Input: In the present studies, the effects of CB (1) agonists [(6aR, 10aR)-3-(1-adamantyl)-6, 6, 9-trimethyl-6a, 7, 10, 10a-tetrahydrobenzo [c] chromen-1-ol (AM411), 9 beta-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol (AM4054), R-(+)-[2, 3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo [1, 2, 3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55, 212. 2), Delta (9)-tetrahydrocannabinol (Delta (9)-THC), (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (methanandamide)], CB (1) antagonists [5-(4-chlorophenyl)-1-(2, 4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (SR141716A), 5-(4-alkylphenyl)-1-(2, 4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (AM4113)], and dopamine (DA)-related [methamphetamine, (+/-)-6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrobromide (SKF82958), (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390), (6aR)-5, 6, 6a, 7-tetrahydro-6-propyl-4H-dibenzo [de, g] quinoline-10, 11-diol (R-(-)-NPA), haloperidol] and opioid (morphine, naltrexone) drugs on scheduled-controlled responding under a 30-response fixed ratio schedule of stimulus-shock termination in squirrel monkeys were compared before and during chronic treatment with the long-acting CB (1) agonist AM411 (1. 0 mg/kg per day, i. m.).

(6aR, 10aR)-3-(1-adamantyl)-6, 6, 9-trimethyl-6a, 7, 10, 10a-tetrahydrobenzo [c] chromen-1-ol

9 beta-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol

R-(+)-[2, 3-dihydro-5-methyl-3-[(morpholinyl) methyl] pyrrolo [1, 2, 3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate

WIN55, 212. 2

Delta (9)-tetrahydrocannabinol

Delta (9)-THC

(R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (methanandamide)

5-(4-chlorophenyl)-1-(2, 4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide

5-(4-alkylphenyl)-1-(2, 4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide

dopamine

methamphetamine

(+/-)-6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrobromide

(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine hydrochloride

(6aR)-5, 6, 6a, 7-tetrahydro-6-propyl-4H-dibenzo [de, g] quinoline-10, 11-diol

R-(-)-NPA

haloperidol

morphine

naltrexone


Input: Prechronic treatment with all drugs except naltrexone (1-10 mg/kg) produced dose-related decreases in responses rates.

naltrexone


Input: Dose-response re-determinations during chronic treatment revealed the following: 1) > 250-fold (AM411, methanandamide) and > 45-fold (AM4054, WIN55, 212. 2, Delta (9)-THC) rightward shifts in the ED (50) values for CB (1) agonists; 2) > 100-fold and > 20-fold leftward shifts in the ED (50) values for SR141716A and AM4113, respectively; and 3) approximately 4. 8-fold and 10-fold rightward shifts in the ED (50) values for methamphetamine and the DA D (2) agonist R-(-)-NPA, respectively.

methanandamide

WIN55, 212. 2

Delta (9)-THC

methamphetamine

R-(-)-NPA


Input: Dose-response relationships for other DA-related and opioid drugs were unchanged by chronic CB (1) agonist treatment.


Input: Differences in the magnitude of tolerance among CB (1) agonists during chronic treatment may be indicative of differences in their pharmacological efficacy, whereas the enhanced sensitivity to behaviorally disruptive effects of CB (1) antagonists may provide evidence for CB (1)-related behavioral and/or physical dependence.


Input: Finally, the development of cross-tolerance to methamphetamine and R-(-)-NPA bolsters previous evidence of interplay between CB (1) and DA D (2) signaling mechanisms.

methamphetamine

R-(-)-NPA


Input: SAXS conformational tracking of amylose synthesized by amylosucrases.


Input: Amylose, a linear polymer of alpha (1, 4)-linked glucosyl units and a major constituent of starch granules, can also be enzymatically synthesized in vitro from sucrose by bacterial amylosucrases.

sucrose


Input: Depending on the initial sucrose concentration and the enzyme used, amylose oligomers (or polymers) are formed and self-associate during synthesis into various semicrystalline morphologies.

sucrose


Input: This work describes for the first time a synchrotron SAXS study of the structure in solution of two amylosucrases, namely, NpAS and the thermostable DgAS, under conditions of polymer synthesis and, simultaneously, the amylose conformation.


Input: The structure in solution of both amylosucrases during the reaction was shown to be similar to the known crystallographic structures.


Input: The conformation of amylose produced at an early stage consists of a mixture of wormlike chains and double helical cylindrical structures.


Input: In the case of NpAS, in a second stage, individual double helices pack into clusters before crystallizing and precipitating.


Input: Amylose produced by DgAS never self-associates in such clusters due to the higher temperature used for amylose synthesis.


Input: All the dimensions determined for wormlike chains and cylindrical conformations at different times of NpAS synthesis are in very good agreement with structural features usually observed on gels of amylose extracted from starch.


Input: This provides new insights in understanding the mechanisms of amylose gelation.


Input: Multiple-time-scale motion in molecularly linked nanoparticle arrays.


Input: We explore the transport of electrons between electrodes that encase a two-dimensional array of metallic quantum dots linked by molecular bridges (such as alpha, omega alkaline dithiols).

dithiols


Input: Because the molecules can move at finite temperatures, the entire transport structure comprising the quantum dots and the molecules is in dynamical motion while the charge is being transported.


Input: There are then several physical processes (physical excursions of molecules and quantum dots, electronic migration, ordinary vibrations), all of which influence electronic transport.


Input: Each can occur on a different time scale.


Input: It is therefore not appropriate to use standard approaches to this sort of electron transfer problem.


Input: Instead, we present a treatment in which three different theoretical approaches-kinetic Monte Carlo, classical molecular dynamics, and quantum transport-are all employed.


Input: In certain limits, some of the dynamical effects are unimportant.


Input: But in general, the transport seems to follow a sort of dynamic bond percolation picture, an approach originally introduced as formal models and later applied to polymer electrolytes.


Input: Different rate-determining steps occur in different limits.


Input: This approach offers a powerful scheme for dealing with multiple time scale transport problems, as will exist in many situations with several pathways through molecular arrays or even individual molecules that are dynamically disordered.


Input: Thermally-limited exciton delocalization in superradiant molecular aggregates.


Input: We present two-dimensional Fourier transform optical spectroscopy measurements of two types of molecular J-aggregate thin films and show that temperature-dependent dynamical effects govern exciton delocalization at all temperatures, even in the presence of significant inhomogeneity.


Input: Our results indicate that in the tested molecular aggregates, even when the static structure disorder dominates exciton dephasing dynamics, the extent of exciton delocalization may be limited by dynamical fluctuations, mainly exciton-phonon coupling.


Input: Thus inhomogeneous dephasing may mediate the exciton coherence time whereas dynamical fluctuations mediate the exciton coherence length.


Input: Assessment of immunotoxicity using precision-cut tissue slices.


Input: 1. When the immune system encounters incoming infectious agents, this generally leads to immunity.


Input: The evoked immune response is usually robust, but can be severely perturbed by potentially harmful environmental agents such as chemicals, pharmaceuticals and allergens.


Input: 2. Immunosuppression, hypersensitivity and autoimmunity may occur due to changed immune activity.


Input: Evaluation of the immunotoxic potency of agents as part of risk assessment is currently established in vivo with animal models and in vitro with cell lines or primary cells.


Input: 3. Although in vivo testing is usually the most relevant situation for many agents, more and more in vitro models are being developed for assessment of immunotoxicity.


Input: In this context, hypersensitivity and immunosuppression are considered to be a primary focus for developing in vitro methods.


Input: Three-dimensional organotypic tissue models are also part of current research in immunotoxicology.


Input: 4. In recent years, there has been a revival of interest in organotypic tissue models.


Input: In the context of immunotoxicity testing, precision-cut lung slices in particular have been intensively studied.


Input: Therefore, this review is very much focused on pulmonary immunotoxicology.


Input: Respiratory hypersensitivity and inflammation are further highlighted aspects of this review.


Input: Immunotoxicity assessment currently is of limited use in other tissue models, which are therefore described only briefly within this review.


Input: Encapsulation of ligninolytic enzymes and its application in clarification of juice.


Input: The thermal stability, physico-chemical properties and effect on juice clarification of hydrogel formulations of ligninolytic enzymes from Phanerochaete chrysosporium were evaluated.


Input: The results showed that enzyme entrapment increase significantly (P < 0. 05) the thermal stability of enzymes at 4 and 75 degrees C.


Input: At 75 degrees C, maximum activity decreased to non detectable values of 7. 9% for free laccase, manganese peroxidase (MnP), lignin peroxidase (LiP), respectively; to 94%, 97%, 93% for laccase, MnP and LiP entrapped into Polyacrylamide/pectin, 94%, 98%, 88% for laccase, MnP and LiP encapsulated respectively into polyacrylamide/gelatine and to 87%, 91%, 87% for laccase, MnP and LiP entrapped, respectively into polyacrylamide/carboxymethylcellulose (CMC).

manganese

Polyacrylamide

polyacrylamide

polyacrylamide


Input: When particle size and viscosity of the formulation increased, enzyme stability increased.


Input: The polyphenolic reduction and clarity amelioration in mixed juice of berry and pomegranate was more significant (p > 0. 05) using encapsulated enzymes treatment than free enzymes.


Input: This suggested that enzymatic treatment was efficient for the juice clarification.


Input: Effect of high-pressure treatment on biogenic amines formation in vacuum-packed trout flesh (Oncorhynchus mykiss).

amines


Input: The effects of vacuum packaging followed by high pressure processing on the shelf-life of fillets of rainbow trout (Oncorhynchus mykiss) were examined.


Input: Samples were pressure-treated at 300 and 500 MPa and were stored at 3. 5 and 12 degrees C for up to 28 days (control--0 MPa) and 42 or 70 days (pressure-treated; 12 and 3. 5 degrees C resp.).


Input: The content of eight biogenic amines (putrescine, cadaverine, spermidine, spermine, histamine, tyramine, tryptamine and phenylethylamine) were determined.

amines

putrescine

cadaverine

spermidine

spermine

histamine

tyramine

tryptamine

phenylethylamine


Input: Putrescine, cadaverine and tyramine showed very good correspondence with the level of applied pressure and organoleptic properties.

Putrescine

cadaverine

tyramine


Input: Samples of very good quality contained less than 10 mg/kg of each of these amines.

amines


Input: Polyamines spermidine and spermine did not show statistically significant changes with the level of applied pressure and the time of storage.

Polyamines spermidine

spermine


Input: Tryptamine, phenylethylamine and histamine (with the single exception of a sample stored for 70 days) were not detected in pressure-treated samples kept at 3. 5 degrees C.

Tryptamine

phenylethylamine

histamine


Input: Changes in the bound aroma profiles of' Hayward' and' Hort16A' kiwifruit (Actinidia spp.) during ripening and GC-olfactometry analysis.


Input: Bound volatiles are recognised as a potential source of aroma compounds in fruits.


Input: In this study, the bound volatiles of Actinidia deliciosa' Hayward' and A. chinensis' Hort16A' were studied at three different ripening stages.


Input: The bound volatile content tended to increase as the fruit ripened from under-ripe to ripe, and then decreased in over-ripe fruit.


Input: Glycosides of (Z)-3-hexen-1-ol and hexanol (green-note volatiles) were present in considerable amounts.

hexanol


Input: beta-Glucosidase activity in' Hayward' and' Hort16A' remained fairly constant throughout ripening.


Input: GC-olfactometry analysis of the hydrolysates of ripe' Hayward' and' Hort16A' revealed the presence of 2-phenylethanol, beta-damascenone, vanillin and 2, 5-dimethyl-4-hydroxy-3 (2H)-furanone (DMHF).

beta-damascenone

vanillin

2, 5-dimethyl-4-hydroxy-3 (2H)-furanone

DMHF


Input: This is the first report of DMHF in' Hayward' kiwifruit.

DMHF


Input: For both' Hayward' and' Hort16A', the odour-active compounds found in the bound volatile extracts were different from those reported as contributors to the aroma of the ripe fruit, suggesting that bound volatiles are probably not significant contributors to the aroma of ripe kiwifruit.


Input: Phase behaviour and in vitro hydrolysis of wheat starch in mixture with whey protein.


Input: Network formation of whey protein isolate (WPI) with increasing concentrations of native wheat starch (WS) has been examined.


Input: Small deformation dynamic oscillation in shear and modulated temperature differential scanning calorimetry enabled analysis of binary mixtures at the macro-and micromolecular level.


Input: Following heat induced gelation, textural hardness was measured by undertaking compression tests.


Input: Environmental scanning electron microscopy provided tangible information on network morphology of polymeric constituents.


Input: Experiments involving in vitro starch digestion also allowed for indirect assessment of phase topology in the binary mixture.


Input: The biochemical component of this work constitutes an attempt to utilise whey protein as a retardant to the enzymatic hydrolysis of starch in a model system with alpha-amylase enzyme.


Input: During heating, rheological profiles of binary mixtures exhibited dramatic increases in G' at temperatures more closely related to those observed for single whey protein rather than pure starch.


Input: Results from this multidisciplinary approach of analysis, utilising rheology, calorimetry and microscopy, argue for the occurrence of phase separation phenomena in the gelled systems.


Input: There is also evidence of whey protein forming the continuous phase with wheat starch being the discontinuous filler, an outcome that is explored in the in vitro study of the enzymatic hydrolysis of starch.


Input: From fish chemical characterisation to the benefit-risk assessment--part A.


Input: Proximate composition, fatty acid profile, cholesterol, alpha-tocoferol content and essential (K, Na, Cl, S, Mg, Ca, Zn, Cu, Fe, Mn, and Se) and contaminant element (Hg/MeHg, Cd, Pb, and As) levels in silver scabbardfish (Lepidopus caudatus), hake (Merluccius merluccius), and ray (Raja spp.) were investigated.

fatty acid

cholesterol

alpha-tocoferol

K

Cl

S

Mg

Ca

Zn

Cu

Fe

Mn

Se

Hg

MeHg

Cd

Pb

As

silver


Input: Results showed that these species contain high protein, low cholesterol and energy levels, being its consumption recommended.

cholesterol


Input: Polyunsaturated fatty acids (PUFA) were the dominant group of the fatty acids, being 80% of the n-3 family.

Polyunsaturated fatty acids

PUFA

fatty acids


Input: Attending to the dietary reference intakes (DRIs), these fish species are a good source of Se and the other minerals can give a relevant contribution to the DRIs in a balanced diet.

Se


Input: More than one weekly meal of silver scabbardfish has to be avoided due to the organic mercury concentration.

silver

mercury


Input: More accurate dietary recommendations require a probabilistic assessment, which will be the focus of this study' s Part B.


Input: Determination of paralytic shellfish poisoning toxins by HILIC-MS/MS coupled with dispersive solid phase extraction.


Input: This paper describes the use of QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) for the extraction, cleanup and detection of 10 paralytic shellfish toxins (PSP) in sea food by HILIC-MS/MS with positive ESI.


Input: Matrix matched calibration standards were used to compensate for matrix effects.


Input: The toxins were extracted with acetonitrile/water (90: 10, v/v) containing 0. 1% formic acid and cleaned by HLB and GCB sorbents.

acetonitrile

formic acid

GCB


Input: Qualitative and quantitative detection for the analytes were carried out under the multiple reaction monitoring (MRM) in positive ionization mode after chromatography separation on a TSK-gel Amide-80 (R) column (150 mm x 2. 0 mm x 3 mu m).

Amide


Input: Studies at three fortification levels for the toxins in the range of 8. 1-225. 5 mu g/kg gave mean recoveries from 71. 3% to 104. 6% with relative standard deviation (RSD) <= 15. 8%.


Input: The limit of detection (LOD) was below the recommended regulatory limit of 170 mu gSTX (equ.)/kg and the proposed method fully meets the needs of daily monitoring.

gSTX


Input: Recently introduced foods as new allergenic sources: sensitisation to Goji berries (Lycium barbarum).


Input: Goji berries (GB) have been introduced in Western diet.


Input: Preliminary reports have demonstrated its allergenic capacity.


Input: The objectives of the study were to investigate the frequency of sensitisation and the allergens involved.


Input: 566 individuals, with respiratory or cutaneous symptoms were skin-prick tested with GB extract.


Input: Thirty three were positive (5. 8%).


Input: 94% were sensitised to other allergens.


Input: Specific IgE to GB, peach, tomato and nut-mix was measured.


Input: Thirteen individuals from 24 available sera (54. 2%) had positive specific IgE.


Input: 92. 3% of GB positive patients were positive to peach.


Input: Seven individuals recognised 8 bands and six recognised a 7kDa band.


Input: This band was identified as a LTP by MS/MS.


Input: Cross-reactivity was demonstrated with tomato, tobacco, nutmix, Artemisia pollen and purified Lyc e 3 and Pru p 3.


Input: GB are a new allergenic source with high prevalence of sensitisation.


Input: LTP seems to be the major allergen involved in sensitisation and cross-reactivity.


Input: Inhibitors of HIV-1 attachment.


Input: Part 10.


Input: The discovery and structure-activity relationships of 4-azaindole cores.


Input: A series of 4-azaindole oxoacetic acid piperazine benzamides was synthesized and evaluated in an effort to identify an oral HIV-1 attachment inhibitor with the potential to improve upon the pre-clinical profile of BMS-378806 (7), an initial clinical compound.

4-azaindole oxoacetic acid piperazine benzamides


Input: Modifications at the 7-position of the 4-azaindole core modulated potency significantly and SAR showed that certain compounds with a 5-membered ring heteroaryl group at that position were the most potent.


Input: Four of the compounds with the best profiles were evaluated in a rat pharmacokinetic model and all had superior oral bioavailability and lower clearance when compared with 7.


Input: Phosphodiesterase inhibitors.


Input: Part 5: hybrid PDE3/4 inhibitors as dual bronchorelaxant/anti-inflammatory agents for inhaled administration.


Input: (-)-6-(7-Methoxy-2-(trifluoromethyl) pyrazolo [1, 5-a] pyridin-4-yl)-5-methyl-4, 5-dihydropyridazin-3 (2H)-one (KCA-1490) exhibits moderate dual PDE3/4-inhibitory activity and promises as a combined bronchodilatory/anti-inflammatory agent.

(-)-6-(7-Methoxy-2-(trifluoromethyl) pyrazolo [1, 5-a] pyridin-4-yl)-5-methyl-4, 5-dihydropyridazin-3 (2H)-one


Input: N-alkylation of the pyridazinone ring markedly enhances potency against PDE4 but suppresses PDE3 inhibition.

N

pyridazinone


Input: Addition of a 6-aryl-4, 5-dihydropyridazin-3 (2H)-one extension to the N-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent PDE3 inhibition.

6-aryl-4, 5-dihydropyridazin-3 (2H)-one

N


Input: Both dihydropyridazinone rings, in the core and extension, can be replaced by achiral 4, 4-dimethylpyrazolone subunits and the core pyrazolopyridine by isosteric bicyclic heteroaromatics.

dihydropyridazinone

4, 4-dimethylpyrazolone

pyrazolopyridine


Input: In combination, these modifications afford potent dual PDE3/4 inhibitors that suppress histamine-induced bronchoconstriction in vivo and exhibit promising anti-inflammatory activity via intratracheal administration.

histamine


Input: Lessons from the dissection of the activation functions (AF-1 and AF-2) of the estrogen receptor alpha in vivo.

estrogen


Input: Estrogens influence most of the physiological processes in mammals, including but not limited to reproduction, cognition, behavior, vascular system, metabolism and bone integrity.

Estrogens


Input: Given this widespread role for estrogen in human physiology, it is not surprising that estrogen influence the pathophysiology of numerous diseases, including cancer (of the reproductive tract as breast, endometrial but also colorectal, prostate, ...), as well as neurodegenerative, inflammatory-immune, cardiovascular and metabolic diseases, and osteoporosis.

estrogen

estrogen


Input: These actions are mediated by the activation of estrogen receptors (ER) alpha (ER alpha) and beta (ER beta), which regulate target gene transcription (genomic action) through two independent activation functions (AF)-1 and AF-2, but can also elicit rapid membrane initiated steroid signals (MISS).

estrogen

steroid


Input: Targeted ER gene inactivation has shown that although ER beta plays an important role in the central nervous system and in the heart, ER alpha appears to play a prominent role in most of the other tissues.


Input: Pharmacological activation or inhibition of ER alpha and/or ER beta provides already the basis for many therapeutic interventions, from hormone replacement at menopause to prevention of the recurrence of breast cancer.


Input: However, the use of these estrogens or selective estrogen receptors modulators (SERMs) have also induced undesired effects.

estrogens

estrogen


Input: Thus, an important challenge consists now to uncouple the beneficial actions from other deleterious ones.


Input: The in vivo molecular " dissection " of ER alpha represents both a molecular and integrated approach that already allowed to delineate in mouse the role of the main " subfunctions " of the receptor and that could pave the way to an optimization of the ER modulation.


Input: Effects of quercetin on mRNA expression of steroidogenesis genes in primary cultures of Leydig cells treated with atrazine.

quercetin

atrazine


Input: The effect of the phytoestrogen, quercetin (QT) on the reproductive toxicity of atrazine (ATZ) was explored in interstitial Leydig cells (ILCs).

quercetin

atrazine

ATZ


Input: We measured the mRNA expressions of steroidogenesis genes: steroidogenic acute regulatory protein (StAR), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), cytochrome-P450 (CYP) 11A1, insulin-like factor 3 (INSL-3), CYP17A1, inhibin-alpha (INH-alpha), androgen receptor (AR), estrogen receptor-alpha (ER-alpha), and luteinising hormone receptor (LHR) in isolated ILCs by real-time-PCR after cultured cells were treated in vitro with ATZ (232 mu M) and QT (50 mu M).

3 beta-hydroxysteroid

androgen

estrogen

ATZ


Input: The mRNA expression of tested genes increased with ATZ treatment and was normalized by quercetin except AR and ER-alpha expression.

ATZ

quercetin


Input: Treatment of cells with QT alone (15-50 mu M) caused a dose-dependent increase in AR and ER-alpha mRNA expression.


Input: We also found that QT (50 mu M) increased the expressions of AR and ER-alpha in the presence of a sub-threshold level of cyclic-AMP at 1h culture period to the levels seen with maximal stimulation of cyclic-AMP.

cyclic-AMP

cyclic-AMP


Input: Furthermore, the expressions of tested genes were unaffected by cyclic-AMP at 6h when the stimulatory effects of ATZ on tested genes were sustained.

cyclic-AMP

ATZ


Input: These findings suggest that ATZ may stimulate the expression of tested steroidogenesis genes in ILCs via a mechanism independent of cyclic-AMP which was partially antagonize by QT.

ATZ

cyclic-AMP


Input: Effects of pubertal exposure to thiazole-Zn on thyroid function and development in female rats.

thiazole

Zn


Input: Thiazole-Zn is a newly Chinese-created systemic fungicide, and belongs to the sort of thiadiazole compounds, some of which have been found to be thyroid disrupters.

Thiazole

Zn

thiadiazole


Input: To determine the probable adverse effects of thiazole-Zn on thyroid gland and development function, the rodent 20-day Pubertal Female Assay in this study was used.

thiazole

Zn


Input: Postnatal days (PND) 22-old Sprague-Dawley rats were administered with thiazole-Zn daily by oral gavage at doses 0, 40, 100, 200 mg/kg/day for 20 days.

thiazole

Zn


Input: The thyroid endpoints and development endpoints were assessed.


Input: The results indicated that serum TT4 and TSH levels were significantly increased at all concentrations, serum TT3 levels were significantly reduced only at 40 mg/kg thiazole-Zn, but had no difference from controls at the other doses.

thiazole

Zn


Input: Thyroid histology was significantly altered at all doses with a clear dose-dependent hypertrophy and hyperplasia of thyroid cell.


Input: No histological changes were observed in any of the other observed organs.


Input: In addition, this study also found that ovarian weights were significantly decreased, but age and weight at vaginal opening (VO), serum E2 levels were unaffected in all treatment groups.


Input: These results demonstrate that thiazole-Zn is likely a thyroid disrupter, but did not demonstrate that it has estrogenic/anti-estrogenic activity.

thiazole

Zn


Input: A 10-minute point-of-care assay for detection of blood protein adducts resulting from low level exposure to organophosphate nerve agents.

organophosphate


Input: The OrganoTox test is a rapid, point-of-care assay capable of detecting clinically relevant organophosphate (OP) poisoning after low-level exposure to sarin, soman, tabun, or VX chemical nerve agents.

organophosphate

sarin

soman

tabun


Input: The test utilizes either a finger stick peripheral blood sample or plasma specimen.


Input: While high-level nerve agent exposure can quickly lead to death, low-level exposure produces vague, nondescript signs and symptoms that are not easily clinically differentiated from other conditions.


Input: In initial testing, the OrganoTox test was used to detect the presence of blood protein-nerve agent adducts in exposed blood samples.


Input: In order to mimic the in vivo exposure as closely as possible, nerve agents stored in organic solvents were spiked in minute quantities into whole blood samples.


Input: For performance testing, 40 plasma samples were spiked with sarin, soman, tabun, or VX and 10 normal plasma samples were used as the negative control.

sarin

soman

tabun


Input: The 40 nerve agent-spiked plasma samples included 10 replicates of each agent.


Input: At the clinically relevant low-level exposure of 10ng/ml, the OrganoTox test demonstrated 100% sensitivity for soman, tabun, and VX and 80% sensitivity for sarin.

soman

tabun

sarin


Input: The OrganoTox test demonstrated greater than 97% specificity with 150 blood samples obtained from healthy adults.


Input: No cross-reactivity or interference from pesticide precursor compounds was found.


Input: A rapid test for nerve agent exposure will help identify affected patients earlier in the clinical course and trigger more appropriate medical management in a more timely manner.


Input: Altered expression of genes involved in progesterone biosynthesis, metabolism and action in endometrial cancer.

progesterone


Input: Endometrial cancer (EC) is one of the most common gynecological malignancies worldwide.


Input: It is associated with prolonged exposure to estrogens that is unopposed by the protective effects of progesterone, which suggests that altered progesterone biosynthesis, metabolism and actions might be implicated in the development of EC.

progesterone

progesterone


Input: Our aim was to evaluate these processes through quantitative real-time PCR expression analysis in up to 47 pairs of EC tissue and adjacent control endometrium.


Input: First, we examined the expression of genes encoding proteins associated with progesterone biosynthesis: steroidogenic acute regulatory protein (STAR); a side chain cleavage enzyme (CYP11A1); and 3 beta-hydroxysteroid dehydrogenase/ketosteroid isomerase (HSD3B).

progesterone

3 beta-hydroxysteroid

ketosteroid


Input: There were 1. 9-and 10. 0-fold decreased expression of STAR and CYP11A1, respectively, in EC versus adjacent control endometrium, with no significant differences in the expression of HSD3B1 and HSD3B2.


Input: Next, we examined expression of genes encoding five progesterone metabolizing enzymes: the 3-keto and 20-ketosteroid reductases (AKR1C1-AKR1C3) and 5 alpha-reductases (SRD5A1 and SRD5A2); and the opposing 20 alpha-hydroxysteroid dehydrogenase (HSD17B2).

progesterone

3-keto and 20-ketosteroid

20 alpha-hydroxysteroid


Input: These genes are expressed in EC and adjacent control endometrium.


Input: No statistically significant differences were seen in mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1.


Input: Expression of HSD17B2 was 3. 0-fold increased, and expression of SRD5A2 was 3. 7-fold decreased, in EC versus adjacent control endometrium.


Input: We also examined mRNA levels of progesterone receptors A and B (PGR), and separately the expression of progesterone receptor B (PR-B).

progesterone

progesterone


Input: Here we saw 1. 8-and 2. 0-fold lower mRNA levels of PGR and PR-B, respectively, in EC versus adjacent control endometrium.


Input: This down-regulation of STAR, CYP11A1 and PGR in endometrial cancer may lead to decreased progesterone biosynthesis and actions although the effects on progesterone levels should be further studied.

progesterone

progesterone


Input: Origin and evolution of medium chain alcohol dehydrogenases.

alcohol


Input: Different lines of alcohol dehydrogenases (ADHs) have separate superfamily origins, already recognized but now extended and re-evaluated by re-screening of the latest databank update.

alcohol


Input: The short-chain form (SDR) is still the superfamily with most abundant occurrence, most multiple divergence, most prokaryotic emphasis, and most non-complicated architecture.


Input: This pattern is compatible with an early appearance at the time of the emergence of prokaryotic cellular life.


Input: The medium-chain form (MDR) is also old but second in terms of all the parameters above, and therefore compatible with a second emergence.


Input: However, this step appears seemingly earlier than previously considered, and may indicate sub-stages of early emergences at the increased resolution available from the now greater number of data entries.


Input: The Zn-MDR origin constitutes a third stage, possibly compatible with the transition to oxidative conditions on earth.

Zn


Input: Within all these three lines, repeated enzymogeneses gave the present divergence.


Input: MDR-ADH origin (s), at a fourth stage, may also be further resolved in multiple or extended modes, but the classical liver MDR-ADH of the liver type can still be traced to a gene duplication ~ 550 MYA (million years ago), at the early vertebrate radiation, compatible with the post-eon-shift, " Cambrian explosion ".


Input: Classes and isozymes correspond to subsequent and recent duplicatory events, respectively.


Input: They illustrate a peculiar pattern with functional and emerging evolutionary distinctions between parent and emerging lines, suggesting a parallelism between duplicatory and mutational events, now also visible at separate sub-stages.


Input: Combined, all forms show distinctive patterns at different levels and illustrate correlations with global events.


Input: They further show that simple molecular observations on patterns, multiplicities and occurrence give much information, suggesting common divergence rules not much disturbed by horizontal gene transfers after the initial origins.


Input: pH-responsive lipid core micelles for tumour targeting.


Input: A new acid-sensitive drug-delivery nanocarrier has been developed for tumour targeting.


Input: The self-assembling co-polymer stearoyl-PEG-poly-sulfadimethoxine methacrylate (stearoyl-PEG-polySDM) was prepared to obtain micelles with responsive behaviour in the physiopathologic pH range.

stearoyl-PEG-poly-sulfadimethoxine methacrylate

stearoyl-PEG-polySDM


Input: Stearoyl-PEG-polySDM was synthesised using a multi-step procedure that includes pH-sensitive sulfadimethoxine methacrylate polymerisation by AGET-ATRP at the amino terminal side of stearoyl-PEG-NH2.

Stearoyl-PEG-polySDM

sulfadimethoxine methacrylate

amino


Input: Chemical analysis showed that the stearoyl-PEG-polySDM co-polymer contained a mean of seven methacryloyl sulfadimethoxines per molecule.

stearoyl-PEG-polySDM

methacryloyl sulfadimethoxines


Input: Potentiometric and turbidimetric analyses showed that stearoyl-PEG-polySDM has an apparent pKa of 7. 2 and a cloud point at pH 7. 0.

stearoyl-PEG-polySDM


Input: In water at pH 7. 4, the co-polymer assembled spontaneously into 13. 2 +/- 3. 1 nm micelles with a critical micelle concentration (CMC) of 36 mu M.


Input: Cell-culture studies showed that the material was more biocompatible with respect to the control Brij-700 (R).


Input: The paclitaxel loading capacity of the micelles was 3. 25 +/- 0. 25% (w/w,%).


Input: The colloidal formulations were stable at pH 7. 4 for several hours, while at pH 6. 5, they rapidly rearranged and aggregated.


Input: Fluorescence spectroscopic and cytofluorimetric studies showed that the incubation of MCF-7 tumour cells with fluorescein-labelled stearoyl-PEG-polySDM at pH 6. 5 resulted in massive time-dependent cell association, while the incubation at pH 7. 4 showed significantly lower cell interaction.

fluorescein

stearoyl-PEG-polySDM


Input: Confocal microscopy confirmed that at pH 6. 5, the micelles are taken up by cells and that the fluorescein-labelled stearoyl-PEG-polySDM is distributed into the cytosol.

fluorescein

stearoyl-PEG-polySDM


Input: At pH 6. 5, paclitaxel-loaded stearoyl-PEG-polySDM micelles had a higher cytotoxic effect than the micelles incubated at pH 7. 4.

paclitaxel

stearoyl-PEG-polySDM


Input: The former displayed similar cytotoxic activity to free paclitaxel.

paclitaxel


Input: Evidences for the regulation of GnRH and GTH expression by GnIH in the goldfish, Carassius auratus.

GnIH


Input: Gonadotrophin-inhibitory hormone (GnIH) plays an important role in regulating of reproduction in teleosts.

Gonadotrophin-inhibitory hormone

GnIH


Input: To clarify the mode of action of GnIH on the synthesis of gonadotropin releasing hormone (GnRH) and gonadotrophin (GtH), three GnIHR cDNAs were cloned from the goldfish brain.


Input: In situ hybridization results showed that GnIHRs were localized to the hypothalamus and pituitary.


Input: In the hypothalamus, GnIHRs were found in the NPP, NPO and NLT, whereas sGnRH neurons were reported to be located, and potentially regulated by GnIH.

GnIHRs


Input: In the pituitary, only two GnIHRs were observed and they were localized to the PI instead of the adenohypophysis where GtH-expressing cells are localized, suggesting indirect regulation of GtH by GnIH.

GnIHRs


Input: In vivo, intraperitoneal (i. p.) injections of synthetic goldfish GnIH-II peptide and GnIH-III peptide significantly decreased sGnRH and FSH beta mRNA levels.

GnIH

GnIH


Input: Only GnIH-II decreased LH beta mRNA levels significantly.

GnIH


Input: In vitro, both GnIH-II and GnIH-III showed no effect on GtH synthesis, but an inhibition of GnRH-stimulated LH beta and FSH beta synthesis was observed when GnIH-III was applied to primary pituitary cells in culture.

GnIH

GnIH

GnIH


Input: Thus, GnIH could contribute to the regulation of gonadotropin in the brain and pituitary in teleosts.

GnIH


Input: Aggression-and sex-induced neural activity across vasotocin populations in the brown anole.

vasotocin


Input: Activity within the social behavior neural network is modulated by the neuropeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP).

arginine vasotocin

AVT

arginine vasopressin

AVP


Input: However, central AVT/AVP release causes different behavioral effects across species and social environments.

AVT

AVP


Input: These differences may be due to the activation of different neuronal AVT/AVP populations or to similar activity patterns causing different behavioral outputs.

AVT

AVP


Input: We examined neural activity (assessed as Fos induction) within AVT neurons in male brown anole lizards (Anolis sagrei) participating in aggressive or sexual encounters.

AVT


Input: Lizards possess simple amniote nervous systems, and their examination provides a comparative framework to complement avian and mammalian studies.


Input: In accordance with findings in other species, AVT neurons in the anole paraventricular nucleus (PVN) were activated during aggressive encounters; but unlike in other species, a positive correlation was found between aggression levels and activation.

AVT


Input: Activation of AVT neurons within the supraoptic nucleus (SON) occurred nonspecifically with participation in either aggressive or sexual encounters.

AVT


Input: Activation of AVT neurons in the preoptic area (POA) and bed nucleus of the stria terminalis (BNST) was associated with engagement in sexual behaviors.

AVT


Input: The above findings are congruent with neural activation patterns observed in other species, even when the behavioral outputs (i. e., aggression level) differed.


Input: However, aggressive encounters also increased activation of AVT neurons in the BNST, which is incongruous with findings in other species.

AVT


Input: Thus, some species differences involve the encoding of social stimuli as different neural activation patterns within the AVT/AVP network, whereas other behavioral differences arise downstream of this system.

AVT

AVP


Input: Fenamiphos is recalcitrant to the hydrolysis by alloforms PON1 Q192R of human serum.

Fenamiphos


Input: Fenamiphos (ethyl 4-methylthio-m-tolyl isopropylphosphoramidate) is a racemic organophosphorus nematicide widely used in agriculture around the world.

Fenamiphos

ethyl 4-methylthio-m-tolyl isopropylphosphoramidate

organophosphorus


Input: The paraoxonase 1 from human serum (PON1) is a phosphotriesterase (PTE) that hydrolyses several xenobiotics including drugs and organophosphorus compounds (OPs).

organophosphorus


Input: In this work, the separation of the enantiomers of fenamiphos by HPLC using the column CHIRALCEL OJ and a mobile phase of hexane/ethanol (99/1) is presented.

fenamiphos

hexane

ethanol


Input: A liquid-liquid extraction method was implemented for the characterization of commercial nematicide hydrolysis by PON1 Q192R alloforms of human serum from children and adults.


Input: The results show a recovery of 94% for each isomer from the biological matrix.


Input: The method resulted linear response in a range concentration between 50 and 800 mu M with a detection and quantification limit between 0. 6 and 2 mu M for the (+)-fenamiphos, and between 0. 7 and 2. 3 mu M for the (-)-fenamiphos.

(+)-fenamiphos

(-)-fenamiphos


Input: The levels of the Ca (2 +)-dependent hydrolysis (residual concentration [mu M]) quantified during 30min of reaction were only just 4-14% for both fenamiphos enantiomers with the three alloforms of PON1 Q192R of the two groups of serum studied.

Ca (2 +)

fenamiphos


Input: These results demonstrate that human serum PON1 is could be involved in the detoxification of a limited number of organophosphorus insecticides.

organophosphorus


Input: Reduced plasma oxytocin levels in female patients with borderline personality disorder.

oxytocin


Input: The neuropeptide oxytocin is involved in social cognition and interaction across species and plays a crucial role in the regulation of affiliative behaviors.

oxytocin


Input: Oxytocin levels in cerebrospinal fluid (CSF), but also in plasma or urine, have been shown to be negatively associated with childhood traumata, aggressive behavior, and suicide attempts.

Oxytocin


Input: Recently, an altered activity of the oxytocin system has been discussed to play a prominent role in borderline personality disorder (BPD), which is thought to be closely related to traumatic experiences in childhood and is characterized by (para) suicidal behaviors as well as aggressive outbursts.

oxytocin


Input: In the present study, we compared plasma oxytocin levels of women with and without BPD in the follicular phase and assessed the relationship between oxytocin concentrations and childhood traumata.

oxytocin

oxytocin


Input: Women diagnosed with BPD had significantly reduced oxytocin concentrations, even after controlling for estrogen, progesterone, and contraceptive intake.

oxytocin

estrogen

progesterone


Input: In addition, plasma oxytocin correlated negatively with experiences of childhood traumata, in particular with emotional neglect and abuse.

oxytocin


Input: The results of mediation analyses do not support a model of oxytocin being a prominent mediator in the link between childhood trauma and BPD.

oxytocin


Input: Thus, the findings indicate dysregulations in the oxytocin system of patients diagnosed with BPD with more longitudinal research being necessary to disentangle the relationship between childhood adversities, oxytocin system, and psychopathology.

oxytocin

oxytocin


Input: Antimutagenic evaluation of vitamins B1, B6 and B12 in vitro and in vivo, with the Ames test.

vitamins B1, B6 and B12


Input: The aim of this work is to evaluate vitamins B antimutagenic effect against alkylatings methyl-N-nitro-N-nitrosoguanidine (MNNG), ethyl-N-nitro-N'-nitrosoguanidine (ENNG), frameshift mutagens 2-aminoanthracene (2AA) and 2-acetyl-amino-fluorene (2AF) and ROS-generating antibiotics norfloxacin (NOR) and nalidixic acid (NLX), using the in vitro Ames test.

vitamins B

methyl-N-nitro-N-nitrosoguanidine

MNNG

ethyl-N-nitro-N'-nitrosoguanidine

ENNG

norfloxacin

NOR

nalidixic acid

NLX


Input: In vivo antimutagenesis studies were performed against urinary mutagens induced by NOR (70 mg/kg) or NLX (100 mg/kg) in CD1 mice.

NOR

NLX


Input: Vitamin B1 was antimutagenic against alkylatings MNNG (P < 0. 05) or ENNG (P < 0. 001).

Vitamin B1

MNNG

ENNG


Input: In fact as per the results observed during the current study, none of the vitamins reduced mutagenesis caused by frameshift mutagens.


Input: All of them reduced mutagenesis of NOR or NLX (P < 0. 001).

NOR

NLX


Input: In vivo studies showed that vitamins B1 and B6 (10 or 100 mg/kg) reduced urinary mutagens from NOR (P < 0. 001) or NLX (P < 0. 02) either free or beta-glucoronidase-conjugates.

vitamins B1 and B6

NOR

NLX


Input: None of the studied samples were toxic for the employed antimutagenic system.


Input: Vitamin B12 (4 mg/kg) reduced urinary mutagens of NOR or NLX (P < 0. 02).

Vitamin B12

NOR

NLX


Input: Vitamins B inhibited DNA mutations induced by ROS generated by NLX or NOR, both in vitro and in vivo.

Vitamins B

NLX

NOR


Input: Vitamin B1is antimutagenic against mutations induced by the alkylating MNNG or ENNG.

Vitamin B1is

MNNG

ENNG


Input: Based on the observations, employment of vitamins B in vivo can be a promising alternative to reduce genotoxic risk exposure to ROS.

vitamins B


Input: Effect of body-weight loading onto the articular cartilage on the occurrence of quinolone-induced chondrotoxicity in juvenile rats.

quinolone


Input: The effect of body-weight loading onto the articular cartilage on the occurrence of chondrotoxicity was investigated in male juvenile Sprague-Dawley rats given ofloxacin (OFLX) orally once at 900 mg/kg.

ofloxacin

OFLX


Input: Just after dosing of OFLX, hindlimb unloading was performed for 0, 2, 4, or 8 h by a tail-suspension method.

OFLX


Input: Animals were sacrificed at 8h post-dose, and then the distal femoral articular cartilage was subjected to a histological examination and an investigation for gene expression of tumor necrosis factor receptor superfamily, member 12a (Tnfrsf12a); prostaglandin-endoperoxide synthase 2 (Ptgs2); plasminogen activator, urokinase receptor (Plaur); and matrix metalloproteinase 3 (Mmp3) by qRT-PCR analysis.

prostaglandin


Input: As a result, cartilage lesions and up-regulations of these 4 genes that were seen in rats without the tail suspension were not observed in rats with the 8-h tail suspension, and a tendency to decrease in the incidence of the cartilage lesions and the gene expression was noted in a tail-suspension time dependent manner.


Input: Our results clearly indicate that body-weight loading onto the cartilage is necessary to induce cartilage lesions and gene expression of Tnfrsf12a, Ptgs2, Plaur, and Mmp3 in juvenile rats treated with OFLX.

OFLX


Input: Acute and sub-chronic (28days) oral toxicity evaluation of hydroethanolic extract of Bridelia ferruginea Benth root bark in male rodent animals.


Input: The present investigation was carried out to evaluate the safety of hydro-ethanol extract of Bridelia ferruginea Benth (Euphorbiaceae) root bark.

ethanol


Input: For acute toxicity study, a single dose of 2000 and 5000 mg/kg of the B. ferruginea root bark extract was given orally to healthy male Wistar rats and Balb/c mice.


Input: The animals were observed for mortality and clinical signs for 3 h and then daily for 14 days.


Input: In the sub-chronic toxicity study, the extract was administered orally at doses of 250, 500 and 1000 mg/kg/day for 28 days to male Wistar rats.


Input: Animals were sacrificed to examine their organs, and urine and blood serum were analyzed.


Input: In the acute toxicity study, B. ferruginea root bark extract caused neither significant visible signs of toxicity, nor mortality in Wistar rats and Balb/c mice.


Input: In sub-chronic toxicity study, administration of the B. ferruginea root bark extract at 250, 500, and 1000 mg/kg for 28 consecutive days to Wistar rats did not produce mortality.


Input: No significant differences were found in relative organ weights, biochemical studied parameters in treated groups compared to control group.


Input: No obvious histological changes were observed in organs of B. ferruginea extract treated animals compared to controls.


Input: High levels of ephrinB2 over-expression increases the osteogenic differentiation of human mesenchymal stem cells and promotes enhanced cell mediated mineralisation in a polyethyleneimine-ephrinB2 gene-activated matrix.

polyethyleneimine


Input: Gene therapy can be combined with tissue engineering constructs to produce gene-activated matrices (GAMs) with enhanced capacity for repair.


Input: Polyethyleneimine (PEI), a non-viral vector, has previously been optimised for high efficiency gene transfer in rat mesenchymal stem cells (rMSCs).

Polyethyleneimine

PEI


Input: The use of PEI to transfect human MSCs (hMSCs) with ephrinB2 is assessed here.

PEI


Input: Recently a role for the ephrinB2 ligand and EphB4 receptor duo has been proposed in bone remodelling.


Input: Herein, over-expression of the ephrinB2 ligand resulted in increased osteogenic differentiation in hMSCs.


Input: As ephrinB2 is a cell surface anchored ligand which only interacts with cells expressing the cognate EphB4 receptor through direct contact, we have shown that direct cell-cell contact between two neighbouring cells is responsible for enhanced osteogenesis.


Input: In an effort to begin to elucidate the molecular mechanisms at play downstream of ephrinB2 over-expression, RT-PCR was performed on the GAMs which revealed no significant changes in runx2 or BMP2 expression but an upregulation of osterix (Osx) and Dlx5 expression prompting the belief that the mode of osteogenesis is independent of the BMP2 pathway.


Input: This select interaction, coupled with the transient gene expression profile of PEI, makes the PEI-ephrinB2 GAM an ideal candidate matrix for a bone targeted GAM.

PEI

PEI


Input: Cardioprotective effect of salvianolic acid B against arsenic trioxide-induced injury in cardiac H9c2 cells via the PI3K/Akt signal pathway.

salvianolic acid B

arsenic trioxide


Input: The clinical use of arsenic trioxide (ATO), a potent anti-neoplastic agent, is often limited because of its severe cardiotoxicity.

arsenic trioxide

ATO


Input: Salviae miltiorrhiza is widely used for the treatment of cardiovascular diseases.


Input: One of the most abundant ingredients of S. miltiorrhiza is salvianolic acid B (Sal B).

salvianolic acid B

Sal B


Input: The present study was designed to evaluate whether Sal B protects against ATO-induced cardiac cell injury in vitro.

Sal B

ATO


Input: With MTT cell viability assay, LDH release, ROS generation, caspase-3 activity assay and Hoechst 33342/PI staining, we found that Sal B pretreatment provided significantly protection against ATO-induced cell death.

MTT

Hoechst 33342

Sal B

ATO


Input: The effect was correlated with the activation of the PI3K/Akt signal pathway.


Input: Conversely, blocking Akt activation with the PI3K inhibitor LY294002 effectively suppressed the protective effect of Sal B against ATO-induced cell apoptosis.

Sal B

ATO


Input: In addition, the PI3K inhibitor partially blocked the effects of Sal B on the upregulation of Bcl-2 and Bcl-xl protein expression, and downregulation of Bax protein expression.

Sal B


Input: Collectively, the results showed that Sal B decreased the apoptosis and necrosis of H9c2 cardiomyocytes caused by ATO treatment, and PI3K played a crucial role in enhancing cell survival during this process.

Sal B

ATO


Input: These observations indicate that Sal B has the potential to exert cardioprotective effects against ATO toxicity.

Sal B

ATO


Input: Differences in lead tolerance between Kandelia obovata and Acanthus ilicifolius seedlings under varying treatment times.


Input: The effects of short-term (1 day) and long-term (49 days) of lead (Pb) stress on growth and physiological responses in the leaves and roots of two mangrove plants, Kandelia obovata and Acanthus ilicifolius, were compared.

Pb


Input: The growth of both species was affected by Pb at Day 49, whereas the root to shoot ratio of K. obovata remained unchanged.

Pb


Input: Compared with A. ilicifolius, less Pb accumulated in leaves of K. obovata, which indicates that this species is a typical Pb-excluder.

Pb

Pb


Input: Significant linear relationships were observed between the Pb concentrations in the roots and leaves and the Pb treatment concentrations in the sediments in A. ilicifolius but not in K. obovata.

Pb

Pb


Input: The proline concentration increased in both mangrove species at Day 49, especially in A. ilicifolius, but no changes were observed at Day 1.


Input: The tolerant species K. obovata tended to acclimate to metal stress by restricting the translocation of toxic metals and by increasing and/or maintaining high superoxide dismutase (SOD) activity, minimizing lipid peroxidation, and exhibiting prolonged unaltered growth (49 days) under Pb treatment.

superoxide

Pb


Input: The non-tolerant species, A. ilicifolius, did not acclimate to metal stress, its leaves were seriously damaged with significant increased MDA content, and its SOD activity was decreased.

MDA


Input: An increase of endogenous jasmonic acid concentration was observed only in K. obovata, both at Day 1 and at Day 49, which suggests that this hormone plays an important role in metal tolerance under short-term and long-term metal treatment.

jasmonic acid


Input: Tightly bound trions in monolayer MoS2.


Input: Two-dimensional (2D) atomic crystals, such as graphene and transition-metal dichalcogenides, have emerged as a new class of materials with remarkable physical properties.

graphene

transition-metal dichalcogenides


Input: In contrast to graphene, monolayer MoS (2) is a non-centrosymmetric material with a direct energy gap.

graphene

MoS (2)


Input: Strong photoluminescence, a current on/off ratio exceeding 10 (8) in field-effect transistors, and efficient valley and spin control by optical helicity have recently been demonstrated in this material.


Input: Here we report the spectroscopic identification in a monolayer MoS (2) field-effect transistor of tightly bound negative trions, a quasiparticle composed of two electrons and a hole.

MoS (2)


Input: These quasiparticles, which can be optically created with valley and spin polarized holes, have no analogue in conventional semiconductors.


Input: They also possess a large binding energy (~ 20 meV), rendering them significant even at room temperature.


Input: Our results open up possibilities both for fundamental studies of many-body interactions and for optoelectronic and valleytronic applications in 2D atomic crystals.


Input: A rechargeable room-temperature sodium superoxide (NaO2) battery.

sodium superoxide


Input: In the search for room-temperature batteries with high energy densities, rechargeable metal-air (more precisely metal-oxygen) batteries are considered as particularly attractive owing to the simplicity of the underlying cell reaction at first glance.

oxygen


Input: Atmospheric oxygen is used to form oxides during discharging, which-ideally-decompose reversibly during charging.

oxygen

oxides


Input: Much work has been focused on aprotic Li-O (2) cells (mostly with carbonate-based electrolytes and Li (2) O (2) as a potential discharge product), where large overpotentials are observed and a complex cell chemistry is found.

Li-O (2)

carbonate

Li (2) O (2)


Input: In fact, recent studies evidence that Li-O (2) cells suffer from irreversible electrolyte decomposition during cycling.

Li-O (2)


Input: Here we report on a Na-O (2) cell reversibly discharging/charging at very low overpotentials (< 200 mV) and current densities as high as 0. 2 mA cm (-2) using a pure carbon cathode without an added catalyst.

Na-O (2)

carbon


Input: Crystalline sodium superoxide (NaO (2)) forms in a one-electron transfer step as a solid discharge product.

sodium superoxide

NaO (2)


Input: This work demonstrates that substitution of lithium by sodium may offer an unexpected route towards rechargeable metal-air batteries.

lithium

sodium


Input: High-resolution solid-state 13C NMR spectroscopy of the paramagnetic metal-organic frameworks, STAM-1 and HKUST-1.


Input: Solid-state (13) C magic-angle spinning (MAS) NMR spectroscopy is used to investigate the structure of the Cu (II)-based metal-organic frameworks (MOFs), HKUST-1 and STAM-1, and the structural changes occurring within these MOFs upon activation (dehydration).

(13) C

Cu (II)


Input: NMR spectroscopy is an attractive technique for the investigation of these materials, owing to its high sensitivity to local structure, without any requirement for longer-range order.


Input: However, interactions between nuclei and unpaired electrons in paramagnetic systems (e. g., Cu (II)-based MOFs) pose a considerable challenge, not only for spectral acquisition, but also in the assignment and interpretation of the spectral resonances.

Cu (II)


Input: Here, we exploit the rapid T (1) relaxation of these materials to obtain (13) C NMR spectra using a spin-echo pulse sequence at natural abundance levels, and employ frequency-stepped acquisition to ensure uniform excitation of resonances over a wide frequency range.

(13) C


Input: We then utilise selective (13) C isotopic labelling of the organic linker molecules to enable an unambiguous assignment of NMR spectra of both MOFs for the first time.

(13) C


Input: We show that the monomethylated linker can be recovered from STAM-1 intact, demonstrating not only the interesting use of this MOF as a protecting group, but also the ability (for both STAM-1 and HKUST-1) to recover isotopically-enriched linkers, thereby reducing significantly the overall cost of the approach.


Input: Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases.

nitrile


Input: Coronaviral infection is associated with up to 5% of respiratory tract diseases.


Input: The 3C-like protease (3CL (pro)) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection.


Input: We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL (pro) of severe-acute-respiratory-syndrome-coronavirus.

nitrile

N


Input: The IC (50) values of the inhibitors were in the range of 4. 6-49 mu M, demonstrating that the nitrile warhead can effectively inactivate the 3CL (pro) autocleavage process.

nitrile


Input: The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was ~ 10x more potent than the other inhibitors tested.

Cbz

CN

N

carbobenzyloxy


Input: Crystal structures of the enzyme-inhibitor complexes showed that the nitrile warhead inhibits 3CL (pro) by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1-S4 substrate-binding pockets.

nitrile


Input: We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CL (pro) from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC (50) values ranging from 1. 3 to 3. 7 mu M, but no detectable inhibition against caspase-3.

Cbz

CN


Input: In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL (pro), and they inhibit 3CL (pro) from a broad range of coronaviruses.

nitrile


Input: Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection.


Input: Synthesis and antibacterial and antifungal evaluation of some chalcone based sulfones and bisulfones.

chalcone

sulfones

bisulfones


Input: Two series of chalcone based sulfone and bisulfone derivatives were synthesized using chalcone, thiophenol and sodium metal at room temperature, followed by oxidation of chalcone sulfides with m-CPBA at 0 degrees C in a novel method.

chalcone

sulfone

bisulfone

chalcone

thiophenol

sodium

chalcone sulfides

m-CPBA


Input: Both sulfones and bisulfones were evaluated for their antimicrobial activities against Aspergillus niger and Candida albicans (yeast), Bacillus subtilis and Staphylococcus aureus (Gram (+) bacteria) and Pseudomonas aeruginosa and Salmonella typhimurium (Gram (-) bacteria) strains.

sulfones

bisulfones


Input: Among them, compounds 2c, 3c, 6c, 7c, 8c and 9c have shown high antifungal activity against C. albicans compare to reference drugs viz.


Input: Amphotericin-B and Nystatin.

Amphotericin-B

Nystatin


Input: Compound 1c has shown slightly better antibacterial activity against B. subtilis and compounds 5c, 6c and 7c have shown excellent antibacterial activity against S. typhimurium in compare to reference drugs Ampicillin and Kanamycin.

Ampicillin

Kanamycin


Input: Identification of novel chromenone derivatives as interleukin-5 inhibitors.

chromenone


Input: A series of (E)-5-alkoxy-3-(3-phenyl-3-oxoprop-1-enyl)-4H-chromen-4-ones (4) and (E)-5-alkoxy-3-(3-hydroxy-3-phenylprop-1-enyl)-4H-chromen-4-ones (5) were synthesized and evaluated for their IL-5 inhibitory activity.

(E)-5-alkoxy-3-(3-phenyl-3-oxoprop-1-enyl)-4H-chromen-4-ones

(E)-5-alkoxy-3-(3-hydroxy-3-phenylprop-1-enyl)-4H-chromen-4-ones


Input: Propenone analogs 4 possess some of the structurally important characteristics of isoflavone 2 and chalcone 3 previously known as potent IL-5 inhibitor.

Propenone

isoflavone

chalcone


Input: However, the inhibitory activity of 4 was weak and therefore this structural hybridization appears to be ineffective for the design of IL-5 inhibitor.


Input: Meanwhile the potent activity profile of compounds 5 was discovered.


Input: This enhanced activity of 5 compared to 4 could be due to the effective location of hydroxyl group of allylic alcohol moiety of 5 in the 3D structure.

hydroxyl

allylic alcohol


Input: The electron withdrawing substituents at position 4 of phenyl ring of 5 enhances the activity possibly due to an increase in the strength of hydrogen bonding property of hydroxyl group of allylic alcohol moiety.

phenyl

hydrogen

hydroxyl

allylic alcohol


Input: Synthesis, antibacterial activity and docking of 14-membered 9-O-(3-arylalkyl) oxime 11, 12-cyclic carbonate ketolides.

14-membered 9-O-(3-arylalkyl) oxime 11, 12-cyclic carbonate ketolides


Input: A series of 9-O-(3-aryl-2-propargyl) oxime ketolides 8 was synthesized and evaluated for in vitro antibacterial activity.

9-O-(3-aryl-2-propargyl) oxime ketolides


Input: Among 8, 8b-8d, and 8h-8l displayed dramatically improved potency against inducibly MLS (B)-resistant and efflux-resistant pathogens as compared to clarithromycin and azithromycin.

clarithromycin

azithromycin


Input: Especially, 8i (Ar = 4-isoquinolyl) possessed an MIC of 0. 064 mu g/mL against constitutively MLS (B)-resistant Streptococcus pneumoniae, and MICs of 0. 032-0. 064 mu g/mL against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus hominis.

methicillin

methicillin


Input: The analog 10 with a propyl linker was less effective than both the corresponding 8 and 9 containing propynyl and propenyl linkers.

propyl

propynyl

propenyl


Input: A docking study was performed to gain insight into the binding mode of series 8 and 9 and to rationalize the disparity found in the SAR of 8 and 9.


Input: Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates.

furoxanyl N-acylhydrazone


Input: Neglected diseases represent a major health problem.


Input: It is estimated that one third of the world population is infected with tuberculosis and additionally Leishmaniosis and Chagas disease affect approximately 30 million people.


Input: N-Acylhydrazone moiety is a repeated functional group present in several prototypes and drug candidates for these neglected diseases.

N-Acylhydrazone


Input: On the other hand, furoxan system has been studied as pharmacophore for Leishmaniosis and Chagas diseases.

furoxan


Input: Here we report on the design and preparation of forty hybrid furoxanyl N-acylhydrazones and on their activity on Mycobacterium tuberculosis, H37Rv and MDR strains, Trypanosoma cruzi, and Leishmania amazonensis.

furoxanyl N-acylhydrazones


Input: Among them, four derivatives displayed excellent to good selectivity indexes against the three different microorganisms.


Input: Hybrid compound N'-(4-phenyl-3-furoxanylmethylidene) isoniazide 9 showed the best antibacterial profile with MIC value 4. 5 lesser than the value for the reference isoniazid against MDR strain.

N'-(4-phenyl-3-furoxanylmethylidene) isoniazide

isoniazid


Input: Furoxanyl N-acylhydrazone (E)-2-methyl-N'-(4-phenyl-3-furoxanylmethylidene)-4H-imidazo [1, 2-a] pyridine-3-carbohydrazide 15 was ten-fold more potent against T. cruzi Amastigotes than the standard drug nifurtimox.

Furoxanyl N-acylhydrazone (E)-2-methyl-N'-(4-phenyl-3-furoxanylmethylidene)-4H-imidazo [1, 2-a] pyridine-3-carbohydrazide


Input: On the other hand, derivatives (E)-N'-(5-benzofuroxanylmethylidene) benzo [d] [1, 3] dioxole-5-carbohydrazide 25 and (E)-N'-(4-hydroxy-3-methoxyphenylmethylidene)-3-methylfuroxan-4-carbohydrazide 37 emerged as leads for the development of new leishmanicidal agents.

(E)-N'-(5-benzofuroxanylmethylidene) benzo [d] [1, 3] dioxole-5-carbohydrazide

(E)-N'-(4-hydroxy-3-methoxyphenylmethylidene)-3-methylfuroxan-4-carbohydrazide


Input: The adequate stability, in simulated biological system and plasma, and the lack of mutagenicity of these derivatives allow us to propose them as candidates for further pre-clinical studies.


Input: The protein amide (1) H (N) chemical shift temperature coefficient reflects thermal expansion of the N-H... O = C hydrogen bond.

(1) H (N)

N-H

O = C hydrogen


Input: The protein amide (1) H (N) chemical shift temperature coefficient can be determined with high accuracy by recording spectra at different temperatures, but the physical mechanism responsible for this temperature dependence is not well understood.

(1) H (N)


Input: In this work, we find that this coefficient strongly correlates with the temperature coefficient of the through-hydrogen-bond coupling, (3h) J (NC'), based on NMR measurements of protein GB3.

hydrogen


Input: Parallel tempering molecular dynamics simulation suggests that the hydrogen bond distance variation at different temperatures/replicas is largely responsible for the (1) H (N) chemical shift temperature dependence, from which an empirical equation is proposed to predict the hydrogen bond thermal expansion coefficient, revealing responses of individual hydrogen bonds to temperature changes.

hydrogen

(1) H (N)

hydrogen

hydrogen


Input: Different expansion patterns have been observed for various networks formed by beta strands.


Input: Synthesis, characterization and pharmacodynamics of vitamin-B (12)-conjugated glucagon-like peptide-1.

vitamin-B (12)


Input: Clearing the way: Glucagon-like peptide-1 (GLP-1) receptor agonists are proving a potent weapon in the treatment of type II diabetes.


Input: A new vitamin B (12)-GLP-1 conjugate is investigated and shown to have insulinotropic properties similar to the unmodified peptide.

vitamin B (12)


Input: These results are critical to the exploitation of the vitamin B (12) oral uptake pathway for peptide delivery.

vitamin B (12)


Input: TCDD inhibits heart regeneration in adult zebrafish.

TCDD


Input: Normal adult zebrafish can completely regenerate lost myocardium following partial amputation of the ventricle apex.


Input: We report that 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) significantly impairs this regeneration.

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

TCDD


Input: Adult male zebrafish were injected with vehicle (control) or TCDD (70ng/g, ip) 1 day prior to partial amputation of the ventricle apex.

TCDD


Input: Gross observation and histological analysis of the amputated heart at 21 days postamputation revealed that TCDD-exposed fish had not progressed beyond the initial clot formation stage, whereas the vehicle control fish showed substantial recovery and almost complete resolution of the formed clot.

TCDD


Input: In contrast, hearts that were not surgically wounded showed no signs of TCDD toxicity.

TCDD


Input: Striking features in the TCDD-exposed hearts were the absence of the normal sheath of new tissue enveloping the wound and the absence of intense cell proliferation at the site of the wound.

TCDD


Input: In addition, the patterns of collagen deposition at the wound site were different between the TCDD and vehicle groups.

TCDD


Input: Because the receptor for TCDD is the aryl hydrocarbon receptor ligand-activated transcriptional regulator, we examined the effects of TCDD exposure on gene expression in the ventricle using DNA microarrays.

TCDD

aryl hydrocarbon

TCDD


Input: Samples were collected just prior to amputation and at 6h and 7 days postamputation.


Input: TCDD-pretreated hearts had dysregulated expression of genes involved in heart function, tissue regeneration, cell growth, and extracellular matrix.

TCDD


Input: Because embryonic, but not adult, hearts are major targets for TCDD-induced cardiotoxicity, we speculate that the need for embryonic-like cells in regeneration is connected with the effects of TCDD in inhibiting the response to wounding.

TCDD

TCDD


Input: iReckon: simultaneous isoform discovery and abundance estimation from RNA-seq data.


Input: High-throughput RNA sequencing (RNA-seq) promises to revolutionize our understanding of genes and their role in human disease by characterizing the RNA content of tissues and cells.


Input: The realization of this promise, however, is conditional on the development of effective computational methods for the identification and quantification of transcripts from incomplete and noisy data.


Input: In this article, we introduce iReckon, a method for simultaneous determination of the isoforms and estimation of their abundances.


Input: Our probabilistic approach incorporates multiple biological and technical phenomena, including novel isoforms, intron retention, unspliced pre-mRNA, PCR amplification biases, and multimapped reads.


Input: iReckon utilizes regularized expectation-maximization to accurately estimate the abundances of known and novel isoforms.


Input: Our results on simulated and real data demonstrate a superior ability to discover novel isoforms with a significantly reduced number of false-positive predictions, and our abundance accuracy prediction outmatches that of other state-of-the-art tools.


Input: Furthermore, we have applied iReckon to two cancer transcriptome data sets, a triple-negative breast cancer patient sample and the MCF7 breast cancer cell line, and show that iReckon is able to reconstruct the complex splicing changes that were not previously identified.


Input: QT-PCR validations of the isoforms detected in the MCF7 cell line confirmed all of iReckon' s predictions and also showed strong agreement (r (2) = 0. 94) with the predicted abundances.


Input: The calmodulin regulator protein, PEP-19, sensitizes ATP-induced Ca2 + release.

ATP

Ca2 +


Input: PEP-19 is a small, intrinsically disordered protein that binds to the C-domain of calmodulin (CaM) via an IQ motif and tunes its Ca (2 +) binding properties via an acidic sequence.

Ca (2 +)


Input: We show here that the acidic sequence of PEP-19 has intrinsic Ca (2 +) binding activity, which may modulate Ca (2 +) binding to CaM by stabilizing an initial Ca (2 +)-CaM complex or by electrostatically steering Ca (2 +) to and from CaM.

Ca (2 +)

Ca (2 +)

Ca (2 +)

Ca (2 +)


Input: Because PEP-19 is expressed in cells that exhibit highly active Ca (2 +) dynamics, we tested the hypothesis that it influences ligand-dependent Ca (2 +) release.

Ca (2 +)

Ca (2 +)


Input: We show that PEP-19 increases the sensitivity of HeLa cells to ATP-induced Ca (2 +) release to greatly increase the percentage of cells responding to sub-saturating doses of ATP and increases the frequency of Ca (2 +) oscillations.

ATP

Ca (2 +)

ATP

Ca (2 +)


Input: Mutations in the acidic sequence of PEP-19 that inhibit or prevent it from modulating Ca (2 +) binding to CaM greatly inhibit its effect on ATP-induced Ca (2 +) release.

Ca (2 +)

ATP

Ca (2 +)


Input: Thus, this cellular effect of PEP-19 does not depend simply on binding to CaM via the IQ motif but requires its acidic metal binding domain.


Input: Tuning the activities of Ca (2 +) mobilization pathways places PEP-19 at the top of CaM signaling cascades, with great potential to exert broad effects on downstream CaM targets, thus expanding the biological significance of this small regulator of CaM signaling.

Ca (2 +)


Input: Effects of single or repeated silymarin administration on pharmacokinetics of risperidone and its major metabolite, 9-hydroxyrisperidone in rats.

risperidone


Input: 1. The interactions between herbal dietary supplements and therapeutic drugs have emerged as an important issue and P-glycoprotein (P-gp) has been reported as one of the significant factors of these interactions.


Input: 2. The objective of this article is to examine the effects of single and repeated administrations of silymarin on pharmacokinetics of a P-gp substrate, risperidone, and its major metabolite, 9-hydroxyrisperidone, in rats.

risperidone


Input: 3. To determine the plasma levels of risperidone and 9-hydroxyrisperidone in rats, a HPLC method was developed using a liquid-liquid acid back extraction.

risperidone


Input: When risperidone (6 mg/kg) was co-administered with silymarin (40 mg/kg) to rats orally, the C (max) of 9-hydroxyrisperidone was significantly increased to1. 3-fold (p < 0. 05), while the other pharmacokinetic parameters did not show any significant differences.

risperidone


Input: Expanding the experiment where rats were repeatedly administered with silymarin for 5 days prior to giving risperidone, the C (max) of risperidone and 9-hydroxyrisperidone were significantly increased to 2. 4-fold (p < 0. 001) and 1. 7-fold (p < 0. 001), respectively, and the AUC (0-t), as well to 1. 7-fold (p < 0. 05) and 2. 1-fold (p < 0. 01), respectively.

risperidone

risperidone


Input: 4. The repeated exposures of silymarin, compared to single administration of silymarin, increased oral bioavailability and affected the pharmacokinetics of risperidone and 9-hydroxyrisperidone, by inhibiting P-gp.

risperidone


Input: Acute pulmonary effects of sidestream secondhand smoke at simulated car concentrations.


Input: 1. Exposure to secondhand smoke (SHS) can occur in many places; however, regulations banning smoking may reduce the sources of exposure to SHS to personal areas such as the family car, a source of brief but potently intense exposure.


Input: 2. Fifteen non-smoking volunteers were exposed to sidestream SHS concentrations of 5000 micro g/m (3), within a simulated car setting.


Input: The Fraction of Exhaled Nitric Oxide (FeNO) was calculated, dynamic flow volumes were assessed through spirometry; while airway impedance (Z), resistance (R), and reactance (X) was assessed through impulse oscillometry before and after exposure.

Nitric Oxide


Input: 3. Exposure to sidestream SHS within this experimental condition did not affect dynamic flow volumes, however FENO decreased from 15. 34 ppb to 11. 15 ppb, (p < 0. 001).


Input: Increases in airway resistance at R5Hz by 0. 114 kPa/(L/s) (p = 0. 002), at R10Hz by 0. 093 [kPa/(L/s)] (p = 0. 006) and at R20Hz by 0. 093 [kPa/(L/s)] (p = 0. 008) were noted.


Input: Correspondingly overall peripheral and central airway resistance was also found to increase by 40% (by 0. 083 kPa/(L/s), p = 0. 038) and 25% (by 0. 045 kPa/(L/s), p = 0. 047) respectively.


Input: 4. Brief but elevated exposure to sidestream SHS can alter airway resistance, and impedance indicating a potential additional mechanistic pathway between exposure to SHS and the development of respiratory disease.


Input: Further research is needed to verify these pilot results.


Input: A new perfluoropolyether-based hydrophobic and chemically resistant photoresist structured by two-photon polymerization.

perfluoropolyether


Input: Two-photon polymerization technology has been used to fabricate submicrometer three-dimensional (3D) structures using a new polyfunctional perfluoropolyether-based resist, which is a polymer intrinsically hydrophobic and chemically resistant.

perfluoropolyether


Input: The fluorinated resist was designed and synthesized in this work and successfully employed to fabricate woodpile structures in various experimental conditions.


Input: This is the first demonstration of the capability to fabricate hydrophobic and chemically resistant 3D structures with submicrometer resolution and arbitrary geometry.


Input: Effects of the lipid environment, cholesterol and bile acids on the function of the purified and reconstituted human ABCG2 protein.

cholesterol

bile acids


Input: The human ABCG2 multidrug transporter actively extrudes a wide range of hydrophobic drugs and xenobiotics recognized by the transporter in the membrane phase.


Input: In order to examine the molecular nature of the transporter and its effects on the lipid environment, we have established an efficient protocol for the purification and reconstitution of the functional protein.


Input: We found that the drug-stimulated ATPase and the transport activity of ABCG2 are fully preserved by applying excess lipids and mild detergents during solubilization, whereas a detergent-induced dissociation of the ABCG2 dimer causes an irreversible inactivation.


Input: By using the purified and reconstituted protein we demonstrate that cholesterol is an essential activator, whereas bile acids are important modulators of ABCG2 activity.

cholesterol

bile acids


Input: Both wild-type ABCG2 and its R482G mutant variant require cholesterol for full activity, although they exhibit different cholesterol sensitivities.

cholesterol

cholesterol


Input: Bile acids strongly decrease the basal ABCG2-ATPase activity both in the wild-type ABCG2 and in the mutant variant.

Bile acids


Input: These data reinforce the results for the modulatory effects of cholesterol and bile acids of ABCG2 investigated in a complex cell membrane environment.

cholesterol

bile acids


Input: Moreover, these experiments open the possibility to perform functional and structural studies with a purified, reconstituted and highly active ABCG2 multidrug transporter.


Input: Spontaneous periodic diameter oscillations in InP nanowires: the role of interface instabilities.

InP


Input: We have observed that thin InP nanowires generated by vapor-liquid-solid growth display spontaneous periodic diameter oscillations when large group III supersaturations are used.

InP


Input: Diameter variations are associated with a large number of stacking faults and crystallographic phase changes (wurtzite/zinc-blende); also the axial distance between oscillations depends on the indium precursor flow used during the run.

wurtzite

zinc-blende

indium


Input: We attribute the morphology changes to a substantial deformation of the triple phase line (vapor-liquid-solid) at the catalyst nanoparticle edge originated from multistep nucleation during growth.


Input: The deformation alters the mechanical force balance acting on the nanoparticle during growth in such a way that the particle displaces from the nanowire top and wets the nanowire sidewall.


Input: Subsequently, as catalytic growth occurs at the sidewall, the associated increase in diameter will eventually push the NP back to its original wire-top position until the onset of a new instability at the triple phase line.


Input: Flexible fiber nanogenerator with 209 V output voltage directly powers a light-emitting diode.


Input: On the basis of a vertically aligned ultralong Pb (Zr (0. 52) Ti (0. 48)) O (3) (PZT) nanowire array fabricated using electrospinning nanofibers, we developed a new type of integrated nanogenerator (NG) with ultrahigh output voltage of 209 V and current density of 23. 5 mu A/cm (2), which are 3. 6 times and 2. 9 times of the previous record values, respectively.

Pb (Zr (0. 52) Ti (0. 48)) O (3)

PZT


Input: The output electricity can be directly used to stimulate the frog' s sciatic nerve and to induce a contraction of a frog' s gastrocnemius.


Input: The NG can instantaneously power a commercial light-emitting diode (LED) without the energy storage process.


Input: Interactions of sarin with polyelectrolyte membranes: a molecular dynamics simulation study.

sarin


Input: Nanostructured polyelectrolyte membranes (PEMs), which are widely used as permselective diffusion barriers in fuel cell technologies and electrochemical processing, are considered as protective membranes suitable for blocking warfare toxins, including water-soluble nerve agents such as sarin.

sarin


Input: In this article, we examine the mechanisms of sorption and diffusion of sarin in hydrated PEMs by means of atomistic molecular dynamics simulations.

sarin


Input: Three PEMs are considered: Nafion, sulfonated polystyrene (sPS) that forms the hydrophilic subphase of segregated sPS-polyolefin block copolymers, and random sPS-polyethylene copolymer.

Nafion

sulfonated polystyrene

sPS

sPS

polyolefin

sPS

polyethylene


Input: We found that sarin concentrates at the interface between the hydrophilic and hydrophobic subphases of hydrated Nafion acting as a surfactant.

sarin

hydrated Nafion


Input: In hydrated sPS, where the scale of water-polymer segregation is much smaller (1-2 nm), sarin also interacts favorably with hydrophobic and hydrophilic components.

hydrated sPS

sarin


Input: Water diffusion slows as the sarin content increases despite the overall increase in solvent content, which suggests that sarin and water have somewhat different pathways through the segregated membrane.

sarin

sarin


Input: Upon replacement of counterions of monovalent potassium with those of divalent calcium, sarin diffusion slows but remains substantial in all ionomers considered, especially at high sarin concentrations.

potassium

calcium

sarin

sarin


Input: The behavior of sarin is similar to that of its common simulant, dimethyl methylphosphonate.

sarin

dimethyl methylphosphonate


Input: Invasion genetics of the introduced black rat (Rattus rattus) in Senegal, West Africa.


Input: An understanding of the evolutionary history and dynamics of invasive species is required for the construction of predictive models of future spread and the design of biological management measures.


Input: The black rat (Rattus rattus) is a major vertebrate invader with a worldwide distribution.


Input: Despite the severe ecological, economic and health impacts of this species, its evolutionary history has been little studied.


Input: We carried out extensive specimen sampling in Senegal, West Africa, and used microsatellite markers to describe the pattern and processes of invasion in this large continental area.


Input: The genetic data obtained were combined with historical knowledge concerning the presence of this species in Senegal.


Input: Data were analysed by a combination of Bayesian clustering and approximate Bayesian computation methods.


Input: The invasion pathways closely paralleled the history of human trade routes in Senegal.


Input: In several places, we detected the occurrence of multiple introductions from genetically different sources.


Input: Long-distance migration between towns and villages was also observed.


Input: Our findings suggest that genetic bottlenecks and admixture have played a major role in shaping the genetics of invasive black rats.


Input: These two processes may generate genetic novelty and favour rapid evolution along the invasion pathways.


Input: Multifunctional Fe3O4 @Ag/SiO2/Au core-shell microspheres as a novel SERS-activity label via long-range plasmon coupling.

Ag

Au


Input: Noble metallic nanostructures exhibit a phenomenon known as surface-enhanced Raman scattering (SERS) in which the Raman scattering cross sections are dramatically enhanced for the molecules adsorbed thereon.


Input: Due to their wide accessible potential range in aqueous solutions and the high biocompatibility, Au supports are preferred for spectro-electrochemical investigations.

Au


Input: However, the optical range in SERS spectroscopy is restricted to excitation lines above 600 nm, which is shorter than the Ag supports.

Ag


Input: In addition, these SERS-activity materials are not easy to separate and reused.


Input: Herein, the present article reports the novel multifunctional Fe (3) O (4) @Ag/SiO (2)/Au core-shell microspheres that display long-range plasmon transfer of Ag to Au leading to enhanced Raman scattering.

Fe (3) O (4)

Ag

SiO (2)

Au

Ag

Au


Input: The well-designed microspheres have high magnetization and uniform sphere size.


Input: As a result, Fe (3) O (4) @Ag/SiO (2)/Au microspheres have the best enhancement effect in the Raman active research by using Rhodamine-b (RdB) as a probe molecule.

Fe (3) O (4)

Ag

SiO (2)

Au

Rhodamine-b

RdB


Input: The enhancement factor is estimated to be 2. 2 x 10 (4) for RdB from the long-range plasmon transfer of Ag to Au, corresponding to an attenuation of the enhancement by a factor of only 0. 672 x 10 (4) compared to RdB adsorbed directly on the Fe (3) O (4) @Ag microspheres.

RdB

Ag

Au

RdB

Fe (3) O (4)

Ag


Input: RdB can be detected down to 10 (-9) M even without the resonance SERS effect.

RdB


Input: The unique nanostructure makes the microspheres novel stable and a high-enhancement effect for Raman detection.


Input: Belatacept utilization recommendations: an expert position.


Input: INTRODUCTION: There is a continuing need for an immunosuppressive therapy that offers a high benefit-risk profile for renal transplant recipients, supporting long-term patient and graft survival while minimizing cumulative nephrotoxicity and other side effects.


Input: Belatacept, the first biological agent developed for primary maintenance immunosuppression, was recently approved for use in Europe.


Input: Belatacept combined with corticosteroids and a mycophenolic acid is indicated for prophylaxis of graft rejection in adults receiving renal transplant.

corticosteroids

mycophenolic acid


Input: Its use is contraindicated in Epstein-Barr virus seronegative or serostatus unknown patients due to increased risk of developing posttransplant lymphoproliferative disorder.


Input: AREAS COVERED: This review provides practical recommendations for the use of belatacept, based on safety and efficacy data from Phase II and Phase III clinical trials in de novo kidney transplant recipients.


Input: EXPERT OPINION: Treatment with belatacept is associated with improved long-term graft function, making belatacept an important option for prevention of kidney allograft rejection.


Input: Furthermore, efficacy and safety data over several years of therapy suggest that belatacept is particularly suitable for long-term immunosuppression, and the selective targeting offered by belatacept may help avoid some of the non-specific chronic safety risks associated with calcineurin inhibitors and steroids.


Input: Future studies will clarify the optimal regimen for belatacept usage.


Input: Highly solvatochromic fluorescent naphthalimides: design, synthesis, photophysical properties and fluorescence switch-on sensing of ct-DNA.

naphthalimides


Input: We report the design, synthesis and photophysical properties of highly solvatochromic donor/acceptor substituted naphthalimide based fluorophores.

naphthalimide


Input: The synthesized naphthalimides containing propargyl ends showed highly solvatochromic intramolecular charge transfer (ICT) feature as was revealed from the UV-visible, fluorescence photophysical properties of these fluorophores and DFT/TDDFT calculation.

naphthalimides

propargyl


Input: Fluorescence life times for the imide fluorophores were also measured in different solvents.

imide


Input: The solid state photophysical property of donor substituted naphthalimide 1 showed promising for future application in material sciences.

naphthalimide


Input: Furthermore, both the donor/acceptor substituted naphthalimide fluorophores 1-2 were exploited in sensing calf-thymus DNA via switch-on fluorescence response.

naphthalimide


Input: The propargyl linker containing naphthalimides can further be exploited for the synthesis of labeled biomolecular building blocks.

propargyl

naphthalimides


Input: Design, synthesis and bioevalution of novel benzamides derivatives as HDAC inhibitors.

benzamides


Input: A series of novel benzamides derivatives was designed and synthesized as HDAC inhibitors.

benzamides


Input: Exploration of the structure-activity relationships resulted in compounds that are potent in vitro.


Input: In addition, the best compound 1a exhibited an acceptable pharmacokinetic profile with bioavailability in rat of 81% and could be considered as a candidate compound for further development.


Input: A systematic study of the degradation of dimethyl phthalate using a high-frequency ultrasonic process.

dimethyl phthalate


Input: A comprehensive study of the sonochemical degradation of dimethyl phthalate (DMP) was carried out using high-frequency ultrasonic processes.

dimethyl phthalate

DMP


Input: The effects of various operating parameters were investigated, including ultrasonic frequency, power density, initial DMP concentration, solution pH and the presence of hydrogen peroxide.

DMP

hydrogen peroxide


Input: In general, a frequency of 400kHz was the optimum for achieving the highest DMP degradation rate.

DMP


Input: The degradation rate was directly proportional to the power density and inversely related to the initial DMP concentration.

DMP


Input: It was interesting to find that faster removal rate was observed under weakly acidic condition, while hydrolysis effect dominated in extreme-basic condition.


Input: The addition of hydrogen peroxide can increase the radical generation to some extent.

hydrogen peroxide


Input: Furthermore, both hydroxylation of the aromatic ring and oxidation of the aliphatic chain appear to be the major mechanism of DMP degradation by sonolysis based on LC/ESI-MS analysis.

DMP


Input: Among the principle reaction intermediates identified, tri-and tetra-hydroxylated derivatives of DMP, as well as hydroxylated monomethyl phthalates and hydroxylated phthalic acid were reported for the first time in this study.

DMP

hydroxylated monomethyl phthalates

hydroxylated phthalic acid


Input: Reaction pathways for DMP sonolysis are proposed based on the detected intermediates.


Input: Comparison of hydroxyl radical formation in aqueous solutions at different ultrasound frequencies and powers using the salicylic acid dosimeter.

hydroxyl

salicylic acid


Input: Ultrasonic frequencies of 20kHz, 382kHz, 584kHz, 862kHz (and 998kHz) have been compared with regard to energy output and hydroxyl radical formation utilising the salicylic acid dosimeter.

hydroxyl

salicylic acid


Input: The 862kHz frequency inputs 6 times the number of Watts into water, as measured by calorimetry, with the other frequencies having roughly the same value under very similar conditions.


Input: A plausible explanation involving acoustic fountain formation is proposed although enhanced coupling between this frequency and water cannot be discounted.


Input: Using the salicylic acid dosimeter and inputting virtually the same Wattages it is established that 862kHz is around 10% more efficient at generating hydroxyl radicals than the 382kHz but both of these are far more effective than the other frequencies.

salicylic acid

hydroxyl


Input: Also, it is found that as temperature increases to 42 degrees C then the total dihydroxybenzoic acid (Total DHBA) produced is virtually identical for 382kHz and 862kHz, though 582kHz is substantially lower, when the power levels are set at approximately 9W for all systems.

dihydroxybenzoic acid

DHBA


Input: An equivalent power level of 9W could not be obtained for the 998kHz transducer so a direct comparison could not be made in this instance.


Input: These results have implications for the optimum frequencies chosen for both Advanced Oxidation Processes (AOPs) and organic synthesis augmented by ultrasound.


Input: Ion-exchange and iontophoresis-controlled delivery of apomorphine.

apomorphine


Input: The objective of this study was to test a drug delivery system that combines iontophoresis and cation-exchange fibers as drug matrices for the controlled transdermal delivery of antiparkinsonian drug apomorphine.

apomorphine


Input: Positively charged apomorphine was bound to the ion-exchange groups of the cation-exchange fibers until it was released by mobile counter-ions in the external solution.

apomorphine


Input: The release of the drug was controlled by modifying either the fiber type or the ionic composition of the external solution.


Input: Due to high affinity of apomorphine toward the ion-exchanger, a clear reduction in the in vitro transdermal fluxes from the fibers was observed compared to the respective fluxes from apomorphine solutions.

apomorphine

apomorphine


Input: Changes in the ionic composition of the donor formulations affected both the release and iontophoretic flux of the drug.


Input: Upon the application of higher co-ion concentrations or co-ions of higher valence in the donor formulation, the release from the fibers was enhanced, but the iontophoretic steady-state flux was decreased.


Input: Overall, the present study has demonstrated a promising approach using ion-exchange fibers for controlling the release and iontophoretic transdermal delivery of apomorphine.

apomorphine


Input: Combining QSAR classification models for predictive modeling of human monoamine oxidase inhibitors.


Input: Due to their role in the metabolism of monoamine neurotransmitters, MAO-A and MAO-B present a significant pharmacological interest.


Input: For instance the inhibitors of human MAO-B are considered useful tools for the treatment of Parkinson Disease.


Input: Therefore, the rational design and synthesis of new MAOs inhibitors is considered of great importance for the development of new and more effective treatments of Parkinson Disease.


Input: In this work, Quantitative Structure Activity Relationships (QSAR) has been developed to predict the human MAO inhibitory activity and selectivity.


Input: The first step was the selection of a suitable dataset of heterocyclic compounds that include chromones, coumarins, chalcones, thiazolylhydrazones, etc.

chromones

coumarins

chalcones

thiazolylhydrazones


Input: These compounds were previously synthesized in one of our laboratories, or elsewhere, and their activities measured by the same assays and for the same laboratory staff.


Input: Applying linear discriminant analysis to data derived from a variety of molecular representations and feature selection algorithms, reliable QSAR models were built which could be used to predict for test compounds the inhibitory activity and selectivity toward human MAO.


Input: This work also showed how several QSAR models can be combined to make better predictions.


Input: The final models exhibit significant statistics, interpretability, as well as displaying predictive power on an external validation set made up of chromone derivatives with unknown activity (that are being reported here for first time) synthesized by our group, and coumarins recently reported in the literature.

coumarins


Input: Triterpene saponins from Clethra barbinervis and their hyaluronidase inhibitory activities.

Triterpene saponins


Input: An extract of Clethra barbinervis with an inhibitory effect on hyaluronidase activity was fractionated guided by the results of an assay.


Input: From the active fractions, seven new triterpene saponins (1-4, 6-8) and a new lignan glycoside (14) were isolated together with 14 known compounds (5, 9-13, 15-22).

triterpene saponins

lignan glycoside


Input: Some of the saponins (2, 3, 9) were revealed as hyaluronidase inhibitors similar to epicatechin (17).

saponins

epicatechin


Input: Simple colorimetric bacterial detection and high-throughput drug screening based on a graphene-enzyme complex.

graphene


Input: A simple, colorimetric, sensitive, cost-effective and high-throughput system based on a positively charged graphene oxide-enzyme complex was developed for bacterial detection and drug screening.

graphene oxide


Input: From in situ to in vivo: an in situ click-chemistry-derived carbonic anhydrase II imaging agent for positron emission tomography.


Input: CA II makes a good PET: Discovering positron emission tomography (PET) probes with high target affinities is challenging.


Input: PET probe discovery using in situ click chemistry uses (19) F-bearing fragments as (18) F surrogates.

(19) F

(18) F


Input: This ensures that the lead hits and PET probes have equivalent chemical or biological characteristics, making PET probe discovery predictable and reliable.


Input: Enantiospecific total synthesis of (-)-bengamide E.

(-)-bengamide E


Input: Total synthesis of the polyhydroxy caprolactam amide natural product, bengamide E, is accomplished starting from tartaric acid.

polyhydroxy caprolactam amide

bengamide E

tartaric acid


Input: Key reactions in the synthesis include desymmetrization of the bis (dimethylamide) unit of tartaric acid, Zn (BH (4)) (2)-mediated anti-selective reduction, and a Horner-Wadsworth-Emmons olefination.

bis (dimethylamide)

tartaric acid

Zn (BH (4)) (2)


Input: Protein-DNA arrays as tools for detection of protein-protein interactions by mass spectrometry.


Input: Analysis of multiple protein-protein interactions using microarray technology remains challenging, and site-specific immobilization of functional proteins is a key step in these approaches.


Input: Here we establish the efficient synthesis of protein-DNA conjugates for several members of a small family of GTPases.


Input: The family of Rab/Ypt GTPases is intimately involved in vesicular trafficking in yeast and serves as a model for the much larger group of analogous human proteins, the Rab protein family, with more than 60 members.


Input: The Ypt-DNA hybrid molecules described here are used for DNA-directed immobilization on glass-and silica-based microarrays.

silica


Input: Methods for the detection of protein-DNA conjugates, as well as approaches for nucleotide exchange and distinguishing between GDP-and GTP-bound Ypts on microarrays, are reported.

nucleotide

GDP

GTP


Input: The high specificity of different Rab/Ypt-effector interactions, which also depends on the bound nucleotide, is shown by fluorescence readout of microarrays.

nucleotide


Input: Furthermore, initial experiments demonstrate that direct readout by mass spectrometry can be achieved with commercially available instruments.


Input: These developments will significantly contribute to the elucidation of complex transport networks in eukaryotic cells.


Input: Functional requirement for a highly conserved charged residue at position 75 in the gap junction protein connexin 32.


Input: Charcot Marie Tooth disease (CMT) is a group of inherited disorders characterized clinically by exclusively or predominantly peripheral nerve dysfunction.


Input: CMT1X, the most common form of X-linked CMT is caused by mutations in connexin 32 (Cx32).


Input: In this work, we used dual whole cell patch clamp recording to examine the functional effects of mutations at the Arg (75) position.

Arg


Input: This residue is highly conserved among members of the connexin family, and disease-causing mutations have been identified at this (or the corresponding) position in Cx26, Cx43, and Cx46.