Input: Differences in total parent drug clearance and metabolite clearance are attenuated by the reduction in lipophilicity introduced by the metabolic step and resultant compensatory changes in unbound clearance and protein binding.


Input: A small subclass of these drugs (e. g., terfenadine) is unintentional prodrugs with very high parent drug clearance, resulting in very high M/P ratios.

terfenadine


Input: In contrast, arenol metabolites show a more complex relationship with fm due largely to the new metabolic routes (conjugation) available to the metabolite compared with the parent drug molecule.

arenol


Input: For these metabolites, a more thorough understanding of the elimination clearance of the metabolite is critical to discern the likelihood of whether the phenol will constitute a major circulating metabolite.

phenol


Input: Alternariol induces abnormal nuclear morphology and cell cycle arrest in murine RAW 264. 7 macrophages.

Alternariol


Input: The mycotoxin alternariol (AOH), a frequent contaminant in fruit and cereal products, is known to induce DNA damage with subsequent cell cycle arrest.

alternariol

AOH


Input: Here we elucidated the effects of AOH on stages of cell cycle progression using the RAW 264. 7 macrophage model.

AOH


Input: AOH resulted in an accumulation of cells in the G2/M-phase (4N).

AOH


Input: Most cells exhibited a large G2 nucleus whereas numbers of true mitotic cells were reduced relative to control.


Input: Both cyclin B1 and p-cdc2 levels increased, while cyclin B1 remained in the cytoplasm; suggesting arrest in the G2/M transition point.


Input: Remarkably, after exposure to AOH for 24h, most of the cells exhibited abnormally shaped nuclei, as evidenced by partly divided nuclei, nuclear blebs, polyploidy and micronuclei (MN).

AOH


Input: AOH treatment also induced abnormal Aurora B bridges, suggesting that cytokinesis was interfered within cells undergoing karyokinesis.

AOH


Input: A minor part of the resultant G1 tetraploid (4N) cells re-entered the S-phase and progressed to 8N cells.


Input: pH-sensitive nanocargo based on smart polymer functionalized graphene oxide for site-specific drug delivery.

graphene oxide


Input: Graphene oxide (GO) was functionalized covalently with pH-sensitive poly (2-(diethylamino) ethyl methacrylate) (PDEA) by surface-initiated in situ atom transfer radical polymerization.

Graphene oxide

poly (2-(diethylamino) ethyl methacrylate)

PDEA


Input: The structure of the PDEA-grafted GO (GO-PDEA) were examined by Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis and atomic force microscopy.

PDEA-grafted GO

GO-PDEA


Input: The grafted PDEA endowed the GO sheets with good solubility and stability in physiological solutions.

PDEA


Input: Simple physisorption by pi-pi stacking and hydrophobic interactions on GO-PDEA can be used to load camptothecin (CPT), a widely used water-insoluble cancer drug.

GO-PDEA

camptothecin

CPT


Input: The loaded CPT was released only at the lower (acidic) pH normally found in a tumor environment but not in basic and neutral pH.

CPT


Input: GO-PDEA did not show practical toxicity to N2a cancer cells but the GO-PDEA-CPT complex exhibited high potency in killing N2a cancer cells in vitro.

GO-PDEA

GO-PDEA-CPT


Input: These results suggest that the GO-PDEA nanocargo carrier might be a promising material for site-specific anticancer drug delivery and controlled release.

GO-PDEA


Input: Revised conformational assignments and conformational evolution of tyrosine by laser desorption supersonic jet laser spectroscopy.

tyrosine


Input: The number of conformers and their structures of tyrosine are reassigned on the basis of resonance enhanced multiphoton ionization (REMPI), ultraviolet-ultraviolet hole burning (UV-UV HB), infrared (IR) dip spectra, and quantum chemical calculations.

tyrosine


Input: From comparison between REMPI and UV-UV HB spectra, it was found that 12 conformers coexist in the supersonic jet.


Input: The structures of these conformers are determined by the IR spectra and theoretical calculations.


Input: The number of conformers is more than that reported in the previous reports (8 conformers), and is rationalized by the systematic formation of conformers from simpler molecules without substituents, just like evolution.


Input: The importance of dipole-dipole interaction between an amino-acid chain and hydroxyl group at the benzene ring was also discussed.

amino-acid

hydroxyl

benzene


Input: Mutant B-RAF-Mcl-1 survival signaling depends on the STAT3 transcription factor.


Input: Approximately 50% of melanomas depend on mutant B-RAF for proliferation, metastasis and survival.


Input: The inhibition of oncogenic B-RAF with highly targeted compounds has produced remarkable albeit short-lived clinical responses in B-RAF mutant melanoma patients.


Input: Reactivation of signaling downstream of B-RAF is frequently associated with acquired resistance to B-RAF inhibitors, and the identification of B-RAF targets may provide new strategies for managing melanoma.


Input: Oncogenic B-RAF (V600E) is known to promote the stabilizing phosphorylation of the anti-apoptotic protein Mcl-1, implicated in melanoma survival and chemoresistance.


Input: We now show that B-RAF (V600E) signaling also induces the transcription of Mcl-1 in melanocytes and melanoma.


Input: We demonstrate that activation of STAT3 serine-727 and tyrosine-705 phosphorylations is promoted by B-RAF (V600E) activity and that the Mcl-1 promoter is dependent on a STAT consensus-site for B-RAF-mediated activation.

serine

tyrosine


Input: Consequently, suppression of STAT3 activity disrupted B-RAF (V600E)-mediated induction of Mcl-1 and reduced melanoma cell survival.


Input: We propose that STAT3 has a central role in the survival and contributes to chemoresistance of B-RAF (V600E) melanoma. Oncogene advance online publication, 4 March 2013; doi: 10. 1038/onc. 2013. 45.


Input: Active silver nanoparticles for wound healing.

silver


Input: In this preliminary study, the silver nanoparticle (Ag NP)-based dressing, Acticoat (TM) Flex 3, has been applied to a 3D fibroblast cell culture in vitro and to a real partial thickness burn patient.

silver

Ag


Input: The in vitro results show that Ag NPs greatly reduce mitochondrial activity, while cellular staining techniques show that nuclear integrity is maintained, with no signs of cell death.

Ag


Input: For the first time, transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) analyses were carried out on skin biopsies taken from a single patient during treatment.


Input: The results show that Ag NPs are released as aggregates and are localized in the cytoplasm of fibroblasts.

Ag


Input: No signs of cell death were observed, and the nanoparticles had different distributions within the cells of the upper and lower dermis.


Input: Depth profiles of the Ag concentrations were determined along the skin biopsies.

Ag


Input: In the healed sample, most of the silver remained in the surface layers, whereas in the unhealed sample, the silver penetrated more deeply.

silver

silver


Input: The Ag concentrations in the cell cultures were also determined.

Ag


Input: Clinical observations and experimental data collected here are consistent with previously published articles and support the safety of Ag NP-based dressing in wound treatment.

Ag


Input: Assessment of the abuse liability of ABT-288, a novel histamine H3 receptor antagonist.

histamine


Input: RATIONALE: Histamine H3 receptor antagonists, such as ABT-288, have been shown to possess cognitive-enhancing and wakefulness-promoting effects.

Histamine


Input: On the surface, this might suggest that H3 antagonists possess psychomotor stimulant-like effects and, as such, may have the potential for abuse.


Input: OBJECTIVES: The aim of the present study was to further characterize whether ABT-288 possesses stimulant-like properties and whether its pharmacology gives rise to abuse liability.


Input: METHODS: The locomotor-stimulant effects of ABT-288 were measured in mice and rats, and potential development of sensitization was addressed.


Input: Drug discrimination was used to assess amphetamine-like stimulus properties, and drug self-administration was used to evaluate reinforcing effects of ABT-288.

amphetamine


Input: The potential development of physical dependence was also studied.


Input: RESULTS: ABT-288 lacked locomotor-stimulant effects in both rats and mice.


Input: Repeated administration of ABT-288 did not result in cross-sensitization to the stimulant effects of d-amphetamine in mice, suggesting that there is little overlap in circuitries upon which the two drugs interact for motor activity.

d-amphetamine


Input: ABT-288 did not produce amphetamine-like discriminative stimulus effects in drug discrimination studies nor was it self-administered by rats trained to self-administer cocaine.

amphetamine

cocaine


Input: There were no signs of physical dependence upon termination of repeated administration of ABT-288 for 30 days.


Input: CONCLUSIONS: The sum of these preclinical data, the first of their kind applied to H3 antagonists, indicates that ABT-288 is unlikely to possess a high potential for abuse in the human population and suggests that H3 antagonists, as a class, are similar in this regard.


Input: Optimized templates for bottom-up growth of high-performance integrated biomolecular detectors.


Input: Electrochemical deposition of metals represents an important approach in the bottom-up fabrication of nanostructures and microstructures.


Input: We have used this approach to generate high-performance chip-based biosensors using silicon as a platform for the generation of sensor arrays.

silicon


Input: Here, we explore the applicability of different materials to support the electrodeposition and identify the parameters that are essential for robust sensor growth.


Input: We show that inexpensive materials can be used as templates for electrodeposition, and demonstrate that these low-cost sensors exhibit clinically-relevant levels of sensitivity and specificity.


Input: In particular, we prove herein that the glass-based sensors successfully detect E. coli in urine, when present at the 100 cfu mu L (-1) levels found typically in samples of patients with urinary tract infections.


Input: Current self-complianced and self-rectifying resistive switching in Ag-electroded single Na-doped ZnO nanowires.

Ag

ZnO


Input: We demonstrate current self-complianced and self-rectifying bipolar resistive switching in an Ag-electroded Na-doped ZnO nanowire device.

Ag

ZnO


Input: The resistive switching is controlled by the formation and rupture of an Ag nanoisland chain on the surface along the Na-doped ZnO nanowire.

Ag

ZnO


Input: Na-doping plays important roles in both the self-compliance and self-rectifying properties.


Input: Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration?


Input: The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies.


Input: Mesenchymal stem cells (MSCs) have been proposed as a possible therapeutic tool for CNS disorders.


Input: In addition to their differentiation potential, it is well accepted nowadays that their beneficial actions can also be mediated by their secretome.


Input: Indeed, it was already demonstrated, both in vitro and in vivo, that MSCs are able to secrete a broad range of neuroregulatory factors that promote an increase in neurogenesis, inhibition of apoptosis and glial scar formation, immunomodulation, angiogenesis, neuronal and glial cell survival, as well as relevant neuroprotective actions on different pathophysiological contexts.


Input: Considering their protective action in lesioned sites, MSCs' secretome might also improve the integration of local progenitor cells in neuroregeneration processes, opening a door for their future use as therapeutical strategies in human clinical trials.


Input: Thus, in this review we analyze the current understanding of MSCs secretome as a new paradigm for the treatment of CNS neurodegenerative diseases.


Input: The hazardous effects of the three natural food dyes on developmental stages and longevity of Drosophila melanogaster.


Input: Nowadays, food dyes obtained from herbal, animal, microbial and mineral sources are widely used as food additives.


Input: In this study, the toxic effects of three different natural food dyes (carmine, turmeric and annatto) on 72 +/- 4 h larvae of Oregon-R wild type of Drosophila melanogaster were investigated.

carmine


Input: For this purpose, four different application doses (50, 75, 100, 125 mg mL (-1)) were chosen by means of preliminary studies.


Input: It was determined that larval mortality increased with increasing concentration in the application groups and the toxicity order was carmine > turmeric > annatto.

carmine


Input: It was observed that the survival rate was highest in the control with 98% and lowest in 125 mg mL (-1) carmine with 16%.

carmine


Input: In addition, the average lifespan of the adult individuals obtained from third instar larvae was also studied.


Input: While the average lifespan was 40. 88 +/- 1. 44 days in the control group, these values were 10. 81 +/- 0. 55-23. 90 +/- 1. 27 days in the carmine group, 15. 00 +/- 0. 80-22. 42 +/- 1. 43 days in the turmeric group and 10. 33 +/- 1. 03-35. 68 +/- 1. 54 days in the annatto group, respectively.

carmine


Input: According to the obtained results, when both the developmental period from larvae into adults and the lifespan of the developing adults were compared with the control group, the food dyes were found to be toxic and the toxicity order of carmine > turmeric > annatto was identified.

carmine


Input: Which density functional is close to CCSD accuracy to describe geometry and interaction energy of small non-covalent dimers?


Input: A benchmark study using gaussian09.


Input: A benchmark study on all possible density functional theory (DFT) methods in Gaussian09 is done to locate functionals that agree well with CCSD/aug-cc-pVTZ geometry and Ave-CCSD (T)/(Q-T) interaction energy (Eint) for small non-covalently interacting molecular dimers in " dispersion-dominated " (class 1), " dipole-induced dipole " (class 2), and " dipole-dipole " (class 3) classes.


Input: A DFT method is recommended acceptable if the geometry showed close agreement to CCSD result (RMSD < 0. 045) and Eint was within 80-120% accuracy.


Input: Among 382 tested functionals, 1-46% gave good geometry, 13-44% gave good Eint, while 1-33% satisfied geometry and energy criteria.


Input: Further screening to locate the best performing functionals for all the three classes was made by counting the acceptable values of energy and geometry given by each functionals.


Input: The meta-generalized gradient approximation (GGA) functional M06L was the best performer with total 14 hits; seven acceptable energies and seven acceptable geometries.


Input: This was the only functional " recommended " for at least two dimers in each class.


Input: The functionals M05, B2PLYPD, B971, mPW2PLYPD, PBEB95, and CAM-B3LYP gave 11 hits while PBEhB95, PW91B95, Wb97x, BRxVP86, BRxP86, HSE2PBE, HSEh1PBE, PBE1PBE, PBEh1PBE, and PW91TPSS gave 10 hits.


Input: Among these, M05, B971, mPW2PLYPD, Wb97x, and PW91TPSS were among the " recommended " list of at least one dimer from each class.


Input: Long-range correction (LC) of Hirao and coworkers to exchange-correlation functionals showed massive improvement in geometry and Eint.


Input: The best performing LC-functionals were LC-G96KCIS and LC-PKZBPKZB.


Input: Our results predict that M06L is the most trustworthy DFT method in Gaussian09 to study small non-covalently interacting systems.


Input: (c) 2013 Wiley Periodicals, Inc.


Input: Unusual amino acids and monofluoroacetate from Dichapetalum michelsonii (Umutambasha), a toxic plant from Rwanda.

amino acids

monofluoroacetate


Input: In the course of our investigations on Umutambasha in order to identify its convulsant principles, small quantities of monofluoroacetate were observed in stem bark, leaves, and fruits of this plant newly identified as Dichapetalum michelsonii Hauman.

monofluoroacetate


Input: Conclusive evidence for a monofluoroacetate presence came from its isolation from the freeze-dried extract of stem bark.

monofluoroacetate


Input: Three free unusual amino acids, named N-methyl-alpha-alanine, N-methyl-beta-alanine, and 2, 7-diaminooctan-1, 8-dioic acid, described for the first time in a plant, and known trigonelline were also isolated from the stem bark of D. michelsonii.

amino acids

N-methyl-alpha-alanine

N-methyl-beta-alanine

2, 7-diaminooctan-1, 8-dioic acid

trigonelline


Input: Structure elucidations were mainly achieved by spectroscopic methods (1H-NMR, 2D-NMR, MS) and by comparison with authentic references.


Input: These unusual amino acids were detected by a fast, reliable TLC analysis in all our batches of Umutambasha, suggesting that they could be used for identification purposes in case of human or livestock intoxications.

amino acids


Input: Finally, EEG recordings and behavioural observations performed in mice suggested that the convulsive patterns produced by Umutambasha are the consequence of monofluoroacetate presence in D. michelsonii.

monofluoroacetate


Input: Robust Synthesis of Gold Cubic Nanoframes through a Combination of Galvanic Replacement, Gold Deposition, and Silver Dealloying.

Silver


Input: A facile, robust approach to the synthesis of Au cubic nanoframes is described.

Au


Input: The synthesis involves three major steps: 1) preparation of Au-Ag alloyed nanocages using a galvanic replacement reaction between Ag nanocubes and HAuCl4; 2) deposition of thin layers of pure Au onto the surfaces of the nanocages by reducing HAuCl4 with ascorbic acid, and; 3) formation of Au cubic nanoframes through a dealloying process with HAuCl4.

Au-Ag

Ag

Au

ascorbic acid

Au


Input: The key to the formation of Au cubic nanoframes is to coat the surfaces of the Au-Ag nanocages with sufficiently thick layers of Au before they are dealloyed.

Au

Au-Ag

Au


Input: The Au layer could prevent the skeleton of a nanocage from being fragmented during the dealloying step.

Au


Input: The as-prepared Au cubic nanoframes exhibit tunable localized surface plasmon resonance peaks in the near-infrared region, but with much lower Ag content as compared with the initial Au-Ag nanocages.

Au

Ag

Au-Ag


Input: Prenatal bisphenol a exposure alters sex-specific estrogen receptor expression in the neonatal rat hypothalamus and amygdala.

bisphenol a

estrogen


Input: Bisphenol A (BPA) exposure is ubiquitous, and in laboratory animals, early-life BPA exposure has been shown to alter sex-specific neural organization, neuroendocrine physiology, and behavior.

Bisphenol A

BPA

BPA


Input: The specific mechanisms underlying these brain-related outcomes, however, remain largely unknown, constraining the capacity to ascertain the potential human relevance of neural effects observed in animal models.


Input: In the perinatal rat brain, estrogen is masculinizing, suggesting that BPA-induced perturbation of estrogen receptor (ESR) expression may underpin later in-life neuroendocrine effects.

estrogen

BPA

estrogen


Input: We hypothesized that prenatal BPA exposure alters sex-specific ESR1 (ER alpha) and ESR2 (ER beta) expression in postnatal limbic nuclei.

BPA


Input: Sprague Dawley rats were mated and gavaged on gestational days (GDs) 6-21 with vehicle, 2. 5 or 25 mu g/kg bw/day BPA, or 5 or 10 mu g/kg bw/day ethinyl estradiol.

BPA

ethinyl estradiol


Input: An additional group was restrained but not gavaged (na i ve control).


Input: Offspring were sacrificed the day after birth to quantify ESR gene expression throughout the hypothalamus and amygdala by in situ hybridization.


Input: Relative to the vehicle group, significant effects of BPA were observed on ESR1 and ESR2 expression throughout the mediobasal hypothalamus and amygdala in both sexes.

BPA


Input: Significant differences in ESR expression were also observed in the mediobasal hypothalamus and amygdala of the na i ve control group compared with the vehicle group, highlighting the potential for gavage to influence gene expression in the developing brain.


Input: These results indicate that ESR expression in the neonatal brain of both sexes can be altered by low-dose prenatal BPA exposure.

BPA


Input: Ultrasensitive optical shape characterization of gold nanoantennas using second harmonic generation.


Input: Second harmonic generation from plasmonic nanoantennas is investigated numerically using a surface integral formulation for the calculation of both the fundamental and the second harmonic electric field.


Input: The comparison between a realistic and an idealized gold nanoantenna shows that second harmonic generation is extremely sensitive to asymmetry in the nanostructure shape even in cases where the linear response is barely modified.


Input: Interestingly, minute geometry asymmetry and surface roughness are clearly revealed by far-field analysis, demonstrating that second harmonic generation is a promising tool for the sensitive optical characterization of plasmonic nanostructures.


Input: Furthermore, defects located where the linear field is strong (e. g., in the antenna gap) do not necessarily have the strongest impact on the second harmonic signal.


Input: Cellulose-ethylenediaminetetraacetic Acid conjugates protect Mammalian cells from bacterial cells.

ethylenediaminetetraacetic Acid


Input: Cellulose-ethylenediaminetetraacetic acid (EDTA) conjugates were synthesized by the esterification of cellulose with ethylenediaminetetraacetic dianhydride (EDTAD).

ethylenediaminetetraacetic acid

EDTA

ethylenediaminetetraacetic dianhydride

EDTAD


Input: The new materials provided potent antimicrobial activities against Staphylococcus aureus (S. aureus, Gram-positive bacteria) and Pseudomonas aeruginosa (P. aeruginosa, Gram-negative bacteria), and inhibited the formation of bacterial biofilms.


Input: The biocompatibility of the new cellulose-EDTA conjugates was evaluated with mouse skin fibroblasts for up to 14 days.

EDTA


Input: SEM observation and DNA content analysis suggested that the new materials sustained the viability of fibroblast cells.


Input: Moreover, in mouse skin fibroblast-bacteria co-culture systems, the new cellulose-EDTA conjugates prevented bacterial biofilm formation and protected the mammalian cells from the bacterial cells for at least one day.

EDTA


Input: High quality CdHgTe nanocrystals with strong near-infrared emission: relationship between composition and cytotoxic effects.

CdHgTe


Input: High quality CdHgTe quasi core/shell nanocrystals (NCs) were prepared via the one-step method.

CdHgTe


Input: The relationship between the composition, structure, and property was systematically investigated by the combination of X-ray photoelectron spectroscopy (XPS), inductively coupled plasma atomic emission (ICP), and the photoluminescence (PL) measurements.


Input: The quantum yield (QY) was ~ 50% when the feed ratio of Cd (2 +) to Hg (2 +) was equal to 1.

Cd (2 +)

Hg (2 +)


Input: The PL property was further polished, and the QY was improved to ~ 80% through the variance of the prepared conditions such as the ratio of ligand to metal ion and HTe (-) to metal ion, pH value, and temperature.

HTe (-)


Input: In addition, the cytotoxic effects of CdHgTe NCs were systematically studied.

CdHgTe


Input: The results showed that, for Cd0. 21Hg0. 79Te NCs, its quasi core/shell structure was very stable and little cadmium ions were released.

Cd0. 21Hg0. 79Te

cadmium


Input: As a result, such NCs showed little cytotoxicity and would find applications in tissue imaging or detection.


Input: Isolation of thermally stable cellulose nanocrystals by phosphoric Acid hydrolysis.

phosphoric Acid


Input: On account of their intriguing mechanical properties, low cost, and renewable nature, high-aspect-ratio cellulose nanocrystals (CNCs) are an attractive component for many nanomaterials.


Input: Due to hydrogen bonding between their surface hydroxyl groups, unmodified CNCs (H-CNCs) aggregate easily and are often difficult to disperse.

hydrogen

hydroxyl


Input: It is shown here that on account of ionic repulsion between charged surface groups, slightly phosphorylated CNCs (P-CNCs, average dimensions 31 +/- 14 x 316 +/- 127 nm, surface charge density = 10. 8 +/- 2. 7 mmol/kg cellulose), prepared by controlled hydrolysis of cotton with phosphoric acid, are readily dispersible and form stable dispersions in polar solvents such as water, dimethyl sulfoxide, and dimethylformamide.

phosphoric acid

dimethyl sulfoxide

dimethylformamide


Input: Thermogravimetric analyses reveal that these P-CNCs exhibit a much higher thermal stability than partially sulfated CNCs (S-CNCs), which are frequently employed, but suffer from limited thermal stability.


Input: Nanocomposites of an ethylene oxide-epichlorohydrin copolymer and H-CNCs, S-CNCs, and P-CNCs were prepared, and their mechanical properties were studied by dynamic mechanical thermal analysis.

ethylene oxide

epichlorohydrin


Input: The results show that P-CNCs offer a reinforcing capability that is comparable to that of H-CNCs or S-CNCs.


Input: Electronic transitions of protonated and deprotonated amino acids in aqueous solution in the region 145-300 nm studied by attenuated total reflection far-ultraviolet spectroscopy.

amino acids


Input: The electronic transitions of 20 naturally occurring amino acids in aqueous solution were studied with attenuated total reflection far-ultraviolet (ATR-FUV) spectroscopy in the region from 145 to 300 nm.

amino acids


Input: From the measured ATR spectra of sample solutions, the FUV absorption spectra attributed to the amino acids were separated from the intense solvent absorption by using a modified Kramers-Kronig transformation method.

amino acids


Input: The FUV absorption spectra of the amino acids reflect the protonation states of the backbone and side-chain structures.

amino acids


Input: The contributions of the side chains to the spectra were also examined from the difference spectra subtracting the corresponding Gly spectrum from each spectrum.

Gly


Input: The observed spectra were compared mostly with the electronic transition studies of the molecular fragments of the amino acids in gas phase.

amino acids


Input: The FUV spectra of the amino acids exhibited the intra-and intermolecular electronic interactions of the solute-solute as well as the solute-solvent, and those are essential factors to elucidate UV photochemical processes of the amino acids in aqueous solution.

amino acids

amino acids


Input: Perspectives offered by single-domain antibodies in clinical diagnostic of pediatric tumors.


Input: The results accrued in the last few years have clearly showed that recombinant antibodies, and specifically single-domain antibodies, represent valid alternatives to conventional IgGs for in vivo imaging.


Input: It does not simply mean that antibody fragments can substitute full-length antibodies, but that they are substantially more suitable for some applications and can perform other functions for which no real alternative is available.


Input: Brain imaging with multi-functional probes is an evident example, but the promising results obtained with micro-PET and-SPECT in murine models could lead in short time to a revolutionary change in clinical diagnostics.


Input: Brilliant applications of single-domain antibody-dependent imaging have enabled us to understand how the tracer mass and avidity can be engineered to modulate pharmacokinetic features such as clearance, tumor penetration, and binding affinity with the aim of optimizing specific responses.


Input: The potential of these reagents and the increasing interest for them is evidenced by the exponential growth of publications and the multiplication of the proposed applications in which they are used.


Input: This review wishes to provide an update of this fast moving subject and to indicate what may be the next foreseeable technical progress.


Input: Artificial neural network analysis of data from multiple in vitro assays for prediction of skin sensitization potency of chemicals.


Input: In order to develop in vitro risk assessment systems for skin sensitization, it is important to predict a threshold from the murine local lymph node assay (LLNA).


Input: We first confirmed that the combination of the human Cell Line Activation Test (h-CLAT) and the SH test improved the accuracy and sensitivity of prediction of LLNA data compared with each individual test.


Input: Next, we assessed the mutual correlations among maximum amount of change of cell-surface thiols (MAC value) in the SH test, CV75 value (concentration giving 75% cell viability) in a cytotoxicity assay, EC150 and EC200 values (thresholds concentrations of CD86 and CD54 expression, respectively) in h-CLAT and published LLNA thresholds of 64 chemicals.

thiols


Input: Based on the results, we selected MAC value and the minimum of CV75, EC150 (CD86) and EC200 (CD54) as descriptors for the input layer of an artificial neural network (ANN) system.


Input: The ANN-predicted values were well correlated with reported LLNA thresholds.


Input: We also found a correlation between the SH test and the peptide-binding assay used to evaluate hapten-protein complex formation.


Input: Thus, this model, which we designate as the " iSENS ver.


Input: 1 ", may be useful for risk assessment of skin sensitization potential of chemicals from in vitro test data.


Input: Considering the impact drug-like properties have on the chance of success.


Input: Many definitions of' drug-like' compound properties have been published; based on the analysis of simple molecular properties of successful drugs.


Input: These are typically presented as rules that define acceptable boundaries for these properties.


Input: When a compound does not' fit' within these boundaries then its properties differ from those of the majority of drugs, which could indicate a higher risk of poor pharmacokinetics or safety outcomes in vivo.


Input: Here, we review the strengths and weaknesses of these rules and note, in particular, that the overly rigid application of strict cut-off points can introduce artificial distinctions between similar compounds, running the risk of missing valuable opportunities.


Input: Alternatively, compounds can be ranked according to their similarity to marketed drugs using a continuous measure of drug-likeness.


Input: However, being similar to known drugs does not necessarily mean that a compound is more likely to become a drug and we demonstrate how a new approach, employing Bayesian methods, can be used to compare a set of successful drugs with a set of non-drug compounds to identify those properties that give the greatest distinction between the two sets, and hence the greatest increase in the likelihood of a compound becoming a successful drug.


Input: This analysis further illustrates that guidelines for drug-likeness might not be generally applicable across all compound and target classes or therapeutic indications.


Input: Therefore, it might be more appropriate to consider specific guidelines for drug-likeness that are project specific.


Input: Synthesis of a paraffin phase change material microencapsulated in a siloxane polymer.

paraffin

siloxane


Input: The coemulsification method suitable for the formulation of microcapsules of n-eicosane coated with a polysiloxane is developed.

n-eicosane

polysiloxane


Input: This method allows to synthesize core-shell microcapsules of paraffin which have the shape of spheres or distorted spheres and are designed for the use as phase change materials.

paraffin


Input: The microcapsules are formed in aqueous phase by the precipitation of n-eicosane together with modified polyhydromethylsiloxane from a common solvent which is miscible with aqueous media.

n-eicosane

polyhydromethylsiloxane


Input: The polysiloxane is modified by the attachment of silylvinyl and alkoxy functions before coemulsification with the paraffin.

polysiloxane

silylvinyl

alkoxy

paraffin


Input: It also contains the Pt (0) Karstedt catalyst.

Pt (0) Karstedt catalyst


Input: The microcapsules formed by coemulsification are stabilized by the in situ cross-linking of the polysiloxane shell.

polysiloxane


Input: The shell is additionally modified by the in situ generation of silanol groups which provide colloidal stabilization of microspheres in aqueous phase.

silanol


Input: Microcapsules were studied by DSC, SEM, optical polarized microscope, and by thermooptical analysis (TOA).


Input: Differential surface properties of commercial crystalline telmisartan samples.

telmisartan


Input: The aim of the present study was to investigate differences in surface chemistry of commercially available telmisartan (TMS) samples in Indian market and to correlate them to the surface molecular environment.

telmisartan

TMS


Input: Comprehensive characterization of material properties of four TMS samples from different sources showed that all samples exhibited same polymorphic form, but different particle shape, particle size distribution, surface energetics and surface chemistry.

TMS


Input: Wettability and surface free energy were determined using sessile drop contact angle technique.


Input: TMS samples exhibited significant variations in their wetting behavior.

TMS


Input: The role of crystal shape, particle size distribution, surface energetics and surface chemistry in controlling TMS powder wettability was collectively explored by contact angle experiments.

TMS


Input: Evaluation of work of adhesion (Wa), immersion (Wi) and spreading (Ws) indicated that samples had differential wetting behavior.


Input: The surface chemistry was elucidated by X-ray photoelectron spectroscopy (XPS).


Input: The surface polarity index was determined by XPS and expressed as (oxygen + nitrogen)-to-(carbon) atomic concentration ratio.

oxygen

nitrogen

carbon


Input: It was found to be different for all four TMS samples.

TMS


Input: Crystal morphology of TMS polymorph A was predicted using Bravais-Friedel Donnay-Harker (BFDH) method.

TMS


Input: Molecular lipophilic surface potential (MLSP) data for TMS showed the varied surface lipophilic environment throughout the molecule.

TMS


Input: Hence it can be concluded that the differential abundance of surface elements play an important role in controlling the biopharmaceutical performance of TMS powder samples.

TMS


Input: Analytical chemistry, toxicology, epidemiology and health impact assessment of melamine in infant formula: Recent progress and developments.

melamine


Input: This review summarizes the most recent scientific literature and regulations regarding analytical chemistry, toxicology, epidemiology, exposure, and risk assessment of melamine in infant formula.

melamine


Input: For analyses, enzyme-linked immunosorbent assay, high-performance liquid chromatography, capillary electrophoresis, gas chromatography coupled with mass spectrometry and liquid chromatography coupled with tandem mass spectrometry have commonly been used.


Input: Organization of proficiency test programs provided good evidence to facilitate granting laboratories accreditation and to ascertain the measurement reliability of melamine methods.

melamine


Input: Metabolic studies demonstrated that melamine is predominantly restricted to blood or extracellular fluid and is not extensively distributed to organs and tissues.

melamine


Input: Studies of human renal histopathology and clinical diagnoses indicated that melamine-related obstructive nephropathy derives from melamine precipitation in the lower urinary tract, with stones that are thought to be melamine-uric acid complexes.

melamine

melamine

melamine

uric acid


Input: Epidemiologic studies showed that the occurrence of melamine-related urolithiasis is related to both the concentration of melamine in ingested milk products and the duration of ingestion.

melamine

melamine


Input: Long-term follow-up cohort studies should be continued to further investigate the epidemic and chronic hazard of melamine-induced nephrotoxicity.

melamine


Input: The World Health Organization set a tolerable daily intake of 0. 2mg/kgbw/day to be applied to " the whole population including infants ".


Input: Other authorities and research institutes have set/proposed lower values.


Input: Differential phosphoproteome of the striatum from pleiotrophin knockout and midkine knockout mice treated with amphetamine: Correlations with amphetamine-induced neurotoxicity.

amphetamine

amphetamine


Input: The neurotrophic factors pleiotrophin (PTN) and midkine (MK) have been shown to modulate amphetamine-induced neurotoxicity.

amphetamine


Input: Accordingly, PTN-/-and MK-/-mice show an increased vulnerability to amphetamine-induced neurotoxic effects.

amphetamine


Input: In an effort to uncover new pharmacological targets to prevent amphetamine neurotoxic effects, we have now used a proteomic approach to study protein phosphorylation, in which we combined phosphoprotein enrichment, by immobilized metal affinity chromatography (IMAC), with two-dimensional gel electrophoresis and mass spectrometry, in order to identify the phosphoproteins regulated in the striatum of PTN-/-, MK-/-and wild type (WT) mice treated with amphetamine.

amphetamine

amphetamine


Input: We identified 13 differentially expressed phosphoproteins that are judged to be relevant in the neuroprotective roles of PTN and MK against amphetamine-induced neurotoxicity.

amphetamine


Input: It is very interesting to note that 4 of these phosphoproteins, annexin A7 (ANXA7), COP9 signalosome subunit 5 (COPS5), aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and creatine kinase U-type (CKMT1), are known to be involved in Parkinson' s disease, a result of significant importance since PTN and MK have been also demonstrated to limit Parkinson' s disease (PD) progress and have been suggested to be among the important genetic factors possibly preventing the development of PD in methamphetamine abusers.

aldehyde

creatine

methamphetamine


Input: The data identify phosphoproteins differentially regulated by amphetamine treatment and/or the presence of endogenous PTN/MK which may be relevant mediators of PTN/MK neuroprotective effects against amphetamine-induced neurotoxicity.

amphetamine

amphetamine


Input: The data support further studies to validate the phosphoproteins here identified as possible new pharmacological targets to prevent amphetamine neurotoxic effects.

amphetamine


Input: COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers.

nicotine


Input: The catechol-O-methyltransferase (COMT) Val158Met polymorphism may be a risk factor for nicotine addiction.

catechol

O

nicotine


Input: This study examined the influence of the COMT Val158Met polymorphism on subjective, physiological and cognitive effects of intravenous (IV) nicotine use in African Americans (AAs; n = 56) and European Americans (EAs; n = 68) smokers.

nicotine


Input: Overnight abstinent smokers received saline followed by 0. 5 and 1. 0 mg per 70 kg doses of nicotine, administered 30 min apart.

nicotine


Input: Smokers with valine (Val)/Val genotype, compared with methionine (Met) carriers, had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking.

valine

Val

Val

methionine

Met

nicotine


Input: Women with Val/Val genotype reported greater difficulty concentrating and irritability than men with Val/Val or Met carrier genotypes.

Val

Val

Val

Val

Met


Input: The Val/Val genotype was associated with better performance on the math task and in AA smokers it was associated with greater systolic blood pressure.

Val

Val


Input: These results support the rationale of pharmacologically inhibiting COMT to aid with smoking cessation among Val/Val genotype smokers. The Pharmacogenomics Journal advance online publication, 5 March 2013; doi: 10. 1038/tpj. 2013. 1.

Val

Val


Input: Exclusive skeletal muscle correction does not modulate dystrophic heart disease in the aged mdx model of Duchenne cardiomyopathy.


Input: Duchenne muscular dystrophy (DMD) is characterized by severe degeneration and necrosis of both skeletal and cardiac muscle.


Input: While many experimental therapies have shown great promise in treating skeletal muscle disease, an effective therapy for Duchenne cardiomyopathy remains a challenge in large animal models and human patients.


Input: The current views on cardiac consequences of skeletal muscle-centered therapy are controversial.


Input: Studies performed in young adult mdx mice (a mild DMD mouse model) have yielded opposing results.


Input: Since mdx mice do not develop dystrophic cardiomyopathy until >= 21 months of age, we reasoned that old mdx mice may represent a better model to assess the impact of skeletal muscle rescue on dystrophic heart disease.


Input: Here, we aged skeletal muscle-specific micro-dystrophin transgenic mdx mice to 23 months and examined the cardiac phenotype.


Input: As expected, transgenic mdx mice had minimal skeletal muscle disease and they also outperformed original mdx mice on treadmill running.


Input: On cardiac examination, the dystrophin-null heart of transgenic mdx mice displayed severe cardiomyopathy matching that of non-transgenic mdx mice.


Input: Specifically, both the strains showed similar heart fibrosis and cardiac function deterioration in systole and diastole.


Input: Cardiac output and ejection fraction were also equally compromised.


Input: Our results suggest that skeletal muscle rescue neither aggravates nor alleviates cardiomyopathy in aged mdx mice.


Input: These findings underscore the importance of treating both skeletal and cardiac muscles in DMD therapy.


Input: Transfection of Mammalian Cells Using Block Copolypeptide Vesicles.


Input: An arginine-leucine block copolypeptide (R60 L20) is synthesized, which is capable of forming vesicles with controllable sizes, able to transport hydrophilic cargo across the cell membrane, and exhibit relatively low cytotoxicity.

arginine

leucine


Input: The R60 L20 vesicles also possess the ability to deliver DNA into mammalian cells for transfection.


Input: Although the transfection efficiency is lower than that of the commercially available transfection agent Lipofectamine 2000, the R60 L20 vesicles are able to achieve transfection with significantly lower cytotoxicity and immunogenicity.

Lipofectamine 2000


Input: This behavior is potentially due to its stronger interaction with DNA which subsequently provides better protection against anionic heparin.


Input: Buffer-Stable Chitosan-Polyglutamic Acid Hybrid Nanoparticles for Biomedical Applications.

Polyglutamic Acid


Input: In spite of their attractive features, widespread biomedical applications of CS nanoparticles are yet to be realized due to their poor stability in physiological conditions, such as in buffer system at pH 7. 4.


Input: Buffer-stable chitosan-based hybrid NPs (HNPs) are reported and characterized.


Input: Buffer stability is achieved by introducing polyglutamic acid to chitosan.

polyglutamic acid


Input: The effect of PGA to CS molar ratio and crosslinking on HNP integrity, buffer stability, and biodegradability are studied.

PGA


Input: Preliminary in vitro studies are carried out to evaluate targeted uptake efficiency of folate conjugated HNPs.

folate


Input: Successful demonstration of buffer stability and cancer cell targeting by HNPs achieves important milestones for chitosan-based nanoparticle technology.


Input: Ni (II)-NTA Modified Poly (ethylene imine) Glycopolymers: Physicochemical Properties and First In Vitro Study of Polyplexes Formed with HIV-Derived Peptides.

Ni (II)-NTA

Poly (ethylene imine)


Input: Alternative delivery entities are desirable in immunotherapies in which polyplexes are widely formed by electrostatic interactions to induce cellular uptake processes for bioactive molecules.


Input: In our study, biocompatible Ni (II)-nitrilo (triacetic acid)-modified poly (ethylene imine)-maltose (Ni-NTA-DG) is realized and evaluated as complexation agent against His-tagged peptides using fluorescence polarization and dynamic light scattering.

Ni (II)-nitrilo (triacetic acid)

poly (ethylene imine)-maltose

Ni-NTA-DG

His


Input: The polyplexes are stable until a pH of 6. 5-6. 0, and also up to 50 mM of imidazole.

imidazole


Input: A first uptake approach shows that polyplexes lead to an increase in peptide uptake in monocyte-derived immature dendritic cells.


Input: In summary, Ni-NTA-DG represents a promising (delivery) platform for forthcoming in vitro applications.

Ni-NTA-DG


Input: Supramolecular cl... h and o... h interactions in self-assembled 1, 5-dichloroanthraquinone layers on au (111).

cl

h

o

h

1, 5-dichloroanthraquinone

au (111)


Input: The role of halogen bonds in self-assembled networks for systems with Br and I ligands has recently been studied with scanning tunneling microscopy (STM), which provides physical insight at the atomic scale.

halogen

Br

I


Input: Here, we study the supramolecular interactions of 1, 5-dichloroanthraquinone molecules on Au (111), including Cl ligands, by using STM.

1, 5-dichloroanthraquinone

Au (111)

Cl


Input: Two different molecular structures of chevron and square networks are observed, and their molecular models are proposed.


Input: Both molecular structures are stabilized by intermolecular Cl... H and O... H hydrogen bonds with marginal contributions from Cl-related halogen bonds, as revealed by density functional theory calculations.

Cl

H

O

H hydrogen

Cl

halogen


Input: Our study shows that, in contrast to Br-and I-related halogen bonds, Cl-related halogen bonds weakly contribute to the molecular structure due to a modest positive potential (sigma hole) of the Cl ligands.

Br

I

halogen

Cl

halogen

Cl


Input: Dissecting the relative contribution of OATP1B1-mediated uptake of xenobiotics into human hepatocytes using siRNA.


Input: Abstract 1.


Input: Organic anion transporting polypeptide 1B1 plays a pivotal role in the disposition of many anionic drugs.


Input: Significant overlap in substrate specificity between individual OATP isoforms has hampered the identification of the relative importance of individual isoforms for hepatic uptake of xenobiotics.


Input: The present study focused on the use of siRNA technology to decrease OATP1B1 selectively in human hepatocytes.


Input: Following delivery of siRNA by the novel lipid, AtuFECT01, mRNA expression of OATP1B1 was reduced by 94%-98% with no significant toxicity.


Input: Off-target effects were also shown to be minimal as evidenced by the expression of common drug metabolizing enzymes, transporters, nuclear receptors and associated co-regulators.


Input: Uptake of estrone-3-sulfate (5 nM) by OATP1B1 was reduced by 82%-95%.


Input: This methodology was subsequently used to assess the relative contribution of OATP1B1 uptake in human hepatocytes for olmesartan (42%-62%), valsartan (28%-81%), rosuvastatin (64%-72%), pitavastatin (84%-98%) and lopinavir (64%-89%).

olmesartan

valsartan

rosuvastatin

pitavastatin

lopinavir


Input: These data are consistent with previous values obtained using a relative activity factor approach.


Input: The siRNA approach provides a robust and reproducible method for assessing the relative contribution of OATP1B1 to hepatic uptake of new chemical entities.


Input: The technique also has potential utility in facilitating detailed characterization of drug-drug interactions involving hepatic drug transporters.


Input: Synthesis of mixed ceramic Mg (x) Zn (1-x) O nanofibers via Mg2 + doping using sol-gel electrospinning.

Mg (x) Zn (1-x) O

Mg2 +


Input: We report on the synthesis of tuned energy band gap Mg (x) Zn (1-x) O nanofibers (NFs) with different Mg (2 +) content via the sol-gel electrospinning (ES) technique wherein the addition of the doping material affects not only the morphologies of as-spun ZnAc/PVA and MgAc/ZnAc/PVA nanofibers but also the crystal microstructure and optical properties of calcined ZnO and Mg (x) Zn (1-x) O nanofibers.

Mg (x) Zn (1-x) O

Mg (2 +)

ZnAc

PVA

MgAc

ZnAc

PVA

ZnO

Mg (x) Zn (1-x) O


Input: Following an appropriate aqueous solution preparation of magnesium acetate (MgAc) and zinc acetate (ZnAc) with poly (vinyl alcohol) (PVA), electrospinning is performed and then as-spun nanofibers are calcined in an air atmosphere at 600 degrees C for 3 h.

magnesium acetate

MgAc

zinc acetate

ZnAc

poly (vinyl alcohol)

PVA


Input: As-spun and calcined nanofiber diameters and morphologies are evaluated with scanning (SEM) and transmission (TEM) electron microscopies, whereas crystalline microstructural interpretations of ZnO and Mg (x) Zn (1-x) O are conducted with wide-angle X-ray diffraction spectra (XRD).

ZnO

Mg (x) Zn (1-x) O


Input: Surface chemical composition and elemental evaluation of calcined nanofibers are examined with X-ray photoelectron spectroscopy (XPS), and optical properties and crystal defect analyses of the calcined nanofibers are conducted with photoluminescence spectra (PL).


Input: We observe a sharp reduction in fiber diameter upon calcination as a result of the removal of organic species from the fibers and conversion of ceramic precursors into ceramic nanofibers, and the appearance of a range of fiber morphologies from " bead in a string " to " sesame seed " coverage depending on fiber composition.


Input: Because Zn (2 +) and Mg (2 +) have similar ionicity and atomic radii, some Zn (2 +) atoms are replaced by Mg (2 +) atoms in the crystals, leading to a change in the properties of crystal lattices.

Zn (2 +)

Mg (2 +)

Zn (2 +)

Mg (2 +)


Input: The band gap energy of the calcined fibers increases significantly with addition of Mg (2 +) along with an increase in the ultraviolet (UV) photoluminescence emission of the fibers.

Mg (2 +)


Input: Fengycin C Produced by Bacillus subtilis EA-CB0015.

Fengycin C


Input: Bacillus subtilis EA-CB0015 was isolated from the phyllosphere of a banana plant and tested for its potential to produce bioactive compounds against Mycosphaerella fijiensis.


Input: Using a dual plate culture technique the cell-free supernatant of B. subtilis EA-CB0015 produced inhibition values of 89 +/- 1%.


Input: The active compounds were purified by solid-phase extraction and HPLC, and their primary structures determined using mass spectrometry and amino acid analysis.

amino acid


Input: A new fengycin isoform, fengycin C, with the amino acid sequence Glu-Orn-Tyr-Thr-Glu-Val-Pro-Gln-Thr-Ile was isolated.

fengycin

fengycin C

amino acid

Glu-Orn-Tyr-Thr-Glu-Val-Pro-Gln-Thr-Ile


Input: The peptidic moiety differs from fengycin B at position 9 and from fengycin A at positions 6 and 9.

fengycin B

fengycin A


Input: The beta-hydroxy fatty acyl chain is connected to the N-terminal of the decapeptide and can be saturated or unsaturated, ranging from 14 to 18 carbons.

beta-hydroxy fatty acyl

N

decapeptide

carbons


Input: The C-terminal residue of the peptidic moiety is linked to the tyrosine residue at position 3, forming the branching point of the acyl peptide and the eight-membered cyclic lactone.

C

tyrosine

acyl

cyclic lactone


Input: Controlling spontaneous emission with plasmonic optical patch antennas.


Input: We experimentally demonstrate the control of the spontaneous emission rate and the radiation pattern of colloidal quantum dots deterministically positioned in a plasmonic patch antenna.


Input: The antenna consists of a thin gold microdisk separated from a planar gold layer by a few tens of nanometers thick dielectric layer.


Input: The emitters are shown to radiate through the entire patch antenna in a highly directional and vertical radiation pattern.


Input: Strong acceleration of spontaneous emission is observed, depending on the antenna geometry.


Input: Considering the double dipole structure of the emitters, this corresponds to a Purcell factor up to 80 for dipoles perpendicular to the disk.


Input: Redox regulation of protein kinases.


Input: Reactive oxygen species (ROS) have been long regarded as by-products of a cascade of reactions stemming from cellular oxygen metabolism, which, if they accumulate to toxic levels, can have detrimental effects on cellular biomolecules.

oxygen

oxygen


Input: However, more recently, the recognition of ROS as mediators of cellular communications has led to their classification as signalling mediators in their own right.


Input: The prototypic redox-regulated targets downstream of ROS are the protein tyrosine phosphatases, and the wealth of research that has focused on this area has come to shape our understanding of how redox-signalling contributes to and facilitates protein tyrosine phosphorylation signalling cascades.

tyrosine

tyrosine


Input: However, it is becoming increasingly apparent that there is more to this system than simply the negative regulation of protein tyrosine phosphatases.

tyrosine


Input: Identification of redox-sensitive kinases such as Src led to the slow emergence of a role for redox regulation of tyrosine kinases.

tyrosine


Input: A flow of evidence, which has increased exponentially in recent times as a result of the development of new methods for the detection of oxidative modifications, demonstrates that, by concurrent oxidative activation of tyrosine kinases, ROS fine tune the duration and amplification of the phosphorylation signal.

tyrosine


Input: A more thorough understanding of the complex regulatory mechanism of redox-modification will allow targeting of both the production of ROS and their downstream effectors for therapeutic purposes.


Input: The present review assesses the most relevant recent literature that demonstrates a role for kinase regulation by oxidation, highlights the most significant findings and proposes future directions for this crucial area of redox biology.


Input: Antitubercular diterpenoids from Vitex trifolia.

diterpenoids


Input: A new halimane diterpenoid, 13-hydroxy-5 (10), 14-halimadien-6-one (1) and two new labdane diterpenoids, 6 alpha, 7 alpha-diacetoxy-13-hydroxy-8 (9), 14-labdadien (2) and 9-hydroxy-13 (14)-labden-15, 16-olide (3), were isolated for the first time, along with fifteen known compounds, from the hexane soluble fraction of methanolic extract of Vitex trifolia leaves.

halimane diterpenoid

13-hydroxy-5 (10), 14-halimadien-6-one

labdane diterpenoids

6 alpha, 7 alpha-diacetoxy-13-hydroxy-8 (9), 14-labdadien

9-hydroxy-13 (14)-labden-15, 16-olide

hexane


Input: The structures of these new diterpenoids were elucidated by spectral analysis.

diterpenoids


Input: Their relative configurations were established using analysis of NOESY correlations and coupling constants observed in (1) H NMR.

(1) H


Input: Compounds 2, 3 and another known diterpenoid, isoambreinolide (4) were evaluated for antitubercular activity.

diterpenoid

isoambreinolide


Input: 3 and 4 exhibited antitubercular activity (MIC = 100 and 25 mu g/ml) against Mycobacterium tuberculosis H37Rv in BACTEC-460 assay.


Input: Aldehyde oxidase importance in vivo in xenobiotic metabolism: imidacloprid nitroreduction in mice.

Aldehyde

imidacloprid


Input: Aldehyde oxidase (AOX) metabolizes many xenobiotics in vitro, but its importance in vivo is usually unknown relative to cytochrome P450s (CYPs) and other detoxification systems.

Aldehyde


Input: Currently, the most important insecticides are neonicotinoids, which are metabolized in vitro by AOX on reduction of the nitroimino group and by CYPs via oxidation reactions.

neonicotinoids

nitroimino


Input: The goal of this study was to establish the relative importance of AOX and CYPs in vivo using the mouse model.


Input: The procedure was to reduce liver AOX activity by providing tungsten or hydralazine in the drinking water or to use the AOX-deficient DBA/2 mouse strain.

tungsten

hydralazine


Input: None of these approaches reduced CYP activity measured in vitro with an isozyme nonspecific substrate.


Input: Liver AOX activity was reduced by 45% with tungsten and 61% with hydralazine and 81% in AOX-deficient mice relative to controls.

tungsten

hydralazine


Input: When mice were treated ip with the major neonicotinoid imidacloprid (IMI), metabolism by CYP oxidation reactions was not appreciably affected, whereas the AOX-generated nitrosoguanidine metabolite was decreased by 30% with tungsten and 56% with hydralazine and 86% in the AOX-deficient mice.

imidacloprid

IMI

nitrosoguanidine

tungsten

hydralazine


Input: The other IMI nitroreduction metabolite, desnitro-IMI, was decreased by 55%, 65%, and 81% with tungsten, hydralazine, and in the AOX-deficient mice, respectively.

IMI

IMI

tungsten

hydralazine


Input: Thus, decreasing liver AOX activity by three quite different procedures gave a corresponding decrease for in vivo reductive metabolites in the liver of IMI-treated mice.

IMI


Input: Possible AOX involvement in IMI metabolism in insects was evaluated using AOX-expressing and AOX-deficient Drosophila, but no differences were found in IMI nitroreduction or sensitivity between the two strains.

IMI

IMI


Input: This is the first study to establish the in vivo relevance of AOX in neonicotinoid metabolism in mammals and one of the first for xenobiotics in general.

neonicotinoid


Input: Modulation of membrane phospholipids, the cytosolic calcium influx and cell proliferation following treatment of B16-F10 cells with recombinant phospholipase-D from Loxosceles intermedia (brown spider) venom.

calcium


Input: The mechanism through which brown spiders (Loxosceles genus) cause dermonecrosis, dysregulated inflammatory responses, hemolysis and platelet aggregation, which are effects reported following spider bites, is currently attributed to the presence of phospholipase-D in the venom.


Input: In the present investigation, through two-dimensional immunoblotting, we observed immunological cross-reactivity for at least 25 spots in crude Loxosceles intermedia venom, indicating high expression levels for different isoforms of phospholipase-D.


Input: Using a recombinant phospholipase-D from the venom gland of L. intermedia (LiRecDT1) in phospholipid-degrading kinetic experiments, we determined that this phospholipase-D mainly hydrolyzes synthetic sphingomyelin in a time-dependent manner, generating ceramide 1-phosphate plus choline, as well as lysophosphatidylcholine, generating lysophosphatidic acid plus choline, but exhibits little activity against phosphatidylcholine.

sphingomyelin

ceramide 1-phosphate

choline

lysophosphatidylcholine

lysophosphatidic acid

choline

phosphatidylcholine


Input: Through immunofluorescence assays with antibodies against LiRecDT1 and using a recombinant GFP-LiRecDT1 fusion protein, we observed direct binding of LiRecDT1 to the membrane of B16-F10 cells.


Input: We determined that LiRecDT1 hydrolyzes phospholipids in detergent extracts and from ghosts of B16-F10 cells, generating choline, indicating that the enzyme can access and modulate and has activity against membrane phospholipids.

choline


Input: Additionally, using Fluo-4, a calcium-sensitive fluorophore, it was shown that treatment of cells with phospholipase-D induced an increase in the calcium concentration in the cytoplasm, but without altering viability or causing damage to cells.

calcium

calcium


Input: Finally, based on the known endogenous activity of phospholipase-D as an inducer of cell proliferation and the fact that LiRecDT1 binds to the cell surface, hydrolyzing phospholipids to generate bioactive lipids, we employed LiRecDT1 as an exogenous source of phospholipase-D in B16-F10 cells.


Input: Treatment of the cells was effective in increasing their proliferation in a time-and concentration-dependent manner, especially in the presence of synthetic sphingomyelin in the medium.

sphingomyelin


Input: The results described herein indicate the ability of brown spider phospholipase-D to induce the generation of bioactive phospholipids, calcium influx into the cytoplasm and cell proliferation, suggesting that this molecule can be used as a bioactive tool for experimental protocols in cell biology.

calcium


Input: Identification of functionally relevant lysine residues that modulate human farnesoid x receptor activation.

lysine


Input: Base amino acid lysine residues play an important role in regulation of nuclear receptors [e. g., farnesyl X receptor (FXR)], leading to enhanced or suppressed biologic activity.

amino acid lysine

farnesyl


Input: To understand the molecular mechanisms and the subsequent effects in modulating FXR functions in diverse biologic processes, we individually replaced eight highly conserved lysine residues of human FXR (hFXR) with arginine.

lysine

arginine


Input: The effects of each mutated FXR on target gene activation, subcellular localization, protein-protein association, and protein-DNA interaction were investigated.


Input: Results demonstrated that K122R, K210R, K339R, and K460R mutants of hFXR significantly impaired target gene [organic solute transporter alpha/beta and bile salt export pump (BSEP)] promoter reporter activity in a ligand-dependent fashion.

bile salt


Input: None of the four mutants affected the nuclear localization of FXR.


Input: Protein interaction studies show that K210R slightly but significantly decreased FXR/retinoid X receptor (RXR) binding affinity but enhanced the interaction of FXR with lysine methyltransferase Set7/9 by ~ 21%.

retinoid

lysine


Input: K460R decreased the FXR interaction with Set7/9 by ~ 45% but had no significant effects on interaction with RXR.


Input: Electrophoretic mobility shift assays demonstrated that hFXR-K210R and-K339R reduced the protein-DNA (IR1 element at hBSEP promoter) binding affinity by ~ 80 and ~ 90%, respectively.


Input: Computational-based protein modeling studies were consistent with these results and provided further insights into the potential underlying mechanisms responsible for these results.


Input: In conclusion, four highly conserved lysine residues of hFXR, K122, K210, K339, and K460, have been identified that play a critical role in FXR target gene regulation and molecular interaction (protein-protein and protein-DNA).

lysine


Input: NMR-based metabonomic in hippocampus, nucleus accumbens and prefrontal cortex of methamphetamine-sensitized rats.

methamphetamine


Input: (1) H NMR spectroscopy was applied to investigate the changes of cerebral metabolites in brain hippocampus, nucleus accumbens (NAC) and prefrontal cortex (PFC) of the rats subjected to subcutaneous twice-daily injections of 2. 5mg/kg methamphetamine (MAP) for 7 days.

(1) H

methamphetamine

MAP


Input: The results indicated that MAP exposure induced significant behavioral sensitization and altered cerebral metabolites in rats.

MAP


Input: The neurotransmitters glutamate, glutamine and GABA significantly decreased in hippocampus, NAC and PFC.

glutamate

glutamine

GABA


Input: Specifically, increased succinic acid semialdehyde, a metabolism product of GABA, was observed in hippocampus.

succinic acid semialdehyde

GABA


Input: Additionally, decreased serotonin was observed in both NAC and PFC, whereas decreased dopamine was only observed in NAC after repeated MAP treatment.

serotonin

dopamine

MAP


Input: Glutathione obviously decreased in above brain regions, whereas acetylcysteine declined in hippocampus and NAC, and taurine declined in NAC and PFC.

Glutathione

acetylcysteine

taurine


Input: Homocysteic acid was elevated in hippocampus and NAC by repeated MAP administration.

Homocysteic acid

MAP


Input: Membrane ingredients like phosphocholine elevated in response to MAP administration in NAC and PFC.

phosphocholine

MAP


Input: N-Acetyl-aspartate, a marker of neuronal viability, decreased in the three regions; however, myo-inositol, a glial cell marker, increased in hippocampus and PFC.

N-Acetyl-aspartate

myo-inositol


Input: Tricarboxylic acid cycle intermediate products, such as alpha-ketoglutarate, succinate, citrate and the methionine significantly decreased in above three brain regions after MAP administration; however, ADP decreased in hippocampus.

Tricarboxylic acid

alpha-ketoglutarate

succinate

citrate

methionine

MAP

ADP


Input: These results indicate that repeated MAP treatment causes neurotransmitters disturbance, imbalance between oxidative stress and antioxidants, and gliosis in hippocampus, NAC and PFC.

MAP


Input: Profound metabolic changes detected across brain regions provide the first evidence of metabonomic changes in MAP-induced sensitized rats.

MAP


Input: Alcohol cirrhosis alters nuclear receptor and drug transporter expression in human liver.

Alcohol


Input: Unsafe use of alcohol results in approximately 2. 5 million deaths worldwide, with cirrhosis contributing to 16. 6% of reported deaths.

alcohol


Input: Serum insulin levels are often elevated in alcoholism and may result in diabetes, which is why alcoholic liver disease and diabetes often are present together.


Input: Because there is a sizable population with these diseases alone or in combination, the purpose of this study was to determine whether transporter expression in human liver is affected by alcoholic cirrhosis, diabetes, and alcoholic cirrhosis coexisting with diabetes.


Input: Transporters aid in hepatobiliary excretion of many drugs and toxic chemicals and can be determinants of drug-induced liver injury.


Input: Drug transporter expression and transcription factor-relative mRNA and protein expression in normal, diabetic, cirrhotic, and cirrhosis with diabetes human livers were quantified.


Input: Cirrhosis significantly increased ABCC4, 5, ABCG2, and solute carrier organic anion (SLCO) 2B1 mRNA expression and decreased SLCO1B3 mRNA expression in the liver.


Input: ABCC1, 3-5, and ABCG2 protein expression was also upregulated by alcoholic cirrhosis.


Input: ABCC3-5 and ABCG2 protein expression was also upregulated in diabetic cirrhosis.


Input: Cirrhosis increased nuclear factor E2-related factor 2 mRNA expression, whereas it decreased pregnane-X-receptor and farnesoid-X-receptor mRNA expression in comparison with normal livers.

pregnane


Input: Hierarchical cluster analysis indicated that expressions of ABCC2, 3, and 6; SLCO1B1 and 1B3; and ABCC4 and 5 were more closely related in the livers from this cohort.


Input: Overall, alcoholic cirrhosis altered transporter expression in human liver.


Input: Octahedral Co3O4 particles threaded by carbon nanotube arrays as integrated structure anodes for lithium ion batteries.

carbon

lithium


Input: Octahedral Co3O4 particles threaded by ultra-long multi-walled carbon nanotube (MWCNT) arrays were prepared by a hydrothermal process and subsequent calcination.

carbon


Input: The Co3O4 octahedron with the (111) facets attaches to MWCNTs uniformly and closely.


Input: The composite can be used as an integrated anode for lithium ion batteries (LIBs) without any other additives (such as conductive additives and polymer binder), which exhibits a high reversible capacity of 725 mA h g (-1) at a current density of 100 mA g (-1), and excellent cyclic stability without capacity degradation over 100 cycles at a current density of 500 mA g (-1).

lithium


Input: The high performance can be attributed to the unique structure: (i) the ultra-long MWCNT array facilitates fast electron transfer; (ii) the tight adhesion between Co3O4 and MWCNTs prevents particle drifting and agglomeration; (iii) the free space between MWCNTs promotes fast ion transport and alleviates the large volume variation during discharge-charge process.


Input: This work demonstrates the great potential of MWCNT arrays as substrate and provides insights for the design and direct use of MWCNT array-based materials in LIBs, which will be helpful for future development of high-performance electrode materials.


Input: Clinical proof-of-concept study with MSDC-0160, a prototype mTOT-modulating insulin sensitizer.


Input: It may be possible to achieve insulin sensitivity through the recently identified mitochondrial target of thiazolidinediones (mTOT), thereby avoiding peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-dependent side effects.

thiazolidinediones


Input: In this phase IIb clinical trial, 258 patients with type 2 diabetes completed a 12-week protocol with 50, 100, or 150 mg of MSDC-0160 (an mTOT modulator), 45 mg pioglitazone HCl (a PPAR-gamma agonist), or a placebo.

pioglitazone HCl


Input: The two active treatments lowered fasting glucose levels to the same extent.

glucose


Input: The decreases in glycated hemoglobin (HbA1c) observed with the two higher doses of MSDC-0160 were not different from those associated with pioglitazone.

pioglitazone


Input: By contrast, fluid retention as evidenced by reduction in hematocrit, red blood cells, and total hemoglobin was 50% less in the MSDC-0160-treated groups.


Input: There was also a smaller increase in high-molecular-weight (HMW) adiponectin with MSDC-0160 than with pioglitazone (P < 0. 0001), suggesting that MSDC-0160 produces less expansion of white adipose tissue.

pioglitazone


Input: Thus, mTOT modulators may have glucose-lowering effects similar to those of pioglitazone but without the adverse effects associated with PPAR-gamma agonists.

glucose

pioglitazone


Input: Novel insights into the biology of interleukin-32.


Input: Interleukin (IL)-32 is known as a proinflammatory cytokine that is likely involved in several diseases, including infections, chronic inflammation, and cancer.


Input: Since the first report in 2005, IL-32 has been the subject of numerous studies to unravel the biological function of this molecule.


Input: For example, silencing of endogenous IL-32 in primary or cell lines of human origin consistently suppressed responses to Toll-like receptors.


Input: The protein folding structure of the six isoforms of IL-32 does not resemble that of any classical cytokine and as of this writing, a specific IL-32 receptor has not been identified.


Input: Instead, we propose a mechanism by which exposure to extracellular IL-32 or overexpression of the molecule results in binding to intracellular partners that influences functions such as gene expression, cell death, or survival.


Input: As such, this review offers insights into the role of IL-32 in several diseases, host defense, inflammation, immune function, and cancer.


Input: Finally, possibilities to target IL-32 in several diseases are proposed.


Input: A method for non-invasive full-field imaging and quantification of chemical species.


Input: We present a novel method for full-field scalar visualization and quantification of species concentration fields.


Input: We term this method species-altered fluorescence imaging (SAFI).


Input: The method employs electrically neutral fluorescent dyes whose quantum yields are selectively quenched or enhanced by species of interest.


Input: SAFI enables simultaneous imaging of material interfaces and provides non-invasive, scalar-field quantitation of two-dimensional species concentration fields.


Input: We describe criteria for choosing SAFI dyes and tabulate 35 promising SAFI dyes and their relevant properties.


Input: Next, we describe species concentration quantification with SAFI via Stern-Volmer quenching and discuss the sensitivity and resolution of our method.


Input: We demonstrate this method with two dyes, 6-methoxy-N-(3-sulfopropyl) quinolinium (SPQ) and 10-(3-sulfopropyl) acridinium betaine (SAB).

6-methoxy-N-(3-sulfopropyl) quinolinium

SPQ

10-(3-sulfopropyl) acridinium betaine

SAB


Input: We demonstrate our method in full-field visualization of several challenging electrokinetic flows: isotachophoresis (ITP) in both cationic and anionic modes, and in a convective electrokinetic instability (EKI) flow.


Input: Through these experiments we collectively quantify ion concentration shock velocities, simultaneously measure concentrations of five species, and quantify the development of an unsteady, chaotic, 2D flow.


Input: Gram-scale synthesis of graphene sheets by a catalytic arc-discharge method.

graphene


Input: Flake graphite is used as carbon source and ZnO or ZnS as catalyst in the synthesis of high-quality graphene sheets.

graphite

carbon

ZnO

ZnS

graphene


Input: A catalytic growth mechanism for cathode-part graphene synthesis in the arc-discharge apparatus and an exfoliation mechanism for wall-part graphene synthesis are introduced.

graphene

graphene


Input: N-doped cathode-part graphene and undoped wall-part graphene are formed simultaneously.

N

graphene

graphene


Input: Peptides as the next generation of anti-infectives.


Input: Synthesis and large-scale manufacturing technologies are now available for the commercial production of even the most complex peptide anti-infectives.


Input: Married with the potential of this class of molecule as the next generation of effective, resistance-free and safe antimicrobials, and a much better understanding of their biology, pharmacology and pharmacodynamics, the first regulatory approvals and introduction into clinical practice of these promising drug candidates will likely be soon.


Input: This is a key juncture in the history/life cycle of peptide anti-infectives and, perhaps, their commercial and therapeutic potential is about to be realized.


Input: This review highlights the promise of these agents as the next generation of therapeutics and summarizes the challenges faced in, and lessons learned from, the past.


Input: Simultaneously strong and tough ultrafine continuous nanofibers.


Input: Strength of structural materials and fibers is usually increased at the expense of strain at failure and toughness.


Input: Recent experimental studies have demonstrated improvements in modulus and strength of electrospun polymer nanofibers with reduction of their diameter.


Input: Nanofiber toughness has not been analyzed; however, from the classical materials property trade-off, one can expect it to decrease.


Input: Here, on the basis of a comprehensive analysis of long (5-10 mm) individual polyacrylonitrile nanofibers, we show that nanofiber toughness also dramatically improves.

polyacrylonitrile


Input: Reduction of fiber diameter from 2. 8 mu m to ~ 100 nm resulted in simultaneous increases in elastic modulus from 0. 36 to 48 GPa, true strength from 15 to 1750 MPa, and toughness from 0. 25 to 605 MPa with the largest increases recorded for the ultrafine nanofibers smaller than 250 nm.


Input: The observed size effects showed no sign of saturation.


Input: Structural investigations and comparisons with mechanical behavior of annealed nanofibers allowed us to attribute ultrahigh ductility (average failure strain stayed over 50%) and toughness to low nanofiber crystallinity resulting from rapid solidification of ultrafine electrospun jets.


Input: Demonstrated superior mechanical performance coupled with the unique macro-nano nature of continuous nanofibers makes them readily available for macroscopic materials and composites that can be used in safety-critical applications.


Input: The proposed mechanism of simultaneously high strength, modulus, and toughness challenges the prevailing 50 year old paradigm of high-performance polymer fiber development calling for high polymer crystallinity and may have broad implications in fiber science and technology.


Input: Diameter-Dependent Photocurrent in InAsSb Nanowire Infrared Photodetectors.

InAsSb


Input: Photoconductors using vertical arrays of InAs/InAs1-xSbx nanowires with varying Sb composition x have been fabricated and characterized.

InAs

Sb


Input: The spectrally resolved photocurrents are strongly diameter dependent with peaks, which are red-shifted with diameter, appearing for thicker wires.


Input: Results from numerical simulations are in good agreement with the experimental data and reveal that the peaks are due to resonant modes that enhance the coupling of light into the wires.


Input: Through proper selection of wire diameter, the absorptance can be increased by more than 1 order of magnitude at a specific wavelength compared to a thin planar film with the same amount of material.


Input: A maximum 20% cutoff wavelength of 5. 7 mu m is obtained at 5 K for a wire diameter of 717 nm at a Sb content of x = 0. 62, but simulations predict that detection at longer wavelengths can be achieved by increasing the diameter.

Sb


Input: Furthermore, photodetection in InAsSb nanowire arrays integrated on Si substrates is also demonstrated.

InAsSb

Si


Input: Slip length measurement of confined air flow on three smooth surfaces.


Input: An experimental measurement of the slip length of air flow close to three different solid surfaces is presented.


Input: The substrate was driven by a nanopositioner moving toward an oscillating glass sphere glued to an atomic force microscopy (AFM) cantilever.


Input: A large separation distance was used to get more effective data.


Input: The slip length value was obtained by analyzing the amplitude and phase data of the cantilever.


Input: The measurements show that the slip length does not depend on the oscillation amplitude of the cantilever.


Input: Because of the small difference among the slip lengths of the three surfaces, a simplified analysis method was used.


Input: The results show that on glass, graphite, and mica surfaces the slip lengths are 98, 234, and 110 nm, respectively.

graphite

mica


Input: Templating Sub-10 nm Atomic Layer Deposited Oxide Nanostructures on Graphene via One-Dimensional Organic Self-Assembled Monolayers.

Oxide

Graphene


Input: Molecular-scale control over the integration of disparate materials on graphene is a critical step in the development of graphene-based electronics and sensors.

graphene

graphene


Input: Here, we report that self-assembled monolayers of 10, 12-pentacosadiynoic acid (PCDA) on epitaxial graphene can be used to template the reaction and directed growth of atomic layer deposited (ALD) oxide nanostructures with sub-10 nm lateral resolution.

10, 12-pentacosadiynoic acid

PCDA

graphene

oxide


Input: PCDA spontaneously assembles into well-ordered domains consisting of one-dimensional molecular chains that coat the entire graphene surface in a manner consistent with the symmetry of the underlying graphene lattice.

PCDA

graphene

graphene


Input: Subsequently, zinc oxide and alumina ALD precursors are shown to preferentially react with the functional moieties of PCDA, resulting in templated oxide nanostructures.

zinc oxide

alumina

PCDA

oxide


Input: The retention of the original one-dimensional molecular ordering following ALD is dependent on the chemical reaction pathway and the stability of the monolayer, which can be enhanced via ultraviolet-induced molecular cross-linking.


Input: Oversampling to Overcome Overfitting: Exploring the Relationship between Data Set Composition, Molecular Descriptors, and Predictive Modeling Methods.


Input: The traditional biological assay is very time-consuming, and thus the ability to quickly screen large numbers of compounds against a specific biological target is appealing.


Input: To speed up the biological evaluation of compounds, high-throughput screening is widely used in the fields of biomedical, biological information, and drug discovery.


Input: The research presented in this study focuses on the use of support vector machines, a machine learning method, various classes of molecular descriptors, and different sampling techniques to overcome overfitting to classify compounds for cytotoxicity with respect to the Jurkat cell line.


Input: The cell cytotoxicity data set is imbalanced (a few active compounds and very many inactive compounds), and the ability of the predictive modeling methods is adversely affected in these situations.


Input: Commonly imbalanced data sets are overfit with respect to the dominant classified end point; in this study the models routinely overfit toward inactive (noncytotoxic) compounds when the imbalance was substantial.


Input: Support vector machine (SVM) models were used to probe the proficiency of different classes of molecular descriptors and oversampling ratios.


Input: The SVM models were constructed from 4D-FPs, MOE (1D, 2D, and 21/2D), noNP + MOE, and CATS2D trial descriptors pools and compared to the predictive abilities of CATS2D-based random forest models.


Input: Compared to previous results in the literature, the SVM models built from oversampled data sets exhibited better predictive abilities for the training and external test sets.


Input: Isolation of Ciliatamide D from a Marine Sponge Stelletta sp. and a Reinvestigation of the Configuration of Ciliatamide A.

Ciliatamide D

Ciliatamide A


Input: A new lipopeptide, ciliatamide D (1), was isolated from a marine sponge Stelletta sp., collected at Oshimashinsone, together with the known compound ciliatamide A (2).

ciliatamide D

ciliatamide A


Input: Ciliatamide D (1) is a congener of 2, in which N-Me-Phe is replaced by N-Me-Met (O).

Ciliatamide D

N-Me-Phe

N-Me-Met (O)


Input: Marfey' s analysis of the acid hydrolysate of 1 demonstrated that the two constituent amino acids were both in the l-form.

amino acids


Input: This result prompted us to carefully investigate the configuration of 2, resulting in the assignment of the l-form for both residues.


Input: Chemical ligation of oligodeoxynucleotides by X-irradiation and its application to regulation of G-quadruplex formation.


Input: We demonstrated radiolytic ligation of oligodeoxynucleotides (ODNs) possessing disulfide bond and its application to regulation of DNA quadruplex formation.

disulfide


Input: G-rich hexamer ODNs had poor ability to form quadruplex, while X-irradiation of the ODNs induced interstrand exchange reaction at disulfide bond to form ligated 12 mer ODNs, leading to the ready formation of quadruplex due to the entropic effect.

disulfide


Input: Since complexation of the ligated ODNs with hemin in the presence of K (+) showed strong soret band absorption and also catalyzed the H (2) O (2)-mediated oxidation of luminol, it appears that the quadruplex formed from ligated ODNs showed a function similar to native DNA quadruplex.

hemin

K (+)

H (2) O (2)

luminol


Input: Anti-adipogenic diarylheptanoids from Alnus hirsuta f. sibirica on 3T3-L1 cells.

diarylheptanoids


Input: A new diarylheptanoid, (5S)-hydroxy-1-(3, 4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-hepta-1E-en-3-one (1), was isolated along with seventeen known diarylheptanoids (2-18) from the methanol extract of Alnus hirsuta f. sibirica leaves using bioactivity-guided fractionation.

diarylheptanoid

(5S)-hydroxy-1-(3, 4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-hepta-1E-en-3-one

diarylheptanoids

methanol


Input: Among the isolated compounds, compounds 1 and 2 and 4-12 reduced lipid accumulation dose-dependently in 3T3-L1 preadipocytes.


Input: Of the compounds active in the present assay system, the most potent compound 7, platyphyllonol-5-O-beta-d-xylopyranoside, significantly suppressed the induction of peroxisome proliferator activated receptor gamma (PPAR gamma and CCAAT/enhancer binding protein alpha (C/EBP alpha) protein expression, and inhibited adipocyte differentiation induced by troglitazone, a PPAR gamma agonist.

platyphyllonol-5-O-beta-d-xylopyranoside

troglitazone


Input: It was demonstrated that compound 7 has anti-adipogenic activity mediated by the regulation of PPAR gamma dependent pathways.


Input: Experience-dependent homeostatic synaptic plasticity in neocortex.


Input: The organism' s ability to adapt to the changing sensory environment is due in part to the ability of the nervous system to change with experience.


Input: Input and synapse specific Hebbian plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), are critical for sculpting the nervous system to wire its circuit in tune with the environment and for storing memories.


Input: However, these synaptic plasticity mechanisms are innately unstable and require another mode of plasticity that maintains homeostasis to allow neurons to function within a desired dynamic range.


Input: Several modes of homeostatic adaptation are known, some of which work at the synaptic level.


Input: This review will focus on the known mechanisms of experience-induced homeostatic synaptic plasticity in the neocortex and their potential function in sensory cortex plasticity.


Input: This article is part of a Special Issue entitled' Homeostatic Plasticity'.


Input: Gimatecan and other camptothecin derivatives poison Leishmania DNA-topoisomerase IB leading to a strong leishmanicidal effect.

Gimatecan

camptothecin


Input: The aim of this work is the in vitro and ex vivo assessment of the leishmanicidal activity of camptothecin and three analogues used in cancer therapy: topotecan (Hycantim ((R))), gimatecan (ST1481) and the pro-drug irinotecan (Camptosar ((R))) as well as its active metabolite SN-38 against Leishmania infantum.

camptothecin

topotecan

Hycantim

gimatecan

irinotecan

Camptosar


Input: The activity of camptothecin and its derivatives was studied on extracellular L. infantum infrared-emitting promastigotes and on an ex vivo murine model of infected splenocytes with L. infantum fluorescent amastigotes.

camptothecin


Input: In situ formation of SDS/KCl precipitable DNA-protein complexes in Leishmania promastigotes indicated that these drugs are DNA topoisomerase IB poisons.


Input: The inhibitory potency of camptothecin derivatives on recombinant L. infantum topoisomerase IB was assessed in vitro showing that gimatecan is the most active compound preventing the relaxation of supercoiled DNA at submicromolar concentrations.

camptothecin

gimatecan


Input: Cleavage equilibrium assays in Leishmania topoisomerase IB show that gimatecan changes the equilibrium towards cleavage at much lower concentrations than the other camptothecin derivatives and that this effect persists over time.

gimatecan

camptothecin


Input: Gimatecan and camptothecin were the most powerful compounds preventing cell growth of free-living L. infantum promastigotes within the same concentration range.

Gimatecan

camptothecin


Input: All these compounds killed L. infantum splenocyte-infecting amastigotes within the nanomolar range.


Input: The amastigote form showed higher sensitivity to topoisomerase IB poisons (with high therapeutic selectivity indexes) than free-living promastigotes.


Input: All the compounds assayed poisoned L. infantum DNA topoisomerase IB leading to a strong leishmanicidal effect.


Input: Camptothecin derivatives are suitable for reducing the parasitic burden of ex vivo infected splenocytes.

Camptothecin


Input: The selectivity index of gimatecan makes it a promising drug against this neglected disease.

gimatecan


Input: Molecular markers from three organellar genomes unravel complex taxonomic relationships within the coralline algal genus Chiharaea (Corallinales, Rhodophyta).


Input: The use of molecular markers in taxonomic studies has become a standard practice in biology.


Input: However, consensus on which markers to use at the species level is lacking because evolutionary lineages show differences in divergence rates between organellar genomes.


Input: Ideally, researchers use multiple lines of evidence when first describing a species, such as the incorporation of several molecular markers from varied genomes (mitochondrion, plastid and nucleus).


Input: This study examined species boundaries in the red algal genus Chiharaea.


Input: We used five molecular markers, with at least one marker from each genome, coupled with thorough morphological analyses.


Input: We recognized three species in Chiharaea (C. americana, C. rhododactyla sp. nov., C. silvae) and two forms (C. americana f. americana and C. americana f. bodegensis (H. W. Johansen) stat. nov.).


Input: For C. americana f. americana and C. americana f. bodegensis differentiation based on morphological data was reflected in the plastid-encoded large subunit of RuBisCO (rbcL), but was not concordant with either the mitochondrial cytochrome c oxidase subunit 1 (COI-5P) or nuclear internal transcribed spacer (ITS) sequence data.


Input: We suggest that this discordance is indicative of ongoing hybridization and introgression between populations of C. americana f. americana and C. americana f. bodegensis.


Input: In addition, we used a PCR assay with ITS specific primers to amplify multiple ITS variants for collections assignable to C. americana indicating that there is genetic variability within ITS copies most likely due to introgression, crossing over and/or the retention of ancestral variants.


Input: Theoretical realization of robust broadband transparency in ultrathin seamless nanostructures by dual blackbodies for near infrared light.


Input: We propose a counter-intuitive mechanism of constructing an ultrathin broadband transparent device with two perfect blackbodies.


Input: By introducing hybridization of plasmon modes, resonant modes with different symmetries coexist in this system.


Input: A broadband transmission spectrum in the near infrared regime is achieved through controlling their coupling strengths, which is governed by the thickness of high refractive index layer.


Input: Meanwhile, the transparency bandwidth is found to be tunable in a large range by varying the geometric dimension.


Input: More significantly, from the point view of applications, the proposed method of achieving broadband transparency can perfectly tolerate the misalignment and asymmetry of periodic nanoparticles on the top and bottom, which is empowered by the unique dual of coupling-in and coupling-out processes within the pair of blackbodies.


Input: Moreover, roughness has little influence on its transmission performance.


Input: According to the coupled mode theory, the distinguished transmittance performance is physically interpreted by the radiative decay rate of the entire system.


Input: In addition to the feature of uniquely robust broadband transparency, such a ultrathin seamless nanostructure (in the presence of a uniform silver layer) also provides polarization-independent and angle-independent operations.


Input: Therefore, it may power up a wide spectrum of exciting applications in thin film protection, touch screen techniques, absorber-emitter transformation, etc.


Input: Benzenesulfonamides: a unique class of chemokine receptor type 4 inhibitors.

Benzenesulfonamides


Input: The interaction of CXCR4 with CXCL12 (SDF-1) plays a critical role in cancer metastasis by facilitating the homing of tumor cells to metastatic sites.


Input: Based on our previously published work on CXCR4 antagonists, we have synthesized a series of aryl sulfonamides that inhibit the CXCR4/CXCL12 interaction.

aryl sulfonamides


Input: Analogue bioactivities were assessed with binding affinity and Matrigel invasion assays.


Input: Computer modeling was employed to evaluate a selection of the new analogues docked into the CXCR4 X-ray structure and to rationalize discrepancies between the affinity and Matrigel in vitro assays.


Input: A lead compound displays nanomolar potency in the binding affinity assay (IC (50) = 8. 0 nM) and the Matrigel invasion assay (100% blockade of invasion at 10 nM).


Input: These data demonstrate that benzenesulfonamides are a unique class of CXCR4 inhibitors with high potency.

benzenesulfonamides


Input: Hydrogen-bond reinforced vanadia nanofiber paper of high stiffness.

Hydrogen

vanadia


Input: Low-temperature, solution-based self-assembly of vanadia nanofibers yields a free-standing, ceramic paper with an outstanding combination of high strength, stiffness, and macroscopic flexibility.

vanadia


Input: Its excellent mechanical performance results from a brick-and-mortar like architecture, which combines strong covalent bonding within the single-crystalline nanofibers with an intricate hydrogen bonding network between them.

hydrogen


Input: Hedgehog signaling acts with the temporal cascade to promote neuroblast cell cycle exit.


Input: In Drosophila postembryonic neuroblasts, transition in gene expression programs of a cascade of transcription factors (also known as the temporal series) acts together with the asymmetric division machinery to generate diverse neurons with distinct identities and regulate the end of neuroblast proliferation.


Input: However, the underlying mechanism of how this " temporal series " acts during development remains unclear.


Input: Here, we show that Hh signaling in the postembryonic brain is temporally regulated; excess (earlier onset of) Hh signaling causes premature neuroblast cell cycle exit and under-proliferation, whereas loss of Hh signaling causes delayed cell cycle exit and excess proliferation.


Input: Moreover, the Hh pathway functions downstream of Castor but upstream of Grainyhead, two components of the temporal series, to schedule neuroblast cell cycle exit.


Input: Interestingly, hh is likely a target of Castor.


Input: Hence, Hh signaling provides a link between the temporal series and the asymmetric division machinery in scheduling the end of neurogenesis.


Input: Influence of aqueous media properties on aggregation and solubility of four structurally related meso-porphyrin photosensitizers evaluated by spectrophotometric measurements.

meso-porphyrin


Input: Porphyrin photosensitizers tend to aggregate in aqueous solutions even in the micromolar concentration range.

Porphyrin


Input: This is a challenge during formulation of e. g., parenteral preparations for photodynamic cancer therapy, or preparations for local or topical administration in antimicrobial photodynamic therapy.


Input: Monomerization is essential to achieve biocompatible drug formulations of high bioavailability and physiological response (i. e., photoreactivity) and low toxicity.


Input: The aggregation and solubilization of four structurally related meso-tetraphenyl porphyrin photosensitizers with nonionic (4-hydroxy), anionic (4-sulphonate; 4-carboxy) and cationic (4-trimethylanilinium) substituents were evaluated in various vehicles by use of UV-Vis spectroscopy.

meso-tetraphenyl porphyrin


Input: Substituents, overall charge and charge distribution influenced the pKa-values and interaction of the porphyrins with different solvents, excipients and impurities.

porphyrins


Input: Modification of medium polarity and solubilization by the nonionic surfactant Tween 80 adjusted the acid-base equilibria and increased the solubility by reduction of porphyrin aggregation.

Tween 80

porphyrin


Input: The selected porphyrins were sensitive towards ionic strength, temperature and inorganic impurities to various extents.

porphyrins


Input: The results will be further used during development of parenteral and topical formulations of porphyrin photosensitizers for use in photodynamic therapy of cancer and bacterial infections.

porphyrin


Input: Folate Conjugation to Polymeric Micelles via Boronic Acid Ester to Deliver Platinum Drugs to Ovarian Cancer Cell Lines.

Folate

Boronic Acid Ester

Platinum


Input: In this study, a novel technique was used for the reversible attachment of folic acid on the surface of polymeric micelles for a tumor-specific drug delivery system.

folic acid


Input: The reversible conjugation is based on the interaction between phenylboronic acid (PBA) and dopamine to form a borate ester.

phenylboronic acid

PBA

dopamine

borate ester


Input: The conjugation is fast and efficient and in vitro experiments via confocal fluorescent microscopy show that the linker is stable in for several hours.


Input: Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize two various sized water-soluble block copolymer of oligoethylene glycol methylether methacylate and methyl acrylic acid (POEGMEMA35-b-PMAA200 and POEGMEMA26-b-PMAA90).

oligoethylene glycol methylether methacylate

methyl acrylic acid


Input: The platinum drug, oxoplatin, was then subsequently attached to the polymer via ester formation leading to platinum loading of 12 wt% as determined by TGA.

platinum

oxoplatin

platinum


Input: The platinum-induced amphiphilic block copolymers that consequently led to the formation of micelles of sizes 150 and 20 nm in an aqueous environment with the longer PMAA block forming larger micelles.

platinum

PMAA


Input: The small micelles were in addition cross-linked using 1, 8-diaminooctane to further stabilize their structure.

1, 8-diaminooctane


Input: The targeting ability of folate conjugated polymeric micelles was investigated against two types of tumor cell lines: A549 (-FR) and OVCAR-3 (+ FR).

folate


Input: The cell line growth inhibitory efficacy of material synthesized was evaluated by using SRB method.


Input: The results revealed that folate conjugated micelles showed higher activity in FR + OVCAR-3 cells but not in FR-A549 cells.

folate


Input: Similar results were obtained for both small and large micelles without the conjugation of folate.

folate


Input: Comparing large and small micelles it can be observed that larger micelles are more efficient, which has been attributed to the lower stability of the smaller micelles.


Input: Micelle stabilization via cross-linking could indeed increase the toxicity of the drug carrier.


Input: Synthesis and relaxometric characterization of a MRI Gd-based probe responsive to glutamic acid decarboxylase enzymatic activity.

Gd

glutamic acid


Input: Novel contrast agent based systems, which selectively visualize specific cells, e. g., neurons in the brain, would be of substantial importance for the fast developing field of molecular magnetic resonance imaging (MRI).


Input: We report here the synthesis and in vitro validation of a Gd (III)-based contrast agent designed to act as an MRI responsive probe for imaging the activity of the enzyme glutamic acid decarboxylase (GAD) present in neurons.

Gd (III)

glutamic acid


Input: Upon the action of the enzyme, the Gd (III) complex increases its hydration sphere and takes on a residual positive charge that promotes its binding to endogenous macromolecules.

Gd (III)


Input: Both effects contribute in a synergic way to generate a marked relaxation enhancement, which directly reports enzyme activity and will allow activity detection of GAD positive cells in vitro and in vivo selectively.