Input: Maximum stress of 16 MPa at mCNC fraction of 80 wt% was obtained.


Input: The mechanical properties of the composites show exceptional insensitivity to air humidity.


Input: The shown simple concept of percolative intercalated nanocomposites suggests searching for more general biomimetic compositions involving several deformation mechanisms for improved mechanical properties.


Input: Paths to selection on life history loci in different natural environments across the native range of Arabidopsis thaliana.


Input: Selection on quantitative trait loci (QTL) may vary among natural environments due to differences in the genetic architecture of traits, environment-specific allelic effects or changes in the direction and magnitude of selection on specific traits.


Input: To dissect the environmental differences in selection on life history QTL across climatic regions, we grew a panel of interconnected recombinant inbred lines (RILs) of Arabidopsis thaliana in four field sites across its native European range.


Input: For each environment, we mapped QTL for growth, reproductive timing and development.


Input: Several QTL were pleiotropic across environments, three colocalizing with known functional polymorphisms in flowering time genes (CRY2, FRI and MAF2-5), but major QTL differed across field sites, showing conditional neutrality.


Input: We used structural equation models to trace selection paths from QTL to lifetime fitness in each environment.


Input: Only three QTL directly affected fruit number, measuring fitness.


Input: Most QTL had an indirect effect on fitness through their effect on bolting time or leaf length.


Input: Influence of life history traits on fitness differed dramatically across sites, resulting in different patterns of selection on reproductive timing and underlying QTL.


Input: In two oceanic field sites with high prereproductive mortality, QTL alleles contributing to early reproduction resulted in greater fruit production, conferring selective advantage, whereas alleles contributing to later reproduction resulted in larger size and higher fitness in a continental site.


Input: This demonstrates how environmental variation leads to change in both QTL effect sizes and direction of selection on traits, justifying the persistence of allelic polymorphism at life history QTL across the species range.


Input: Binding Specificity and Thermodynamics of Cellulose-Binding Modules from Trichoderma reesei Cel7A and Cel6A.


Input: In this work, Family 1 cellulose binding modules CBMCel7A and CBMCel6A were heterologously expressed and purified from Escherichia coli, and the binding properties between these CBMs and cellulose substrates were studied.


Input: Cellulose nanowhiskers (CNWs, the crystalline portion of cellulose), microcrystalline cellulose Avicel PH101 (partially crystalline cellulose), and phosphoric acid swollen cellulose (PASC, amorphous cellulose) were used as representative models for cellulose to better understand the binding interactions between the CBMs and different regions of native cellulose.

phosphoric acid


Input: Isothermal titration calorimetry (ITC) was combined with adsorption-isotherm experiment to analyze the thermodynamics of CBM binding to various cellulose substrates.


Input: N2 adsorption and static light scattering (SLS) data were used to estimate the accessible surface area of cellulose which was then used for ITC data analysis.


Input: A new method of determining the cellulose molarity based on the available surface area for CBM binding was developed, which allows different cellulose substrates to be compared for binding experiments.


Input: The ITC results showed that the binding constant (Ka) to crystalline CNWs was ~ 10 (5) M (-1) for CBMCel7A, while ~ 10 (6) M (-1) for CBMCel6A, suggesting a higher binding affinity of CBMCel6A to CNWs.


Input: For Avicel, lower binding constants for both CBMs were observed, and weak bindings to PASC were characterized, suggesting that the binding between CBMCel7A, Cel6A and cellulose to some extent relates to the crystallinity of cellulose.


Input: Additionally, the binding reactions were driven by a favorable enthalpy change, offset partially by an unfavorable entropy change.


Input: It is suggested that CBMCel6A preferentially binds to the reducing end of cellulose chain, while CBMCel7A does not show such end binding specificities.


Input: Cello-oligosaccharides less than two glucose units did not bind with CBMs, and improved binding affinities were observed for cello-oligosaccharides with longer glucose units.

glucose

glucose


Input: PCNA trimer instability inhibits translesion synthesis by DNA polymerase eta and by DNA polymerase delta.


Input: Translesion synthesis (TLS), the process by which DNA polymerases replicate through DNA lesions, is the source of most DNA damage-induced mutations.


Input: Sometimes TLS is carried out by replicative polymerases that have evolved to synthesize DNA on non-damaged templates.


Input: Most of the time, however, TLS is carried out by specialized translesion polymerases that have evolved to synthesize DNA on damaged templates.


Input: TLS requires the mono-ubiquitylation of the replication accessory factor proliferating cell nuclear antigen (PCNA).


Input: PCNA and ubiquitin-modified PCNA (UbPCNA) stimulate TLS by replicative and translesion polymerases.


Input: Two mutant forms of PCNA, one with an E113G substitution and one with a G178S substitution, support normal cell growth but inhibit TLS thereby reducing mutagenesis in yeast.


Input: A re-examination of the structures of both mutant PCNA proteins revealed substantial disruptions of the subunit interface that forms the PCNA trimer.


Input: Both mutant proteins have reduced trimer stability with the G178S substitution causing a more severe defect.


Input: The mutant forms of PCNA and UbPCNA do not stimulate TLS of an abasic site by either replicative Pol delta or translesion Pol eta.


Input: Normal replication by Pol eta was also impacted, but normal replication by Pol delta was much less affected.


Input: These findings support a model in which reduced trimer stability causes these mutant PCNA proteins to occasionally undergo conformational changes that compromise their ability to stimulate TLS by both replicative and translesion polymerases.


Input: Biomarkers of prolonged exposure to microcystin-LR in mice.

microcystin-LR


Input: The effects of prolonged exposure to microcystins (MCs) on health are not yet sufficiently understood and this type of poisoning is often undiagnosed.


Input: Even though chronic exposure has been linked with liver cancer and alterations have been described in liver damage marker enzymes in exposed populations, there are not profile parameters that indicate prolonged exposure to microcystins.


Input: The aim of this work is to determine, based on an animal model of prolonged exposure to successive i. p. doses of 25 mu g MC-LR/kg body weight, several plasma parameters which could be useful as exposure biomarkers.

MC-LR


Input: Hemoglobin (Hb) and methemoglobin (MetHb) levels were determined on blood samples.


Input: We also studied plasma levels of hydroperoxides (ROOHs), alpha-tocopherol, glutathione and lipid profile as well as superoxide dismutase (SOD) and catalase (CAT) erythrocyte activities.

hydroperoxides

ROOHs

alpha-tocopherol

glutathione

superoxide


Input: In addition, the determination of MC-LR levels in liver, kidney, plasma, urine and feces of treated mice was carried out.

MC-LR


Input: We found that alteration in MetHb, ROOHs, glutathione, alpha-tocopherol levels, SOD activity and plasma lipid profile, correlates with those expected if the alteration derived from hepatic damage.

ROOHs

glutathione

alpha-tocopherol


Input: The alterated plasma paramenters together with MC-LR determination could be used as biomarkers, helpful tools in screening and epidemiological studies.

MC-LR


Input: LC-MS/MS Determination of Isoprostanes in Plasma Samples Collected from Mice Exposed to Doxorubicin or Tert-Butyl Hydroperoxide.

Isoprostanes

Doxorubicin

Tert-Butyl Hydroperoxide


Input: Isoprostanes are stable products of arachidonic acid peroxidation and are regarded as the most reliable markers of oxidative stress in vivo.

Isoprostanes

arachidonic acid


Input: Here we describe the LC-MS/MS procedure enabling simultaneous determination of four regioisomers (8-iso prostaglandin F2 alpha, 8-iso-15 (R)-prostaglandin F2 alpha, 11 beta-prostaglandin F2 alpha, 15 (R)-prostaglandin F2 alpha) in plasma samples collected from mice.

8-iso prostaglandin F2 alpha

8-iso-15 (R)-prostaglandin F2 alpha

11 beta-prostaglandin F2 alpha

15 (R)-prostaglandin F2 alpha


Input: The four plasma isoprostanes are determined by LC-ESI-MS/MS with deuterated 8-iso-PGF2 alpha-d4 as an internal standard (I. S.).

isoprostanes

8-iso-PGF2 alpha-d4


Input: For plasma samples spiked with the isoprostanes at a level of 200 pg/mL each, the method imprecision has been below 7. 1% and mean inaccuracy equaled 8. 7%.

isoprostanes


Input: The applicability of the proposed approach has been verified by the assessment of changes in isoprostane levels in plasma samples derived from mice exposed to tert-butyl hydroperoxide (TBHP), a model inducer of oxidative stress, or to antitumor drug doxorubicin (DOX) known for potent stimulation of redox cycling.

isoprostane

tert-butyl hydroperoxide

TBHP

doxorubicin

DOX


Input: Compared to the control group of mice, both oxidative stress inducers tested increased the levels of three out of four isoprostanes in exposed animals; 11 beta-prostaglandin F2 alpha being the exception.

11 beta-prostaglandin F2 alpha


Input: The greatest rise was observed in the case of 15 (R)-prostaglandin F2 alpha, by about 50% and 70% in plasma samples derived from mice exposed to DOX and TBHP, respectively.

15 (R)-prostaglandin F2 alpha

DOX

TBHP


Input: Droplet-based microfluidic platform for heterogeneous enzymatic assays.


Input: Heterogeneous enzymatic reactions are used in many industrial processes including pulp and paper, food, and biofuel production.


Input: Industrially-relevant optimization of the enzymes used in these processes requires assaying them with insoluble substrates.


Input: However, platforms for high throughput heterogeneous assays do not exist thereby severely increasing the cost and time of enzyme optimization, or leading to the use of assays with soluble substrates for convenient, but non-ideal, optimization.


Input: We present an innovative approach to perform heterogeneous reactions in a high throughput fashion using droplet microfluidics.


Input: Droplets provide a facile platform for heterogeneous reactions as internal recirculation allows rapid mixing of insoluble substrates with soluble enzymes.


Input: Moreover, it is easy to generate hundreds or thousands of picoliter droplets in a small footprint chip allowing many parallel reactions.


Input: We validate our approach by screening combinations of cellulases with real-world insoluble substrates, and demonstrate that the chip-based screening is in excellent agreement with the conventional screening methods, while offering advantages of throughput, speed and lower reagent consumption.


Input: We believe that our approach, while demonstrated for a biofuel application, provides a generic platform for high throughput monitoring of heterogeneous reactions.


Input: Lysophosphatidic acid impairs glucose homeostasis and inhibits insulin secretion in high-fat diet obese mice.

Lysophosphatidic acid

glucose


Input: AIMS/HYPOTHESIS: Lysophosphatidic acid (LPA) is a lipid mediator produced by adipocytes that acts via specific G-protein-coupled receptors; its synthesis is modulated in obesity.

Lysophosphatidic acid

LPA


Input: We previously reported that reducing adipocyte LPA production in high-fat diet (HFD)-fed obese mice is associated with improved glucose tolerance, suggesting a negative impact of LPA on glucose homeostasis.

LPA

glucose

LPA

glucose


Input: Here, our aim was to test this hypothesis.


Input: METHODS: First, glucose tolerance and plasma insulin were assessed after acute (30 min) injection of LPA (50 mg/kg) or of the LPA1/LPA3 receptor antagonist Ki16425 (5 mg kg (-1) day (-1), i. p.) in non-obese mice fed a normal diet (ND) and in obese/prediabetic (defined as glucose-intolerant) HFD mice.

glucose

LPA

glucose


Input: Glucose and insulin tolerance, pancreas morphology, glycogen storage, glucose oxidation and glucose transport were then studied after chronic treatment (3 weeks) of HFD mice with Ki16425.

Glucose

glucose

glucose


Input: RESULTS: In ND and HFD mice, LPA acutely impaired glucose tolerance by inhibiting glucose-induced insulin secretion.

LPA

glucose

glucose


Input: These effects were blocked by pre-injection of Ki16425 (5 mg/kg, i. p.).


Input: Inhibition of glucose-induced insulin secretion by LPA also occurred in isolated mouse islets.

glucose

LPA


Input: Plasma LPA was higher in HFD mice than in ND mice and Ki16425 transiently improved glucose tolerance.

LPA

glucose


Input: The beneficial effect of Ki16425 became permanent after chronic treatment and was associated with increased pancreatic islet mass and higher fasting insulinaemia.


Input: Chronic treatment with Ki16425 also improved insulin tolerance and increased liver glycogen storage and basal glucose use in skeletal muscle.

glucose


Input: CONCLUSIONS/INTERPRETATION: Exogenous and endogenous LPA exerts a deleterious effect on glucose disposal through a reduction of plasma insulin; pharmacological blockade of LPA receptors improves glucose homeostasis in obese/prediabetic mice.

LPA

glucose

LPA

glucose


Input: Higher levels of trait impulsiveness and a less effective response inhibition are linked to more intense cue-elicited craving for alcohol in alcohol-dependent patients.

alcohol

alcohol


Input: RATIONALE: Cue-elicited craving is a well-researched phenomenon in alcohol literature.

alcohol


Input: However, not all alcohol-dependent people display the same reactivity to alcohol cues.

alcohol

alcohol


Input: Personality factors such as multiple impulsivity traits may be responsible for individual differences in cue reactivity by modulating its intensity.


Input: Nevertheless, there has been a scarcity of empirical studies testing this assumption in alcohol literature.

alcohol


Input: OBJECTIVES: The aim of the present study was to investigate the effects of response inhibition and trait impulsiveness on cue-elicited craving for alcohol in alcohol-dependent drinkers.

alcohol

alcohol


Input: METHODS: Participants (n = 41) were inpatients of the private clinic U-Center, Netherlands.


Input: Alcohol exposure took place in a real bar-restaurant close to the premises of the clinic, and participants were exposed to real alcohol cues.

Alcohol

alcohol


Input: Response inhibition was assessed with the stop-signal task and trait impulsiveness with the Barratt impulsivity scale version 11.


Input: RESULTS: The cue exposure was successful as alcohol-dependent patients experienced higher craving for alcohol when exposed to alcohol rather than to neutral cues.

alcohol

alcohol

alcohol


Input: Additionally, both response inhibition and trait impulsiveness predicted cue-elicited craving for alcohol.

alcohol


Input: Trait impulsiveness predicted both the absolute craving in the bar-restaurant and the increase in cue-elicited craving during the whole alcohol cue exposure, while response inhibition predicted only the former.

alcohol


Input: CONCLUSIONS: The results clearly implicate both trait impulsiveness and response inhibition in the modulation of cue-elicited craving in alcohol dependence.

alcohol


Input: Theoretical and methodological issues in the findings and their clinical implications in alcohol treatment and relapse are discussed.

alcohol


Input: Molecular Basis for Sialic Acid-dependent Receptor Recognition by the Plasmodium falciparum Invasion Protein Erythrocyte-binding Antigen-140/BAEBL.

Sialic Acid


Input: Plasmodium falciparum erythrocyte invasion is dependent on high affinity recognition of sialic acid on cell surface receptors.

sialic acid


Input: The erythrocyte binding-like (EBL) family of invasion ligands mediates recognition of sialic acid on erythrocyte glycoproteins.

sialic acid


Input: Erythrocyte-binding antigen-140 (PfEBA-140/BAEBL) is a critical EBL ligand that binds sialic acid on its receptor glycophorin C.

sialic acid


Input: We present here the crystal structure of the two-domain receptor-binding region of PfEBA-140 in complex with a glycan containing sialic acid.

sialic acid


Input: The structure identifies two glycan-binding pockets unique to PfEBA-140 and not shared by other EBL ligands.


Input: Specific molecular interactions that enable receptor engagement are identified and reveal that the glycan binding mode is distinct from that of apicomplexan and viral cell surface recognition ligands as well as host immune factors that bind sialic acid.

sialic acid


Input: Erythrocyte binding experiments elucidated essential glycan contact residues and identified divergent functional roles for each receptor-binding site.


Input: One of four polymorphisms proposed to affect receptor binding was localized to a glycan-binding site, providing a structural basis for altered erythrocyte engagement.


Input: The studies described here provide the first full description of sialic acid-dependent molecular interactions at the P. falciparum erythrocyte invasion interface and define a framework for development of PfEBA-140-based therapeutics, vaccines, and diagnostics assessing vaccine efficacy and natural immunity to infection.

sialic acid


Input: De novo fragment design: a medicinal chemistry approach to fragment-based lead generation.


Input: The use of fragments with low binding affinity for their targets as starting points has received much attention recently.


Input: Screening of fragment libraries has been the most common method to find attractive starting points.


Input: Herein, we describe a unique, alternative approach to generating fragment leads.


Input: A binding model was developed and a set of guidelines were then selected to use this model to design fragments, enabling our discovery of a novel fragment with high LE.


Input: Surface Thermodynamic and Adhesion Force Evaluation of the Role of Chitin-Binding Protein in the Physical Interaction between Pseudomonas aeruginosa and Candida albicans.


Input: Candida albicans and Pseudomonas aeruginosa are able to form pathogenic polymicrobial communities.


Input: P. aeruginosa colonizes and kills hyphae but is unable to attach to yeast.


Input: It is unknown why the interaction of P. aeruginosa is different with yeast than with hyphae.


Input: Here we aim to evaluate the role of P. aeruginosa chitin-binding protein (CbpD) in its physical interaction with C. albicans hyphae or yeast, based on surface thermodynamic and atomic force microscopic analyses.


Input: A P. aeruginosa mutant lacking CbpD was unable to express strong adhesion forces with hyphae (-2. 9 nN) as compared with the parent strain P. aeruginosa PAO1 (-4. 8 nN) and showed less adhesion to hyphae.


Input: Also blocking of CbpD using N-acetyl-glucosamine yielded a lower adhesion force (-4. 3 nN) with hyphae.

N-acetyl-glucosamine


Input: Strong adhesion forces were restored after complementing the expression of CbpD in P. aeruginosa PAO1 Delta cbpD yielding an adhesion force of-5. 1 nN.


Input: These observations were confirmed with microscopic evaluation of adhesion tests.


Input: Regardless of the absence or presence of CbpD on the bacterial cell surfaces, or their blocking, P. aeruginosa experienced favorable thermodynamic conditions for adhesion with hyphae, which were absent with yeast.


Input: In addition, adhesion forces with yeast were less than 0. 5 nN in all cases.


Input: Concluding, CbpD in P. aeruginosa is responsible for strong physical interactions with C. albicans hyphae.


Input: The development of this interaction requires time due to the fact that CbpDs have to invade the outermost mannoprotein layer on the hyphal cell surfaces.


Input: In order to do this, thermodynamic conditions at the outermost cell surfaces have to be favorable.


Input: Degradable Cationic Shell Cross-Linked Knedel-like Nanoparticles: Synthesis, Degradation, Nucleic Acid Binding, and in Vitro Evaluation.


Input: In this work, degradable cationic shell cross-linked knedel-like (deg-cSCK) nanoparticles were developed as an alternative platform to replace similar nondegradable cSCK nanoparticles that have been utilized for nucleic acids delivery.


Input: An amphiphilic diblock copolymer poly (acrylamidoethylamine) 90-block-poly (dl-lactide) 40 (PAEA90-b-PDLLA40) was synthesized, self-assembled in aqueous solution, and shell cross-linked using a hydrolyzable cross-linker to afford deg-cSCKs with an average core diameter of 45 +/- 7 nm.

poly (acrylamidoethylamine) 90-block-poly (dl-lactide) 40


Input: These nanoparticles were fluorescently labeled for in vitro tracking.


Input: The enzymatic-and hydrolytic-degradability, siRNA binding affinity, cell uptake and cytotoxicity of the deg-cSCKs were evaluated.


Input: Esterase-catalyzed hydrolysis of the nanoparticles resulted in the degradation of ca.


Input: 24% of the PDLLA core into lactic acid within 5 d, as opposed to only ca.

PDLLA

lactic acid


Input: 9% degradation from aqueous solutions of the deg-cSCK nanoparticles in the absence of enzyme.


Input: Cellular uptake of deg-cSCKs was efficient, while exhibiting low cytotoxicity with LD50 values of ca.


Input: 90 and 30 mu g/mL in RAW 264. 7 mouse macrophages and MLE 12 cell lines, respectively, ca.


Input: 5-to 6-fold lower than the cytotoxicity observed for nondegradable cSCK analogs.


Input: Additionally, deg-cSCKs were able to complex siRNA at an N/P ratio as low as 2, and were efficiently able to facilitate cellular uptake of the complexed nucleic acids.


Input: Therapeutic Nanocarriers with Hydrogen Peroxide-Triggered Drug Release for Cancer Treatment.

Hydrogen Peroxide


Input: Chemotherapy is an important modality in cancer treatment.


Input: The major challenge of recent works in this research field is to develop new types of smart nanocarriers that can respond selectively to cancer cell-specific conditions and realize rapid drug release in target cells.


Input: In the present study, a reactive oxygen species-responsive nanocarrier has been successfully self-assembled from an amphiphilic hyperbranched polymer consisting of alternative hydrophobic selenide groups and hydrophilic phosphate segments in the dendritic backbone.

oxygen

selenide

phosphate


Input: Because the hydrophobic selenide groups transformed into the hydrophilic selenone groups after oxidation under the exclusive oxidative microenvironment within cancer cells, the amphiphilic hyperbranched precursors become hydrophilic ones.

selenide

selenone


Input: As a result, the nanocarriers were rapidly disassembled in target cells, resulting in fast intracellular drug release.


Input: The hydrophilic products of oxidation can be degraded into harmless small molecular species via the enzymatic digestion of the phosphate segments and then eliminated by renal excretion.

phosphate


Input: Meanwhile, the reactive selenium-containing nanocarrier possesses a potent intrinsic anticancer effect since selenium compounds can produce antitumor metabolites which induce apoptosis of cancer cells efficiently.

selenium

selenium


Input: Therefore, this type of therapeutic nanocarriers with a unique drug release mechanism based on an amphiphilic-to-hydrophilic transition provides a new platform for targeted drug delivery and combined therapy.


Input: Modeling Adsorption of Cationic Surfactants at Air/Water Interface without Using the Gibbs Equation.


Input: The Gibbs adsorption equation has been indispensable in predicting the surfactant adsorption at the interfaces, with many applications in industrial and natural processes.


Input: This study uses a new theoretical framework to model surfactant adsorption at the air/water interface without the Gibbs equation.


Input: The model was applied to two surfactants, C14TAB and C16TAB, to determine the maximum surface excesses.


Input: The obtained values demonstrated a fundamental change, which was verified by simulations, in the molecular arrangement at the interface.


Input: The new insights, in combination with recent discoveries in the field, expose the limitations of applying the Gibbs adsorption equation to cationic surfactants at the air/water interface.


Input: Carbonic anhydrase inhibitors: Inhibition of the beta-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides, sulfamates and sulfamides.

sulfonamides

sulfamates

sulfamides


Input: The fungal pathogen Candida glabrata encodes for a beta-carbonic anhydrase (CA, EC 4. 2. 1. 1), CgNce103, recently discovered.


Input: Only anions have been investigated as CgNce103 inhibitors up until now.


Input: Here we report the first sulfonamides inhibition study of this enzyme.

sulfonamides


Input: Simple sulfonamides showed weak or moderate CgNce103 inhibitory properties, whereas acetazolamide, and a series of 4-substituted ureido-benzene-sulfonamides, sulfamates and sulfamides showed effective CgNce103 inhibitory properties, with KIs in the range of 4. 1-115nM, being also ineffective as human CA II inhibitors.

sulfonamides

acetazolamide

4-substituted ureido-benzene-sulfonamides

sulfamates

sulfamides


Input: As there is significant resistance of C. glabrata clinical isolates to many classical antifungal agents, inhibition of the beta-CA from this organism may allow an interesting means of controlling the pathogen growth, eventually leading to antifungals with a novel mechanism of action.


Input: Optoacoustic tweezers: a programmable, localized cell concentrator based on opto-thermally generated, acoustically activated, surface bubbles.


Input: We present a programmable, biocompatible technique for dynamically concentrating and patterning particles and cells in a microfluidic device.


Input: Since our technique utilizes opto-thermally generated, acoustically activated, surface bubbles, we name it " optoacoustic tweezers ".


Input: The optoacoustic tweezers are capable of concentrating particles/cells at any prescribed locations in a microfluidic chamber without the use of permanent structures, rendering it particularly useful for the formation of flexible, complex cell patterns.


Input: Additionally, this technique has demonstrated excellent biocompatibility and can be conveniently integrated with other microfluidic units.


Input: In our experiments, micro-bubbles were generated by focusing a 405 nm diode laser onto a gold-coated glass chamber.


Input: By properly tuning the laser, we demonstrate precise control over the position and size of the generated bubbles.


Input: Acoustic waves were then applied to activate the surface bubbles, causing them to oscillate at an optimized frequency.


Input: The resulting acoustic radiation force allowed us to locally trap particles/cells, including 15 mu m polystyrene beads and HeLa cells, around each bubble.

polystyrene


Input: Cell-adhesion tests were also conducted after cell concentrating to confirm the biocompatibility of this technique.


Input: Population pharmacokinetics of intramuscular artesunate in african children with severe malaria: implications for a practical dosing regimen.

artesunate


Input: Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria.

artesunate

ARS


Input: Pharmacokinetics data on intramuscular ARS are limited with respect to the main treatment group that carries the highest mortality, namely, critically ill children with severe malaria.

ARS


Input: A population pharmacokinetic study of ARS and dihydroartemisinin (DHA) was conducted from sparse sampling in 70 Tanzanian children of ages 6 months to 11 years.

ARS

dihydroartemisinin

DHA


Input: All the children had been admitted with severe falciparum malaria and were treated with intramuscular ARS (2. 4 mg/kg at 0, 12, and 24 h).

ARS


Input: Venous plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling (NONMEM).


Input: A one-compartment disposition model accurately described first-dose population pharmacokinetics of ARS and DHA.

ARS

DHA


Input: Body weight significantly affected clearance and apparent volume of distribution (P < 0. 001), resulting in lower ARS and DHA exposure levels in smaller children.

ARS

DHA


Input: An adapted dosing regimen including a practical dosing table per weight band is proposed for young children based on the pharmacokinetic model.


Input: If you don' t know where you are going, you can' t tell if you have arrived: defining goals for drug safety announcements.


Input: One of the responses available to drug regulators facing a potential drug safety issue is to release a " Dear Doctor " letter describing the problem.


Input: Although numerous such safety alerts are issued every year, we know almost nothing about their effectiveness in improving patient outcomes.


Input: The article by Reber et al. in this issue is important because it is one of the few studies to examine the effect of such safety alerts on physician behavior.


Input: A copper hyperaccumulation phenotype correlates with pathogenesis in Cryptococcus neoformans.

copper


Input: Cryptococcus neoformans is a major human pathogen and a cause of meningoencephalitis in immunocompromised patients.


Input: Many factors contribute to the extraordinary survivability and pathogenicity of this fungus in humans, including copper homeostasis pathways.

copper


Input: Previous work has shown that deletion of the copper-dependent regulator Cuf1 results in decreased virulence and dissemination in brain infection, suggesting that copper acquisition is important to the persistence of this pathogen.

copper

copper


Input: Here, we show that the minimal copper quota of C. neoformans is maintained at a high level even when grown under conditions of stringent copper limitation.

copper

copper


Input: Intriguingly, when this fungal pathogen is grown in standard and copper-enriched media, it sequesters even higher levels of this essential metal, achieving levels that are far higher than non-pathogenic S. cerevisiae.

copper


Input: The hypothesis that copper acquisition plays an essential role in virulence is further corroborated by the findings that a hypovirulent CUF1-deletant strain of C. neoformans retrieved from infected mice contains almost a 6-fold lower concentration of intracellular copper than the pathogenic wild-type strain.

copper

copper


Input: The concentration difference arises in part from larger-sized cuf1 Delta cell.


Input: Under in vitro growth conditions, the size of the cuf1 Delta cells is normal and the hypertrophy phenotype is readily induced in vitro under conditions of copper starvation.

copper


Input: Taken together, these data suggest that acquisition of extraordinary levels of copper is an important factor in the survivability of the pathogen in the copper-deplete environment of infection, and effective copper concentration may play an important role in the pathogenesis of C. neoformans.

copper

copper

copper


Input: Effect of voltage polarity and amplitude on electroforming of TiO2 based memristive devices.


Input: Pt/TiO2/Pt/Ti memristive devices were electrically formed to either the ON or OFF state using voltages of the same polarity but with different amplitudes.

Pt

Pt

Ti


Input: The forming step dictated the subsequent switching behaviour.


Input: A qualitative model based on the creation and migration of oxygen vacancies was proposed to explain the experimental results.

oxygen


Input: Is Artemisinin the Only Antiplasmodial Compound in the Artemisia annua Tea Infusion?

Artemisinin


Input: An in Vitro Study.


Input: In our ongoing investigation into Artemisia annua for the treatment of malaria, we decided to study the possibility that synergism might enhance the efficacy of artemisinin.

artemisinin


Input: Our main objective was to test tea infusions and nonpolar extracts prepared from different A. annua varieties against Plasmodium falciparum in vitro in order to determine if synergism will increase the effectiveness of artemisinin in the samples as compared to pure artemisinin.

artemisinin

artemisinin


Input: We found that the IC50 of artemisinin in the tea and nonpolar extracts was not significantly different to the IC50 of pure artemisinin.

artemisinin

artemisinin


Input: We could show that the year and country of harvest or storage conditions did not have any influence on the activity and that it narrowly followed the concentration of artemisinin in all the extracts.

artemisinin


Input: In conclusion, based on these in vitro results, artemisinin seems to be the only active antiplasmodial compound in A. annua.

artemisinin


Input: Hop Extracts and Hop Substances in Treatment of Menopausal Complaints.


Input: Hop extract is a long used medicinal product and, regarding hormonal activities, in 1999 a number of prenylflavanones have been identified as its major constituents with 8-prenylnaringenin (8-PN) being the main active estrogenic compound.

prenylflavanones


Input: There have been several in vivo studies performed that demonstrate the potential of hop extract and the single compound 8-PN to alleviate climacteric symptoms like osteoporosis, vasomotoric complaints, and sexual motivation.


Input: On the other hand, only a few clinical studies have been performed so far, and these mainly focused on menopausal discomforts, especially hot flushes, yielding rather inconclusive results.


Input: Despite preferentially activating estrogen receptor alpha, 8-PN is only slightly uterotrophic, but it also elucidates estrogenic effects on the mammary gland.

estrogen


Input: In conclusion, although hop extract and especially 8-PN are promising candidates as a relief for climacteric symptoms, data on the safety and efficacy is still scarce.


Input: Cardamonin Ameliorates Insulin Resistance Induced by High Insulin and High Glucose through the mTOR and Signal Pathway.

Cardamonin

Glucose


Input: The mammalian target of rapamycin is crucial in the regulation of cell growth and metabolism.

rapamycin


Input: Recent studies suggest that the mammalian target of rapamycin and its downstream 70-kDa ribosomal S6 kinase 1 negatively modulate the insulin-signaling pathway, which is considered the main cause of insulin resistance.

rapamycin


Input: The aim of this study is to investigate the effects of cardamonin, a potential inhibitor of the mammalian target of the rapamycin, on insulin-resistant vascular smooth muscle cells and the molecular mechanisms involved.

cardamonin

rapamycin


Input: Vascular smooth muscle cells were cultured with high glucose and high insulin to induce insulin resistance.

glucose


Input: The mammalian target of rapamycin was overstimulated in cells that were incubated with high glucose and high insulin, as reflected by the excessive activation of S6 kinase 1.

rapamycin

glucose


Input: Insulin-resistant vascular smooth muscle cells displayed hyperphosphorylation of insulin receptor substrate-1 at Ser residues 636/639, which decreased the activity of insulin receptor substrate-1.

Ser


Input: Also, the activation of protein kinase B and phosphorylation of glycogen synthesis kinase-3 beta were inhibited.


Input: Cardamonin increased the 2-deoxyglucose uptake and glycogen concentration, which was reduced by insulin resistance.

Cardamonin


Input: As with rapamycin, cardamonin inhibited the activity of the mammalian target of rapamycin and S6 kinase 1, decreased the Ser 636/639 phosphorylation of insulin receptor substrate-1 and increased the activation of protein kinase B.

rapamycin

cardamonin

rapamycin

Ser


Input: Both of them increased the Ser9 phosphorylation of glycogen synthesis kinase-3 beta and decreased the expression of glycogen synthesis kinase-3 beta.


Input: However, neither cardamonin nor rapamycin increased the expression of glucose transport 4 which decreased in insulin-resistant vascular smooth muscle cells.

cardamonin

rapamycin

glucose


Input: This study suggests that cardamonin inhibited the activity of the mammalian target of rapamycin and eliminated the negative feedback of the mammalian target of rapamycin and S6 kinase 1 on the insulin-signaling pathway.

cardamonin

rapamycin

rapamycin


Input: NAD (P) H: Quinone Oxidoreductase 1 Inducer Activity of Some Saudi Arabian Medicinal Plants.

NAD (P) H

Quinone


Input: Medicinal plants are a rich source of biologically-active phytochemicals and have been used in traditional medicine for centuries.


Input: Specific phytochemicals and extracts of their plant sources have the ability to reduce the risk for chronic degenerative diseases by induction of enzymes involved in xenobiotic metabolism, many of which also have antioxidant and anti-inflammatory functions.


Input: One such multifunctional cytoprotective enzyme is NAD (P) H: quinone oxidoreductase.

NAD (P) H

quinone


Input: In this study, we prepared extracts of 27 Saudi Arabian medicinal plants which belong to 18 different plant families and tested their ability to induce NAD (P) H: quinone oxidoreductase in murine hepatoma cells grown in microtiter plate wells.

NAD (P) H

quinone


Input: In addition to the Brassicaceae, a known source of NAD (P) H: quinone oxidoreductase inducer activity, we found substantial inducer activity in extracts from the Apiaceae, Apocynaceae, and the Asteraceae families.

NAD (P) H

quinone


Input: Five out of a total of eight active extracts are from plants which belong to the Asteraceae family.


Input: We further show that artemisinin, an agent which is used clinically for the treatment of malaria, contributes but does not fully account for the inducer activity of the extract of Artemisia monosperma.

artemisinin


Input: In contrast to artemisinin, deoxyartemisinin is inactive in this assay, demonstrating the critical role of the endoperoxide moiety of artemisinin for inducer activity.

artemisinin

deoxyartemisinin

artemisinin


Input: Thus, the NAD (P) H: quinone oxidoreductase inducer activity of extracts of some Saudi Arabian medicinal plants indicates the presence of specific phytochemicals which have the potential to protect against chronic degenerative diseases.

NAD (P) H

quinone


Input: The protective effects of omega-3 fatty acids on doxorubicin-induced hepatotoxicity and nephrotoxicity in rats.

omega-3 fatty acids

doxorubicin


Input: This study aims to evaluate the protective effects of omega-3 fatty acids (FAs) on doxorubicin (DOX)-induced hepatotoxicity and nephrotoxicity in rats.

omega-3 fatty acids

FAs

doxorubicin

DOX


Input: A total of 24 adult male Sprague Dawley rats were divided into three groups.


Input: Control group was given only saline by intragastric gavage.


Input: DOX group received DOX at the dose of 30 mg/kg intraperitoneally on day 28.

DOX

DOX


Input: DOX-omega-3 FA group was given as omega-3 FAs at the dose of 400 mg/kg daily by intragastric gavage for 30 days and received DOX at the dose of 30 mg/kg intraperitoneally on day 28.

DOX-omega-3 FA

omega-3 FAs

DOX


Input: At the end of the 30-day experimental period, the serum, liver and kidney tissue specimens were taken from the animals by giving a general anesthesia.


Input: Glutathione (GSH) and malondialdehyde (MDA) levels in serum and GSH and MDA levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and kidney tissues were measured spectrophotometrically.

Glutathione

GSH

malondialdehyde

MDA

GSH

MDA

superoxide

glutathione

GSH


Input: In our study, a significant increase in MDA levels was observed in rats when given a dose of DOX and a significant decrease in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues was determined when compared with control group.

MDA

DOX

GSH

GSH


Input: In addition, a significant decrease in MDA levels was observed in rats when a dose of omega-3 FAs was given with DOX and a significant increase was determined in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues, when compared with DOX group.

MDA

omega-3 FAs

DOX

GSH

GSH

DOX


Input: We concluded that omega-3 FA had favorable effects in rat liver and kidney tissues by preventing oxidative damage.

omega-3 FA


Input: Metabolism of Beclomethasone Dipropionate by Cytochrome P450 3A Enzymes.

Beclomethasone Dipropionate


Input: Inhaled glucocorticoids, such as beclomethasone dipropionate (BDP), are the mainstay treatment of asthma.

beclomethasone dipropionate

BDP


Input: However, ~ 30% of patients exhibit little to no benefit from treatment.


Input: It has been postulated that glucocorticoid resistance, or insensitivity, is attributable to individual differences in glucocorticoid receptor-mediated processes.


Input: It is possible that variations in cytochrome P450 3A enzyme-mediated metabolism of BDP may contribute to this phenomenon.

BDP


Input: This hypothesis was explored by evaluating the contributions of CYP3A4, 3A5, 3A7, and esterase enzymes in the metabolism of BDP in vitro and relating metabolism to changes in CYP3A enzyme mRNA expression via the glucocorticoid receptor in lung and liver cells.

BDP


Input: CYP3A4 and CYP3A5 metabolized BDP via hydroxylation ([M4] and [M6]) and dehydrogenation ([M5]) at similar rates; CYP3A7 did not metabolize BDP.

BDP

BDP


Input: A new metabolite [M6], formed by the combined action of esterases and CYP3A4 hydroxylation, was also characterized.


Input: To validate the results observed using microsomes and recombinant enzymes, studies were also conducted using A549 lung and DPX2 liver cells.


Input: Both liver and lung cells produced esterase-dependent metabolites [M1-M3], with [M1] correlating with CYP3A5 mRNA induction in A549 cells.


Input: Liver cells produced both hydroxylated and dehydrogenated metabolites [M4, M5, and M6], but lung cells produced only the dehydrogenated metabolite [M5].


Input: These studies show that CYP3A4 and CYP3A5 metabolize BDP to inactive metabolites and suggest that differences in the expression or function of these enzymes in the lung and/or liver could influence BDP disposition in humans.

BDP

BDP


Input: The Tumor Suppressor Kruppel-Like Factor 6 is a Novel Aryl Hydrocarbon Receptor DNA Binding Partner.

Aryl Hydrocarbon


Input: The Aryl Hydrocarbon Receptor (AhR) is a ligand mediated basic helix-loop-helix transcription factor of Per/Arnt/Sim family that regulates adaptive and toxic responses to variety of chemical pollutants including polycyclic aromatic hydrocarbons (PAH) and halogenated aromatic hydrocarbons, most notably 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

Aryl Hydrocarbon

polycyclic aromatic hydrocarbons

PAH

halogenated aromatic hydrocarbons

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

TCDD


Input: Ligand activation leads to AhR nuclear translocation and binding to a xenobiotic response element (XRE) in association with the aryl receptor nuclear translocator (Arnt) to regulate gene expression.


Input: Several recent genome-wide transcriptional studies identified numerous AhR target genes that lack the canonical XRE recognition site in the promoter regions.


Input: Characterization of one such target gene, the Plasminogen Activator Inhibitor 1 (PAI-1) identified a novel non-consensus XRE (NC-XRE) that confers TCDD responsiveness independently of the Arnt protein.

TCDD


Input: Studies reported here show that the NC-XRE is a recognition site for the AhR and a new binding partner, the Kruppel-like Factor (KLF) family member KLF6.


Input: In vivo chromatin immunoprecipitations and in vitro DNA binding studies demonstrate that the AhR and KLF6 proteins form an obligatory heterodimer necessary for NC-XRE binding.


Input: Mutational analyzes show that the protein-protein interactions involve the AhR C-terminus and KLF6 N-terminus, respectively.


Input: Moreover, NC-XRE binding depends on the 5' basic region in KLF6 rather than the previously characterized zinc finger DNA binding domain.

zinc


Input: Collectively, the results unmask a novel AhR signaling mechanism distinct from the canonical XRE-driven process that will enrich our future understanding of AhR biology.


Input: Epigallocatechin-3-Gallate Inhibits Collagen Production of Nasal Polyp-Derived Fibroblasts.


Input: Nasal polyps are chronic inflammatory conditions characterized by myofibroblast differentiation and extracelluar matrix accumulation.


Input: The major catechin from green tea is (-)-epigallocatechin-3-gallate (EGCG), which has garnered attention for its potential to prevent oxidative stress-related diseases.

catechin

EGCG


Input: The purpose of this study was twofold: (i) to determine the effect of EGCG on fibroblast differentiation into myofibroblasts and extracellular matrix accumulation in transforming growth factor (TGF)-beta 1-induced nasal polyp-derived fibroblasts (NPDFs) and (ii) to determine if the antioxidative effect of EGCG on reactive oxygen species (ROS) production in TGF-beta 1-induced NPDFs is involved in the aforementioned processes.

EGCG

EGCG

oxygen


Input: TGF-beta 1-induced NPDFs were treated with or without EGCG.

EGCG


Input: alpha-smooth muscle actin (alpha-SMA) and collagen type I mRNA were analyzed by reverse transcription-polymerase chain reaction.


Input: alpha-SMA protein was also detected using immunofluorescent staining.


Input: The amount of total soluble collagen was analyzed by Sircol collagen assay.

Sircol


Input: ROS activity was measured by the nitroblue tetrazolium reduction assay and visualized by fluorescent microscopy.

nitroblue tetrazolium


Input: EGCG significantly inhibited expressions of alpha-SMA and collagen type I mRNA and reduced alpha-SMA and collagen protein levels at concentrations of 10-20 micro g/mL.

EGCG


Input: EGCG also inhibited TGF-beta 1-induced ROS production at the same concentrations.

EGCG


Input: These results suggest the possibility that EGCG may be effective at inhibiting the development of nasal polyps through an anti-oxidant effect.

EGCG


Input: Copyright (c) 2013 John Wiley & Sons, Ltd.


Input: Neuroprotective Effects of Puerarin on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine induced Parkinson' s Disease Model in Mice.

Puerarin

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


Input: Puerarin, an active component of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep is well-known for its anti-oxidative and neuroprotective activities.

Puerarin


Input: Although anti-Parkinson' s disease activity of puerarin was reported in both of in vivo and in vitro model, detailed mechanisms are not clarified.

puerarin


Input: In this study, we addressed that puerarin attenuated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced behavioral deficits, dopaminergic neuronal degeneration and dopamine depletion.

puerarin

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

MPTP

dopaminergic


Input: Puerarin administration enhanced glutathione (GSH) activity, glial cell line-derived neurotrophic factor (GDNF) expression and PI3K/Akt pathway activation, which might ameliorate MPTP injection-induced progressive elevation of reactive oxygen species (ROS) formation in mice.

Puerarin

glutathione

GSH

MPTP

oxygen


Input: In addition to the effect on ROS, puerarin ameliorated MPTP-reduced lysosome-associated membrane protein type 2A (Lamp 2A) expression.

puerarin

MPTP


Input: Taken together, our data demonstrate that puerarin attenuates MPTP-induced dopaminergic neuronal degeneration via modulating GDNF expression, PI3K/Akt pathway and GSH activation, which subsequently ameliorate MPTP-induced ROS formation and decrease of Lamp 2A expression.

puerarin

MPTP

GSH

MPTP


Input: Copyright (c) 2013 John Wiley & Sons, Ltd.


Input: The Minimum Activation Peptide from ilvH Can Activate the Catalytic Subunit of AHAS from Different Species.


Input: Acetohydroxyacid synthases (AHASs), which catalyze the first step in the biosynthesis of branched-chain amino acids, are composed of a catalytic subunit (CSU) and a regulatory subunit (RSU).

amino acids


Input: The CSU harbors the catalytic site, and the RSU is responsible for the activation and feedback regulation of the CSU.


Input: Previous results from Chipman and co-workers and our lab have shown that heterologous activation can be achieved among isozymes of Escherichia coli AHAS.


Input: It would be interesting to find the minimum peptide of ilvH (the RSU of E. coli AHAS III) that could activate other E. coli CSUs, or even those of ##species.


Input: In this paper, C-terminal, N-terminal, and C-and N-terminal truncation mutants of ilvH were constructed.

C

N

C

N


Input: The minimum peptide to activate ilvI (the CSU of E. coli AHAS III) was found to be Delta N 14-Delta C 89.


Input: Moreover, this peptide could not only activate its homologous ilvI and heterologous ilvB (CSU of E. coli AHAS I), but also heterologously activate the CSUs of AHAS from Saccharomyces cerevisiae, Arabidopsis thaliana, and Nicotiana plumbaginifolia.


Input: However, this peptide totally lost its ability for feedback regulation by valine, thus suggesting different elements for enzymatic activation and feedback regulation.

valine


Input: Additionally, the apparent dissociation constant (Kd) of Delta N 14-Delta C 89 when binding CSUs of different species was found to be 9. 3-66. 5 mu M by using microscale thermophoresis.


Input: The ability of this peptide to activate different CSUs does not correlate well with its binding ability (Kd) to these CSUs, thus implying that key interactions by specific residues is more important than binding ability in promoting enzymatic reactions.


Input: The high sequence similarity of the peptide Delta N 14-Delta C 89 to RSUs across species hints that this peptide represents the minimum activation motif in RSU and that it regulates all AHASs.


Input: Cognitive impairment and dietary habits among elders: the velestino study.


Input: Abstract To investigate the association of dietary habits with cognitive function among elders (> 65 years).


Input: Complete sociodemographic, dietary information, serum measurements, and Mini-Mental State Examination (MMSE) assessments were available for 237 elderly men and 320 women residing in Velestino, Greece (a rural Greek town).


Input: All models were adjusted for age, education, social activity, smoking, depression symptomatology (using the Geriatric Depression Scale), MedDietScore (range 0-55), and metabolic syndrome.


Input: About 49. 8% men and 66. 6% women had MMSE scores < 24, with a mean MMSE score of 22. 7 +/- 4. 43 and 21. 1 +/- 4. 73, respectively.


Input: Adherence to the Mediterranean diet was moderate (mean MedDietScore of 34. 1 +/- 3. 25 in men and 35. 1 +/- 2. 48 in women).


Input: Indicative cognitive impairment (MMSE score < 24) was positively associated with age and low education in women and with depressive symptoms, low education status, and low social activity in men.


Input: Adherence to the Mediterranean diet was positively associated with MMSE score in men (P =. 02), but inversely associated in women (P =. 04).


Input: Concerning the food groups studied, intake of pulses, nuts, and seeds was associated with lower likelihood of having MMSE score < 24 in men (P =. 04).


Input: Only the Mediterranean dietary pattern showed a significant association with MMSE score positive for cognitive impairment (i. e., protective in men, but not in women), while individual food groups or nutrients did not achieve significance.


Input: The latter findings support the role of whole diet in the prevention of mental disorders, and state a research hypothesis for a sex-diet interaction on cognitive function among elders.


Input: Oxidative and Photoxidative Polymerization of Humic Suprastructures by Heterogeneous Biomimetic Catalysis.


Input: The meso-tetra (2, 6-dichloro-3-sulfonatophenyl) porphyrinate of manganese (III) chloride [Mn-(TDCPPS) Cl] biomimetic catalyst immobilized on spacer-functionalized kaolinite clay mineral was employed in the oxidative coupling reaction of a dissolved humic acid (HA) suprastructure with either chemical (H2O2) or UV-light oxidation.

meso-tetra (2, 6-dichloro-3-sulfonatophenyl) porphyrinate

manganese (III) chloride [Mn-(TDCPPS) Cl]

kaolinite


Input: The changes in molecular size of humic matter subjected to catalyzed oxidative reaction were followed by high-performance size exclusion chromatography (HPSEC) with UV-vis and refractive index (RI) detectors in series, and by thermogravimetric (TGA) analysis.


Input: Both the enhanced molecular size shown by differences between HPSEC chromatograms of humic reaction mixtures at either pH 6 or 3. 5 and the increase of thermogravimetric stability suggest that the heterogeneous biomimetic catalysis promoted the stabilization of humic conformations by new intermolecular covalent bonds during oxidative coupling.


Input: The similarity between chemical and light-induced oxidation results suggests potential multiple applications of the kaolinite-supported heterogeneous catalyst in controlling the reactivity of natural organic matter within biogeochemical cycles and environmental reactions.

kaolinite


Input: Stereoselective Potencies and Relative Toxicities of gamma-Coniceine and N-Methylconiine Enantiomers.

gamma-Coniceine

N-Methylconiine


Input: gamma-Coniceine, coniine, and N-methylconiine are toxic alkaloids present in poison hemlock (Conium maculatum).

gamma-Coniceine

coniine

N-methylconiine


Input: We previously reported the comparison of the relative potencies of (+)-and (-)-coniine enantiomers.

(+)-and (-)-coniine


Input: In this study, we synthesized gamma-coniceine and the enantiomers of N-methylconiine and determined the biological activity of gamma-coniceine and each of the N-methylconiine enantiomers in vitro and in vivo.

gamma-coniceine

N-methylconiine

gamma-coniceine

N-methylconiine


Input: The relative potencies of these piperidine alkaloids on cells expressing human fetal muscle-type nicotinic acetylcholine receptors had the rank order of gamma-coniceine > (-)-N-methylconiine > (+/-)-N-methylconiine > (+)-N-methylconiine.

piperidine alkaloids

acetylcholine

gamma-coniceine

(-)-N-methylconiine

(+/-)-N-methylconiine

(+)-N-methylconiine


Input: The relative lethalities of gamma-coniceine and (-)-, (+/-)-, and (+)-N-methylconiine in vivo using a mouse bioassay were 4. 4, 16. 1, 17. 8, and 19. 2 mg/kg, respectively.

gamma-coniceine

(-)-, (+/-)-, and (+)-N-methylconiine


Input: The results from this study suggest gamma-coniceine is a more potent agonist than the enantiomers of N-methylconiine and that there is a stereoselective difference in the in vitro potencies of the enantiomers of N-methylconiine that correlates with the relative toxicities of the enantiomers in vivo.

gamma-coniceine

N-methylconiine

N-methylconiine


Input: Defect Chemistry of Oxide Nanomaterials with High Surface Area: Ordered Mesoporous Thin Films of the Oxygen Storage Catalyst CeO2-ZrO2.

Oxide

Oxygen


Input: Herein we report the electrical transport properties of a series of ordered mesoporous ceria-zirconia (CexZr1-xO2, referred to as mp-CZO) thin films with both a cubic structure of (17 +/- 2) nm diameter pores and nanocrystalline walls.

ceria-zirconia

CZO


Input: Samples over the whole range of composition, including bare CeO2 and ZrO2, were fabricated by templating strategies using the large diblock copolymer KLE as the structure-directing agent.

KLE


Input: Both the nanoscale structure and the chemical composition of the mesoporous materials were analyzed by a combination of scanning and transmission electron microscopy, grazing incidence small-angle X-ray scattering, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry.


Input: The total conductivity as a function of the film composition, temperature, and oxygen partial pressure was measured using impedance spectroscopy.

oxygen


Input: The mesoporous solid solutions of CeO2-ZrO2 prepared in this work showed a higher stability against thermal ripening than both binary oxides, making them ideal model systems to study both the charge transport properties and the oxygen storage at elevated temperatures.


Input: We find that the redox properties of nanocrystalline mp-CZO thin films differ significantly from those of bulk CZO materials reported in the literature and, therefore, propose a defect chemical model of surface regions.

CZO

CZO


Input: Colocalization of the Ganglioside GM1 and Cholesterol Detected by Secondary Ion Mass Spectrometry.

Ganglioside GM1

Cholesterol


Input: The characterization of the lateral organization of components in biological membranes and the evolution of this arrangement in response to external triggers remain a major challenge.


Input: The concept of lipid rafts is widely invoked; however, direct evidence of the existence of these ephemeral entities remains elusive.


Input: We report here the use of secondary ion mass spectrometry (SIMS) to image the cholesterol-dependent cohesive phase separation of the ganglioside GM1 into nano-and microscale assemblies in a canonical lipid raft composition of lipids.

cholesterol

ganglioside GM1


Input: This assembly of domains was interrogated in a model membrane system composed of palmitoyl sphingomyelin (PSM), cholesterol, and an unsaturated lipid (dioleoylphosphatidylcholine, DOPC).

palmitoyl sphingomyelin

PSM

cholesterol

dioleoylphosphatidylcholine

DOPC


Input: Orthogonal isotopic labeling of every lipid bilayer component and monofluorination of GM1 allowed generation of molecule specific images using a NanoSIMS.


Input: Simultaneous detection of six different ion species in SIMS, including secondary electrons, was used to generate ion ratio images whose signal intensity values could be correlated to composition through the use of calibration curves from standard samples.


Input: Images of this system provide the first direct, molecule specific, visual evidence for the colocalization of cholesterol and GM1 in supported lipid bilayers and further indicate the presence of three compositionally distinct phases: (1) the interdomain region; (2) micrometer-scale domains (d > 3 mu m); (3) nanometer-scale domains (d = 100 nm to 1 mu m) localized within the micrometer-scale domains and the interdomain region.

cholesterol


Input: PSM-rich, nanometer-scale domains prefer to partition within the more ordered, cholesterol-rich/DOPC-poor/GM1-rich micrometer-scale phase, while GM1-rich, nanometer-scale domains prefer to partition within the surrounding, disordered, cholesterol-poor/PSM-rich/DOPC-rich interdomain phase.

PSM

cholesterol

DOPC

cholesterol

PSM

DOPC


Input: Structure and Absolute Configuration of Methyl (3R)-Malonyl-(13S)-hydroxycheilanth-17-en-19-oate, a Sesterterpene Derivative from the Roots of Aletris farinosa.

Methyl (3R)-Malonyl-(13S)-hydroxycheilanth-17-en-19-oate

Sesterterpene


Input: We report the isolation and structure elucidation of a new cheilanthane sesterterpene from the roots of Aletris farinosa that possesses an unusual malonate half-ester functional group.

cheilanthane sesterterpene

malonate half-ester


Input: The structure of 1 was determined via mass spectrometry and 1D and 2D NMR spectroscopy, while its absolute configuration was determined via X-ray crystallographic analysis performed on its methyl ester derivative 2.

methyl ester


Input: Baseline Markers of Inflammation Are Associated With Progression to Macroalbuminuria in Type 1 Diabetic Subjects.


Input: OBJECTIVEThe current study aimed to determine in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications cohort whether or not abnormal levels of markers of inflammation and endothelial dysfunction measured in samples collected at DCCT baseline were able to predict the development of macroalbuminuria. RESEARCH DESIGN AND METHODSLevels of inflammation and endothelial cell dysfunction biomarkers were measured in 1, 237 of 1, 441 patients enrolled in the DCCT study who were both free of albuminuria and cardiovascular disease at baseline.


Input: To test the association of log-transformed biomarkers with albuminuria, generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria.


Input: Normal, micro-, and macroalbuminuria were the outcomes of interest. RESULTSIn the logistic regression models adjusted by DCCT treatment assignment, baseline albumin excretion rate, and use of ACE/angiotensin receptor blocker drugs, one unit increase in the standardized levels of soluble E-selectin (sE-selectin) was associated with an 87% increase in the odds to develop macroalbuminuria and one unit increase in the levels of interleukin-6 (IL-6), plasminogen activator inhibitor 1 (PAI-1; total and active), and soluble tumor necrosis factor receptors (TNFR)-1 and-2 lead to a 30-50% increase in the odds to develop macroalbuminuria.


Input: Following adjustment for DCCT baseline retinopathy status, age, sex, HbA1c, and duration of diabetes, significant associations remained for sE-selectin and TNFR-1 and-2 but not for IL-6 or PAI-1. CONCLUSIONSOur study indicates that high levels of inflammatory markers, mainly E-selectin and sTNRF-1 and-2, are important predictors of macroalbuminuria in patients with type 1 diabetes.


Input: Biological activity of Pd (II) complexes with mono-and disubstituted pyridines-Experimental and theoretical studies.

Pd (II)

mono-and disubstituted pyridines


Input: Due to the similarity between Pd and Pt, the complexes of palladium (II) can be considered as potential anticancer agents.

Pd

Pt

palladium (II)


Input: Activity of six PdCl2 (X2Py) 2 complexes (Py = pyridine, and X = CH3 or Cl) was measured by MTT test using MCF7, CCRF-SB, PC3 and human B-lymphoblastoid cell lines.

PdCl2 (X2Py) 2

Py

pyridine

Cl

MTT


Input: We found that the effect of PdCl2 (XnPy) 2 was cell-specific and time-dependent.

PdCl2 (XnPy) 2


Input: Obtained results were discussed and compared with the activation parameters calculated for the hydrolysis of PdCl2 (XnPy) 2, indicating a correlation between viability of MCF7 and CCRF-SB cells and rates of hydrolysis of the Pd (II) complexes.

PdCl2 (XnPy) 2

Pd (II)


Input: The Androgen Metabolite, 5 alpha-Androstane-3 beta, 17 beta-Diol (3 beta-Diol), Activates the Oxytocin Promoter Through an Estrogen Receptor-beta Pathway.

Androgen

5 alpha-Androstane-3 beta, 17 beta-Diol

3 beta-Diol

Oxytocin

Estrogen


Input: Testosterone has been shown to suppress the acute stress-induced activation of the hypothalamic-pituitary-adrenal axis; however, the mechanisms underlying this response remain unclear.

Testosterone


Input: The hypothalamic-pituitary-adrenal axis is regulated by a neuroendocrine subpopulation of medial parvocellular neurons in the paraventricular nucleus of the hypothalamus (PVN).


Input: These neurons are devoid of androgen receptors (ARs).

androgen


Input: Therefore, a possibility is that the PVN target neurons respond to a metabolite in the testosterone catabolic pathway via an AR-independent mechanism.

testosterone


Input: The dihydrotestosterone metabolite, 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol), binds and activates estrogen receptor-beta (ER-beta), the predominant ER in the PVN.

dihydrotestosterone

5 alpha-androstane-3 beta, 17 beta-diol

3 beta-diol

estrogen


Input: In the PVN, ER-beta is coexpressed with oxytocin (OT).

oxytocin


Input: Therefore, we tested the hypothesis that 3 beta-diol regulates OT expression through ER-beta activation.

3 beta-diol


Input: Treatment of ovariectomized rats with estradiol benzoate or 3 beta-diol for 4 days increased OT mRNA selectively in the midcaudal, but not rostral PVN compared with vehicle-treated controls.

estradiol benzoate

3 beta-diol


Input: 3 beta-Diol treatment also increased OT mRNA in the hypothalamic N38 cell line in vitro.

3 beta-Diol


Input: The functional interactions between 3 beta-diol and ER-beta with the human OT promoter were examined using an OT promoter-luciferase reporter construct (OT-luc).

3 beta-diol


Input: In a dose-dependent manner, 3 beta-diol treatment increased OT-luc activity when cells were cotransfected with ER-beta, but not ER-alpha.

3 beta-diol


Input: The 3 beta-diol-induced OT-luc activity was reduced by deletion of the promoter region containing the composite hormone response element (cHRE).

3 beta-diol


Input: Point mutations of the cHRE also prevented OT-luc activation by 3 beta-diol.

3 beta-diol


Input: These results indicate that 3 beta-diol induces OT promoter activity via ER-beta-cHRE interactions.

3 beta-diol


Input: Pathogenesis of preeclampsia: Implications of apoptotic markers and oxidative stress.


Input: This study aimed to investigate the implication of some apoptotic and lipid peroxidation markers in preeclampsia (PE).


Input: A total of 25 women with PE and 25 age-and parity-matched normal pregnant women were enrolled in this study.


Input: The malondialdehyde (MDA) level, caspase-9 activity and the percentage of DNA fragmentation were significantly higher in placental tissue of PE than in control women.

malondialdehyde

MDA


Input: The serum level of MDA was significantly elevated in women with PE having delivery by cesarean section (CS) than in women with PE having vaginal delivery.

MDA


Input: In vitro study demonstrated that the addition of 0. 5 mM Fe (2 +) and 0. 1 mM ascorbate caused increase in the production of MDA level in placental tissue with PE than normal placentas, and vitamin E (100 micro M) caused lower inhibition of in vitro lipid peroxidation in placental tissue with PE when compared with normal tissue.

Fe (2 +)

ascorbate

MDA

vitamin E


Input: The activity of caspase-9 and percentage of DNA fragmentation were associated with the severity of the PE and both could differentiate between PE and control women with 88% and 100% sensitivity and 96% and 100% specificity, respectively.


Input: The activities of caspase-8 and/or-9 were positively correlated with the maternal age but only caspase-8 was negatively correlated with neonatal birth weight and placental weight.


Input: In conclusion, the elevations of MDA, caspase-9 activity and the percentage of DNA fragmentation in the placentas of women with PE implicate the involvement of lipid peroxidation and apoptosis in PE.

MDA


Input: The placenta represents a considerable source of the elevated circulating MDA in PE.

MDA


Input: Ca (2 +)-dependent suicidal erythrocyte death following zearalenone exposure.

Ca (2 +)

zearalenone


Input: Zearalenone, a cereal mycotoxin with mycoestrogen activity and effect on fertility, is known to trigger apoptosis of a variety of nucleated cell types including hematopoietic progenitor cells.

Zearalenone


Input: In analogy to apoptosis of nucleated cells, eryptosis, the suicidal death of erythrocytes, leads to cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface.


Input: The most important stimulator of eryptosis is an increase in cytosolic Ca (2 +) activity ([Ca (2 +)] i).

Ca (2 +)

Ca (2 +)


Input: The present study explored whether zearalenone triggers eryptosis.

zearalenone


Input: Erythrocyte volume was estimated from forward scatter, phosphatidylserine exposure at the erythrocyte surface from annexin-V binding, hemolysis from hemoglobin release, and [Ca (2 +)] i from Fluo3 fluorescence.

Ca (2 +)


Input: A 48-h exposure to zearalenone (>= 25 mu M) was followed by a significant increase in [Ca (2 +)] i and annexin-V binding, and a significant decrease in forward scatter.

zearalenone

Ca (2 +)


Input: The effect on annexin-V binding was significantly blunted in the nominal absence of extracellular Ca (2 +).

Ca (2 +)


Input: Zearalenone stimulates the suicidal erythrocyte death, an effect at least partially due to stimulation of Ca (2 +) entry.

Zearalenone

Ca (2 +)


Input: Oxidative DNA damage is involved in ochratoxin A-induced G2 arrest through ataxia telangiectasia-mutated (ATM) pathways in human gastric epithelium GES-1 cells in vitro.

ochratoxin A


Input: Ochratoxin A (OTA), one of the most abundant mycotoxin food contaminants, is classified as " possibly carcinogenic to humans. " Our previous study showed that OTA could induce a G2 arrest in immortalized human gastric epithelium cells (GES-1).

Ochratoxin A

OTA

OTA


Input: To explore the putative roles of oxidative DNA damage and the ataxia telangiectasia-mutated (ATM) pathways on the OTA-induced G2 arrest, the current study systematically evaluated the roles of reactive oxygen species (ROS) production, DNA damage, and ATM-dependent pathway activation on the OTA-induced G2 phase arrest in GES-1 cells.

OTA

oxygen

OTA


Input: The results showed that OTA exposure elevated intracellular ROS production, which directly induced DNA damage and increased the levels of 8-OHdG and DNA double-strand breaks (DSBs).

OTA


Input: In addition, it was found that OTA treatment induced the phosphorylation of the ATM protein, as well as its downstream molecules Chk2 and p53, in response to DNA DSBs.

OTA


Input: Inhibition of ATM by the pharmacological inhibitor caffeine or siRNA effectively prevented the activation of ATM-dependent pathways and rescued the G2 arrest elicited by OTA.

OTA


Input: Finally, pretreatment with the antioxidant N-acetyl-L-cysteine (NAC) reduced the OTA-induced DNA DSBs, ATM phosphorylation, and G2 arrest.

N-acetyl-L-cysteine

NAC

OTA


Input: In conclusion, the results of this study suggested that OTA-induced oxidative DNA damage triggered the ATM-dependent pathways, which ultimately elicited a G2 arrest in GES-1 cells.

OTA


Input: Mitochondrial disease in childhood: nuclear encoded.


Input: Primary mitochondrial disorders are clinically and genetically heterogeneous, caused by an alteration (s) in either mitochondrial DNA or nuclear DNA, and affect the respiratory chain' s ability to undergo oxidative phosphorylation, leading to decreased production of adenosine triphosphophate and subsequent energy failure.

adenosine triphosphophate


Input: These disorders may present at any age, but children tend to have an acute onset of disease compared with subacute or slowly progressive presentation in adults.


Input: Varying organ involvement also contributes to the phenotypic spectrum seen in these disorders.


Input: The childhood presentation of primary mitochondrial disease is mainly due to nuclear DNA mutations, with mitochondrial DNA mutations being less frequent in childhood and more prominent in adulthood disease.


Input: The clinician should be aware of the pediatric presentation of mitochondrial disease and have an understanding of the myriad of nuclear genes responsible for these disorders.


Input: The nuclear genes can be best understood by utilizing a classification system of location and function within the mitochondria.


Input: Effects of Gentamicin on the Proteomes of Aerobic and Oxygen-Limited Escherichia coli.

Gentamicin

Oxygen


Input: The key role of the bacterial ribosome makes it an important target for antibacterial agents.


Input: Indeed, a large number of clinically useful antibiotics target this complex translational ribonucleoprotein machinery.


Input: Unfortunately, the development of resistant bacterial strains has compromised the effectiveness of most classes of antibacterial agent, including the classes that target the ribosome.


Input: Combinations of two or more drugs can be used to help overcome resistance, and in certain circumstances their action may be synergistic.


Input: In this study we have used proteomic techniques to establish the effects of gentamicin on the proteomes of aerobic and oxygen-limited Escherichia coli.

gentamicin

oxygen


Input: Ribosomal proteins L1, L9, L10, and S2 were found to be up-regulated in both conditions, and we postulate that these are candidate drug targets for the development of synergistic combinations with gentamicin.

gentamicin


Input: Decreased expression of hepatic low-density lipoprotein related protein 1 in hypothyroidism: a novel mechanism of atherogenic dyslipidemia in hypothyroidism.


Input: Background: The atherogenic effects of hypothyroidism on lipid metabolism could result, in part, from the reduced clearance of remnant lipoproteins.


Input: In this study, we investigated the expression of hepatic low-density lipoprotein receptor-related protein 1 (LRP1), a receptor for remnant lipoproteins, in hypothyroidism and the effect of triiodothyronine (T3) treatment on hepatic LRP1 expression.

triiodothyronine


Input: Methods: C57BL/6 mice were fed a normal diet (control group) or a low iodine diet supplemented with 0. 15% propylthiouracil (PTU/LI group) for 4 weeks.

iodine

propylthiouracil

PTU


Input: Mice in PTU/LI group were injected intraperitoneally with T3 (0, 30, and 150 mu g/kg of body weight) for 7 days.

PTU


Input: HepG2 cells were incubated in fetal bovine serum (FBS) or charcoal-stripped FBS (CSS) with various concentrations of T3.


Input: The expression and function of LRP1 in liver samples and cells were analyzed.


Input: Results: Hypothyroidism was successfully induced in PTU/LI group mice.

PTU


Input: Hepatic LRP1 protein expression was lower in the PTU/LI group than the control group.

PTU


Input: T3 treatment up-regulated hepatic LRP1 protein expression in PTU/LI group mice.

PTU


Input: LRP1 expression in HepG2 cells was reduced after incubation in media containing CSS, which mimics hypothyroidism in vitro, and was recovered by T3 treatment.


Input: The protein expression of LRP1 in HepG2 cells was increased by T3 treatment in a dose-dependent manner up to 2. 0 nM T3.


Input: However, LRP1 mRNA transcription was not affected by hypothyroidism conditions or T3 treatment, either in liver samples or HepG2 cells.


Input: T3 treatment on HepG2 cells increased cellular uptake of lipid-conjugated apolipoprotein E through LRP1.


Input: Conclusions: Our data demonstrate that hepatic LRP1 expression and function decrease in hypothyroidism and are regulated by thyroid hormone.

thyroid hormone


Input: These results suggest that in hypothyroidism, decreased expression of hepatic LRP1 may be associated with reduced clearance of circulating remnant lipoproteins.


Input: Outcome of patients with differentiated thyroid cancer risk stratified according to the American Thyroid Association and Latin American Thyroid Society risk of recurrence classification systems.


Input: Objective: To validate the proposed Latin-American Thyroid Society (LATS) risk of recurrence stratification system and to compare the findings with those of the American Thyroid Association (ATA) risk of recurrence stratification system.


Input: Subjects and Methods: Retrospective review of papillary thyroid cancer patients treated with total thyroidectomy and RAI at a single experienced thyroid cancer center and followed according to the LATS management guidelines.


Input: Each patient was risk stratified using both the LATS and ATA staging systems.


Input: The primary endpoints were (1) the best response to initial therapy defined as either remission (stimulated Tg < 1 ng/mL, negative US), or persistent disease (biochemical and/or structural) and (2) clinical status at final follow-up defined as either no evidence of disease (suppressed Tg < 1 ng/mL, negative US), biochemical persistent disease (suppressed Tg > 1 ng/mL in the absence of structural disease), structural persistent disease (loco-regional or distant metastases) or recurrence (biochemical or structural disease identified after a period of no evidence of disease, NED).


Input: Results: One hundred and seventy one papillary thyroid cancer patients were included (mean age 45 +/- 16 yrs, followed for a median of 4 yrs after initial treatment).


Input: Both the ATA and LATS risk stratification systems provided clinically meaningful graded estimates with regard to the (1) likelihood of achieving remission in response to initial therapy, (2) the likelihood of having persistent structural disease in response to initial therapy and at final follow-up, (3) the likely locations of the persistent structural disease (loco-regional vs. distant metastases), (4) the likelihood of recurrence and (5) the likelihood of being NED at final follow-up.


Input: The likelihood of having persistent biochemical evidence of disease was not significantly different across the staging categories.


Input: Conclusions: Both the ATA and LATS risk of recurrence systems effectively risk stratify patients with regard to multiple important clinical outcomes.


Input: When used in conjunction with a staging system that predicts disease specific mortality, either of these systems can be used to guide risk adapted individualized initial management recommendations.


Input: Disordered Nanowrinkle Substrates for Inducing Crystallization over a Wide Range of Concentration of Protein and Precipitant.


Input: There are large number of proteins, the existence of which are known but not their crystal structure, because of difficulty in finding the exact condition for their crystallization.


Input: Heterogeneous nucleation on disordered porous substrates with small yet large distribution of pores is considered a panacea for this problem, but a universal nucleant suitable for crystallizing large variety of proteins does not really exist.


Input: To this end, we report here a nanowrinkled substrate which displays remarkable ability and control over protein crystallization.


Input: Experiments with different proteins show that on these substrates crystals nucleate even at very low protein concentration in buffer.


Input: A small number of very large crystals appear for precipitant concentrations varied over orders of magnitude, ~ 0. 003-0. 3 M; for some proteins, crystals appear even without addition of any precipitant, not seen with any other heterogeneous substrates.


Input: In essence, these substrates significantly diminish the influence of the above two parameters, thought to be key factors for crystallization, signifying that this advantage can be exploited for finding out crystallization condition for other yet-to-be-crystallized proteins.


Input: Collapse of a hydrophobic polymer in a mixture of denaturants.


Input: The solvent quality of an aqueous mixture of two good solvents, urea and guanidinium chloride (GdmCl), for a hydrophobic polymer was investigated using atomistic molecular dynamics simulations.

urea

guanidinium chloride

GdmCl


Input: A counterintuitive collapse of the polymer was found, suggesting that mixing the two denaturants reduces the solvent quality.


Input: This cononsolvency of the polymer in the urea + GdmCl mixture is found to be caused by the preferential adsorption of urea on the polymer.

urea

GdmCl

urea


Input: The polymer collapses as a result of indirect long-range interactions between monomers resulting from the presence of urea clouds surrounding them.

urea


Input: Surprisingly, urea behaves as the better solvent in the mixture not because there exists a stronger affinity of the polymer for urea.

urea

urea


Input: Instead, attractive interactions between two unlike denaturant molecules combined with the direct dispersion interactions of the polymer with both denaturants determine the solvent quality of the mixture.


Input: Tailoring the Dependency between Rigidity and Water Uptake of a Microfabricated Hydrogel with the Conformational Rigidity of a Polymer Cross-Linker.


Input: Many diverse applications utilize hydrogels as carriers, sensors, and actuators, and these applications rely on the refined control of physical properties of the hydrogel, such as elastic modulus and degree of swelling.


Input: Often, hydrogel properties are interdependent; for example, when elastic modulus is increased, degree of swelling is decreased.


Input: Controlling these inverse dependencies remains a major barrier for broader hydrogel applications.


Input: We hypothesized that polymer cross-linkers with varied chain flexibility would allow us to tune the inverse dependency between the elastic modulus and the degree of swelling of the hydrogels.


Input: We examined this hypothesis by using alginate and poly (acrylic acid) (PAA) modified with a controlled number of methacrylic groups as model inflexible and flexible cross-linkers, respectively.

poly (acrylic acid)

PAA

methacrylic


Input: Interestingly, the polyacrylamide hydrogel cross-linked by the inflexible alginate methacrylates exhibited less dependency between the degree of swelling and the elastic modulus than the hydrogel cross-linked by flexible PAA methacrylates.

polyacrylamide

PAA methacrylates


Input: This critical role of the cross-linker' s inflexibility was related to the difference of the degree of hydrophobic association between polymer cross-linkers, as confirmed with pyrene probes added in pregel solutions.

pyrene


Input: Furthermore, hydrogels cross-linked with alginate methacrylates could tune the projection area of adhered cells by solely altering elastic moduli.

methacrylates


Input: In contrast, gels cross-linked with PAA methacrylates failed to modulate the cellular adhesion morphology due to a lower, and smaller, elastic modulus range to be controlled.

PAA methacrylates


Input: Overall, the results of this study will significantly advance the controllability of hydrogel properties and greatly enhance the performance of hydrogels in various biological applications.


Input: Orally Active Opioid Compounds from a Non-Poppy Source.


Input: The basic science and clinical use of morphine and other " opioid " drugs are based almost exclusively on the extracts or analogues of compounds isolated from a single source, the opium poppy (Papaver somniferum).

morphine


Input: However, it now appears that biological diversity has evolved an alternative source.


Input: Specifically, at least two alkaloids isolated from the plant Mitragyna speciosa, mitragynine ((E)-2-[(2S, 3S)-3-ethyl-8-methoxy-1, 2, 3, 4, 6, 7, 12, 12b-octahydroindolo [3, 2-h] quinolizin-2-yl]-3-methoxyprop-2-enoic acid methyl ester; 9-methoxy coryantheidine; MG) and 7-hydroxymitragynine (7-OH-MG), and several synthetic analogues of these natural products display centrally mediated (supraspinal and spinal) antinociceptive (analgesic) activity in various pain models.

mitragynine

(E)-2-[(2S, 3S)-3-ethyl-8-methoxy-1, 2, 3, 4, 6, 7, 12, 12b-octahydroindolo [3, 2-h] quinolizin-2-yl]-3-methoxyprop-2-enoic acid methyl ester

9-methoxy coryantheidine


Input: Several characteristics of these compounds suggest a classic " opioid " mechanism of action: nanomolar affinity for opioid receptors, competitive interaction with the opioid receptor antagonist naloxone, and two-way analgesic cross-tolerance with morphine.

naloxone

morphine


Input: However, other characteristics of the compounds suggest novelty, particularly chemical structure and possible greater separation from side effects.


Input: We review the chemical and pharmacological properties of these compounds.


Input: Intestinal and hepatic first-pass extraction of the 11 beta-HSD1 inhibitor AMG 221 in rats with chronic vascular catheters.

AMG 221


Input: Abstract 1.


Input: A catheterized rat model was used to define the intestinal and hepatic components of oral bioavailability for an 11 beta-HSD1 inhibitor, AMG 221.

AMG 221


Input: These data were integrated with standard in vivo metabolism studies to elucidate the components contributing to the oral disposition of a novel drug candidate.


Input: Intestinal and hepatic extraction ratios of AMG 221 obtained using a five-catheter rat model were 0. 56 and 0. 32, respectively.

AMG 221


Input: Therefore, both intestinal and hepatic extraction contributed to the first-pass component of oral bioavailability.


Input: There was no evidence for significant gut extraction of systemically administered drug.


Input: Mass balance data and in vivo metabolite characterization obtained after administration of [(14) C] AMG 221 to rat showed that AMG 221 was completely absorbed from the gut lumen following an oral dose, primarily excreted in urine and was almost completely metabolized prior to excretion.

[(14) C] AMG 221

AMG 221


Input: Hepatic bioavailability (FH), measured in two animals at various time points after oral dose administration was somewhat variable but generally characterized by an initial reduction during the absorption phase followed by an increase during the elimination phase, consistent with hepatic distribution of AMG 221.

AMG 221


Input: The five-catheter rat model afforded estimates of hepatic and intestinal contribution to oral bioavailability that were used with other data to define the preclinical ADME characteristics of a drug candidate.


Input: Synthesis and biological activities of some novel aminomethyl derivatives of 4-substituted-5-(2-thienyl)-2, 4-dihydro-3H-1, 2, 4-triazole-3-thiones.

aminomethyl

4-substituted-5-(2-thienyl)-2, 4-dihydro-3H-1, 2, 4-triazole-3-thiones


Input: A novel series of compounds were synthesized by cyclic condensation reaction of substituted isothiocyanate (2a-c) with 2-thiophenecarboxylic acid hydrazide (1) in the presence of ethyl alcohol, to obtain intermediate thiosemicarbazides (3a-c), which were further treated with sodium hydroxide in the presence of ethanol to obtain triazole derivatives (4a-c).

isothiocyanate

2-thiophenecarboxylic acid hydrazide

ethyl alcohol

thiosemicarbazides

sodium hydroxide

ethanol

triazole


Input: The latter were refluxed with substituted secondary amines and formaldehyde for 6-10 h to afford Mannich bases (5a-k).

secondary amines

formaldehyde

Mannich bases


Input: The synthesized compounds were characterized on the basis of their spectral (IR, (13) C and (1) H NMR) data and evaluated for biological activities.

(13) C

(1) H


Input: Some of the compounds were found to exhibit significant antimicrobial and antioxidant activity.


Input: Design, modeling, synthesis and biological activity evaluation of camptothecin-linked platinum anticancer agents.

camptothecin

platinum


Input: The design, modeling, synthesis and biological activity evaluation of two hybrid agents formed by 7-oxyiminomethylcamptothecin derivatives and diaminedichloro-platinum (II) complex are reported.

diaminedichloro-platinum (II)


Input: The compounds showed growth inhibitory activity against a panel of human tumor cell lines, including sublines resistant to topotecan and platinum compounds.

topotecan

platinum


Input: The derivatives were active in all the tested cell lines, and compound 1b, the most active one, was able to overcome cisplatin resistance in the osteosarcoma U2OS/Pt cell line.

cisplatin


Input: Platinum-containing camptothecins produced platinum-DNA adducts and topoisomerase I-mediated DNA damage with cleavage pattern and persistence similar to SN38, the active principle of irinotecan.

Platinum

camptothecins

platinum

irinotecan


Input: Compound 1b exhibited an appreciable antitumor activity in vivo against human H460 tumor xenograft, comparable to that of irinotecan at lower well-tolerated dose levels and superior to cisplatin.

irinotecan

cisplatin


Input: The results support the interpretation that the diaminedichloro-platinum (II) complex conjugated via an oxyiminomethyl linker at the 7-position of the camptothecin resulted in a new class of effective antitumor compounds.

diaminedichloro-platinum (II)

oxyiminomethyl

camptothecin


Input: Mesoporous silica-supported lipid bilayers (protocells) for DNA cargo delivery to the spinal cord.

silica


Input: Amorphous mesoporous silica nanoparticles (' protocells') that support surface lipid bilayers recently characterized in vitro as carrier constructs for small drug and DNA delivery are reported here as highly biocompatible both in vitro and in vivo, involving the brain and spinal cord following spinal delivery into the lumbosacral subarachnoid space (intrathecal; i. t.).

silica


Input: Specifically, positively charged, 1, 2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP)-cholesterol (DOTAP: Chol) liposome-formulated protocells revealed stable in vitro cargo release kinetics and cellular interleukin-10 (IL-10) transgene transfection.

1, 2-Dioleoyl-3-Trimethylammonium-Propane

DOTAP

cholesterol

DOTAP

Chol


Input: Recent approaches using synthetic non-viral vector platforms to deliver the pain-suppressive therapeutic transgene, IL-10, to the spinal subarachnoid space have yielded promising results in animal models of peripheral neuropathy, a condition involving aberrant neuronal communication within sensory pathways in the nervous system.


Input: Non-viral drug and gene delivery protocell platforms offer potential flexibility because cargo release-rates can be pH-dependent.


Input: We report here that i. t. delivery of protocells, with modified chemistry supporting a surface coating of DOTAP: Chol liposomes and containing the IL-10 transgene, results in functional suppression of pain-related behavior in rats for extended periods.

DOTAP

Chol


Input: This study is the first demonstration that protocell vectors offer amenable and enduring in vivo biological characteristics that can be applied to spinal gene delivery.


Input: Chemical characterization of domestic oral tobacco products: Total nicotine, pH, unprotonated nicotine and tobacco-specific N-nitrosamines.

nicotine

nicotine

N-nitrosamines


Input: In the United States, moist snuff has been studied more widely than other distinct categories of oral tobacco.


Input: In this study, we measured pH, moisture, nicotine (total and unprotonated), and tobacco-specific N-nitrosamines (TSNAs) for other established (twist, loose leaf, plug, and dry snuff without pouch) and emerging oral tobacco products (dry snuff pouch, US-made snus, and dissolvable tobacco).

nicotine

N-nitrosamines


Input: Among the seven product categories, product pH ranged from 4. 7 to 7. 9, and total nicotine concentration spanned from 3. 9 to 40. 1mg/g.

nicotine


Input: The most readily absorbable form of nicotine (unprotonated nicotine) varied more than 350-fold, ranging from 0. 01 to 3. 7mg/g.

nicotine

nicotine


Input: While the highest total nicotine concentrations were observed in twist products, snus and dissolvable tobacco had the highest unprotonated nicotine levels.

nicotine

nicotine


Input: Among all products, total TSNA concentrations ranged from 313 to 76, 500ng/g with dry snuff having the highest total TSNA concentrations.


Input: This study demonstrates the diversity among oral tobacco products and highlights the potential of these products to deliver a wide range of nicotine and carcinogenic TSNAs.

nicotine


Input: Characterizing the chemical content of these products may be helpful in further understanding the risk of marketing these products to oral tobacco users and smokers as an alternative and discrete form of tobacco.


Input: Design, synthesis and structure-activity relationships of 3, 5-diaryl-1H-pyrazoles as inhibitors of arylamine N-acetyltransferase.

3, 5-diaryl-1H-pyrazoles

arylamine N


Input: The synthesis and inhibitory potencies of a novel series of 3, 5-diaryl-1H-pyrazoles as specific inhibitors of prokaryotic arylamine N-acetyltransferase enzymes is described.

3, 5-diaryl-1H-pyrazoles

arylamine N


Input: The series is based on hit compound 1 3, 5-diaryl-1H-pyrazole identified from a high-throughout screen that has been carried out previously and found to inhibit the growth of Mycobacterium tuberculosis.

1 3, 5-diaryl-1H-pyrazole


Input: SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities.


Input: Smc5-6 is a highly conserved protein complex related to cohesin and condensin involved in the structural maintenance of chromosomes.


Input: In yeasts the Smc5-6 complex is essential for proliferation and is involved in DNA repair and homologous recombination.


Input: siRNA depletion of genes involved in the Smc5-6 complex in cultured mammalian cells results in sensitivity to some DNA damaging agents.


Input: In order to gain further insight into its role in mammals we have generated mice mutated in the Smc6 gene.


Input: A complete knockout resulted in early embryonic lethality, demonstrating that this gene is essential in mammals.


Input: However, mutation of the highly conserved serine-994 to alanine in the ATP hydrolysis motif in the SMC6 C-terminal domain, resulted in mice with a surprisingly mild phenotype.

serine

alanine

ATP


Input: With the neo gene selection marker in the intron following the mutation, resulting in reduced expression of the SMC6 gene, the mice were reduced in size, but fertile and had normal lifespans.


Input: When the neo gene was removed, the mice had normal size, but detailed phenotypic analysis revealed minor abnormalities in glucose tolerance, haematopoiesis, nociception and global gene expression patterns.

glucose


Input: Embryonic fibroblasts derived from the ser994 mutant mice were not sensitive to killing by a range of DNA damaging agents, but they were sensitive to the induction of sister chromatid exchanges induced by ultraviolet light or mitomycin C.

mitomycin C


Input: They also accumulated more oxidative damage than wild-type cells.


Input: Experimental evidence for surface freezing in supercooled n-alkane nanodroplets.

n-alkane


Input: Intermediate chain length (16 <= i <= 50) n-alkanes are known to surface freeze at temperatures that are up to three degrees higher than the equilibrium melting point [B. M. Ocko et al., Phys. Rev. E, 1997, 55, 3164-3182].

n-alkanes


Input: Our recent experimental results suggest that highly supercooled nanodroplets of n-octane and n-nonane also surface freeze, and subsequently bulk crystallization occurs.

n-octane

n-nonane


Input: The data yield surface and bulk nucleation rates on the order of ~ 10 (15) cm (-2) s (-1) and ~ 10 (22) cm (-3) s (-1), respectively, at temperatures between 180 K and 200 K.


Input: Molecular dynamics simulations at the united atom level were used to follow the freezing of a supercooled n-octane drop and show that an ordered monolayer develops on the surface of the droplet almost immediately, and the rest of the droplet then freezes in a layer-by-layer manner.

n-octane


Input: UPR Signal Activation by Luminal Sensor Domains.


Input: The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis.


Input: The presence of unfolded protein is detected by the ER-luminal sensor domains of the three UPR-transducer proteins IRE1, PERK, and ATF6, which then propagate the signal to the cytosol.


Input: In this review, we discuss the various mechanisms of action that have been proposed on how the sensor domains detect the presence of unfolded protein to activate downstream UPR signaling.


Input: Compositional-asymmetry influenced non-linear optical processes of plasmonic nanoparticle dimers.


Input: The influences of compositional asymmetry on the two-photon photoluminescence and the second harmonic generation processes in weakly coupled plasmonic dimers were addressed.


Input: Au-Au homodimer and Au-Ag heterodimer arrays produced using electron-beam lithography were investigated using confocal nonlinear optical imaging and spectroscopy.

Au-Au

Au-Ag


Input: Compared to the Au-Au homodimers, the Au-Ag dimers showed slightly broadened two-photon photoluminescence near the X symmetry point at the first Brillouin zone of Au, whilst that from the L symmetry point stayed the same.

Au-Au

Au-Ag

Au


Input: Additionally, weakly coupled Au-Ag heterodimers generated strong second harmonic signals which were invisible in the Au-Au homodimers.

Au-Ag

Au-Au


Input: The observations highlighted the importance of compositional asymmetry in the non-linear optical studies of plasmonic dimers.


Input: Pregnane X Receptor Mediates Dyslipidemia Induced by the HIV Protease Inhibitor Amprenavir in Mice.

Pregnane

Amprenavir


Input: HIV protease inhibitors (PIs) have been used successfully in extending the lifespan of people infected with HIV.


Input: The use of PIs has also been associated with dyslipidemia and an increased risk of cardiovascular disease but the underlying mechanisms remain elusive.


Input: Several PIs have been implicated to activate the nuclear receptor pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism in the liver and intestine.

pregnane


Input: Recent studies indicate that PXR may also play an important role in the regulation of lipid homeostasis.


Input: In the present study, we identified amprenavir, a widely used HIV PI, as a potent PXR-selective agonist.

amprenavir


Input: Computational docking studies combined with site-direct mutagenesis identified several key residues within the ligand binding pocket of PXR that constitute points of interaction with amprenavir.

amprenavir


Input: Amprenavir efficiently activated PXR and induced PXR target gene expression in vitro and in vivo.

Amprenavir


Input: Short-term exposure to amprenavir significantly increased plasma total cholesterol and atherogenic low-density lipoprotein cholesterol levels in wild-type mice, but not in PXR-deficient mice.

amprenavir

cholesterol

cholesterol


Input: Amprenavir-mediated PXR activation stimulated the expression of several key intestinal genes involved in lipid homeostasis.

Amprenavir


Input: These findings provide critical mechanistic insight for understanding the impact of PIs on cardiovascular disease and demonstrate a potential role of PXR in mediating adverse effects of HIV PIs in humans.


Input: Chd4 and associated proteins function as corepressors of Sox9 expression during BMP-2-induced chondrogenesis.


Input: Mouse embryonic fibroblasts (MEFs) differentiate into fully functional chondrocytes in response to bone morphogenetic protein-2 (BMP-2).


Input: However, the comprehensive proteomic aspect of BMP-2-induced chondrogenesis remains unknown.


Input: We took advantage of quantitative proteomic analysis based on isobaric tag for relative and absolute quantitation (iTRAQ) and on-line 2D nano-liquid chromatography/tandem mass spectrometry (LC/MS/MS) to identify proteins differentially expressed during BMP-2-induced chondrogenic differentiation of MEFs.


Input: We found 85 downregulated proteins, and Ingenuity Pathways Analysis (IPA) revealed a protein-protein network with chromodomain-helicase-DNA-binding protein 4 (Chd4) in the center.