Input: In addition to apparent cliffs due to inaccurate determinations of activity, computationally identified cliffs can be artifacts attributed to the molecular representation and quantitative definition of' high' structural similarity.


Input: This paper brings together and discusses, in a brief and integrated manner, some of the major aspects that raise the question whether all the activity cliffs detected in compound data sets are facts or artifacts.


Input: Structural basis for autoinhibition of the guanine nucleotide exchange factor FARP2.

guanine nucleotide


Input: FARP2 is a Dbl-family guanine nucleotide exchange factor (GEF) that contains a 4. 1, ezrin, radixin and moesin (FERM) domain, a Dbl-homology (DH) domain and two pleckstrin homology (PH) domains.

guanine nucleotide


Input: FARP2 activates Rac1 or Cdc42 in response to upstream signals, thereby regulating processes such as neuronal axon guidance and bone homeostasis.


Input: How the GEF activity of FARP2 is regulated remained poorly understood.


Input: We have determined the crystal structures of the catalytic DH domain and the DH-PH-PH domains of FARP2.


Input: The structures reveal an auto-inhibited conformation in which the GEF substrate-binding site is blocked collectively by the last helix in the DH domain and the two PH domains.


Input: This conformation is stabilized by multiple interactions among the domains and two well-structured inter-domain linkers.


Input: Our cell-based activity assays confirm the suppression of the FARP2 GEF activity by these auto-inhibitory elements.


Input: Chronic, low concentration exposure to pharmaceuticals impacts multiple organ systems in zebrafish.


Input: Pharmaceuticals are found in both receiving and drinking water due to their persistent release in waste-water effluents, raising concerns for environmental and human health.


Input: Chronic, aqueous exposure of zebrafish (Danio rerio) to environmentally relevant concentrations of acetaminophen (ACE), venlafaxaine (VEN) (10 mu gL (-1)), carbamazepine (CBZ) and gemfibrozil (GEM) (0. 5 and 10 mu gL (-1)) decreased reproductive output.

acetaminophen

ACE

venlafaxaine

VEN

carbamazepine

CBZ

gemfibrozil

GEM


Input: Atretic oocytes and altered ovarian histology were seen in female zebrafish exposed to CBZ and GEM, suggesting a direct effect on oocyte development that may account for the reduced fecundity.

CBZ

GEM


Input: Apoptosis within the theca and granulosa cells was identified in exposed female zebrafish with atretic oocytes by TUNEL positive staining.


Input: The incidence of follicular apoptosis was nearly 2-fold higher in exposed females than the controls.


Input: All compounds significantly altered kidney proximal tubule morphology but there was no difference in the incidence of apoptotic cells within the kidney between control and exposed in either males or females.


Input: Liver histology was altered by ACE and GEM exposure.

ACE

GEM


Input: Parental exposure to pharmaceuticals did not increase developmental abnormalities, hatching success, or mortality in embryos.


Input: Yet, direct exposure of embryos to ACE increased developmental abnormalities and mortality; exposure to 0. 5 mu gL (-1) of all pharmaceuticals increased mortality.

ACE


Input: CBZ decreased plasma 11-ketotestosterone concentrations in males and females.

CBZ


Input: Overall, these data suggest that low concentration, chronic exposure of fish to pharmaceuticals impacts fish development as well as multiple organ systems in adult fish, leading to effects on reproduction and histology of liver and kidney.


Input: These results are significant in understanding the consequences of chronic, low concentration pharmaceutical exposure to fish and suggest that exposed populations are at risk of negative impacts to reproduction and health.


Input: Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants.

organochlorine

chlordecone


Input: Chlordecone is a persistent organochlorine pesticide that was used in the French West Indies until the early 1990s for banana weevil borer control.

Chlordecone

organochlorine


Input: Human exposure to this chemical in this area still occurs nowadays due to consumption of contaminated food.


Input: Although adverse effects on neurodevelopment, including tremors and memory deficits, have been documented in experimental studies conducted with rodents exposed during the gestational and neonatal periods, no study has been conducted yet to determine if chlordecone alters child development.

chlordecone


Input: This study examines the relation of gestational and postnatal exposure to chlordecone to infant development at 18 months of age in a birth-cohort of Guadeloupean children.

chlordecone


Input: In a prospective longitudinal study conducted in Guadeloupe (Timoun mother-child cohort study), exposure to chlordecone was measured at birth from an umbilical cord blood sample (n = 141) and from a breast milk sample collected at 3 months postpartum (n = 75).

chlordecone


Input: Toddlers were assessed using an adapted version of the Ages and Stages Questionnaire.


Input: Higher chlordecone concentrations in cord blood were associated with poorer fine motor scores.

chlordecone


Input: When analyses were conducted separately for boys and girls, this effect was only observed among boys.


Input: These results suggest that prenatal exposure to chlordecone is associated with specific impairments in fine motor function in boys, and add to the growing evidence that exposure to organochlorine pesticides early in life impairs child development.

chlordecone

organochlorine


Input: Synthesis of novel 16-spiro steroids: Spiro-7'-(aryl) tetrahydro-1H-pyrrolo [1, 2-c] [1, 3] thiazolo-trans-androsterone hybrid heterocycles.

16-spiro steroids

Spiro-7'-(aryl) tetrahydro-1H-pyrrolo [1, 2-c] [1, 3] thiazolo-trans-androsterone


Input: The 1, 3-dipolar cycloaddition of azomethine ylide derived in situ from the reaction of acenaphthylene-1, 2-dione and 1, 3-thiazolane-4-carboxylic acid to various exocyclic dipolarophiles synthesized from trans-androsterone and trans-dehydroandrosterone afforded a library of novel spiro [5'. 2''] acenaphthylene-1''-one-spiro [16. 6']-(7'-aryl)-tetrahydro-1H-pyrrolo [1, 2-c] [1, 3] thiazolo-trans-androsterone/dehydroandrosterone hybrid heterocycles respectively.

azomethine

acenaphthylene-1, 2-dione

1, 3-thiazolane-4-carboxylic acid

trans-androsterone

trans-dehydroandrosterone

spiro [5'. 2''] acenaphthylene-1''-one-spiro [16. 6']-(7'-aryl)-tetrahydro-1H-pyrrolo [1, 2-c] [1, 3] thiazolo-trans-androsterone

dehydroandrosterone


Input: These reactions proceeded stereo-specifically affording a single isomer of the 16-spiro steroids in excellent yields.

16-spiro steroids


Input: p63 involvement in poly (ADP-ribose) polymerase 1 signaling of topoisomerase I-dependent DNA damage in carcinoma cells.

poly (ADP-ribose)


Input: Poly (ADP-ribose) polymerase 1 (PARP-1) inhibitors are thought as breakthrough for cancer treatment in solid tumors such as breast cancer through their effects on PARP' s enzymatic activity.

Poly (ADP-ribose)


Input: Our previous findings showed that the hydrophilic PARP inhibitor PJ34 enhances the sensitivity of p53 proficient MCF7 breast carcinoma cells to topotecan, a DNA Topoisomerase I (TOP 1) inhibitor.


Input: In the present study, we combine the classical TOP 1 poison camptothecin or its water-soluble derivative topotecan with PJ34 to investigate the potentiation of chemotherapeutic efficiency in MCF7 (p53 (WT)), MDA-MB231 (p53 (mut)) breast carcinoma cells and SCC022 (p53 (null)) squamous carcinoma cells.

camptothecin

topotecan


Input: We show that, following TPT-PJ34 combined treatment, MCF7 cells exhibit apoptotic death while MDA-MB231 and SCC022 cells are more resistant to these agents.

TPT


Input: Specifically, in MCF7, (i) PJ34 in combination with TPT causes a G2/M cell cycle arrest followed by massive apoptosis; (ii) PJ34 addition reverts TPT-dependent PARP-1 automodification and triggers caspase-dependent PARP-1 proteolysis; (iii) TPT, used as a single agent, stimulates p53 expression while in combination with PJ34 increases p53, TAp63 alpha and TAp63 gamma protein levels with a concomitant reduction of MDM2 protein.

TPT

TPT

TPT


Input: The identification of p63 proteins as new players involved in the cancer cell response to TPT-PJ34 is relevant for a better understanding of the PARP1-dependent signaling of DNA damage.

TPT


Input: Furthermore, our data indicate that, in response to TPT-PJ34 combined chemotherapy, a functional cooperation between p53 and TAp63 proteins may occur and be essential to trigger apoptotic cell death.

TPT


Input: Sesquiterpenes from the rhizomes of Alpinia japonica and their inhibitory effects on nitric oxide production.

Sesquiterpenes

nitric oxide


Input: A novel norsesquiterpene (1), three new bisabolenes sesquiterpenes (2-4), along with 7 known compounds (5-11), were isolated from the rhizomes of Alpinia japonica.

bisabolenes sesquiterpenes


Input: The structures of the new compounds were elucidated by analysis of spectroscopic data.


Input: The absolute configuration of C-1 in 3 was deduced via the circular dichroism data of the in situ formed [Rh2 (OCOCF3) 4] complexes.

[Rh2 (OCOCF3) 4]


Input: Inhibitory effects of the isolates on nitric oxide production in lipopolysaccaride-activated RAW264. 7 macrophages were evaluated.

nitric oxide


Input: Compound 6 showed significant inhibitory activity with IC50 value of 5. 3 mu Mu, and compounds 1, 3, 5 and 7-10 exhibited moderate inhibitory activities with IC50 values between 24. 5 and 46. 3 mu M.


Input: Liposomes modified with P-aminophenyl-alpha-d-mannopyranoside: A carrier for targeting cerebral functional regions in mice.

P-aminophenyl-alpha-d-mannopyranoside


Input: Targeting of intracerebral functional regions has been limited by the inability to transport drugs across the blood-brain barrier (BBB) and by poor accumulation in these regions.


Input: To overcome these hurdles, liposomes modified with P-aminophenyl-alpha-d-mannopyranoside (MAN) were used as a fluorescent dye carrier through the BBB and used the specific distribution of liposomes (LIP) modified with MAN (MAN-LIP) to target various functional regions of the brain.

P-aminophenyl-alpha-d-mannopyranoside

MAN

MAN

MAN


Input: An in vitro BBB model was established to evaluate the transendothelial ability of MAN-LIP, and liposomes uptake by C6 glioma cells was analyzed by flow cytometry and live cell imaging.

MAN


Input: Liposome targeting was evaluated using in vivo and ex vivo imaging.


Input: After MAN-LIP administration, the transendothelial ability and the delivery of fluorescent dye to the brain significantly increased.

MAN


Input: MAN-LIP concentrated in the cortex at 4h, shifting distribution to the cerebellum and brainstem at 12h.

MAN


Input: The fluorescence intensity in the hippocampus and pontine nuclei remained high and stable over a period of 12h.


Input: The results demonstrate that MAN-LIP is able to enhance cellular uptake in vitro and also promotes penetration through the BBB and accumulation in the brain with a distinct spatio-temporal pattern.

MAN


Input: Inhibition of protein tyrosine phosphatases in spinal dorsal horn attenuated inflammatory pain by repressing Src signaling.

tyrosine


Input: Tyrosine phosphorylation of N-methyl-d-aspartate (NMDA) subtype glutamate receptors by Src-family protein tyrosine kinases (SFKs) plays a critical role in spinal sensitization.

Tyrosine

N-methyl-d-aspartate

NMDA

glutamate

tyrosine


Input: Besides SFKs, the tyrosine phosphorylation levels of proteins are also determined by protein tyrosine phosphatases (PTPs).

tyrosine

tyrosine


Input: However, whether PTPs are involved in spinal nociceptive processing is largely unknown.


Input: The present study found that intrathecal application of broad-spectrum PTPs inhibitors orthovanadate or Bpv (phen) generated little effects on the paw withdrawal thresholds of intact rats to Von Frey filament stimuli.

orthovanadate

Bpv (phen)


Input: Although the basal nociceptive responses didn' t require the involvement of PTPs, the mechanical allodynia evoked by intrathecal injection of NMDA was greatly attenuated by orthovanadate and Bpv (phen), suggesting that PTPs activity, once stimulated by NMDA receptors, became essential for spinal sensitization.

NMDA

orthovanadate

Bpv (phen)

NMDA


Input: Biochemical analysis demonstrated that PTPs functioned to activate SFKs member Src and promote Src interaction with NR2B subunit-containing NMDA receptors (NR2B receptors).

NMDA


Input: As a result, PTPs inhibition largely suppressed Src-mediated NR2B phosphorylation at Tyr1472 and reduced the synaptic concentration of NR2B receptors in spinal dorsal horn of NMDA-treated rats.

NMDA


Input: Importantly, intraplantar injection of Complete Freund' s Adjuvant (CFA) naturally activated spinal PTPs to initiate Src signaling, because PTPs inhibition significantly repressed Src activity, reduced Src phosphorylation of NR2B, decreased NR2B synaptic accumulation and eventually ameliorated inflammatory pain.


Input: These data indicated an important role played by spinal PTPs in inducing Src-dependent NR2B receptor hyperfunction and suggested that PTPs inhibition might represent an effective strategy for the treatment of inflammatory pain.


Input: Synthesis and biological evaluation of 1, 3, 4-thiadiazole analogues as novel AChE and BuChE inhibitors.

1, 3, 4-thiadiazole


Input: In this paper a series of new 1, 3, 4-thiadiazole derivatives has been designed, synthesized and evaluated as the acetyl-and butyrylcholinesterase inhibitors.

1, 3, 4-thiadiazole

acetyl


Input: Some analogues showed promising inhibition of both enzymes in vitro in the nM range.


Input: Generally, inhibitory potency of compounds was stronger against AChE than BuChE, and one of them was 1154-fold more active inhibiting AChE (IC50 = 0. 17 mu M) than BuChE.


Input: The kinetic studies showed that one of the most active analogues 8 (IC50 = 0. 09 mu M, AChE) acted as a non-competitive AChE inhibitor and was characterized by the high selectivity index (300).


Input: The other derivative (1) exhibited a mixed-type of AChE inhibition.


Input: Docking simulations enabled the detection of key binding interactions of the compounds with AChE and revealed that they occupied mainly the catalytic active site.


Input: The scoring function for the novel compounds was similar or higher than for the reference inhibitor.


Input: Additionally, based on Lipinski and other filters, the drug-likeness of compounds was assessed.


Input: They revealed that the compounds possess properties which can suggest the favourable pharmacokinetics in the human body after oral admission.


Input: cRGD-functionalized polymeric magnetic nanoparticles as a dual-drug delivery system for safe targeted cancer therapy.


Input: In this paper we give a method of integrated treatment for cancer and drug-induced complications in the process of cancer therapy through dual-drug delivery system (DDDS).


Input: Two hydrophilic drugs, doxorubicin (an antitumor drug) and verapamil (an antiangiocardiopathy drug) combined preliminarily with chitosan shell coated on magnetic nanoparticles (MNPs), followed by entrapping into the PLGA nanoparticles.

doxorubicin

verapamil

PLGA


Input: Further modification was conducted by conjugating tumor-targeting ligand, cyclo (Arg-Gly-Asp-D-Phe-Lys) (c (RGDfK)) peptide, onto the end carboxyl groups on the PLGA-NPs.

cyclo (Arg-Gly-Asp-D-Phe-Lys)

carboxyl

PLGA


Input: The size of the resulting cRGD-DOX/VER-MNP-PLGA NPs was approximately 144nm under simulate physiological environment.

DOX

VER

PLGA


Input: Under present experiment condition, the entrapment efficiencies of DOX and VER were approximately 74. 8 and 53. 2wt% for cRGD-DOX/VER-MNP-PLGA NPs.

DOX

VER

DOX

VER

PLGA


Input: This paper contains interesting pilot data such as NIR-triggered drug release, in vivo drug distribution studies and whole-mouse optical imaging.


Input: Histopathological examinations and electrocardiogram comparison demonstrated that the intelligent DDDS could markedly inhibit the growth of tumor and potentially offer an approach for safe cancer therapy.


Input: Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches.


Input: Ion channels are multimeric, transmembrane proteins that selectively mediate ion flux across the plasma membrane in a variety of cells including vascular smooth muscle cells (VSMCs).


Input: The dynamic interplay of Ca (2 +) and K (+) channels on the plasma membrane of VSMCs plays a pivotal role in modulating the vascular tone of small arteries and arterioles.

Ca (2 +)

K (+)


Input: The abnormally-elevated arterial tone observed in hypertension thus points to an aberrant expression and function of Ca (2 +) and K (+) channels in the VSMCs.

Ca (2 +)

K (+)


Input: In this short review, we focus on the three well-studied ion channels in VSMCs, namely the L-type Ca (2 +) (CaV1. 2) channels, the voltage-gated K (+) (KV) channels, and the large-conductance Ca (2 +)-activated K (+) (BK) channels.

Ca (2 +)

K (+)

Ca (2 +)

K (+)


Input: First, we provide a brief overview on the physiological role of vascular CaV1. 2, KV and BK channels in regulating arterial tone.


Input: Second, we discuss the current understanding of the expression changes and regulation of CaV1. 2, KV and BK channels in the vasculature during hypertension.


Input: Third, based on available proof-of-concept studies, we describe the potential therapeutic approaches targeting these vascular ion channels in order to restore blood pressure to normotensive levels.


Input: Developing advanced X-ray scattering methods combined with crystallography and computation.


Input: The extensive use of small angle X-ray scattering (SAXS) over the last few years is rapidly providing new insights into protein interactions, complex formation and conformational states in solution.


Input: This SAXS methodology allows for detailed biophysical quantification of samples of interest.


Input: Initial analyses provide a judgment of sample quality, revealing the potential presence of aggregation, the overall extent of folding or disorder, the radius of gyration, maximum particle dimensions and oligomerization state.


Input: Structural characterizations include ab initio approaches from SAXS data alone, and when combined with previously determined crystal/NMR, atomistic modeling can further enhance structural solutions and assess validity.


Input: This combination can provide definitions of architectures, spatial organizations of protein domains within a complex, including those not determined by crystallography or NMR, as well as defining key conformational states of a protein interaction.


Input: SAXS is not generally constrained by macromolecule size, and the rapid collection of data in a 96-well plate format provides methods to screen sample conditions.


Input: This includes screening for co-factors, substrates, differing protein or nucleotide partners or small molecule inhibitors, to more fully characterize the variations within assembly states and key conformational changes.


Input: Such analyses may be useful for screening constructs and conditions to determine those most likely to promote crystal growth of a complex under study.


Input: Moreover, these high throughput structural determinations can be leveraged to define how polymorphisms affect assembly formations and activities.


Input: This is in addition to potentially providing architectural characterizations of complexes and interactions for systems biology-based research, and distinctions in assemblies and interactions in comparative genomics.


Input: Thus, SAXS combined with crystallography/NMR and computation provides a unique set of tools that should be considered as being part of one' s repertoire of biophysical analyses, when conducting characterizations of protein and other macromolecular interactions.


Input: A review on indole alkaloids isolated from Uncaria rhynchophylla and their pharmacological studies.

indole alkaloids


Input: Uncaria rhynchophylla (Miq.) Jacks, Rubiaceae, is one of the original plants of the important Chinese crude drug, Gou-teng, mainly used for the treatment of convulsion, hypertension, epilepsy, eclampsia, and cerebral diseases.


Input: The pharmacological activities of this plant are related to the presence of active compounds predominantly indole alkaloids.

indole alkaloids


Input: In this article, we have reviewed some reports about the pharmacological activities of the main indole alkaloids isolated from U. rhynchophylla.

indole alkaloids


Input: This review paper will contribute to the studies on the chemistry, safety and quality control of medicinal preparations containing Uncaria species.


Input: In vitro biokinetics of chlorpromazine and the influence of different dose metrics on effect concentrations for cytotoxicity in Balb/c 3T3, Caco-2 and HepaRG cell cultures.

chlorpromazine


Input: The extrapolation of in vitro to in vivo toxicity data is a challenge.


Input: Differences in sensitivity between cell systems may be due to intrinsic properties of the cell but also because of differences in exposure.


Input: In this study, the cytotoxicity and biokinetics of the antipsychotic chlorpromazine (CPZ) were studied in in vitro assays using different cell types and exposure conditions.

chlorpromazine

CPZ


Input: Different dose metrics were assessed to express the sensitivity to CPZ.

CPZ


Input: The biokinetics of CPZ were measured in cell cultures of Balb/c 3T3, Caco-2 and HepaRG cells.

CPZ


Input: Cytotoxicity was measured by Alamar Blue and expressed using different dose metrics, including the nominal, measured total and measured free CPZ medium concentrations.

CPZ


Input: CPZ was taken up by the cells; the highest amounts in the cell compartments were found in the Caco-2 and HepaRG cells.

CPZ


Input: CPZ was highly protein-bound in the Caco-2 cell medium containing 10% fetal bovine serum, resulting in lower bioavailable exposure concentrations.

CPZ


Input: Moreover, also uptake into the cells strongly influenced the concentration in the medium.


Input: The Balb/c 3T3 cells were the most sensitive to the toxic effect of CPZ.

CPZ


Input: The use of different dose metrics influenced the cytotoxicity results found in the three cell types.


Input: The data show that in comparing the sensitivity of the tested cell systems, the freely dissolved concentration is a more appropriate dose metric than total concentration in the medium.


Input: The ranking in sensitivity of the three cell types for CPZ was dependent on the dose metric used.

CPZ


Input: Aspiration toxicology of hydrocarbons and lamp oils studied by in vitro technology.

hydrocarbons


Input: Medical literature regularly reports on accidental poisoning in children after aspiration of combustibles such as lamp oils which usually contain hydrocarbons or rape methyl esters (RMEs).

hydrocarbons

methyl esters


Input: We aimed to analyze the toxic potential of alkanes and different combustible classes in vitro with regard to biologic responses and mechanisms mediating toxicity.

alkanes


Input: Two different in vitro models were used, i. e. (i) a captive bubble surfactometer (CBS) to assess direct influence of combustibles on biophysical properties of surfactant film and (ii) cell cultures (BEAS-2B and R3/1 cells, primary macrophages, re-differentiated epithelia) closely mimicking the inner lung surface.


Input: Biological endpoints included cell viability, cytotoxicity and inflammatory mediator release.


Input: CBS measurements demonstrate that combustibles affect film dynamics, i. e. the surface tension/area characteristics during compression and expansion, in a dose and molecular chain length dependent manner.


Input: Cell culture results confirm the dose dependent toxicity.


Input: Generally, cytotoxicity and cytokine release are higher in short-chained alkanes and hydrocarbon-based combustibles than in long-chained substances, e. g. highest inducible cytotoxicity in BEAS-2B was for hexane 84. 6%, decane 74% and hexadecane 30. 8%.

alkanes

hydrocarbon

hexane

decane

hexadecane


Input: Effects of RME-based combustibles differed between the cell models.


Input: Our results confirm data from animal experiments and give new insights into the mechanisms underlying the adverse health effects observed.


Input: Nonylphenol, an environmental estrogen, affects voltage-gated K + currents and L-type Ca (2) + currents in a non-monotonic manner in GH 3 pituitary cells.

Nonylphenol

estrogen

K +

Ca (2) +


Input: We have investigated the characteristics of voltage-gated K (+) channels and L-type Ca (2 +) channels in GH3 rat pituitary cells and the effects of the xenoestrogen (XEs) nonylphenol (NP) on these ion channel currents.

K (+)

Ca (2 +)

xenoestrogen

nonylphenol


Input: Our results have shown that the lower concentrations (10 (-15)-10 (-14) M) of NP decreased the amplitudes of voltage-gated K (+) currents (IKv) and activated L-type Ca (2 +) currents (ICa-L) by reducing half-activation membrane potentials of activation kinetics curves.

K (+)

Ca (2 +)


Input: However, the higher concentrations (10 (-10)-10 (-9) M) of NP increased the amplitudes of IKv and inhibited ICa-L by reducing the peak values of ICa-L.


Input: Thus, NP affects IKv and ICa-L in an opposite and non-monotonic manner.


Input: Apigenin induces c-Myc-mediated apoptosis in FRO anaplastic thyroid carcinoma cells.

Apigenin


Input: Apigenin promotes apoptosis in cancer cells.

Apigenin


Input: We studied the effect of apigenin on cell survival and c-Myc expression in FRO anaplastic thyroid carcinoma (ATC) cells.

apigenin


Input: Apigenin caused apoptosis via the elevation of c-Myc levels in conjunction with the phosphorylation of p38 and p53.

Apigenin


Input: In the c-Myc siRNA-transfected and apigenin-treated cells, compared with the apigenin-treated control cells, apoptosis and phosphorylation of p38 and p53 were ameliorated.

apigenin

apigenin


Input: In the presence of apigenin, diminution of p38 and p53 did not affect cell survival although apigenin activated the phosphorylation of p38 and p53 via increased c-Myc levels.

apigenin

apigenin


Input: In conclusion, our results indicate that apigenin induces apoptosis mediated via c-Myc with concomitant phosphorylation of p53 and p38 in FRO ATC cells.

apigenin


Input: These findings suggest that augmented c-Myc acts as a core regulator and is necessary for apigenin-induced apoptosis in FRO ATC cells.

apigenin


Input: Tissue distributions of fluoride and its toxicity in the gills of a freshwater teleost, Cyprinus carpio.

fluoride


Input: Fish take up fluoride directly from water and are susceptible to fluoride contamination of their environment.

fluoride


Input: In this study, we examined the tissue distributions of fluoride and its toxicity in the gills of the common carp (Cyprinus carpio) chronically exposed to fluoride.

fluoride

fluoride


Input: Carp were exposed to a range of aqueous fluoride (35-124 mg/L) and sampled at 30, 60 and 90 days.

fluoride


Input: The accumulation of fluoride in the tissues increased with the level and duration of exposure.

fluoride


Input: Steady state was not achieved under the experimental conditions.


Input: The gills accumulated the highest levels of fluoride followed by the liver > brain > kidney > muscle > intestine.

fluoride


Input: A dose-dependent inhibition was observed for the enzyme activities of Na (+)-K (+)-ATPase and Ca (2 +)-ATPase in the gills after the fish were exposed for 90 days.

Na (+)

K (+)

Ca (2 +)


Input: Also, accumulation of fluoride was associated with the inhibition of superoxide dismutase (SOD) activities and a dose-dependent stimulation of malondialdehyde (MDA) levels in the gill tissues, suggesting that fluoride promoted oxidative stress in the fish.

fluoride

superoxide

malondialdehyde

MDA

fluoride


Input: Microscopic examinations revealed injuries to gill tissues and chloride cells, with the severity of injury increasing with exposure concentration.

chloride


Input: These results suggest that chronic exposure to elevated concentrations of fluoride may induce toxicity in the common carp.

fluoride


Input: Developmental abnormalities and changes in cholinesterase activity in sea urchin embryos and larvae from sperm exposed to engineered nanoparticles.


Input: The objective of this study is to examine the toxicity of engineered nanoparticles (NPs) that are dispersed in sea water by using an in vivo model.


Input: Because many products of nanotechnology contain NPs and are commonly used and well-established in the market, the accidental release of NPs into the air and water is quite possible.


Input: Indeed, at the end of their life cycle, some NPs are inevitably released into waste water and can reach marine ecosystem and affect the organisms there.


Input: Although there are few data on the presence of NPs in the marine environment, our awareness of their potential impact on environmental and organismal health is growing.


Input: Shallow-water benthonic organisms such as sea urchins provide planktonic larvae as a trophic base for finfish juveniles and are exposed to water from estuaries and precipitation.


Input: Such organisms can therefore be directly affected by NPs that are dispersed into those media.


Input: We evaluated the effects of exposure to different concentrations of nanosilver, titanium oxide and cobalt NPs on the sperm of the sea urchin Paracentrotus lividus by analyzing the functionality and the morphology and biochemistry of the first developmental stages of the sea urchin.

titanium oxide

cobalt


Input: Sperm were exposed to sea water containing suspensions of NPs ranging from 0. 0001 mg/L to 1 mg/L.


Input: Fertilization ability was not affected, but developmental anomalies were identified in embryos from the gastrula to pluteus stages, including morphological alterations of the skeletal rods.


Input: In addition, the enzymatic activity (cholinesterase, ChE) of the larvae was measured.


Input: Acetylcholinesterase (AChE) and propionylcholinesterase activity (PrChE) was affected in all of the exposed samples.


Input: The results did not vary consistently with the concentration of NP, but controls were significantly different from exposed samples.


Input: Exposure of sea urchin to these NPs may cause neurotoxic damage, and the altered ChE activity may be involved in skeletogenic aberrations.


Input: In conclusion, the sea urchin represents a suitable and sensitive model for testing the toxicity and effects of engineered NPs that are dispersed in sea water.


Input: Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety-like behavior, learning, and memory in mice.

baclofen


Input: gamma-Aminobutyric acid B (GABAB) receptor activation is a potential therapeutic approach for the treatment of drug addiction, pain, anxiety, and depression.

gamma-Aminobutyric acid


Input: However, full agonists of this receptor induce side-effects, such as sedation, muscle relaxation, tolerance, and cognitive disruption.


Input: Positive allosteric modulators (PAMs) of the GABAB receptor may have similar therapeutic effects as agonists with superior side-effect profiles.


Input: The present study behaviorally characterized N-([1R, 2R, 4S]-bicyclo [2. 2. 1] hept-2-yl)-2-methyl-5-(4-[trifluoromethyl] phenyl)-4-pyrimidinamine (BHF177), a GABAB receptor PAM, in mouse models of anxiety-like behavior, learning and memory.

N-([1R, 2R, 4S]-bicyclo [2. 2. 1] hept-2-yl)-2-methyl-5-(4-[trifluoromethyl] phenyl)-4-pyrimidinamine


Input: In addition, the effects of BHF177 were compared with the agonist baclofen.

baclofen


Input: Unlike the anxiolytic chlordiazepoxide, baclofen (0. 5, 1. 5, and 2. 5 mg/kg, intraperitoneally) and BHF177 (10, 20, and 40 mg/kg, orally) had no effect on anxiety-like behavior in the elevated plus maze, light/dark box, or Vogel conflict test.

chlordiazepoxide

baclofen


Input: Baclofen increased punished drinking in the Vogel conflict test, but this effect may be attributable to the analgesic actions of baclofen.

Baclofen

baclofen


Input: At the highest dose tested (2. 5 mg/kg), baclofen-treated mice exhibited sedation-like effects (i. e., reduced locomotor activity) across many of the tests, whereas BHF177-treated mice exhibited no sedation-like effects.

baclofen


Input: BHF177 exhibited pro-convulsion properties only in mice, but not in rats, indicating that this effect may be species-specific.


Input: At doses that were not sedative or pro-convulsant, baclofen and BHF177 had no selective effects on fear memory retrieval in contextual and cued fear conditioning or spatial learning and memory in the Barnes maze.

baclofen


Input: These data suggest that BHF177 has little sedative activity, no anxiolytic-like profile, and minimal impairment of learning and memory in mice.


Input: Consumer and farmer safety evaluation of application of botanical pesticides in black pepper crop protection.


Input: This study presents a consumer and farmer safety evaluation on the use of four botanical pesticides in pepper berry crop protection.


Input: The pesticides evaluated include preparations from clove, tuba root, sweet flag and pyrethrum.


Input: Their safety evaluation was based on their active ingredients being eugenol, rotenone, beta-asarone and pyrethrins, respectively.

eugenol

rotenone

beta-asarone

pyrethrins


Input: Botanical pesticides from Acorus calamus are of possible concern because of the genotoxic and carcinogenic ingredient beta-asarone although estimated margins of exposure (MOE) for consumers indicate a low priority for risk management.

beta-asarone


Input: For the other three botanical pesticides the margin of safety (MOS) between established acute reference doses and/or acceptable daily intake values and intake estimates for the consumer, resulting from their use as a botanical pesticide are not of safety concern, with the exception for levels of rotenone upon use of tuba root extracts on stored berries.

rotenone


Input: Used levels of clove and pyrethrum as botanical pesticides in pepper berry crop production is not of safety concern for consumers or farmers, whereas for use of tuba root and sweet flag some risk factors were defined requiring further evaluation and/or risk management.


Input: It seems prudent to look for alternatives for use of sweet flag extracts containing beta-asarone.

beta-asarone


Input: Effect of dietary treatment with dimethylarsinous acid (DMA (III)) on the urinary bladder epithelium of arsenic (+ 3 oxidation state) methyltransferase (As3mt) knockout and C57BL/6 wild type female mice.

dimethylarsinous acid

DMA (III)

arsenic


Input: Chronic exposure to inorganic arsenic (iAs) is carcinogenic to the human urinary bladder.

arsenic


Input: It produces urothelial cytotoxicity and proliferation in rats and mice.


Input: DMA (V), a major methylated urinary metabolite of iAs, is a rat bladder carcinogen, but without effects on the mouse urothelium.

DMA (V)


Input: DMA (III) was shown to be the likely urinary metabolite of DMA (V) inducing urothelial changes and is also postulated to be one of the active metabolites of iAs.

DMA (III)

DMA (V)


Input: To evaluate potential DMA (III)-induced urothelial effects, it was administered to As3mt knockout mice which cannot methylate arsenicals.

DMA (III)

methylate arsenicals


Input: Female C57BL/6 wild type and As3mt knockout mice (10/group) were administered DMA (III), 77. 3ppm in water for four weeks.

DMA (III)


Input: Urothelial effects were evaluated by light and scanning electron microscopy (EM) and immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation.

bromodeoxyuridine

BrdU


Input: EM findings were rated 1-5, with higher rating indicating greater extent of cytotoxicity visualized.


Input: DMA (III) significantly increased the BrdU labeling index, a ratio of BrdU labeled cells to non-labeled cells, in the treated knockout group compared to control and wild type treated groups.

DMA (III)

BrdU

BrdU


Input: DMA (III) induced simple hyperplasia in more knockout mice (4/10) compared to wild type mice (2/10).

DMA (III)


Input: All treated knockout mice had more and larger intracytoplasmic granules compared to the treated wild type mice.


Input: Changes in EM classification were not significant.


Input: In conclusion, DMA (III) induces urothelial toxicity and regenerative hyperplasia in mice and most likely plays a role in inorganic arsenic-induced urothelial changes.

DMA (III)

arsenic


Input: However, DMA (V) does not induce hyperplasia in mice, suggesting that urinary concentrations of DMA (III) do not reach cytotoxic levels in DMA (V)-treated mice.

DMA (V)

DMA (III)

DMA (V)


Input: Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation.

Arylsulfonamide


Input: Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis.


Input: For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis.


Input: We report herein the synthesis and biological evaluation of a series of arylsulfonamido-based hydroxamates as aggrecanase inhibitors.

arylsulfonamido

hydroxamates


Input: Compound 18 was found to have a nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13 and high selectivity over MMP-1 and MMP-14.


Input: Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity.


Input: Chemically differentiating ascorbate-mediated dissolution of quantum dots in cell culture media.

ascorbate


Input: To investigate the dynamic dissolution of quantum dots (QDs) in cell culture media, in this study we constructed an online automatic analytical system comprising a sequential in-tube solid phase extraction (SPE) device and an inductively coupled plasma (ICP) mass spectrometer.


Input: By means of selectively extracting QDs and cadmium ions (Cd (2 +)) onto the interior surface of the polytetrafluoroethylene (PTFE) tube, this novel SPE device could be used to determine the degree of QD dissolution through a simple adjustment of sample acidity.

cadmium

Cd (2 +)

polytetrafluoroethylene

PTFE


Input: To the best of our knowledge, this study is the first to exploit PTFE tubing as a selective SPE adsorbent for the online chemical differentiation of QDs and Cd (2 +) ions with the goal of monitoring the phenomenon of QD dissolution in complicated biological matrices.

PTFE

Cd (2 +)


Input: We confirmed the analytical reliability of this system through comparison of the measured Cd-to-QD ratios to the expected values.

Cd


Input: When analyzing QDs and Cd (2 +) ions at picomolar levels, a temporal resolution of 8 min was required to load sufficient amounts of the analytes to meet the sensitivity requirements of the ICP mass spectrometer.

Cd (2 +)


Input: To demonstrate the practicability of this developed method, we measured the dynamic variations in the Cd-to-QD705 ratio in the presence of ascorbate as a physiological stimulant to generate reactive oxygen species in cell culture media and trigger the dissolution of QDs; our results suggest that the ascorbate-induced QD dissolution was dependent on the time, treatment concentration, and nature of the biomolecule.

Cd

ascorbate

oxygen

ascorbate


Input: Evaluation of genotoxic effects of five flavour enhancers (glutamates) on the root meristem cells of Allium cepa.

glutamates


Input: The effects of different treatments with flavour enhancers monosodium glutamate, monopotassium glutamate, calcium diglutamate, monoammonium glutamate, and magnesium diglutamate on the cytology, DNA content, and interphase nuclear volume (INV) of A. cepa were investigated.

monosodium glutamate

monopotassium glutamate

calcium diglutamate

monoammonium glutamate

magnesium diglutamate


Input: Three concentrations of these additives-20, 40, and 60 ppm-were applied for 6, 12, and 24 h.


Input: All the concentrations of these chemicals showed an inhibitory effect on cell division in root tips of A. cepa and caused a decrease in mitotic index values.


Input: Additionally, all the treatments changed the frequency of mitotic phases when compared with the control groups.


Input: These compounds increased chromosome abnormalities, among them are micronuclei, c-mitosis, anaphase bridges, stickiness, binucleus, laggards, and breaks.


Input: The nuclear DNA content and INV decreased when compared with control groups.


Input: Preparation of novel monoclonal antibodies against chelated cadmium ions.

cadmium


Input: The detection of cadmium ions using enzyme-linked immunosorbent assays (ELISA) has been reported by several research groups.

cadmium


Input: Because cadmium ions are too small to stimulate the immune system, high molecular weight immunogens of cadmium are constructed using bifunctional chelators.

cadmium

cadmium


Input: At present, the most commonly used bifunctional chelator for the preparation of antigens for heavy metal ions is 1-(4-isothiocyanobenzyl) ethylenediamine N, N, N', N'-tetraacetic acid (ITCBE).

1-(4-isothiocyanobenzyl) ethylenediamine N, N, N', N'-tetraacetic acid

ITCBE


Input: However, the price of ITCBE is high.

ITCBE


Input: So we are interested in a cheaper bifunctional chelator, 1-(4-aminobenzyl) ethylenediamine N, N, N', N'-tetraacetic acid (aminobenzyl-EDTA).

1-(4-aminobenzyl) ethylenediamine N, N, N', N'-tetraacetic acid

aminobenzyl-EDTA


Input: Here, cadmium ions were conjugated to carrier proteins using aminobenzyl-EDTA to make artificial antigens.

cadmium

aminobenzyl-EDTA


Input: Then, several mice were immunized with the antigen.


Input: And monoclonal antibodies (MAbs) against cadmium were produced.

cadmium


Input: Spleen cells of immunized mice were fused with myeloma cells.


Input: The resulting hybridomas were screened using protein conjugates which were covalently bound to metal-free EDTA or cadmium.

EDTA

cadmium


Input: Three hybridoma cell lines (A3, E4 and B5) that produced MAbs with high selectivity and sensitivity were expanded for further study.


Input: Cross-reactivities with other metals were below 1%.


Input: These antibodies were used to construct competitive ELISAs.


Input: The IC50 for A3 was 8. 4 mu g/l.


Input: The detection range and the lowest detection limit using the antibody A3 was 0. 394-64. 39 and 0. 051 mu g/l, respectively.


Input: Spike-recovery studies in tap water showed that the antibody A3 could be used for cadmium detection in drinking water.

cadmium


Input: Decreased zinc availability affects glutathione metabolism in neuronal cells and in the developing brain.

zinc

glutathione


Input: A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells.

zinc

Zn


Input: This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA).

Zn

glutathione

GSH

GSH

dopamine


Input: GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells.

GSH

Zn

Zn


Input: gamma-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD).

gamma-Glutamylcysteine

GSH

Zn


Input: The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls.

Zn


Input: The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD.


Input: Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells.

Zn


Input: Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration.

GSH


Input: Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low.

Zn

GSH


Input: In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels.

Zn

GSH


Input: This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors.

GSH

Zn


Input: Effects of baicalin on airway remodeling in asthmatic mice.

baicalin


Input: Airway remodeling is an important characteristic of asthma, linking inflammation with airway hyperresponsiveness.


Input: Baicalin, a major active component, was isolated from Radix Scutellariae.

Baicalin


Input: Many studies show that baicalin has anti-inflammatory, anti-bacterial, and anti-allergic effects.

baicalin


Input: Here we investigate the influence of baicalin on asthmatic airway remodeling and the mechanism underlining the anti-remodeling effect in vivo. Asthmatic airway remodeling mice model was established by ovalbumin exposure.

baicalin


Input: Seventy female BALB/c mice were randomly assigned to seven experimental groups: blank, ovalbumin, hexadecadrol, control, and baicalin (25 mg/kg, 50 mg/kg, 100 mg/kg) groups.

baicalin


Input: Pulmonary function was measured using a whole-body plethysmograph in conscious and unrestrained mice.


Input: The lung pathology was observed and measured.


Input: The production of cytokines in bronchoalveolar lavage fluid and serum was measured using enzyme-labeled immunosorbent assay kits, and the expression levels of transforming growth factor-beta 1 and vascular endothelial growth factor were detected by immunohistochemistry.


Input: The protein expression levels of transforming growth factor-beta 1, vascular endothelial growth factor, extracellular signal-regulated kinase, and p21ras were measured using Western blot.


Input: The results show that ovalbumin exposure significantly increased the expression of interleukin-13 in BALF and serum, and transforming growth factor-beta 1, vascular endothelial growth factor, extracellular signal-regulated kinase and p21ras expressions in the lungs.


Input: Baicalin attenuated the effects of ovalbumin significantly. It can be concluded that baicalin has significant anti-remodeling effect on ovalbumin-induced asthmatic airway remodeling mice model by decreasing expression of transforming growth factor-beta 1, interleukin-13, and vascular endothelial growth factor and inhibiting the activation of the extracellular signal-regulated kinase pathway.

Baicalin

baicalin


Input: Apelin inhibits diet-induced obesity by enhancing lymphatic and blood vessel integrity.


Input: Angiogenesis is tightly associated with the outgrowth of adipose tissue, leading to obesity, which is a risk factor for type 2 diabetes and hypertension, mainly because expanding adipose tissue requires an increased nutrient supply from blood vessels.


Input: Therefore, induction of vessel abnormality by adipokines has been well studied, whereas how altered vascular function promotes obesity is relatively unexplored.


Input: Also, surviving Prox1 heterozygous mice showed abnormal lymphatic patterning and adult-onset obesity, indicating that accumulation of adipocytes could be closely linked with lymphatic function.


Input: Here we propose a new anti-obesity strategy based on enhancement of lymphatic and blood vessel integrity with apelin.


Input: Apelin-knockout mice given a high-fat diet showed an obese phenotype associated with abnormal lymphatic and blood vessel enlargement.


Input: Fatty acids present in the high-fat diet induced hyperpermeability of endothelial cells, causing adipocyte differentiation, whereas apelin promoted vascular stabilization.

Fatty acids


Input: Moreover, treatment of high-fat-diet-fed apelin-knockout mice with a selective cyclooxygenase-2 inhibitor, celecoxib, improved vascular function, and also attenuated obesity.

celecoxib


Input: Finally, apelin transgenic mice showed decreased subcutaneous adipose tissue owing to inhibition of high-fat-diet-induced hyperpermeability of vessels.


Input: These results indicate that apelin inhibits high-fat-diet-induced obesity by enhancing vessel integrity.


Input: Apelin could serve as a therapeutic target for treating obesity and related diseases.


Input: Absorption, elimination, and metabolism of CS-1036, a novel alpha-amylase inhibitor in rats and monkeys, and the relationship between gastrointestinal distribution and suppression of glucose absorption.

glucose


Input: The absorption, metabolism, and excretion of (2R, 3R, 4R)-4-hydroxy-2-(hydroxymethyl) pyrrolidin-3-yl 4-O-(6-deoxy-beta-d-glucopyranosyl)-alpha-d-glucopyranoside (CS-1036), a novel and potent pancreatic and salivary alpha-amylase inhibitor, were evaluated in F344/DuCrlCrlj rats and cynomolgus monkeys.

(2R, 3R, 4R)-4-hydroxy-2-(hydroxymethyl) pyrrolidin-3-yl 4-O-(6-deoxy-beta-d-glucopyranosyl)-alpha-d-glucopyranoside


Input: The total body clearance and volume of distribution of CS-1036 were low (2. 67-3. 44 ml/min/kg and 0. 218-0. 237 l/kg for rats and 2. 25-2. 84 ml/min/kg and 0. 217-0. 271 l/kg for monkeys).


Input: After intravenous administration of [(14) C] CS-1036 to rats and monkeys, radioactivity was mainly excreted into urine (77. 2% for rats and 81. 1% for monkeys).

[(14) C] CS-1036


Input: After oral administration, most of the radioactivity was recovered from feces (80. 28% for rats and 88. 13% for monkeys) with a low oral bioavailability (1. 73-2. 44% for rats and 0. 983-1. 20% for monkeys).


Input: In rats, intestinal secretion is suggested to be involved in the fecal excretion as a minor component because fecal excretion after intravenous administration was observed (15. 66%) and biliary excretion was almost negligible.


Input: Although intestinal flora was involved in CS-1036 metabolism, CS-1036 was the main component in feces (70. 3% for rats and 48. 7% for monkeys) and in the intestinal contents (33-68% for rats up to 2 hours after the dose) after oral administration.


Input: In Zucker diabetic fatty rats, CS-1036 showed a suppressive effect on plasma glucose elevation after starch loading with a 50% effective dose at 0. 015 mg/kg.

glucose


Input: In summary, CS-1036 showed optimal pharmacokinetic profiles: low oral absorption and favorable stability in gastrointestinal lumen, resulting in suppression of postprandial hyperglycemia by alpha-amylase inhibition.


Input: Identification and characterization of novel alternative splice variants of human constitutive androstane receptor in liver samples of Koreans and Caucasians.

androstane


Input: Human constitutive androstane receptor (hCAR, NR1I3) is a member of the orphan nuclear receptor family and regulates the transcription of many drug-metabolizing enzymes and drug transporters.

androstane


Input: Previous studies have shown that the hCAR gene produces a number of different kinds of mRNA splicing variants (SVs) in non-Asian ethnicities.


Input: In the present study, we identified 18 hCAR SVs (SV1-SV18), including four novel SVs in Korean human livers.


Input: Among the four novel SVs, SV2 showed enhanced transactivation activity when cotransfected with CYP2B6 reporter gene, whereas other SVs were nonfunctional.


Input: When profiles of major hCAR SVs were compared among 30 livers from Korean patients and 20 livers from Caucasian patients, the relative composition of each SV showed interethnic variation as well as interindividual variation.


Input: The most predominant form of hCAR SV was not wild type, but either SV4 or SV7.


Input: The summed relative amounts of SV4 and SV7 ranged from 34. 5 to 57. 6% in the 30 Korean livers and from 47. 2 to 82. 6% in the 20 Caucasian livers, suggesting large interindividual variation.


Input: The mean relative amount of nonfunctional SV9 was significantly higher in Koreans (29. 8%) than in Caucasians (12. 8%).


Input: The mean relative amount of novel SV2 was 9. 7% in Korean livers and 3. 5% in Caucasian livers.


Input: Expression profiling of hCAR proteins in human livers also supported large interindividual variation in the expressional ratio of wild-type and SVs.


Input: Our results describe for the first time the direct comparison of hCAR SV profiles between Koreans and Caucasians.


Input: The functional relevance of these interindividual and interethnic variations of hCAR mRNA expression needs to be further characterized.


Input: Electrochemical Removal Of Selenate From Aqueous Solutions.

Selenate


Input: Removal of selenate from solution is investigated in batch electrochemical systems using reactive iron anodes and copper plate cathode in a bicarbonate medium.

selenate

iron

bicarbonate


Input: Iron anodes produce ferrous hydroxide, which is a major factor in the removal of selenate from solution.

Iron

ferrous hydroxide

selenate


Input: Iron anodes also generate a significant decrease in the oxidation-reduction potential (ORP) of the solution because it prevents generation of oxygen gas at the anode by electrolysis.

Iron

oxygen


Input: The removal rates varied from 45. 1 to 97. 4%, depending on current density and selenate concentration.

selenate


Input: The transformation of selenate by the process is modeled based on a heterogeneous reaction coupled with electrochemical generation of ferrous and hydroxide.

selenate

ferrous

hydroxide


Input: The rates are optimized at lower initial concentrations, higher electrical currents, and the presence of anions.


Input: Presence of dissolved oxygen does not cause any significant effects the removal of selenate.

oxygen

selenate


Input: Introduction of Target Cliffs as a Concept To Identify and Describe Complex Molecular Selectivity Patterns.


Input: The study of target specificity or selectivity of small molecules is an important task in drug design.


Input: In an ideal situation, a compound would exclusively interact with an individual target and hence be target specific.


Input: However, such exclusive binding events are likely to be rare, as increasing evidence suggests.


Input: Because many compounds are active against more than one target, apparent selectivity often results from potency differences, i. e., a compound that is highly potent against a given target and weakly potent against one or more others displays target selectivity.


Input: In a simple case, a compound might have known activity against a pair of targets and be selective for one over the other.


Input: Then, selectivity is straightforward to rationalize.


Input: However, there are many more complex selectivity relationships associated with multi-target activities of compounds that are difficult to analyze and compare in a consistent manner.


Input: For this purpose, we introduce herein target cliffs as a concept to describe complex selectivity patterns.


Input: A target cliff is defined as a pair of targets against which at least one compound displays a large difference in potency.


Input: As such, target cliffs are distinct from activity cliffs.


Input: However, qualifying target pairs (target cliffs) and compound pairs (activity cliffs) can be systematically extracted from the same data structure termed target-compound matrices.


Input: Furthermore, these two types of cliffs can be compared to identify and prioritize compounds that are selective and reveal structure-activity relationship (SAR) information.


Input: Impairment of regulatory T cell function in autoimmune thyroid disease.


Input: Background: Autoimmune thyroid disease (AITD) pathogenesis may result from a loss of immune tolerance to thyroid antigens.


Input: Regulatory T cells (Tregs) control immune responses, prevent excessive inflammation, and may be dysfunctional in AITD.


Input: We investigated the role of Tregs in Hashimoto' s thyroiditis (HT) and Graves' disease (GD).


Input: Our goal was to identify differences in CD4 + CD25hi Treg function or number in patients with GD and HT, compared to healthy controls (HC).


Input: Methods: Treg number was assessed by flow cytometric analysis in samples from twenty AITD patients (7 GD, 13 HT), 9 HC, and 7 individuals with Down syndrome (DS), a genetic disorder associated with multiple autoimmune disorders including AITD.


Input: Treg function was assessed by the inhibition of proliferation (radioactive thymidine incorporation into DNA) of blood-derived T effector cells (Teff) by Tregs in a co-culture.


Input: Various methods of stimulation were contrasted.


Input: Cytokine levels were determined in conditioned media from the co-cultures.


Input: Results: No differences were found in the frequency of Tregs as a percentage of CD4 + cells between AITD and HC.


Input: AITD Tregs were less capable of inhibiting the proliferation of Teff cells when compared to HC, however, the impairment was dependent on the type of stimulation used.


Input: DS patients without AITD exhibited normal Treg function.


Input: We observed few differences in cytokine production between HC and AITD patients.


Input: Conclusions: Tregs from AITD patients are partly dysfunctional, possibly explaining their autoimmunity.


Input: Future work will elucidate the diagnostic potential and pathophysiology of Tregs in AITD.


Input: Petroacetylene, a new polyacetylene from the marine sponge Petrosia solida that inhibits blastulation of starfish embryos.

Petroacetylene

polyacetylene


Input: A new C (30) linear polyacetylene compound designated petroacetylene (1) has been isolated from the marine sponge Petrosia solida Hoshino 1981, collected off the coast of Amami-Oshima, Kagoshima Prefecture, Japan.

polyacetylene

petroacetylene


Input: The structure was elucidated on the basis of spectroscopic data and chemical means.


Input: Petroacetylene (1) inhibited blastulation of starfish embryos at a concentration of 3. 1 mu g mL (-1) or greater.

Petroacetylene


Input: Synthesis, microwave spectrum, and conformational properties of 2-fluoroethyl azide (FCH2CH2N3).

2-fluoroethyl azide


Input: A novel synthesis producing neat 2-fluoroethyl azide (FCH2CH2N3) is described.

2-fluoroethyl azide


Input: A conformational analysis using microwave spectroscopy augmented by quantum chemical calculations at the CCSD (T)/cc-pVTZ, B3LYP/aug-cc-pVTZ, and B3LYP/cc-pVTZ levels of theory has been performed for this compound.


Input: The spectra of the ground vibrational state and two vibrationally excited states of one rotameric form were assigned.


Input: A large number of transitions was assigned, and very accurate values were obtained for the rotational and quartic centrifugal distortion constants.


Input: The identified conformer has synclinal orientations for the F-C-C-N and C-C-N-N chains of atoms bringing the fluorine atom and the azido group into close proximity.

F-C-C-N

C-C-N-N

fluorine

azido


Input: It is concluded from consideration of absolute intensities that this conformer is indeed the preferred form of the molecule in accord with the theoretical calculations.


Input: The experimental and CCSD (T) rotational constants are in very good agreement, whereas much larger discrepancies were seen for the experimental and B3LYP quartic centrifugal distortion constants.


Input: Self-aggregation properties of ionic liquid 1, 3-didecyl-2-methylimidazolium chloride in aqueous solution: from spheres to cylinders to bilayers.

1, 3-didecyl-2-methylimidazolium chloride


Input: The self-aggregation behavior of the double-chained ionic liquid (IL) 1, 3-didecyl-2-methylimidazolium chloride ([C10C10mim] Cl) in aqueous solution has been investigated with a number of different experimental techniques.

1, 3-didecyl-2-methylimidazolium chloride

[C10C10mim] Cl


Input: Two cmc values (cmc1 and cmc2) are obtained from conductivity measurements.


Input: The fraction of neutralized charge on the micellar surface suggests that cmc1 corresponds to the formation of spherical micelles and cmc2 to the transition from spherical to cylindrical micelles.


Input: Data obtained from fluorescence spectroscopy (using pyrene and Nile red as chemical probes), fluorescence anisotropy (using rhodamine B as probe), and chemical shift (1) H NMR (in D2O) provide a picture that is also consistent with a sphere-to-cylinder transition.

pyrene

Nile red

rhodamine B

(1) H


Input: This structural change is further confirmed by diffusion-ordered NMR spectroscopy (DOSY), from the self-diffusion coefficients for surfactant unimer and aggregates.


Input: Furthermore, a third evolution from cylindrical micelles to bilayer aggregates is proposed from the analysis of diffusion coefficients at high surfactant concentration ([IL] > 0. 2 M).


Input: Phase scanning experiments performed with polarized light microscopy clearly demonstrate the presence of a lamellar liquid crystalline phase at very high IL concentration, thus confirming the coexistence of bilayer structures with elongated micelles, found at lower concentration.


Input: Additionally, [C10C10mim] Cl micelles are proposed as novel reaction media, as evidenced by the solvolysis reaction of 4-methoxybenzenesulfonyl chloride (MBSC).

[C10C10mim] Cl

4-methoxybenzenesulfonyl chloride

MBSC


Input: Spiropyran polymeric microcapillary coatings for photodetection of solvent polarity.

Spiropyran


Input: Fused silica microcapillaries were functionalized with spiropyran-polymer brushes using surface-initiated ring-opening metathesis polymerization.

silica

spiropyran


Input: Based on the inherited spiropyran properties, the functionalized capillaries were successfully used to photoidentify solvents of different polarity when passing through the microcapillary in continuous flow.

spiropyran


Input: In the present study, six different solvents (toluene, tetrahydrofuran, acetone, acetonitrile, ethanol, and methanol) can be easily detected while passing through the modified microcapillary by simply irradiating a portion of it with UV light (365 nm).

toluene

tetrahydrofuran

acetone

acetonitrile

ethanol

methanol


Input: This converts the closed spiropyran moiety to the open merocyanine form, and as a consequence, the microcapillary gains a distinct color and spectral response depending on the polarity of the solvent.

spiropyran

merocyanine


Input: The rate of ring-opening of the spiropyran-polymer brushes coatings has been determined in situ in the presence of different solvents, showing that the coloration rate is also influenced by the solvent polarity and therefore can be used as an additional parameter for solvent sensing.

spiropyran


Input: (Quasi-) 2D aggregation of polystyrene-b-dextran at the air-water interface.

polystyrene


Input: Polystyrene-b-dextran (PS-b-Dextran) copolymers can be used to prepare dextran brushes at solid surfaces, applying Langmuir-Blodgett deposition.

Polystyrene


Input: When recording the interfacial pressure versus area isotherms of a PS-b-Dextran monolayer, time-dependent hysteresis was observed upon compression and expansion.


Input: We argue that this is due to (quasi-) 2D aggregation of the copolymer at the air-water surface, with three contributions.


Input: First, at large area per molecule, a zero surface pressure is measured; we ascribe this to self-assembly of block copolymers into surface micelles.


Input: At intermediate area we identify a second regime (" desorption regime ") where aggregation into large patches occurs due to van der Waals attraction between PS blocks.


Input: At high surface pressure (" brush regime ") we observe hysteretic behavior attributed to H-bonding between dextran chains.

H


Input: When compared to hysteresis of other amphiphilic diblock copolymers (also containing PS, e. g., polystyrene-b-poly (ethylene oxide)) a general criterion can be formulated concerning the extent of hysteresis: when the hydrophobic (PS) block is of equal size as (or bigger than) the hydrophilic block, the hysteresis is maximal.

polystyrene

poly (ethylene oxide)


Input: The (quasi-) 2D aggregation of PS-b-Dextran has significant implications for the preparation of dextran brushes at solid surfaces using Langmuir-Blodgett deposition.


Input: For each grafting density the monolayer needs to relax, up to several hours, prior to transfer.


Input: High-yield dispersions of large-diameter semiconducting single-walled carbon nanotubes with tunable narrow chirality distributions.

carbon


Input: Here, we report a thorough study on the ability of fluorene-based semiconducting polymers to disperse large-diameter (average diameter < d > =~ 1. 3 nm) laser vaporization (LV) single-walled carbon nanotubes (SWCNTs).

fluorene

carbon


Input: We demonstrate the ability to select purely semiconducting species using poly [(9, 9-dioctylfluorenyl-2, 7-diyl)-alt-co-(6, 6'-{2, 2'-bipyridine})] (PFO-BPy) and poly [(9, 9-dihexylfluorenyl-2, 7-diyl)-co-(9, 10-anthracene)] (PFH-A), producing samples with narrow and bright excitonic emission relative to comparable aqueous dispersions.

poly [(9, 9-dioctylfluorenyl-2, 7-diyl)-alt-co-(6, 6'-{2, 2'-bipyridine})]

PFO-BPy

poly [(9, 9-dihexylfluorenyl-2, 7-diyl)-co-(9, 10-anthracene)]

PFH-A


Input: Rapid processing and high yields offer the ability to easily incorporate these semiconducting SWCNTs into commercially scalable applications, as demonstrated by large-area thin films prepared by ultrasonic spraying.


Input: By modifying the growth temperature of the LV synthesis, we demonstrate the ability to tune the range of diameters and chiralities within dispersions by exerting synthetic control over the composition of the starting material.


Input: This synthetic control allows us to show that PFH-A preferentially disperses near-armchair semiconducting SWCNTs over a large range of diameters (0. 8 nm < d < 1. 4 nm) and induces unique solvatochromic shifts for the excitonic transitions of nanotubes with particular chiral indices.

PFH-A


Input: Use of the Combination Index to determine interactions between plant-derived phenolic acids on hepatotoxicity endpoints in human and rat hepatoma cells.

phenolic acids


Input: The beneficial or adverse effects of isolated phytochemicals are not always concordant with effects of the botanical dietary supplements from which they were derived.


Input: This disparity could be due to interactions between the various phytochemicals present in the whole plant.


Input: The phenolic acids, rosmarinic acid (RA), caffeic acid (CA) and ferulic acid (FA) are widely present in foods and dietary supplements, and they are assumed to exert various beneficial biological effects.

phenolic acids

rosmarinic acid

caffeic acid

ferulic acid


Input: However, there is little data on the potential biological interactions of these three phenolic acids which commonly occur together and are linked metabolically.

phenolic acids


Input: In the present study, liver toxicity of the three phenolic acids was assessed on the three compounds singly and in various binary and one ternary combinations.

phenolic acids


Input: A series of in vitro endpoints relevant to liver toxicity were evaluated in both a human (HepG2/C3A) and rat (MH1C1) hepatocyte cell line.


Input: The Combination Index (CI) was calculated for each endpoint from both the concentration responses of the single compounds and the responses of the various binary and ternary mixtures.


Input: Both synergistic and antagonistic interactions were observed for some endpoints and some combinations of test agents.


Input: Interactions were most prevalent in measures of oxidative stress and cytochrome P450 activities in both cell types.


Input: There was only a 53% concordance between the rat and human cells which may be suggestive of species differences.


Input: The data suggest an approach for better characterizing the beneficial or adverse effects of complex botanical products through evaluation of interactions between individual phytochemical components.


Input: Epigenetics and pesticides.


Input: Pesticides, a wide class of environmental contaminants, may cause both acute and delayed health effects in exposed subjects.


Input: These effects can range from simple irritation of the skin and eyes to more severe effects such as affecting the nervous system, the reproductive system and cancer.


Input: The molecular mechanisms underlying such effects are still under investigation.


Input: Epigenetics is the study of heritable changes in gene expression that occur without a change in the DNA sequence.


Input: Several epigenetic mechanisms, including DNA methylation, histone modifications and microRNA expression, can be triggered by environmental factors.


Input: We review current evidences indicating that epigenetic modifications may mediate pesticide effects on human health.


Input: In vitro, animal, and human investigations have identified several classes of pesticides that modify epigenetic marks, including endocrine disruptors, persistent organic pollutants, arsenic, several herbicides and insecticides.

arsenic


Input: Several investigations have examined the effects of environmental exposures and epigenetic markers, and identified toxicants that modify epigenetic states.


Input: These modifications are similar to the ones found in pathological tissue samples.


Input: In spite of the current limitations, available evidence supports the concept that epigenetics holds substantial potential for furthering our understanding of the molecular mechanisms of pesticides health effects, as well as for predicting health-related risks due to conditions of environmental exposure and individual susceptibility.


Input: Selective brain region activation by histamine H3 receptor antagonist/inverse agonist ABT-239 enhances acetylcholine and histamine release and increases c-Fos expression.

histamine

acetylcholine

histamine


Input: Histamine axons originate solely from the tuberomamillary nucleus (TMN) to innervate almost all brain regions.

Histamine


Input: This feature is consistent with a function for histamine over a host of physiological processes, including regulation of appetite, body temperature, cognitive processes, pain perception and sleep-wake cycle.

histamine


Input: An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulations.


Input: Here we report that systemic administration of the non-imidazole histamine H3 receptor antagonist 4-(2-{2-[(2R)-2-methylpyrrolidinyl] ethyl}-benzofuran-5-yl) benzonitrile (ABT-239, 3 mg/kg) increased c-Fos expression dose-dependently in rat cortex and nucleus basalis magnocellularis (NBM) but not in the nucleus accumbens (NAcc) nor striatum, and augmented acetylcholine and histamine release from rat prefrontal cortex.

histamine

4-(2-{2-[(2R)-2-methylpyrrolidinyl] ethyl}-benzofuran-5-yl) benzonitrile

acetylcholine

histamine


Input: To further understand functional histaminergic pathways in the brain, dual-probe microdialysis was used to pharmacologically block H3 receptors in the TMN.


Input: Perfusion of the TMN with ABT-239 (10 mu M) increased histamine release from the TMN, NBM, and cortex, but not from the striatum or NAcc.

histamine


Input: When administered locally, ABT-239 increased histamine release from the NBM, but not from the NAcc.

histamine


Input: Systemic as well as intra-TMN administration of ABT-239 increased c-Fos expression in the NBM, and cortex, but not in the striatum or NAcc.


Input: Thus, as defined by their sensitivity to ABT-239, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner.


Input: This implies independent functions of subsets of histamine neurons according to their terminal projections, with relevant consequences for the development of specific compounds that affect only subsets of histamine neurones, thus increasing target specificity.

histamine

histamine


Input: Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis.


Input: PRM-151, recombinant human Pentraxin-2 (PTX-2) also referred to as serum amyloid P (SAP), is under development for treatment of fibrosis.


Input: A First-in-Human (FIH) trial was performed to assess the safety, tolerability, and pharmacokinetics of single ascending intravenous doses of PRM-151 administered to healthy subjects, using a randomized, blinded, placebo controlled study design.


Input: Each cohort included three healthy subjects (PRM-151: placebo; 2: 1).


Input: SAP levels were assessed using a validated ELISA method, non-discriminating between endogenous and exogenous SAP.


Input: At a dose level of 10 mg/kg, at which a physiologic plasma level of SAP was reached, two additional healthy volunteers and three pulmonary fibrosis (PF) patients were enrolled enabling comparison of the pharmacokinetic SAP profile between healthy volunteers and PF patients.


Input: In addition, the percentage of fibrocytes (CD45 +/Procollagen-1 + cells) in whole blood samples was assessed to demonstrate biological activity of PRM-151 in the target population.


Input: PRM-151 administration was generally well tolerated.


Input: In two pulmonary fibrosis patients non-specific, transient skin reactions (urticaria and erythema) were observed.


Input: PRM-151 administration resulted in a 6-to 13-fold increase in mean baseline plasma SAP levels at dose levels of 5, 10, and 20 mg/kg.


Input: The estimated t1/2 of PRM-151 in healthy volunteers was 30 h.


Input: Pharmacokinetic profiles were comparable between healthy volunteers and PF patients.


Input: PRM-151 administration resulted in a 30-50% decrease in fibrocyte numbers 24 h post-dose.


Input: This suggests that administration of PRM-151 may be associated with a reduction of fibrocytes in PF patients, a population for which current pharmacotherapeutic options are limited.


Input: The pharmacological action of PRM-151 should be confirmed in future research.


Input: Autophagy takes place in mutated p53 neuroblastoma cells in response to hypoxia mimetic CoCl (2).

CoCl (2)


Input: Solid tumors like neuroblastoma exhibit hypoxic areas, which can lead both to cell death or aggressiveness increase.


Input: Hypoxia is a known stress able to induce stabilization of p53, implicated in cell fate regulation.


Input: Recently, p53 appeared to be involved in autophagy in an opposite manner, depending on its location: when nuclear, it enhanced transcription of pro-autophagic genes whereas when cytoplasmic, it inhibited the autophagic process.


Input: Today, we used cobalt chloride, a hypoxia mimetic that inhibits proteasomal HIF-1 degradation and generates reactive oxygen species (ROS).

cobalt chloride

oxygen


Input: We focused on CoCl2-induced cell death in a DNA-binding mutated p53 neuroblastoma cell line (SKNBE (2c)).


Input: An autophagic signaling was evidenced by an increase of Beclin-1, ATG 5-12, and LC3-II expression whereas the p53 (mut) presence decreased with CoCl2 time exposure.


Input: Activation of the pathway seemed to protect cells from ROS production and, at least in part, from death.


Input: The autophagic inhibitors activated the apoptotic signaling and the death was enhanced.


Input: To delineate the eventual implication of the p53 (mut) in the autophagic process in response to hypoxia, we monitored signaling in p53 (WT) SHSY5Y cells, after either shRNA-p53 down-regulation or transcriptional activity inhibition by pifithrin alpha.


Input: We did not detect autophagy neither with p53 (wt) nor when p53 was lacking whereas such a response was effective with a mutated or inactivated p53.


Input: To conclude, mutated p53 in neuroblastoma cells could be linked with the switch between apoptotic response and cell death by autophagy in response to hypoxic mimetic stress.


Input: Early steps of double-strand break repair in Bacillus subtilis.


Input: All organisms rely on integrated networks to repair DNA double-strand breaks (DSBs) in order to preserve the integrity of the genetic information, to re-establish replication, and to ensure proper chromosomal segregation.


Input: Genetic, cytological, biochemical and structural approaches have been used to analyze how Bacillus subtilis senses DNA damage and responds to DSBs.


Input: RecN, which is among the first responders to DNA DSBs, promotes the ordered recruitment of repair proteins to the site of a lesion.


Input: Cells have evolved different mechanisms for efficient end processing to create a 3'-tailed duplex DNA, the substrate for RecA binding, in the repair of one-and two-ended DSBs.


Input: Strand continuity is re-established via homologous recombination (HR), utilizing an intact homologous DNA molecule as a template.


Input: In the absence of transient diploidy or of HR, however, two-ended DSBs can be directly re-ligated via error-prone non-homologous end-joining.


Input: Here we review recent findings that shed light on the early stages of DSB repair in Firmicutes.


Input: Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1.

phencyclidine


Input: RATIONALE: Perinatal phencyclidine (PCP) administration in rat blocks the N-methyl D-aspartate receptor (NMDAR) and causes symptoms reminiscent of schizophrenia in human.

phencyclidine

PCP

N-methyl D-aspartate


Input: A growing body of evidence suggests that alterations in gamma-aminobutyric acid (GABA) interneuron neurotransmission may be associated with schizophrenia.

gamma-aminobutyric acid

GABA


Input: Neuregulin-1 (NRG-1) is a trophic factor important for neurodevelopment, synaptic plasticity, and wiring of GABA circuits.

GABA


Input: OBJECTIVES: The aim of this study was to determine the long-term effects of perinatal PCP administration on the projection and local circuit neurons and NRG-1 expression in the cortex and hippocampus.

PCP


Input: METHODS: Rats were treated on postnatal day 2 (P2), P6, P9, and P12 with either PCP (10 mg/kg) or saline.

PCP


Input: Morphological studies and determination of NRG-1 expression were performed at P70.


Input: RESULTS: We demonstrate reduced densities of principal neurons in the CA3 and dentate gyrus (DG) subregions of the hippocampus and a reduction of major interneuronal populations in all cortical and hippocampal regions studied in PCP-treated rats compared with controls.

PCP


Input: For the first time, we show the reduced density of reelin-and somatostatin-positive cells in the cortex and hippocampus of animals perinatally treated with PCP.

PCP


Input: Furthermore, an increase in the numbers of perisomatic inhibitory terminals around the principal cells was observed in the motor cortex and DG.


Input: We also show that perinatal PCP administration leads to an increased NRG-1 expression in the cortex and hippocampus.

PCP


Input: CONCLUSION: Taken together, our findings demonstrate that perinatal PCP administration increases NRG-1 expression and reduces the number of projecting and local circuit neurons, revealing complex consequences of NMDAR blockade.

PCP


Input: Effects of supplementary selenium source on the blood parameters in beef cows and their nursing calves.

selenium


Input: Over 2 years, 32 beef cows nursing calves in southwest Arkansas were randomly selected from a herd of 120 that were managed in six groups and were assigned to six 5. 1-ha bermudagrass (Cynodon dactylon [L.] Pers.) pastures.


Input: Treatments were assigned to pastures (two pastures/treatment) and cows had ad libitum access to one of three free-choice minerals: (1) no supplemental selenium (Se), (2) 26 mg of supplemental Se from sodium selenite per kilogram, and (3) 26 mg of supplemental Se from seleno-yeast per kilogram (designed mineral intake = 113 g/cow daily).

selenium

Se

Se

sodium selenite

Se

seleno


Input: Data were analyzed using a mixed model; year and pasture were the random effects and treatment was the fixed effect.


Input: At the beginning of the calving and breeding seasons, cows supplemented with Se had greater (P < 0. 01) whole blood Se concentration (WBSe) and glutathione peroxidase activities (GSH-Px) than cows receiving no supplemental Se; cows fed seleno-yeast had greater (P <= 0. 05) WBSe than cows fed sodium selenite, but GSH-Px did not differ (P >= 0. 25) between the two sources.

Se

Se

glutathione

GSH

Se

seleno

sodium selenite

GSH


Input: At birth and near peak lactation (late May), calves from cows supplemented with Se had greater (P < 0. 01) WBSe than calves from cows fed no Se and calves from cows fed seleno-yeast had greater (P <= 0. 01) WBSe and GSH-Px than calves from cows fed sodium selenite.

Se

seleno

GSH

sodium selenite


Input: Thyroxine (T4), triiodothyronine (T3), and the T4: T3 ratio in calves did not differ among treatments (P >= 0. 35).

Thyroxine

triiodothyronine


Input: At birth, insulin-like growth factor 1 (IGF-1) was greater (P = 0. 02) in calves nursing cows with no supplemental Se than in ones with supplemental Se; in calves nursing cows with supplemental sodium selenite, IGF-1 did not differ (P = 0. 96) from ones offered supplemental seleno-yeast.

Se

Se

sodium selenite

seleno


Input: Selenium supplementation of gestating beef cows benefited cows and calves by increasing WBSe and GSH-Px.

Selenium

GSH


Input: The use of seleno-yeast as a Se supplement compared to sodium selenite increased the WBSe of both cows and their calves without affecting the T4 to T3 conversion or IGF-1 concentrations.

seleno

Se

sodium selenite


Input: Mechanisms of Pharmacokinetic Enhancement Between Ritonavir and Saquinavir; Micro/Small Dosing Tests Using Midazolam (CYP3A4), Fexofenadine (p-Glycoprotein), and Pravastatin (OATP1B1) as Probe Drugs.

Ritonavir

Saquinavir

Midazolam

Fexofenadine

Pravastatin


Input: We investigated the mechanisms of ritonavir-mediated enhancement effect on the pharmacokinetics of saquinavir using in vivo probes for CYP3A4 (midazolam), p-glycoprotein (fexofenadine), and OATP1B1 (pravastatin) following oral micro/small dosing.

ritonavir

saquinavir

midazolam

fexofenadine

pravastatin


Input: A cocktail of the drugs (2 mg of saquinavir, 100 micro g of each probe) was administered to eight healthy volunteers (phase 1), and then coadministered with 20 mg (phase 2) and 100 mg (phase 3) of ritonavir.

saquinavir

ritonavir


Input: Plasma concentrations of the drugs were measured by validated LC-MS/MS methods.


Input: The mean plasma AUC (0-24) (pg hour/mL) of saquinavir at phases 1, 2, and 3 was 101, 2 540, and 23 900 (P <. 01), respectively.

saquinavir


Input: The relative area under the plasma concentration-time curve (AUC) (0-24) ratios of midazolam and fexofenadine at phases 1, 2, and 3 were 1: 5. 9: 14. 7 (P <. 01), and 1: 1. 4: 2. 2 (P <. 01-. 05), respectively.

midazolam

fexofenadine


Input: In contrast, there was no difference in the pharmacokinetics of pravastatin.

pravastatin


Input: Inhibition of intestinal and hepatic CYP3A-mediated metabolism, and intestinal p-glycoprotein-mediated efflux of saquinavir, but not OATP1B1, is involved in the enhancement mechanism.

saquinavir


Input: Micro/small dosing is useful for examining the mechanism of drug interactions without safety concern.


Input: Pharmacogenetics of Allopurinol-Making an Old Drug Safer.

Allopurinol


Input: Allopurinol is a drug that has been used for decades to lower serum urate levels in patients with gout or chronic renal failure and in cancer patients undergoing chemotherapy at risk of tumor lysis syndrome.

Allopurinol


Input: Patients may develop cutaneous hypersensitivity reactions, ranging from mild rashes to potentially fatal severe cutaneous adverse reactions (SCARs) namely drug hypersensitivity syndrome, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).


Input: Recent studies have demonstrated the association between human leukocyte antigen (HLA) B * 58: 01 allele and allopurinol-induced SCARs, which might explain ethnic differences in their incidences.

allopurinol


Input: Genotyping is now required before starting abacavir and carbamazepine so as to identify individuals susceptible to SJS.

abacavir

carbamazepine


Input: However, no genetic screening is advocated before commencement of allopurinol.

allopurinol


Input: The lack of availability of a rapid and inexpensive screening test for the HLA-B * 58: 01 allele is one of the obstacles to such screening.


Input: Development of a test that is quick, accurate, and cost-effective is warranted.


Input: Graded doping for enhanced colloidal quantum dot photovoltaics.


Input: A novel approach to improving all-inorganic colloidal quantum dot (CQD) homojunction solar cells by engineering the doping spatial profile to produce a doping gradient within the n-type absorber is presented.


Input: The doping gradient greatly improves carrier collection and enhances the voltages attainable by the device, leading to a 1 power point power conversion efficiency (PCE) improvement over previous inorganic CQD solar cells.


Input: Using conditional inference trees and random forests to predict the bioaccumulation potential of organic chemicals.


Input: The present study presents a data-oriented, tiered approach to assessing the bioaccumulation potential of chemicals according to the European chemicals regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).


Input: The authors compiled data for eight physicochemical descriptors (partition coefficients, degradation half-lives, polarity, and so forth) for a set of 713 organic chemicals for which experimental values of the bioconcentration factor (BCF) are available.


Input: The authors employed supervised machine learning methods (conditional inference trees and random forests) to derive relationships between the physicochemical descriptors and the BCF values.


Input: In a first tier, the authors established rules for classifying a chemical as bioaccumulative (B) or nonbioaccumulative (non-B).


Input: In a second tier, the authors developed a new tool for estimating numerical BCF values.


Input: For both cases the optimal set of relevant descriptors was determined; these are biotransformation half-life and octanol-water distribution coefficient (log D) for the classification rules and log D, biotransformation half-life, and topological polar surface area for the BCF estimation tool.

octanol


Input: The uncertainty of the BCF estimates obtained with the new estimation tool was quantified by comparing the estimated and experimental BCF values of the 713 chemicals.


Input: Comparison with existing BCF estimation methods indicates that the performance of this new BCF estimation tool is at least as high as that of existing methods.


Input: The authors recommend the present study' s classification rules and BCF estimation tool for a consensus application in combination with existing BCF estimation methods.


Input: Environ Toxicol Chem 2013; 32: 1187-1195.


Input: (c) 2013 SETAC.


Input: Population pharmacokinetics and dose optimization of mycophenolic acid in HCT recipients receiving oral mycophenolate mofetil.

mycophenolic acid

mycophenolate mofetil


Input: We sought to create a population pharmacokinetic model for total mycophenolic acid (MPA), to study the effects of different covariates on MPA pharmacokinetics, to create a limited sampling schedule (LSS) to characterize MPA exposure (i. e., area under the curve or AUC) with maximum a posteriori Bayesian estimation, and to simulate an optimized dosing scheme for allogeneic hematopoietic cell transplantation (HCT) recipients.

mycophenolic acid

MPA

MPA

MPA


Input: Four thousand four hundred ninety-six MPA concentration-time points from 408 HCT recipients were analyzed retrospectively using a nonlinear mixed effects modeling approach.

MPA


Input: MPA pharmacokinetics was characterized with a two-compartment model with first-order elimination and a time-lagged first-order absorption process.

MPA


Input: Concomitant cyclosporine and serum albumin were significant covariates.

cyclosporine


Input: The median MPA clearance (CL) and volume of the central compartment were 24. 2 L/hour and 36. 4 L, respectively, for a 70 kg patient receiving tacrolimus with a serum albumin of 3. 4 g/dL.

MPA

tacrolimus


Input: Dosing simulations indicated that higher oral MMF doses are needed with concomitant cyclosporine, which increases MPA CL by 33. 8%.

MMF

cyclosporine

MPA


Input: The optimal LSS was immediately before and at 0. 25 hours, 1. 25 hours, 2 hours, and 4 hours after oral mycophenolate mofetil administration.

mycophenolate mofetil


Input: MPA AUC in an individual HCT recipient can be accurately estimated using a five-sample LSS and maximum a posteriori Bayesian estimation.

MPA


Input: Reconstitution of homomeric GluA2 (flop) receptors in supported lipid membranes: functional and structural properties.


Input: AMPA receptors (AMPARs) are glutamate-gated ion channels ubiquitous in the vertebrate central nervous system, where they mediate fast excitatory neurotransmission and act as molecular determinants of memory formation and learning.

AMPA

glutamate


Input: Together with detailed analyses of individual AMPAR domains, structural studies of full-length AMPARs by electron microscopy and x-ray crystallography have provided important insights into channel assembly and function.


Input: However, the correlation between the structure and functional states of the channel remains ambiguous particularly because these functional states can be assessed only with the receptor bound within an intact lipid bilayer.


Input: To provide a basis for investigating AMPAR structure in a membrane environment, we developed an optimized reconstitution protocol using a receptor whose structure has previously been characterized by electron microscopy.


Input: Single-channel recordings of reconstituted homomeric GluA2 (flop) receptors recapitulate key electrophysiological parameters of the channels expressed in native cellular membranes.


Input: Atomic force microscopy studies of the reconstituted samples provide high-resolution images of membrane-embedded full-length AMPARs at densities comparable to those in postsynaptic membranes.


Input: The data demonstrate the effect of protein density on conformational flexibility and dimensions of the receptors and provide the first structural characterization of functional membrane-embedded AMPARs, thus laying the foundation for correlated structure-function analyses of the predominant mediators of excitatory synaptic signals in the brain.


Input: Dicer1 is required to repress neuronal fate during endocrine cell maturation.


Input: MicroRNAs (miRNAs) are important regulators of gene expression programs in the pancreas; however, little is known about the role of miRNA pathways during endocrine cell specification and maturation during neonatal life.


Input: In this study, we deleted Dicer1, an essential RNase for active miRNAs biogenesis, specifically from NGN3 + endocrine progenitor cells.


Input: We found that deletion of Dicer1 in endocrine progenitors did not affect the specification of hormone-expressing endocrine cells.


Input: However, the islets in the mutant mice in the neonatal period exhibited morphological defects in organization and loss of hormone expression, and the mutant mice subsequently developed diabetes.


Input: Dicer1-deficient beta-cells lost insulin expression while maintaining the expression of beta-cell transcription factors such as Pdx1 and Nkx6. 1 early in the postnatal period.


Input: Surprisingly, transcriptional profiling showed that that the Dicer1-deficient endocrine cells expressed neuronal genes before the onset of diabetes.


Input: The derepression of neuronal genes was associated with a loss in binding of the neuronal transcriptional repressor RE-1-silencing transcription factor to its targets in Dicer1-deficient beta-cells.


Input: These studies suggest that miRNAs play a critical role in suppressing neuronal genes during the maturation of endocrine cells.


Input: International Union of Pharmacology.


Input: LXXXVII.


Input: Complement peptide C5a, C4a, and C3a receptors.


Input: The activation of the complement cascade, a cornerstone of the innate immune response, produces a number of small (74-77 amino acid) fragments, originally termed anaphylatoxins, that are potent chemoattractants and secretagogues that act on a wide variety of cell types.

amino acid


Input: These fragments, C5a, C4a, and C3a, participate at all levels of the immune response and are also involved in other processes such as neural development and organ regeneration.


Input: Their primary function, however, is in inflammation, so they are important targets for the development of antiinflammatory therapies.


Input: Only three receptors for complement peptides have been found, but there are no satisfactory antagonists as yet, despite intensive investigation.


Input: In humans, there is a single receptor for C3a (C3a receptor), no known receptor for C4a, and two receptors for C5a (C5a 1 receptor and C5a 2 receptor).


Input: The most recently characterized receptor, the C5a 2 receptor (previously known as C5L2 or GPR77), has been regarded as a passive binding protein, but signaling activities are now ascribed to it, so we propose that it be formally identified as a receptor and be given a name to reflect this.


Input: Here, we describe the complex biology of the complement peptides, introduce a new suggested nomenclature, and review our current knowledge of receptor pharmacology.


Input: An adsorbent performance indicator as a first step evaluation of novel sorbents for gas separations: application to metal-organic frameworks.


Input: An adsorbent performance indicator (API) is proposed in an effort to initially highlight porous materials of potential interest for PSA separation processes.


Input: This expression takes into account working capacities, selectivities, and adsorption energies and additionally uses weighting factors to reflect the specific requirements of a given process.


Input: To demonstrate the applicability of the API, we have performed the adsorption of carbon dioxide and methane at room temperature on a number of metal-organic frameworks, a zeolite and a molecular sieve carbon.

carbon dioxide

methane

zeolite

carbon


Input: The API is calculated for two different CO2/CH4 separation case scenarios: " bulk separation " and " natural gas purification ".


Input: This comparison highlights how the API can be more versatile than previously proposed comparison factors for an initial indication of potential adsorbent performance.


Input: Conjugation with betaine: a facile and effective approach to significant improvement of gene delivery properties of PEI.


Input: Herein, we developed a new gene delivery vector by grafting a betaine monomer (N, N-dimethyl (acrylamidopropyl) ammonium propane sulfonate, DMAAPS) onto 25 KDa polyethylenimine (PEI 25K) via the Michael addition reaction.

N, N-dimethyl (acrylamidopropyl) ammonium propane sulfonate

DMAAPS

polyethylenimine

PEI


Input: The graft ratio for betaine on PEI polymer could be readily controlled, and in this study three PEI-betaine conjugates PEI-DMAAPS23%, PEI-DMAAPS55%, and PEI-DMAAPS95% were prepared with their graft ratios of 23, 55, and 95%, respectively.

PEI

PEI

PEI

PEI


Input: The PEI-betaine conjugates exhibited much lower protein adsorption and cytotoxicities compared with PEI 25K, and they also showed little or no hemolytic effect.

PEI

PEI


Input: Moreover, the PEI-betaine conjugates display satisfactory DNA condensation capability; and in the absence and presence of serum, PEI-DMAAPS23%/pEGFP and PEI-DMAAPS55%/pEGFP complexes exhibited remarkable gene transfection efficiencies determined by flow cytometry, which are in general several times higher than that of PEI 25K.

PEI

PEI

PEI

PEI


Input: With these favorable properties, the PEI-betaine conjugates hold great potential for use as efficient gene delivery vectors.

PEI


Input: This study suggests that the betaine monomer may serve as a biocompatible modifying agent and this facile strategy may provide a facile and effective way for constructing some other biocompatible materials.


Input: Interactions between Pluronics (F127 and F68) and bile salts (NaTDC) in the aqueous phase and the interface of oil-in-water emulsions.

Pluronics (F127 and F68)

bile salts

NaTDC


Input: Pluronics are being introduced in food research in order to delay lipid digestion, with the length of hydrophilic and hydrophobic chains playing an important role in the rate of such a process.

Pluronics


Input: Since bile salts play a crucial role in the lipid digestion process, the aim of this work is to analyze the interactions between Pluronic F127 or F68 and the bile salt NaTDC when the latter is added at physiological concentrations.

bile salts

Pluronic F127 or F68

bile salt NaTDC


Input: These interactions are studied at the Pluronic-covered oil-water interface and in the aqueous phase of Pluronic-stabilized emulsions.

Pluronic

Pluronic


Input: This work has been carried out with techniques such as differential scanning calorimetry, interfacial tension, dilatational rheology, and scanning electron microscopy.


Input: As a result, Pluronic F127 was shown to be more resistant to displacement by bile salt than F68 at the oil-water interface due to the larger steric hindrance and interfacial coverage provided.

Pluronic F127

bile salt


Input: In addition, Pluronics have the ability to compete for the oil-water interface and interact in the bulk with the bile salt.

Pluronics

bile salt


Input: Concretely, Pluronic F127 seems to interact with more molecules of bile salt in the bulk, thus hindering their adsorption onto the oil-water interface.

Pluronic F127

bile salt


Input: As a conclusion, Pluronic F127 affects to a larger extent the ability of bile salt to promote the further cascade of lipolysis in the presence of lipase owing to a combination of interfacial and bulk events.

Pluronic F127

bile salt


Input: Fluorescence (fluidity/hydration) and calorimetric studies of interactions of bile acid-drug conjugates with model membranes.

bile acid