure, or had incomplete serum creatinine (Scr) data.

vancomycin

creatinine


Input: MEASUREMENTS AND MAIN RESULTS: Demographic and laboratory data; vancomycin dose, duration, and concentrations; and concurrent use of nephrotoxic drugs were recorded.

vancomycin


Input: Acute kidney injury was defined as a decrease in estimated glomerular filtration rate of 50% or more from the beginning of vancomycin therapy.

vancomycin


Input: Descriptive statistics, step-wise logistic regression, and repeated measures ANOVA were used to analyze the data.


Input: A total of 284 patients were included, for a total of 391 courses of vancomycin (272 children and 119 infants).

vancomycin


Input: The mean duration of vancomycin therapy was 6. 9 +/- 4. 5 days.

vancomycin


Input: Forty nine (17. 2%) patients developed AKI during 61 (15. 6%) courses.


Input: Elevated Scr concentrations returned to baseline after stopping vancomycin in 53 (87%) courses.

vancomycin


Input: Mortality was higher in children who developed AKI (p < 0. 001; Fisher' s exact test).


Input: Administration of nephrotoxic drugs (odds ratio 2. 23, Confidence Interval 1. 27-3. 93) and presence of high blood urea nitrogen (BUN): Scr ratio before vancomycin therapy (p < 0. 05) were associated with AKI.

urea nitrogen

vancomycin


Input: The BUN and Scr concentrations significantly increased during vancomycin therapy and decreased after vancomycin was discontinued (p < 0. 05).

vancomycin

vancomycin


Input: CONCLUSIONS: In critically ill children, the development of reversible AKI during vancomycin therapy is associated with administration of nephrotoxic drugs and an elevated BUN: Scr ratio.

vancomycin


Input: The Mechanisms of Radical SAM/Cobalamin Methylations: An Evolving Working Hypothesis.

Cobalamin


Input: All about Me: Pierre and co-workers have revealed mechanistic details of a tryptophan methyltransferase (TsrM) involved in the biosynthesis of the thiopeptide antibiotic, thiostrepton.

tryptophan

thiostrepton


Input: Utilising cobalamin and a [4Fe-4S] cluster to generate 2-methyltryptophan from tryptophan, a key difference between this enzyme and other radical SAM methyltransferases is that the reaction is not initiated by a single-electron reduction of SAM to generate 5'-dA..

cobalamin

tryptophan


Input: tert-Butylcarbamate-Containing Histone Deacetylase Inhibitors: Apoptosis Induction, Cytodifferentiation, and Antiproliferative Activities in Cancer Cells.

tert-Butylcarbamate


Input: Herein we report novel pyrrole-and benzene-based hydroxamates (8, 10) and 2'-aminoanilides (9, 11) bearing the tert-butylcarbamate group at the CAP moiety as histone deacetylase (HDAC) inhibitors.

pyrrole

benzene

hydroxamates

tert-butylcarbamate


Input: Compounds 8 b and 10 c selectively inhibited HDAC6 at the nanomolar level, whereas the other hydroxamates effected an increase in acetyl-alpha-tubulin levels in human acute myeloid leukemia U937 cells.

hydroxamates


Input: In the same cell line, compounds 8 b and 10 c elicited 18. 4 and 21. 4% apoptosis, respectively (SAHA: 16. 9%), and the pyrrole anilide 9 c displayed the highest cytodifferentiating effect (90. 9%).

SAHA

pyrrole anilide


Input: In tests against a wide range of various cancer cell lines to determine its antiproliferative effects, compound 10 c exhibited growth inhibition from sub-micromolar (neuroblastoma LAN-5 and SH-SY5Y cells, chronic myeloid leukemia K562 cells) to low-micromolar (lung H1299 and A549, colon HCT116 and HT29 cancer cells) concentrations.


Input: In HT29 cells, 10 c increased histone H3 acetylation, and decreased the colony-forming potential of the cancer cells by up to 60%.


Input: Phospholipid/Carbocyanine Dye-Shelled Microbubbles as Ultrasound-Modulated Fluorescent Contrast Agents.

Carbocyanine


Input: Fluorescent microbubbles have been fabricated with the capacity to have their emission modulated by ultrasound.


Input: These contrast agent particles could potentially be used in the future to extract fluorescence modulation from a strong light background to increase imaging depth and resolution in scattering media.


Input: Fluorescence intensity modulation was demonstrated at the ultrasound driving frequency.


Input: Exploring the effect of N-substitution in nor-lobelane on the interaction with VMAT2: discovery of a potential clinical candidate for treatment of methamphetamine abuse.

N

nor-lobelane

methamphetamine


Input: A series of N-substituted lobelane analogues was synthesized and evaluated for their [(3) H] dihydrotetrabenazine binding affinity at the vesicular monoamine transporter and for their inhibition of vesicular [(3) H] dopamine uptake.

N

lobelane

[(3) H] dihydrotetrabenazine

monoamine

[(3) H] dopamine


Input: Compound 19a, which contains an N-1, 2 (R)-dihydroxypropyl group, had been identified as a potential clinical candidate for the treatment of methamphetamine abuse.

N-1, 2 (R)-dihydroxypropyl

methamphetamine


Input: Using Supramolecular Binding Motifs To Provide Precise Control over the Ratio and Distribution of Species in Multiple Component Films Grafted on Surfaces: Demonstration Using Electrochemical Assembly from Aryl Diazonium Salts.

Aryl Diazonium


Input: Supramolecular interactions between two surface modification species are explored to control the ratio and distribution of these species on the resultant surface.


Input: A binary mixture of aryl diazonium salts bearing oppositely charged para-substituents (either-SO3 (-) or-N (+) (Me) 3), which also reduce at different potentials, has been examined on glassy carbon surfaces using cyclic voltammetry and X-ray photoelectron spectroscopy (XPS).

aryl diazonium

SO3 (-)

N (+) (Me) 3

glassy carbon


Input: Striking features were observed: (1) the two aryl diazonium salts in the mixed solution undergo reductive adsorption at the same potential which is distinctively less negative than the potential required for the reduction of either of the two aryl diazonium salts alone; (2) the surface ratio of the two phenyl derivatives is consistently 1: 1 regardless of the ratio of the two aryl diazonium salts in the modification solutions.

aryl diazonium

aryl diazonium

aryl diazonium


Input: Homogeneous distribution of the two oppositely charged phenyl species on the modified surface has also been suggested by XPS survey spectra.

phenyl


Input: Diffusion coefficient measurements by DOSY NMR and DFT based computation have indicated the association of the two aryl diazonium species in the solution, which has led to changes in the molecular orbital energies of the two species.

aryl diazonium


Input: This study highlights the potential of using intermolecular interactions to control the assembly of multicomponent thin layers.


Input: Does Dietary Copper Supplementation Enhance or Diminish PCB126 Toxicity in the Rodent Liver?

Copper


Input: Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins.

Copper


Input: However, in its free form copper can participate in Fenton-like reactions that produce reactive hydroxyl radicals.

copper

hydroxyl


Input: Aryl-hydrocarbon receptor (AhR) agonists, including the most potent polychlorinated biphenyl (PCB) congener, 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126), increase copper levels in rodent livers.

Aryl-hydrocarbon

polychlorinated biphenyl

PCB

3, 3', 4, 4', 5-pentachlorobiphenyl

copper


Input: This is accompanied by biochemical and toxic changes.


Input: To assess the involvement of copper in PCB toxicity, male Sprague-Dawley rats were fed an AIN-93G diet with differing dietary copper levels: low (2 ppm), adequate (6 ppm), and high (10 ppm).

PCB

copper


Input: After three weeks, rats from each group were given a single ip injection of corn oil (control), 1, or 5 mu mol/kg body weight PCB126.


Input: Two weeks following injections, biochemical and morphological markers of hepatic toxicity, trace metal status, and hepatic gene expression of metalloproteins were evaluated.


Input: Increasing dietary copper was associated with elevated tissue levels of copper and ceruloplasmin.

copper

copper


Input: In the livers of PCB126-treated rats, the hallmark signs of AhR activation were present, including increased cytochrome P450 and lipid levels and decreased glutathione.

glutathione


Input: In addition, a doubling of hepatic copper levels was seen, and overall metal homeostasis was disturbed, resulting in decreased hepatic selenium, manganese, zinc, and iron.

copper

selenium

manganese

zinc

iron


Input: Expression of key metalloproteins was either decreased (cytochrome c oxidase), unchanged (ceruloplasmin and CuZnSOD), or increased (tyrosinase and metallothioneins 1 and 2) with exposure to PCB126.


Input: Increases in metallothionein may contribute/reflect the increased copper seen.

copper


Input: Alterations in dietary copper did not amplify or abrogate the hepatic toxicity of PCB126.

copper


Input: PCB126 toxicity, i. e., oxidative stress and steatosis, is clearly associated with disturbed metal homeostasis.


Input: Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists.


Input: Novel Cellulose Polyampholyte-Gold Nanoparticle-Based Colorimetric Competition Assay for the Detection of Cysteine and Mercury (II).

Cysteine

Mercury (II)


Input: We provide a highly sensitive and selective assay to detect cysteine (Cys) and Hg (2 +) in aqueous solutions using Au nanoparticles (NPs) stabilized by carboxylethyl quaternized cellulose (CEQC).

cysteine

Cys

Hg (2 +)

Au

carboxylethyl


Input: This method is based on the thiophilicity of Hg (2 +) and Au NPs as well as the unique optical properties of CEQC-stabilized Au NPs.

Hg (2 +)

Au

Au


Input: CEQC chains are good stabilizing agents for Au NPs even in a high-salt solution.

Au


Input: The addition of Cys results in the aggregation of CEQC-stabilized Au NPs, which induces the visible color change and obvious redshift in UV-visible absorption spectra.

Cys

Au


Input: On the other hand, Hg (2 +) is more apt to interact with thiols than Au NPs; thus, it can remove the Cys and trigger Au NP aggregate redispersion again.

Hg (2 +)

thiols

Au

Cys

Au


Input: By taking advantage of this mechanism, a novel off-on colorimetric sensor has been established for Cys and Hg (2 +) detection.

Cys

Hg (2 +)


Input: This new assay could selectively detect Cys and Hg (2 +) with the detection limits as low as 20 and 40 nM in aqueous solutions, respectively.

Cys

Hg (2 +)


Input: Nanopore-spanning lipid bilayers on silicon nitride membranes that seal and selectively transport ions.

silicon nitride


Input: We report the formation of POPC lipid bilayers that span 130 nm pores in a freestanding silicon nitride film supported on a silicon substrate.

POPC

silicon nitride

silicon


Input: These solvent-free lipid membranes self-assemble on organosilane-treated Si3N4 via the fusion of 200 nm unilamellar vesicles.

organosilane


Input: Membrane fluidity is verified by fluorescence recovery after photobleaching (FRAP), and membrane resistance in excess of 1 G Omega is demonstrated using electrical impedance spectroscopy (EIS).


Input: An array of 40 000 membranes maintained high impedance over 72 h, followed by rupture of most of the membranes by 82 h.


Input: Membrane incorporation of gramicidin, a model ion channel, resulted in increased membrane conductance.


Input: This membrane conductance was diminished when the gramicidin channels were blocked with CaCl2, indicating that the change in membrane conductance results from gramicidin-mediated ion transport.


Input: These very stable, biologically functional pore-spanning membranes open many possibilities for silicon-based ion-channel devices for applications such as biosensors and high-throughput drug screening.

silicon


Input: Cross-talk between constitutive androstane receptor and hypoxia-inducible factor in the regulation of gene expression.

androstane


Input: Hypoxia inducible factor (HIF) and 5'-AMP-activated protein kinase are often activated under similar physiological conditions.


Input: Constitutive androstane receptor (CAR) translocates into the nucleus in accordance with 5'-AMP-activated protein kinase and thus confers transactivation.

androstane


Input: The aim of the present study was to investigate a possible link between CAR and HIF alpha.


Input: Phenobarbital (PB), a typical CAR activator, increased the gene expression of HIF-target genes in the livers of mice, including erythropoietin, heme oxygenase-1 and vascular endothelial growth factor-a.

Phenobarbital


Input: PB induced an accumulation of nuclear HIF-1 alpha and an increase in the HIF-responsive element-mediated transactivation in HepG2 cells.


Input: Cobalt chloride, a typical HIF activator, induced the gene expression of CAR-target genes, including cyp2b9 and cyp2b10, an accumulation of nuclear CAR and an increase in the PB-responsive enhancer module-mediated transactivation in the mouse liver.

Cobalt chloride


Input: Immunoprecipitation-immunoblot and chromatin immunoprecipitation analyses suggest that CAR binds to the PB-responsive enhancer module with HIF-1 alpha in the liver of untreated mice and that the complex dissociates upon PB treatment.


Input: Taken together these results suggest that CAR and HIF-alpha interact and reciprocally modulate the functions of each other.


Input: Decreased androgen receptor expression may contribute to spermatogenesis failure in rats exposed to low concentration of bisphenol A.

androgen

bisphenol A


Input: To investigate the effects of a low bisphenol A (BPA) concentration on male reproduction, adult rats were administered a concentration of BPA that was less than the no observable adverse effect level (0. 0005-5mg/kg/bw) for 8 weeks.

bisphenol A

BPA

BPA


Input: General toxicity, reproductive hormones, and spermatogenesis were then determined.


Input: The expression of genes related to hormone synthesis and spermatogenesis was also analyzed.


Input: These BPA concentrations generated no general toxicity and no significant changes on serum hormones.

BPA


Input: However, the testicular testosterone, hormone synthesis-related genes StAR and Cyp450scc increased, whereas 3 beta-HSD, 17 beta-HSD, and Cyp450arom decreased.

testosterone


Input: Additionally, BPA significantly decreased the epithelial height and round spermatids in seminiferous tubules, sperm count, androgen receptor expression, and the expression of the spermatogenesis-related genes outer dense fiber protein 1 (ODF1) and transition protein 1.

BPA

androgen


Input: Our results indicate that a low BPA concentration can induce spermatogenesis disorders mainly through decreasing androgen receptor expression.

BPA

androgen


Input: The present results may bring attention to the risk of environmental BPA exposure.

BPA


Input: Design and synthesis of 2-substituted benzoxazoles as novel PTP1B inhibitors.

2-substituted benzoxazoles


Input: A series of benzoxazole compounds containing oxamic acid were synthesized and screened for the PTP1B inhibition.

benzoxazole

oxamic acid


Input: Compound 31d showed best biochemical potency (Ki) of 6. 7 mu M.


Input: Structure-activity relationship were explained with the help of molecular modeling approach.


Input: Antibacterial action of quinolones: From target to network.

quinolones


Input: Quinolones are widely used broad-spectrum antibacterials with incomplete elucidated mechanism of action.

Quinolones


Input: Here, molecular basis for the antibacterial action of quinolones, from target to network, is fully discussed and updated.

quinolones


Input: Quinolones trap DNA gyrase or topoisomerase IV to form reversible drug-enzyme-DNA cleavage complexes, resulting in bacteriostasis.

Quinolones


Input: Cell death arises from chromosome fragmentation in protein synthesis-dependent or-independent pathways according to distinguished quinolone structures.

quinolone


Input: In the former pathway, irreversible oxidative DNA damage caused by reactive oxygen species kills bacteria eventually.

oxygen


Input: Toxin-antitoxin mazEF is triggered as an additional lethal action.


Input: Bacteria survive and develop resistance by SOS and other stress responses.


Input: Enlarged knowledges of quinolone actions and bacterial response will provide new targets for drug design and approaches to prevent bacterial resistance.

quinolone


Input: Epidermal growth factor receptor inhibitor PKI-166 governs cardiovascular protection without beneficial effects on the kidney in hypertensive 5/6 nephrectomised rats.


Input: Transactivation of epidermal growth factor receptor (EGFR) signaling by G-protein-coupled receptors has been implicated in several cardiovascular (CV) conditions, including hypertension, heart failure, cardiac and vascular hypertrophy.


Input: However, the therapeutic potential of EGFR inhibition in these conditions is currently unknown.


Input: Main objective of the present study was to investigate cardiac, vascular and renal effects of EGFR inhibition by PKI-166 in the hypertensive chronic kidney disease (CKD) model.


Input: Rats underwent 5/6 nephrectomy (5/6Nx) and were treated with PKI-166 or lisinopril or vehicle from week 6 after disease induction until week 12.

lisinopril


Input: Sham animals received either PKI-166 or vehicle.


Input: Treatment with PKI-166 did not affect the development of the characteristic renal features in 5/6Nx including proteinuria, diminished creatinine clearance and increased glomerulosclerosis, whereas these were attenuated by lisinopril.

creatinine

lisinopril


Input: Despite absence of effects on progressive renal damage, PKI-166 attenuated the progression of hypertension and maintained cardiac function (LVEDP) to a similar extent as lisinopril.


Input: Also, PKI-166 attenuated the increase in phosphorylated EGFR in heart as induced by 5/6Nx.


Input: Moreover, PKI-166 and lisinopril restored the impaired contraction of isolated thoracic aortic rings to phenylephrine and angiotensin II and impaired myogenic constriction of small mesenteric arteries in 5/6Nx rats.

lisinopril

phenylephrine


Input: Blockade of the EGFR displays a CV benefit independently of limiting the progression of renal injury.


Input: Our findings extend the evidence on EGFR signaling as a target in CV disorders.


Input: Recent progress in nanosensors for sensitive detection of biomolecules.


Input: Developing sensitive, rapid, and cost-effective methods for detection of biomolecules is important for both clinical and numerous non-clinical applications.


Input: During the last two decades, functional nanomaterials with unique physical and chemical properties have provided significant advantages for biological detection.


Input: In this feature article, we introduce recent progress in nanobiosensor development by exploiting the optical, electrical and catalytic properties of a range of nanomaterials, with a focus on gold nanoparticles, carbon nanotubes, graphene and carbon dots.

carbon

graphene

carbon


Input: In addition, the perspectives on future opportunities and unsolved challenges are also discussed.


Input: Evaluation of body weight, insulin resistance, leptin and adiponectin levels in premenopausal women with hyperprolactinemia.


Input: The effects of hyperprolactinemia on metabolic parameters are not clear and a few data evaluating adiponectin levels in prolactinoma and idiopathic hyperprolactinemia exist.


Input: The aim of this study was to evaluate the effects of hyperprolactinemia on body weight, insulin resistance, beta cell function, and leptin and adiponectin levels in premenopausal women with hyperprolactinemia.


Input: Forty premenopausal women with prolactinoma or idiopathic hyperprolactinemia were compared to 41 age-matched healthy premenopausal women with regard to body weight, body mass index, waist and hip circumferences, waist to hip ratio, fasting plasma glucose, insulin levels, insulin resistance measured by homeostasis model assessment (HOMA)-insulin resistance index, beta cell function measured by HOMA-beta index, leptin and adiponectin levels.

glucose


Input: Plasma insulin levels and HOMA indexes (both insulin resistance and beta indexes) were significantly higher in hyperprolactinemic women.


Input: The other parameters were similar between both groups.


Input: There was a positive correlation between prolactin levels and fasting plasma glucose in hyperprolactinemic women.

glucose


Input: The results of this study showed that high prolactin levels may be associated with hyperinsulinemia and insulin resistance in premenopausal women.


Input: This effect seems to be independent of body weight, leptin and adiponectin levels.


Input: High prolactin levels may directly stimulate insulin secretion from pancreas and directly cause hepatic and whole-body insulin resistance.


Input: RANKL subcellular trafficking and regulatory mechanisms in osteocytes.


Input: The receptor activator of the NF-kappa B ligand (RANKL) is the central player in the regulation of osteoclastogenesis and the quantity of RANKL presented to osteoclast precursors is an important factor determining the magnitude of osteoclast formation.


Input: Since osteoblastic cells are thought to be a major source of RANKL, the regulatory mechanisms of RANKL subcellular trafficking have been studied in osteoblastic cells.


Input: However, recent reports showed that osteocytes are a major source of RANKL presentation to osteoclast precursors, prompting a need to reinvestigate RANKL subcellular trafficking in osteocytes.


Input: Investigation of molecular mechanisms in detail needs well-designed in vitro experimental systems.


Input: Thus, we developed a novel co-culture system of osteoclast precursors and osteocytes embedded in collagen gel.


Input: Experiments using this model revealed that osteocytic RANKL is provided as a membrane-bound form to osteoclast precursors through osteocyte dendritic processes and that the contribution of soluble RANKL to the osteoclastogenesis supported by osteocytes is minor.


Input: Moreover, the regulation of RANKL subcellular trafficking, such as OPG-mediated transport of newly synthesized RANKL molecules to lysosomal storage compartments, and the release of RANKL to the cell surface upon stimulation with RANK, are confirmed to be functional in osteocytes.


Input: These results provide a novel understanding of the regulation of osteoclastogenesis.


Input: (c) 2013 American Society for Bone and Mineral Research.


Input: Biomimetic Synthesis and Studies Toward Enantioselective Synthesis of Flindersial Alkaloids.


Input: A strategy allowing both stereocontrol and control over structural isomer formation has been defined for the antimalarial flindersial alkaloids.


Input: The recently reported flinderoles were demonstrated to be derived from the natural product borrerine.

flinderoles

borrerine


Input: The structural isomers of flinderoles, the borreverines, were also produced in vitro along with the flinderoles through the dimerization of borrerine in acidic conditions.

flinderoles

borreverines

flinderoles

borrerine


Input: This result is thought to replicate the biosynthesis of these compounds.


Input: Flinderoles A, B, and C, desmethylflinderole C, isoborreverine, and dimethylisoborreverine can each be synthesized in three steps from tryptamine.

Flinderoles A, B, and C

isoborreverine

dimethylisoborreverine

tryptamine


Input: Furthermore, progress toward a concise enantioselective synthesis of flinderoles A, B, and C is described.

flinderoles A, B, and C


Input: This work includes enantioselective conjugate addition to an unprotected indole-appended enone.

indole

enone


Input: Chirality 00: 000-000, 2013.


Input: (c) 2013 Wiley Periodicals, Inc.


Input: Multifunctional Hybrid Materials From Poly (3-Hydroxybutyrate), TiO2 Nanoparticles, and Chitosan Oligomers by Combining Electrospinning/Electrospraying and Impregnation.

Poly (3-Hydroxybutyrate)


Input: Several types of fibrous material containing poly (3-hydroxybutyrate) (PHB), nanosized TiO2-anatase (nanoTiO2), and chitosan oligomers are prepared by combining the electrospinning, electrospraying, and impregnation techniques.

poly (3-hydroxybutyrate)

PHB


Input: Simultaneous electrospinning/electrospraying provides uniform distribution of electrosprayed nanoTiO2 along the PHB fibers and throughout the mat.

PHB


Input: Hybrid materials of different design manifest excellent photocatalytic activity, even after repeated use.


Input: They exhibit high bactericidal activity against Escherichia coli.


Input: In addition, the fibrous scaffolds are compatible with human mesenchymal stem cells and provide a favorable environment for their development.


Input: Mimicking Nanofibrous Hybrid Bone Substitute for Mesenchymal Stem Cells Differentiation into Osteogenesis.


Input: Mimicking hybrid extracellular matrix is one of the main challenges for bone tissue engineering (BTE).


Input: Biocompatible polycaprolactone/poly (alpha, beta)-DL-aspartic acid/collagen nanofibrous scaffolds were fabricated by electrospinning and nanohydroxyapatite (n-HA) was deposited by calcium phosphate dipping method for BTE.

polycaprolactone

poly (alpha, beta)-DL-aspartic acid


Input: Human mesenchymal stem cells (hMSCs) were cultured on these hybrid scaffolds to investigate the cell proliferation, osteogenic differentiation by alkaline phosphatase activity, mineralization, double immunofluorescent staining using CD90 and expression of osteocalcin.


Input: The present study indicated that the PCL/PAA/collagen/n-HA scaffolds promoted greater osteogenic differentiation of hMSCs, proving to be a potential hybrid scaffolds for BTE.

PCL

PAA


Input: Metabolic Effects of Chronic Cannabis Smoking.


Input: OBJECTIVEWe examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced beta-cell function, or dyslipidemia in healthy individuals. RESEARCH DESIGN AND METHODSIn a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 +/- 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 +/- 6).


Input: Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively.


Input: Insulin-sensitivity indices and various aspects of beta-cell function were derived from oral glucose tolerance tests (OGTT). RESULTSSelf-reported cannabis use was: 9. 5 (2-38) years; joints/day: 6 (3-30) [median (range)].

glucose


Input: Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers.

Carbohydrate

carbohydrates


Input: There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 +/- 9 vs. 12 +/- 5%; P = 0. 004).


Input: Cannabis smokers had lower plasma HDL cholesterol (49 +/- 14 vs. 55 +/- 13 mg/dL; P = 0. 02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different.

cholesterol

glucose

cholesterol

cholesterol

triglycerides

fatty acids


Input: Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P < 0. 05) in cannabis smokers.


Input: However, oral glucose insulin sensitivity index, measures of beta-cell function, or incretin concentrations did not differ between the groups. CONCLUSIONSChronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic beta-cell function, or glucose intolerance.

glucose

glucose


Input: Chalcogenopyrylium Dyes as Differential Modulators of Organic Anion Transport by MRP1, MRP2 and MRP4.

Chalcogenopyrylium


Input: Multidrug resistance proteins (MRPs) mediate the ATP-dependent efflux of structurally diverse compounds, including anticancer drugs and physiological organic anions.

ATP


Input: Five classes of chalcogenopyrylium dyes (CGPs) were examined for their ability to modulate transport of [(3) H] estradiol glucuronide (E217 beta G) (a prototypical MRP substrate) into MRP-enriched inside-out membrane vesicles.

chalcogenopyrylium

CGPs

[(3) H] estradiol glucuronide

E217 beta G


Input: Additionally, some CGPs were tested in intact transfected cells using a calcein efflux assay.

CGPs

calcein


Input: Sixteen of 34 CGPs inhibited MRP1-mediated E217 beta G uptake by > 50% (IC50' s 0. 7-7. 6 mu M).

CGPs

E217 beta G


Input: Of 9 CGPs with IC50' s <= 2 mu M, two belonged to Class I, two to Class III and five to Class V. When tested in the intact cells, only 4 of 16 CGPs (at 10 mu M) inhibited MRP1-mediated calcein efflux by > 50% (III-1, V-3,-4,-6) while a fifth (I-5) inhibited efflux by just 23%.

CGPs

CGPs

calcein


Input: These five CGPs also inhibited [(3) H] E217 beta G uptake by MRP4.

CGPs

[(3) H] E217 beta G


Input: In contrast, their effects on MRP2 varied with two (V-4, V-6) inhibiting E217 beta G transport (IC50' s 2. 0, 9. 2 mu M), two (V-3, III-1) stimulating transport (> 2-fold), while CGP I-5 had no effect.

E217 beta G

CGP


Input: Strikingly, although V-3 and V-4 had opposite effects on MRP2 activity, they are structurally identical except for their chalcogen atom (Se versus Te).

chalcogen

Se

Te


Input: This study is the first to identify Class V CGPs with their distinctive methine or trimethine linkage between two disubstituted pyrylium moieties as a particularly potent class of MRP modulators and also show that within this core structure, differences in the electronegativity associated with a chalcogen atom can be the sole determinant of whether a compound will stimulate or inhibit MRP2.

methine

trimethine

pyrylium

chalcogen


Input: Nicotine Kinetics in Zebra Finches in vivo and in vitro.

Nicotine


Input: Nicotine enhances cognitive performance, and in the zebra finch (Taeniopygia guttata), which is a well-established model of cognition, the effect of nicotine on song production has been reported.

Nicotine

nicotine


Input: Nicotine and cotinine plasma levels were assessed in vivo after s. c. injection of 0. 18 mg/kg nicotine, a dose that elicits changes in song production.

Nicotine

cotinine

nicotine


Input: The half-life of nicotine elimination was 33 min, and levels were undetectable by 4h.

nicotine


Input: Average plasma nicotine over 2 hours was 32 ng/ml, similar to levels seen in human smokers and rat models of nicotine behavior.

nicotine

nicotine


Input: Nicotine brain levels were 30 and 14 ng/g at 1 and 2 h after treatment.

Nicotine


Input: To understand the potential for drug interactions and regulation of nicotine metabolism in zebra finches, we characterized in vitro nicotine metabolism and the hepatic enzyme involved.

nicotine

nicotine


Input: In humans, cytochrome P450 (CYP) 2A6 metabolizes nicotine to cotinine, and CYP2A-like activity and protein have been reported in some birds.

nicotine

cotinine


Input: Zebra finch liver microsomes metabolized nicotine and bupropion (CYP2B substrate) but not coumarin (CYP2A substrate).

nicotine

bupropion

coumarin


Input: Nicotine was metabolized to cotinine with a Km of 96 mu M and Vmax of 56 pmol/min/mg.

Nicotine

cotinine


Input: Nicotine and bupropion metabolism were inhibited by C-8-xanthate (specific CYP2B inhibitor) but not CYP2A-specific inhibitors, and hepatic levels of CYP2B-like but not CYP2A-like proteins correlated with nicotine (r = 0. 52, p = 0. 04) and bupropion metabolism (r = 0. 81, p < 0. 001), suggesting CYP2B-mediation of nicotine metabolism as seen in rats.

Nicotine

bupropion

nicotine

bupropion

nicotine


Input: These results will facilitate further investigation of nicotine' s effects in zebra finches.

nicotine


Input: Prilocaine-and Lidocaine-induced Methemoglobinemia is Caused by Human Carboxylesterase-, CYP2E1-and CYP3A4-mediated Metabolic Activation.

Prilocaine

Lidocaine


Input: Prilocaine and lidocaine are classified as amide-type local anesthetics whose serious adverse effects include methemoglobinemia.

Prilocaine

lidocaine

amide


Input: Although the hydrolyzed metabolites of prilocaine (o-toluidine) and lidocaine (2, 6-xylidine) have been suspected to induce methemoglobinemia, the metabolic enzymes that are involved remain uncharacterized.

prilocaine

o-toluidine

lidocaine

2, 6-xylidine


Input: In the present study, we aimed to identify the human enzymes that are responsible for prilocaine-and lidocaine-induced methemoglobinemia.

prilocaine

lidocaine


Input: Our experiments revealed that prilocaine was hydrolyzed by recombinant human carboxylesterase (CES) 1A and CES2, whereas lidocaine was hydrolyzed only by human CES1A.

prilocaine

lidocaine


Input: When the parent compounds (prilocaine and lidocaine) were incubated with HLM, Met-Hb formation was lower than when the hydrolyzed metabolites were incubated with HLM.

prilocaine

lidocaine


Input: In addition, Met-Hb formation when prilocaine and o-toluidine were incubated with HLM was higher than that when lidocaine and 2, 6-xylidine were incubated with HLM.

prilocaine

o-toluidine

lidocaine

2, 6-xylidine


Input: Incubation with diisopropyl fluorophosphate and bis-(4-nitrophenyl) phosphate, which are general inhibitors of CES, significantly decreased Met-Hb formation when prilocaine and lidocaine were incubated with HLM.

diisopropyl fluorophosphate

bis-(4-nitrophenyl) phosphate

prilocaine

lidocaine


Input: An anti-CYP3A4 antibody further decreased the residual formation of Met-Hb.


Input: Met-Hb formation following the incubation of o-toluidine and 2, 6-xylidine with HLM was only markedly decreased by incubation with an anti-CYP2E1 antibody.

o-toluidine

2, 6-xylidine


Input: o-Toluidine and 2, 6-xylidine were further metabolized by CYP2E1 to 4-and 6-hydroxy-o-toluidine and 4-hydroxy-2, 6-xylidine, respectively, and these metabolites were shown to more efficiently induce Met-Hb formation than the parent compounds.

o-Toluidine

2, 6-xylidine

4-and 6-hydroxy-o-toluidine

4-hydroxy-2, 6-xylidine


Input: Collectively, we found that the metabolites produced by human CES-, CYP2E1-and CYP3A4-mediated metabolism were involved in prilocaine-and lidocaine-induced methemoglobinemia.

prilocaine

lidocaine


Input: The Hyaluronan Receptor for Endocytosis (HARE) activates NF-kappa B mediated gene expression in response to 40-400 kDa, but not smaller or larger, hyaluronan.


Input: The Hyaluronan (HA) Receptor for Endocytosis (HARE) binds and clears 14 different ligands, including HA and heparin, via clathrin-mediated endocytosis.


Input: HA binding to HARE stimulates ERK1/2 activation (Kyosseva et al. J. Biol. Chem. 283, 15047, 2008).


Input: To assess a possible HA size-dependence for signaling, we tested purified HA fractions of different weight-average molar mass (Mw) and with narrow size distributions and Select-HA for stimulation of HARE-mediated gene expression using an NF-kappa B promoter-driven luciferase reporter system.


Input: Human HARE-mediated gene expression was stimulated in a dose-dependent manner with small HA (SHA) > 40 kDa and intermediate HA (IHA) < 400 kDa.


Input: The hyperbolic dose-response saturated at 20-50 nM with an apparent Km ~ 10 nM, identical to the Kd for HA-HARE binding.


Input: Activation was not detected with oligomeric HA (OHA), SHA < 40 kDa, IHA > 400 kDa or large HA (LHA).


Input: Similar responses occurred with rat HARE.


Input: Activation by SHA-IHA was blocked by excess nonsignaling SHA, IHA or LHA, deletion of the HA-binding LINK domain, or HA-blocking antibody.


Input: Endogenous NF-kappa B activation also occurred in the absence of luciferase plasmids, as assessed by degradation of I kappa B-alpha.


Input: ERK1/2 activation was also HA-size dependent.


Input: The results show that HA-HARE interactions stimulate NF-kappa B activated gene expression and that HARE senses a narrow size-range of HA degradation products.


Input: We propose a model in which optimal length HA binds multiple HARE proteins to allow cytoplasmic domain interactions that stimulate intracellular signaling.


Input: This HARE signaling system during continuous HA clearance could monitor the homeostasis of tissue biomatrix turnover throughout the body.


Input: Discoidin Domain Receptor 1 is a novel modulator of megakaryocyte-collagen interactions.


Input: Growing evidence demonstrates that extracellular matrices (ECMs) regulate many aspects of megakaryocyte (MK) development; however, among the different ECM receptors, integrin alpha2beta1 and GPVI are the only collagen receptors studied in platelets and MKs.


Input: In this study, we demonstrate the expression of the novel collagen receptor Discoidin Domain Receptor 1 (DDR1) by human MKs at both mRNA and protein levels and provide evidence of DDR1 involvement in the regulation of MK motility on type I collagen through a mechanism based on the activity of SHP1 phosphatase and Syk tyrosine kinase.

tyrosine


Input: Specifically, we demonstrated that inhibition of DDR1 binding to type I collagen, preserving the engagement of the other collagen receptors, GPVI, alpha2beta1 and LAIR-1 determines a decrease in MK migration due to the reduction in SHP1 phosphatase activity and consequent increase in the phosphorylation level of its main substrate Syk.


Input: Consistently, inhibition of Syk activity restored MK migration on type I collagen.


Input: In conclusion, we report the expression and function of a novel collagen receptor on human MKs and we point out that increasing level of complexity is necessary to better understand MK-collagen interactions in the bone marrow environment.


Input: Maternal adiposity as an independent risk factor for pre-eclampsia: a meta-analysis of prospective cohort studies.


Input: Studies investigating the association between maternal adiposity and risk of pre-eclampsia showed contradictory results.


Input: Therefore, we performed a meta-analysis of prospective cohort studies to estimate the effect of maternal adiposity on pre-eclampsia.


Input: We reviewed 1, 286 abstracts and finally included 29 prospective cohort studies with 1, 980, 761 participants and 67, 075 pre-eclampsia events.


Input: We pooled data with a random-effects model, and obtained risk estimates for five predetermined bodyweight groups: low, normal-weight (reference), overweight, obese and severely obese.


Input: In the cohort studies that unadjusted for pre-eclampsia risk factors, the pooled unadjusted relative risks (RR) with 95% confidence intervals (95% CI) for pre-eclampsia of overweight, obese and severely obese women were 1. 58 (95% CI 1. 44-1. 72, P < 0. 001), 2. 68 (95% CI 2. 39-3. 01, P < 0. 001) and 3. 12 (95% CI 2. 24-4. 36, P < 0. 001), respectively.


Input: In those cohorts that adjusted for pre-eclampsia risk factors, the pooled unadjusted RRs for pre-eclampsia of overweight, obese and severely obese women were 1. 70 (95% CI 1. 60-1. 81, P < 0. 001), 2. 93 (95% CI 2. 58-3. 33, P < 0. 001) and 4. 14 (95% CI 3. 61-4. 75, P < 0. 001), respectively.


Input: Sensitivity analysis showed maternal adiposity was associated with increased risk of pre-eclampsia in both nulliparous and multiparas women.


Input: In conclusion, overweight or obese pregnant women have a substantially increased risk of pre-eclampsia, and maternal adiposity is an independent risk factor of pre-eclampsia.


Input: Electron Paramagnetic Resonance Spectroscopic Study of Copper Hopping in Doped Bis (l-histidinato) cadmium Dihydrate.

Copper

Bis (l-histidinato) cadmium Dihydrate


Input: Electron paramagnetic resonance (EPR) spectroscopy was used to study Cu (II) dynamic behavior in a doped biological model crystal, bis (l-histidinato) cadmium dihydrate, in order to gain better insight into copper site stability in metalloproteins.

Cu (II)

bis (l-histidinato) cadmium dihydrate

copper


Input: Temperature-dependent changes in the low temperature X-band EPR spectra became visible around 100 K and continued up to room temperature.


Input: The measured 298 K g-tensor (principal values: 2. 17, 2. 16, 2. 07) and copper hyperfine coupling tensor (principal values:-260,-190,-37 MHz) were similar to the average of the 77 K tensor values pertaining to two neighboring histidine binding sites.

copper

histidine


Input: The observed temperature dependence was interpreted using Anderson' s theory of motional narrowing, where the magnetic parameters for the different states are averaged as the copper rapidly hops between sites.

copper


Input: The EPR pattern was also found to undergo a sharp sigmoidal-shaped, temperature-dependent conversion between two species with a critical temperature Tc =~ 160 K.


Input: The species below Tc hops between the two low temperature site patterns, and the one above Tc represents an average of the molecular spin Hamiltonian coupling tensors of the two 77 K sites.


Input: In addition, the low and high temperature species hop between one another, contributing to the dynamic averaging.


Input: Spectral simulations using this 4-state model determined a hop rate between the two low temperature sites nu h4 = 4. 5 x 10 (8) s (-1) and between the low and high temperature states nu h2 = 1. 7 x 10 (8) s (-1) at 160 K.


Input: An Arrhenius relationship of hop rate and temperature gave energy barriers of Delta E4 = 389 cm (-1) and Delta E2 = 656 cm (-1) between the two low temperature sites and between the low and high temperature states, respectively.


Input: Preventing Interfacial Recombination in Colloidal Quantum Dot Solar Cells by Doping the Metal Oxide.

Metal Oxide


Input: Recent research has pushed the efficiency of colloidal quantum dot solar cells toward a level that spurs commercial interest.


Input: Quantum dot/metal oxide bilayers form the most efficient colloidal quantum dot solar cells, and most studies have advanced the understanding of the quantum dot component.

metal oxide


Input: We study the interfacial recombination process in depleted heterojunction colloidal quantum dot (QD) solar cells formed with ZnO as the oxide by varying (i) the carrier concentration of the ZnO layer and (ii) the density of intragap recombination sites in the QD layer.

ZnO

oxide

ZnO


Input: We find that the open-circuit voltage and efficiency of PbS QD/ZnO devices can be improved by 50% upon doping of the ZnO with nitrogen to reduce its carrier concentration.

PbS

ZnO

ZnO

nitrogen


Input: In contrast, doping the ZnO did not change the performance of PbSe QD/ZnO solar cells.

ZnO

PbSe

ZnO


Input: We use X-ray photoemission spectroscopy, ultraviolet photoemission spectroscopy, transient photovoltage decay measurements, transient absorption spectroscopy, and intensity-dependent photocurrent measurements to investigate the origin of this effect.


Input: We find a significant density of intragap states within the band gap of the PbS quantum dots.

PbS


Input: These states facilitate recombination at the PbS/ZnO interface, which can be suppressed by reducing the density of occupied states in the ZnO.

PbS

ZnO

ZnO


Input: For the PbSe QD/ZnO solar cells, where fewer intragap states are observed in the quantum dots, the interfacial recombination channel does not limit device performance.

PbSe

ZnO


Input: Our study sheds light on the mechanisms of interfacial recombination in colloidal quantum dot solar cells and emphasizes the influence of quantum dot intragap states and metal oxide properties on this loss pathway.

metal oxide


Input: Low-temperature NMR studies on the geometry of base pairs involving 5-substituted uracil derivatives.

5-substituted uracil


Input: Uridine (U) imino proton chemical shifts, measured in the slow hydrogen-bond exchange regime at low temperatures in a freonic solution, show that electron-withdrawing 5-bromo and 5-fluoro substituents on the uracil base strengthen NHN hydrogen bonds in (X) U. A base pairs formed by the free nucleosides.

Uridine

hydrogen

uracil

NHN hydrogen

nucleosides


Input: Whereas the halogens do not alter the preferential formation of Watson-Crick geometries, self-associates of the halouracils point to a more favorable engagement of the 2-carbonyl as proton acceptor in the cyclic hydrogen bonds, suggesting increased formation of reverse geometries and wobble base pairs with guanine when compared to the thymine base.

halogens

halouracils

hydrogen

guanine

thymine


Input: Employing (15) N-labeled 5-bromouridine, no noticeable population of minor enol tautomers is found in the freonic mixture at 113 K.

(15) N

enol


Input: Inflammation, serotonin and major depression.

serotonin


Input: The understanding of the neurobiological processes leading to major depressive disorder (MDD) is an active field of research in the scientific community.


Input: For years, the alteration of monoamine neurotransmission, in particular serotonin (5-HT), has been considered the most significant pathophysiological mechanism of the disorder.

monoamine

serotonin


Input: However, biological data supporting the postulated MDD-related monoamine alterations have been inconclusive, and the use of monoaminergic antidepressants has not yielded the expected results.


Input: In the last few years, it has been demonstrated that inflammatory pathways have a significant role in the pathophysiology of MDD.


Input: According to the cytokine hypothesis, the disorder would be due to a stress-related increased production of cytokines, including interleukins, tumor necrosis factor-alpha and interferon-alpha and gamma.


Input: These, in turns, would cause the activation of the indoleamine 2, 3 dioxygenase (IDO), with subsequent production of tryptophan (TRP) catabolites along the IDO pathway (TRYCATs) and decreased availability of TRP and 5-HT.

indoleamine

tryptophan

TRP

TRP


Input: Besides monoamines, other molecular mechanisms, as those within the inflammatory pathways, should be taken into account in the attempt to clarify the pathophysiology of MDD and to improve its treatment.

monoamines


Input: Study on medicinal chemistry of k203 in wistar rats and beagle dogs.


Input: K203 is an experimental bis-pyridinium mono-aldoxime type cholinesterase reactivator of potential use in organophosphate/organophosphonate poisoning.

bis-pyridinium mono-aldoxime

organophosphate

organophosphonate


Input: Pharmacokinetics of K203 were examined in Wistar rats and beagle dogs using ion-pair HPLC.


Input: Serum and cerebrospinal fluid concentrations of K203 were determined using ion-pair reversedphase chromatography on octadecyl silica column.

octadecyl silica


Input: HPLC with ultraviolet detection was used for determination of serum concentration of K203 higher than 0. 1 mu g/mL while its low concentrations in cerebrospinal fluid required electrochemical detection (0. 015 through 4 mu g/mL range).


Input: In rats the serum levels of K203 followed zero order pharmacokinetics from 15 to 120 minutes post administration.


Input: Zero order pharmacokinetics was also observed in beagle dogs after low dose (15 mu mol/kg) of K203 administration.


Input: High dose administration (250 mu mol/kg) led to subsequent hindered elimination from both cerebrospinal fluid and serum.


Input: Transgenerational, dynamic methylation of stomata genes in response to low relative humidity.


Input: Transgenerational inheritance of abiotic stress-induced epigenetic modifications in plants has potential adaptive significance and might condition the offspring to improve the response to the same stress, but this is at least partly dependent on the potency, penetrance and persistence of the transmitted epigenetic marks.


Input: We examined transgenerational inheritance of low Relative Humidity-induced DNA methylation for two gene loci in the stomatal developmental pathway in Arabidopsis thaliana and the abundance of associated short-interfering RNAs (siRNAs).


Input: Heritability of low humidity-induced methylation was more predictable and penetrative at one locus (SPEECHLESS, entropy <= 0. 02; chi 2 < 0. 001) than the other (FAMA, entropy <= 0. 17; chi 2 ns).


Input: Methylation at SPEECHLESS correlated positively with the continued presence of local siRNAs (r2 = 0. 87; p = 0. 013) which, however, could be disrupted globally in the progeny under repeated stress.


Input: Transgenerational methylation and a parental low humidity-induced stomatal phenotype were heritable, but this was reversed in the progeny under repeated treatment in a previously unsuspected manner.


Input: Transfer of highly porous nanoparticle layers to various substrates through mechanical compression.


Input: A new two-step layer transfer process is introduced that is capable of fabricating mechanically stabilized highly porous nanoparticle layers on various substrates.


Input: In a first step titanium dioxide nanoparticles were synthesized with Flame-Spray-Pyrolysis and accumulated on a filter paper in the gas phase.

titanium dioxide


Input: In a second step this highly porous filter cake is subsequently transferred to a final substrate via low pressure lamination at room temperature.


Input: This leads to mechanical restructuring and stabilization of the porous layer.


Input: Pore size analysis indicates homogenization of the layers through rearrangement of the aggregates inside the layers that increases with applied pressure.


Input: Additionally, the Young' s moduli of the layers were quantified through Colloidal-Probe-Technique indentation measurements with an Atomic-Force-Microscope.


Input: The highest lamination pressure of 2. 5 MPa resulted in triplication of the Young' s modulus.


Input: The results show that our novel two-step layer transfer process leads to mechanically stabilized layers that preserve their high porosity.


Input: Through the decoupling of the high temperature nanoparticle synthesis and the final substrate the process also enables the possibility to apply temperature sensitive substrates such as polypropylene foil.

polypropylene


Input: Structural and Functional Aspects of Hetero-oligomers Formed by the Small Heat-Shock Proteins alpha B crystallin and HSP27.


Input: Small heat shock proteins (sHSPs) exist as large polydisperse species in which there is constant dynamic subunit exchange between oligomeric and dissociated forms.


Input: Their primary role in vivo is to bind destabilized proteins and prevent their misfolding and aggregating.


Input: alpha B Crystallin (alpha B) and HSP27 are the two most widely distributed and most studied sHSPs in the human body.


Input: They are co-expressed in different tissues where they are known to associate with each other and form hetero-oligomeric complexes.


Input: This study aimed to determine how these two sHSPs interact to form hetero-oligomers in vitro and whether, by doing so, there is an increase in their chaperone activity and stability compared to their homo-oligomeric forms.


Input: Results demonstrate that HSP27 and alpha B form polydisperse hetero-oligomers in vitro which have an average molecular mass higher than each of the homo-oligomers and are more thermostable than alpha B, but less so than HSP27.


Input: The hetero-oligomer chaperone function was found to be equivalent to that of alpha B, with each being significantly better at preventing the amorphous aggregation of alpha-lactalbumin and the amyloid fibril formation of alpha-synuclein in comparison to HSP27.


Input: Using mass spectrometry to monitor subunit exchange over time it was found that HSP27 and alpha B exchange subunits 23% faster than the reported rate for HSP27/alpha A, and almost twice that of alpha A/alpha B.


Input: This represents the first quantitative evaluation of HSP27/alpha B subunit exchange and the results are discussed in the broader context of regulation of function and cellular proteostasis.


Input: Impact of the Proline Residue on Ligand Binding of Neurotensin Receptor 2 (NTS2)-Selective Peptide-Peptoid Hybrids.

Proline


Input: To investigate the binding mode and structure-activity relationships (SARs) of selective neurotensin receptor 2 (NTS2) ligands, novel peptide-peptoid hybrids that simulate the function of the endogenous ligand were developed.


Input: Starting from our recently described NTS2 ligands of type 1, structural variants of type 2 and the metabolically stable analogues 3 a, b were developed.


Input: Replacement of the proline unit by a collection of structural surrogates and evaluation of the respective molecular probes for NTS2 affinity and selectivity indicated similar SARs as described for NT (8-13) derivatives bound to the subtype NTS1.

proline


Input: Peptide-peptoid hybrids 2 d, 3 a, b showed substantial NTS2 binding affinity (Ki = 8. 1-16 nM) and 2400-8600-fold selectivity over NTS1.


Input: The thiazolidine derivative 3 b showed metabolic stability over 32 h in a serum degradation assay.

thiazolidine


Input: In an inositol phosphate accumulation assay, the neurotensin mimetics 3 a and 3 b displayed an inhibition of constitutive activity exceeding 1. 7-2. 0 times the activity of NT (8-13).

inositol phosphate


Input: The fluorinated derivative 3 a could afford attractive opportunities to detect NTS2 by (19) F magnetic resonance imaging.


Input: Enhanced Striatal beta 1-Adrenergic Receptor Expression Following Hormone Loss in Adulthood Is Programmed by Both Early Sexual Differentiation and Puberty: A Study of Humans and Rats.


Input: After reproductive senescence or gonadectomy, changes occur in neural gene expression, ultimately altering brain function.


Input: The endocrine mechanisms underlying these changes in gene expression beyond immediate hormone loss are poorly understood.


Input: To investigate this, we measured changes in gene expression the dorsal striatum, where 17 beta-estradiol modulates catecholamine signaling.

17 beta-estradiol

catecholamine


Input: In human caudate, quantitative PCR determined a significant elevation in beta 1-adrenergic receptor (beta 1AR) expression in menopausal females when compared with similarly aged males.


Input: No differences were detected in beta 2-adrenergic and D1-and D2-dopamine receptor expression.

dopamine


Input: Consistent with humans, adult ovariectomized female rats exhibited a similar increase in beta 1AR expression when compared with gonadectomized males.


Input: No sex difference in beta 1AR expression was detected between intact adults, prepubertal juveniles, or adults gonadectomized before puberty, indicating the necessity of pubertal development and adult ovariectomy.


Input: Additionally, increased beta 1AR expression in adult ovariectomized females was not observed if animals were masculinized/defeminized with testosterone injections as neonates.

testosterone


Input: To generate a model system for assessing functional impact, increased beta 1AR expression was induced in female-derived cultured striatal neurons via exposure to and then removal of hormone-containing serum.


Input: Increased beta 1AR action on cAMP formation, cAMP response element-binding protein phosphorylation and gene expression was observed.

cAMP

cAMP


Input: This up-regulation of beta 1AR action was eliminated with 17 beta-estradiol addition to the media, directly implicating this hormone as a regulator of beta 1AR expression.

17 beta-estradiol


Input: Beyond having implications for the known sex differences in striatal function and pathologies, these data collectively demonstrate that critical periods early in life and at puberty program adult gene responsiveness to hormone loss after gonadectomy and potentially reproductive senescence.


Input: Antithrombotic activity of a newly synthesized coumarin derivative 3-(5-hydroxy-2, 2-dimethyl-chroman-6-yl)-N-{2-[3-(5-hydroxy-2, 2-dimethyl-chroman-6-yl)-propionylamino]-ethyl}-propionamide.

coumarin

3-(5-hydroxy-2, 2-dimethyl-chroman-6-yl)-N-{2-[3-(5-hydroxy-2, 2-dimethyl-chroman-6-yl)-propionylamino]-ethyl}-propionamide


Input: Anti-platelet therapy is a useful strategy to prevent acute thromboembolic artery occlusions.


Input: This study was designed to assess the efficacy of seselin derivatives against murine pulmonary thromboembolism, bleeding time, platelet activation and thrombosis.

seselin


Input: Administration of C3 (16 mg/kg) offered 70% protection against collagen-and epinephrine-induced pulmonary thromboembolism and 30% protection against arachidonic acid-induced death in mice, without adversely affecting bleeding time.

epinephrine

arachidonic acid


Input: No significant difference was observed by C3 in ferric chloride-induced arterial thrombosis in rats.

ferric chloride


Input: Significant reduction in thrombus weight was observed in arteriovenous shunt model.


Input: In rat PRP, C3 reduced ADP and collagen-induced platelet aggregation.

ADP


Input: In chronic hamster model of dyslipidemia, administration of C3 (16 mg/kg p. o. for 90 days) had no effect on plasma lipids, vasoreactivity and platelet adhesion.


Input: C3 fed hamsters showed reduced whole-blood aggregation response to ADP and collagen compared to HC-fed hamsters.

ADP


Input: In addition, C3 augmented thrombin time; however, time to occlusion was not increased.


Input: These results convincingly demonstrated that C3 is a novel molecule that reduces the risk of thrombosis and alleviates prothrombotic state associated with hyperlipidemia without any adverse effect on bleeding time.


Input: The high benefit/risk ratio of this compound makes it a suitable candidate for future valid studies.


Input: Virtual and in vitro bioassay screening of phytochemical inhibitors from flavonoids and isoflavones against xanthine oxidase and cyclooxygenase-2 for gout treatment.

flavonoids

isoflavones

xanthine


Input: Synthetic drugs such as allopurinol and benzbromarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid.

allopurinol

benzbromarone

uric acid


Input: We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase and cyclooxygenase-2 enzymes.

xanthine


Input: In this study, we report the screening of nine compounds of flavonoids from the ZINC and PubChem databases (containing 2092 flavonoids) using the IGEMDOCK software tool against the xanthine oxidase and cyclooxygenase-2 3D protein structures.

flavonoids

flavonoids

xanthine


Input: Each compound was also evaluated by an in vitro bioassay testing the inhibition of xanthine oxidase and cyclooxygenase-2.

xanthine


Input: Myricetin and luteolin were found to be the potential dual inhibitors of xanthine oxidase and cyclooxygenase-2 as demonstrated by IC (50): 62. 7 and 3. 29 mu g/mL (xanthine oxidase)/70. 8 and 16. 38 mu g/mL (cyclooxygenase-2), respectively.

Myricetin

luteolin

xanthine

xanthine


Input: In addition, structure-activity relationships and other important factors of the flavonoids binding to the active site of xanthine oxidase and cyclooxygenase-2 were discussed, which is expected for further rational drug design.

flavonoids

xanthine


Input: Bioinformatics and Molecular Dynamics Simulation Study of L1 Stalk Non-Canonical rRNA Elements: Kink-Turns, Loops, and Tetraloops.


Input: The L1 stalk is a prominent mobile element of the large ribosomal subunit.


Input: We explore the structure and dynamics of its non-canonical rRNA elements, which include two kink-turns, an internal loop, and a tetraloop.


Input: We use bioinformatics to identify the L1 stalk RNA conservation patterns and carry out over 11. 5 mu s of MD simulations for a set of systems ranging from isolated RNA building blocks up to complexes of L1 stalk rRNA with the L1 protein and tRNA fragment.


Input: We show that the L1 stalk tetraloop has an unusual GNNA or UNNG conservation pattern deviating from major GNRA and YNMG RNA tetraloop families.


Input: We suggest that this deviation is related to a highly conserved tertiary contact within the L1 stalk.


Input: The available X-ray structures contain only UCCG tetraloops which in addition differ in orientation (anti vs syn) of the guanine.

guanine


Input: Our analysis suggests that the anti orientation might be a mis-refinement, although even the anti interaction would be compatible with the sequence pattern and observed tertiary interaction.


Input: Alternatively, the anti conformation may be a real substate whose population could be pH-dependent, since the guanine syn orientation requires protonation of cytosine in the tertiary contact.

guanine

cytosine


Input: In absence of structural data, we use molecular modeling to explore the GCCA tetraloop that is dominant in bacteria and suggest that the GCCA tetraloop is structurally similar to the YNMG tetraloop.


Input: Kink-turn Kt-77 is unusual due to its 11-nucleotide bulge.

nucleotide


Input: The simulations indicate that the long bulge is a stalk-specific eight-nucleotide insertion into consensual kink-turn only subtly modifying its structural dynamics.

nucleotide


Input: We discuss a possible evolutionary role of helix H78 and a mechanism of L1 stalk interaction with tRNA.


Input: We also assess the simulation methodology.


Input: The simulations provide a good description of the studied systems with the latest bsc0 chi OL3 force field showing improved performance.


Input: Still, even bsc0 chi OL3 is unable to fully stabilize an essential sugar-edge H-bond between the bulge and non-canonical stem of the kink-turn.

sugar

H


Input: Inclusion of Mg (2 +) ions may deteriorate the simulations.

Mg (2 +)


Input: On the other hand, monovalent ions can in simulations readily occupy experimental Mg (2 +) binding sites.

Mg (2 +)


Input: Novel analgesic/anti-inflammatory agents: 1, 5-diarylpyrrole nitrooxyalkyl ethers and related compounds as cyclooxygenase-2 inhibiting nitric oxide donors.

1, 5-diarylpyrrole nitrooxyalkyl ethers

nitric oxide


Input: A series of 3-substituted 1, 5-diarylpyrroles bearing a nitrooxyalkyl side chain linked to different spacers were designed.

3-substituted 1, 5-diarylpyrroles

nitrooxyalkyl


Input: New classes of pyrrole-derived nitrooxyalkyl inverse esters, carbonates, and ethers (7-10) as COX-2 selective inhibitors and NO donors were synthesized and are herein reported.

pyrrole

nitrooxyalkyl

esters

carbonates

ethers

NO


Input: By taking into account the metabolic conversion of nitrooxyalkyl ethers (9, 10) into corresponding alcohols, derivatives 17 and 18 were also studied.

nitrooxyalkyl ethers

alcohols


Input: Nitrooxy derivatives showed NO-dependent vasorelaxing properties, while most of the compounds proved to be very potent and selective COX-2 inhibitors in in vitro experimental models.

Nitrooxy

NO


Input: Further in vivo studies on compounds 9a, c and 17a highlighted good anti-inflammatory and antinociceptive activities.


Input: Compound 9c was able to inhibit glycosaminoglycan (GAG) release induced by interleukin-1 beta (IL-1 beta), showing cartilage protective properties.


Input: Finally, molecular modeling and (1) H-and (13) C-NMR studies performed on compounds 6c, d, 9c, and 10b allowed the right conformation of nitrooxyalkyl ester and ether side chain of these molecules within the COX-2 active site to be assessed.

(1) H

(13) C

nitrooxyalkyl ester and ether


Input: Electrohydrodynamic Bubbling: An Alternative Route to Fabricate Porous Structures of Silk Fibroin Based Materials.


Input: Conventional fabrication techniques and structures employed in the design of silk fibroin (SF) based porous materials provide only limited control over pore size and require several processing stages.


Input: In this study, it is shown that, by utilizing electrohydrodynamic bubbling, not only can new hollow spherical structures of SF be formed in a single step by means of bubbles, but the resulting bubbles can serve as pore generators when dehydrated.


Input: The bubble characteristics can be controlled through simple adjustments to the processing parameters.


Input: Bubbles with diameters in the range of 240-1000 mu m were fabricated in controlled fashion.


Input: FT-IR characterization confirmed that the rate of air infused during processing enhanced beta-sheet packing in SF at higher flow rates.


Input: Dynamic mechanical analysis also demonstrated a correlation between air flow rate and film tensile strength.


Input: Results indicate that electrohydrodynamically generated SF and their composite bubbles can be employed as new tools to generate porous structures in a controlled manner with a range of potential applications in biocoatings and tissue engineering scaffolds.


Input: Generalized structural description of calcium-sodium aluminosilicate hydrate gels: the cross-linked substituted tobermorite model.

calcium-sodium aluminosilicate hydrate

tobermorite


Input: Structural models for the primary strength and durability-giving reaction product in modern cements, a calcium (alumino) silicate hydrate gel, have previously been based solely on non-cross-linked tobermorite structures.

calcium (alumino) silicate

tobermorite


Input: However, recent experimental studies of laboratory-synthesized and alkali-activated slag (AAS) binders have indicated that the calcium-sodium aluminosilicate hydrate [C-(N)-A-S-H] gel formed in these systems can be significantly cross-linked.

calcium-sodium aluminosilicate hydrate

C-(N)-A-S-H


Input: Here, we propose a model that describes the C-(N)-A-S-H gel as a mixture of cross-linked and non-cross-linked tobermorite-based structures (the cross-linked substituted tobermorite model, CSTM), which can more appropriately describe the spectroscopic and density information available for this material.

C-(N)-A-S-H

tobermorite

tobermorite


Input: Analysis of the phase assemblage and Al coordination environments of AAS binders shows that it is not possible to fully account for the chemistry of AAS by use of the assumption that all of the tetrahedral Al is present in a tobermorite-type C-(N)-A-S-H gel, due to the structural constraints of the gel.

tobermorite

C-(N)-A-S-H


Input: Application of the CSTM can for the first time reconcile this information, indicating the presence of an additional activation product that contains highly connected four-coordinated silicate and aluminate species.

silicate

aluminate


Input: The CSTM therefore provides a more advanced description of the chemistry and structure of calcium-sodium aluminosilicate gel structures than that previously established in the literature.

calcium-sodium aluminosilicate


Input: Methionine salvage and S-adenosylmethionine: essential links between sulfur, ethylene and polyamine biosynthesis.

Methionine

S-adenosylmethionine

sulfur

ethylene


Input: Both Met (methionine) and SAM (S-adenosylmethionine), the activated form of Met, participate in a number of essential metabolic pathways in plants.

Met

methionine

SAM

S-adenosylmethionine

Met


Input: The subcellular compartmentalization of Met fluxes will be discussed in the present review with respect to regulation and communication with the sulfur assimilation pathway, the network of the aspartate-derived amino acids and the demand for production of SAM.

Met

sulfur

aspartate

amino acids

SAM


Input: SAM enters the ethylene, nicotianamine and polyamine biosynthetic pathways and provides the methyl group for the majority of methylation reactions required for plant growth and development.

SAM

ethylene

nicotianamine

methyl


Input: The multiple essential roles of SAM require regulation of its synthesis, recycling and distribution to sustain these different pathways.

SAM


Input: A particular focus of the present review will be on the function of recently identified genes of the Met salvage cycle or Yang cycle and the importance of the Met salvage cycle in the metabolism of MTA (5'-methylthioadenosine).

Met

Met

MTA


Input: MTA has the potential for product inhibition of ethylene, nicotianamine and polyamine biosynthesis which provides an additional link between these pathways.

MTA

ethylene

nicotianamine


Input: Interestingly, regulation of Met cycle genes was found to differ between plant species as shown for Arabidopsis thaliana and Oryza sativa.

Met


Input: Galangin attenuates mast cell-mediated allergic inflammation.

Galangin


Input: A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis.


Input: Therefore discovery of drugs for the treatment of these diseases is an important subject in human health.


Input: In this study, we investigated anti-allergic inflammatory effect of galangin and underlying mechanisms of action using in vitro and in vivo models.

galangin


Input: Galangin inhibited histamine release by the reduction of intracellular calcium in phorbol 12-mystate 13-acetate plus calcium ionophore A23187-stimulated human mast cells (HMC-1).

Galangin

histamine

calcium

phorbol 12-mystate 13-acetate

calcium


Input: Galangin decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1 beta, and IL-8.

Galangin


Input: The inhibitory effect of galangin on theses pro-inflammatory cytokines was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-kappa B, and caspase-1.

galangin

N


Input: Furthermore, galangin attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue.

galangin

histamine


Input: The inhibitory effects of galangin were more potent than cromolyn, a known anti-allergic drug.

galangin

cromolyn


Input: Our results showed that galangin down-regulates mast cell-derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory cytokines.

galangin

histamine


Input: In light of in vitro and in vivo anti-allergic inflammatory effects, galangin could be a beneficial anti-allergic inflammatory agent.

galangin


Input: Scoparone attenuates d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure through inhibition of toll-like receptor 4 signaling in mice.

Scoparone

d-galactosamine


Input: The purpose of this study was to investigate the protective effects and molecular mechanisms of scoparone on d-galactosamine (d-GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF) in mice.

scoparone

d-galactosamine

d-GalN


Input: FHF was induced in mice by intraperitoneal injection of d-GalN (800mg/kg)/LPS (40 mu g/kg).

d-GalN


Input: Mice were treated intraperitoneally with scoparone 1h before d-GalN/LPS treatment.

scoparone

d-GalN


Input: Treatment with d-GalN/LPS markedly increased mortality, serum aminotransferase activity, and tolllike receptor 4 (TLR4) protein expression, and these increases were attenuated by scoparone.

d-GalN

scoparone


Input: Treatment with d-GalN/LPS markedly increased myeloid differentiation primary response gene 88 protein expression, phosphorylation of p38, extracellular signal-regulated kinase and c-Jun N-terminal kinase, nuclear protein expression of nuclear factor kappa B and phosphorylated c-Jun, and levels of serum tumor necrosis factor-alpha and interleukin-6 and these increases were attenuated by scoparone.

d-GalN

N

scoparone


Input: In addition, increased levels of toll-receptor-associated activator of interferon protein expression, phosphorylation of interferon (IFN) regulatory factor 3, and serum IFN-beta level in d-GalN/LPS-treated mice were attenuated by scoparone.

d-GalN

scoparone


Input: Our results suggest that scoparone attenuates d-GalN/LPSinduced liver damage by inhibition of the TLR-mediated inflammatory pathway.

scoparone

d-GalN


Input: Aberrant activation of M phase proteins by cell proliferation-evoking carcinogens after 28-day administration in rats.


Input: We have previously reported that hepatocarcinogens increase liver cells expressing p21 (Cip1), a G1 checkpoint protein and M phase proteins after 28-day treatment in rats.


Input: This study aimed to identify early prediction markers of carcinogens available in many target organs after 28-day treatment in rats.


Input: Immunohistochemical analysis was performed on Ki-67, p21 (Cip1) and M phase proteins [nuclear Cdc2, phospho-Histone H3 (p-Histone H3), Aurora B and heterochromatin protein 1 alpha (HP1 alpha)] with carcinogens targeting different organs.


Input: Carcinogens targeting thyroid (sulfadimethoxine; SDM), urinary bladder (phenylethyl isothiocyanate), forestomach (butylated hydroxyanisole; BHA), glandular stomach (catechol; CC), and colon (2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine and chenodeoxycholic acid) were examined using a non-carcinogenic toxicant (caprolactam) and carcinogens targeting other organs as negative controls.

sulfadimethoxine

SDM

phenylethyl isothiocyanate

butylated hydroxyanisole

BHA

catechol

2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine

chenodeoxycholic acid

caprolactam


Input: All carcinogens increased Ki-67 (+), nuclear Cdc2 (+), p-Histone H3 (+) or Aurora B (+) carcinogenic target cells, except for both colon carcinogens, which did not increase cell proliferation.


Input: On the other hand, p21 (Cip1 +) cells increased with SDM and CC.


Input: HP1 alpha responded only to BHA.

BHA


Input: Results revealed carcinogens evoking cell proliferation concurrently induced cell cycle arrest at M phase or showing chromosomal instability reflecting aberration in cell cycle regulation, irrespective of target organs, after 28-day treatment.


Input: Therefore, M phase proteins may be early prediction markers of carcinogens evoking cell proliferation in many target organs.


Input: Potent naphthoquinones against antimony-sensitive and-resistant Leishmania parasites: Synthesis of novel alpha-and nor-alpha-lapachone-based 1, 2, 3-triazoles by copper-catalyzed azide-alkyne cycloaddition.

naphthoquinones

alpha-and nor-alpha-lapachone

1, 2, 3-triazoles

copper

azide

alkyne


Input: Continuing our screening program for novel anti-parasite compounds, we synthesized seven 1, 4-naphthoquinones coupled to 1, 2, 3-triazoles, five nor-beta-lapachone-based 1, 2, 3-triazoles and ten alpha-lapachone-based 1, 2, 3-triazoles.

1, 4-naphthoquinones

1, 2, 3-triazoles

nor-beta-lapachone

1, 2, 3-triazoles

alpha-lapachone

1, 2, 3-triazoles


Input: These and other naphthoquinonoid compounds were evaluated for their activity against promastigote forms of antimony-sensitive and-resistant strains of Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis.


Input: The toxicity of these compounds to mammalian cells was also examined.


Input: The substances were more potent than an antimonial drug, with IC50 values ranging from 1. 0 to 50. 7 mu M.


Input: Nor-alpha-lapachone derivatives showed the highest antileishmanial activity, with selectivity indices in the range of 10-15.

Nor-alpha-lapachone


Input: These compounds emerged as important leads for further investigation as antileishmanial agents.


Input: Additionally, one of these compounds exhibited cross-resistance in Sb-resistant Leishmania and could provide a molecular tool for investigating the multidrug resistance mechanisms in Leishmania parasites.


Input: Heterocyclic bismuth carboxylates based on a diphenyl sulfone scaffold: Synthesis and antifungal activity against Saccharomycescerevisiae.

Heterocyclic bismuth carboxylates

diphenyl sulfone


Input: A series of heterocyclic organobismuth (III) carboxylates 4 and 5 [RCO2Bi (C6H4-2-SO2C6H4-1'-)] derived from diphenyl sulfone was synthesized to determine the influence of the carboxylate ligand structure on the lipophilicity and antifungal activity against the yeast Saccharomyces cerevisiae.

heterocyclic organobismuth (III) carboxylates

RCO2Bi (C6H4-2-SO2C6H4-1'-)

diphenyl sulfone

carboxylate


Input: In contrast to the clear structure-activity relationship between the size of the inhibition zone and the value of ClogP for specific substitution on diphenyl sulfone scaffold 1 [ClBi (5-RC6H3-2-SO2C6H4-1'-)], scaffolds 4 and 5 showed similar inhibition activities irrespective of the ClogP value.

diphenyl sulfone

ClBi (5-RC6H3-2-SO2C6H4-1'-)


Input: This suggests that these molecules function inside the yeast cell by separating into the cationic heterocyclic bismuth scaffold and the anionic carboxylate moiety, and that the bismuth scaffold plays an important role in the inhibition activity.

bismuth

carboxylate

bismuth


Input: Novel and highly potent histamine H3 receptor ligands.

histamine


Input: Part 3: An alcohol function to improve the pharmacokinetic profile.

alcohol


Input: Synthesis and biological evaluation of potent histamine H3 receptor antagonists incorporating a hydroxyl function are described.

histamine

hydroxyl


Input: Compounds in this series exhibited nanomolar binding affinities for human receptor, illustrating a new possible component for the H3 pharmacophore.


Input: As demonstrated with compound BP1. 4160 (cyclohexanol 19), the introduction of an alcohol function counter-intuitively allowed to reach high in vivo efficiency and favorable pharmacokinetic profile with reduced half-life.

BP1. 4160

cyclohexanol

alcohol


Input: Impact of cell wall composition on maize resistance to pests and diseases.


Input: In cereals, the primary cell wall is built of a skeleton of cellulosic microfibrils embedded in a matrix of hemicelluloses and smaller amounts of pectins, glycoproteins and hydroxycinnamates.

hydroxycinnamates


Input: Later, during secondary wall development, p-coumaryl, coniferyl and sinapyl alcohols are copolymerized to form mixed lignins.

p-coumaryl, coniferyl and sinapyl alcohols


Input: Several of these cell wall components show a determinative role in maize resistance to pest and diseases.


Input: However, defense mechanisms are very complex and vary among the same plant species, different tissues or even the same tissue at different developmental stages.


Input: Thus, it is important to highlight that the role of the cell wall components needs to be tested in diverse genotypes and specific tissues where the feeding or attacking by the pathogen takes place.


Input: Understanding the role of cell wall constituents as defense mechanisms may allow modifications of crops to withstand pests and diseases.


Input: Management of schizophrenia: clinical experience with asenapine.

asenapine


Input: Schizophrenia is a chronic brain disorder comprising a range of clinical features, including positive and negative symptoms, cognitive dysfunction and mood symptoms (particularly depression and anxiety).


Input: The management of schizophrenia requires effective short-and long-term treatment with antipsychotic medication that is effective across these symptom domains, while being well tolerated over the long term.


Input: Asenapine is the first tetracyclic atypical antipsychotic to be licensed in the USA and several other countries outside Europe for the acute and maintenance treatment of schizophrenia in adults.

Asenapine


Input: It has a unique receptor-binding profile and a broad range of therapeutic effects.


Input: Since clinical trials are conducted under strict conditions in tightly defined patient populations, evidence of an agent' s efficacy and tolerability under' real-world' clinical practice conditions is also required.


Input: As in clinical trials, real-life case reports demonstrate that asenapine is effective in treating the positive symptoms of schizophrenia, both in the acute setting and for relapse prevention.

asenapine


Input: It is also effective in treating negative symptoms and shows promise in the treatment of depressive symptoms associated with schizophrenia.


Input: Asenapine has a favourable tolerability profile, having a minimal impact on weight and metabolic parameters.

Asenapine


Input: As such, asenapine is valuable option for the treatment of schizophrenia in adults.

asenapine


Input: Reactivity of Chemical Sensitizers Toward Amino Acids In Cellulo Plays a Role in the Activation of the Nrf2-ARE Pathway in Human Monocyte Dendritic Cells and the THP-1 Cell Line.

Amino Acids


Input: Allergic contact dermatitis resulting from skin sensitization is an inflammatory skin disease linked to the use of chemicals termed haptens.


Input: Chemical reactivity is necessary for a chemical to be a sensitizer, allowing both covalent binding to proteins and maturation of dendritic cells (DCs) by mimicking " danger signals. " The aim of this study was to evaluate how the reactivity of chemical sensitizers toward amino acids translates into a biological response using the activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway, which was assessed by the induction of three Nrf2 target genes (ho-1, nqo1, and il-8) and Nrf2 protein accumulation.

amino acids


Input: Nrf2 activation is known to play a role in numerous detoxification mechanisms that could regulate danger signal outcomes in myeloid cells.


Input: Monocyte-derived DCs and THP-1 cells were exposed to (a) haptens with cysteine, lysine, or cysteine/lysine reactivity, (b) pro-/prehaptens, and (c) nonsensitizing molecules with reducing or oxidative properties (17 molecules in total).

cysteine

lysine

cysteine

lysine


Input: Chemicals were classified as " Nrf2 pathway activators " when at least two Nrf2 target genes associated with Nrf2 protein expression were induced.


Input: Results showed that most chemical sensitizers having cysteine and cysteine/lysine affinities were inducers of the Nrf2 pathway in both cell models, whereas lysine-reactive chemicals were less efficient.

cysteine

cysteine

lysine

lysine


Input: In THP-1 cells, the Nrf2 pathway was also activated by pro-/prehaptens.


Input: Regression analysis revealed that ho-1 and nqo1 expressions were found to be associated with chemical sensitizer reactivity to cysteine, providing evidence of the importance of chemical reactivity, as a part of danger signals, in DC biology.

cysteine


Input: An overview on the marine neurotoxin, saxitoxin: genetics, molecular targets, methods of detection and ecological functions.

saxitoxin


Input: Marine neurotoxins are natural products produced by phytoplankton and select species of invertebrates and fish.


Input: These compounds interact with voltage-gated sodium, potassium and calcium channels and modulate the flux of these ions into various cell types.

sodium

potassium

calcium


Input: This review provides a summary of marine neurotoxins, including their structures, molecular targets and pharmacologies.


Input: Saxitoxin and its derivatives, collectively referred to as paralytic shellfish toxins (PSTs), are unique among neurotoxins in that they are found in both marine and freshwater environments by organisms inhabiting two kingdoms of life.

Saxitoxin


Input: Prokaryotic cyanobacteria are responsible for PST production in freshwater systems, while eukaryotic dinoflagellates are the main producers in marine waters.