Input: Here, we summarize multiple studies from pre-clinical animal models to human in vivo imaging and post-mortem experiments demonstrating changes in nAChR regulation and expression in psychiatric illness.


Input: CONCLUSIONS: We conclude that a mechanistic explanation of nAChR abnormalities in psychiatric illness will arise from a fuller understanding of normal nAChR trafficking, along with the detailed study of human tissue, perhaps using novel biotechnological advances, such as induced pluripotent stem cells.


Input: Hyperphosphataemia: Treatment Options.


Input: Hyperphosphataemia can be induced by three main conditions: a massive acute phosphate load, a primary increase in renal phosphate reabsorption, and an impaired renal phosphate excretion due to acute or chronic renal insufficiency.

phosphate

phosphate

phosphate


Input: Renal excretion is so efficient in normal subjects that balance can be maintained with only a minimal rise in serum phosphorus concentration even for a large phosphorus load.

phosphorus

phosphorus


Input: Therefore, acute hyperphosphataemia usually resolves within few hours if renal function is intact.


Input: The most frequent cause of chronic hyperphosphataemia is chronic renal failure.


Input: Hyperphosphataemia in chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality.


Input: Lowering the phosphate load and maintaining serum phosphorus levels within the normal range are considered important therapeutic goals to improve clinical outcomes in CKD patients.

phosphate

phosphorus


Input: Treatment consists of diminishing intestinal phosphate absorption by a low phosphate diet and phosphate binders.

phosphate

phosphate

phosphate


Input: In CKD patients on dialysis an efficient dialysis removal of phosphate should be ensured.

phosphate


Input: Dietary restriction of phosphorus while maintaining adequate protein intake is not sufficient to control serum phosphate levels in most CKD patients; therefore, the prescription of a phosphate binder is required.

phosphorus

phosphate

phosphate


Input: Aluminium-containing agents are efficient but no longer widely used because of their toxicity.

Aluminium


Input: Calcium-based salts are inexpensive, effective and most widely used, but there is now concern about their association with hypercalcaemia, parathyroid gland suppression, adynamic bone disease, and vascular and extraosseous calcification.

Calcium


Input: The average daily dose of calcium acetate or carbonate prescribed in the randomised controlled trials to control hyperphosphataemia in dialysis patients ranges between 1. 2 and 2. 3 g of elemental calcium.

calcium acetate or carbonate

calcium


Input: Such doses are greater than the recommended dietary calcium intake and can lead to a positive calcium balance.

calcium

calcium


Input: Although large amounts of calcium salts should probably be avoided, modest doses (< 1 g of elemental calcium) may represent a reasonable initial approach to reduced serum phosphorus levels.

calcium

calcium


Input: A non-calcium-based binder can then be added when large doses of binder are required.

calcium


Input: At present, there are three types of non-calcium-based phosphate binders available: sevelamer, lanthanum carbonate and magnesium salts.

calcium

sevelamer

lanthanum carbonate

magnesium


Input: Each of these compounds is as effective as calcium salts in lowering serum phosphorus levels depending on an adequate prescribed dose and adherence of the patient to treatment.

calcium

phosphorus


Input: Sevelamer is the only non-calcium-containing phosphate binder that does not have potential for systemic accumulation and presents pleiotropic effects that may impact on cardiovascular disease.

Sevelamer

calcium

phosphate


Input: In contrast, lanthanum carbonate and magnesium salts are absorbed in the gut and their route of excretion is biliary for lanthanum and urinary for magnesium.

lanthanum carbonate

magnesium

lanthanum

magnesium


Input: There are insufficient data to establish the comparative superiority of non-calcium binding agents over calcium salts for such important patient-level outcomes as all-cause mortality and cardiovascular end points.

calcium

calcium


Input: Moreover, full adoption of sevelamer and lanthanum by government drug reimbursement agencies in place of calcium salts would lead to a large increase in health-care expenditure.

sevelamer

lanthanum

calcium


Input: Therefore, the choice of phosphate binder should be individualised, considering the clinical context, the costs, and the individual tolerability the concomitant effects on other parameters of mineral metabolism, such as serum calcium and parathyroid hormone, besides those on serum phosphorus.

phosphate

calcium

phosphorus


Input: Solvated protein-DNA docking using HADDOCK.


Input: Interfacial water molecules play an important role in many aspects of protein-DNA specificity and recognition.


Input: Yet they have been mostly neglected in the computational modeling of these complexes.


Input: We present here a solvated docking protocol that allows explicit inclusion of water molecules in the docking of protein-DNA complexes and demonstrate its feasibility on a benchmark of 30 high-resolution protein-DNA complexes containing crystallographically-determined water molecules at their interfaces.


Input: Our protocol is capable of reproducing the solvation pattern at the interface and recovers hydrogen-bonded water-mediated contacts in many of the benchmark cases.

hydrogen


Input: Solvated docking leads to an overall improvement in the quality of the generated protein-DNA models for cases with limited conformational change of the partners upon complex formation.


Input: The applicability of this approach is demonstrated on real cases by docking a representative set of 6 complexes using unbound protein coordinates, model-built DNA and knowledge-based restraints.


Input: As HADDOCK supports the inclusion of a variety of NMR restraints, solvated docking is also applicable for NMR-based structure calculations of protein-DNA complexes.


Input: The Cost-Effectiveness of Oral Direct Factor Xa Inhibitors Compared with Low-Molecular-Weight Heparin for the Prevention of Venous Thromboembolism Prophylaxis in Total Hip or Knee Replacement Surgery.


Input: INTRODUCTION: Major orthopedic surgery is associated with a high risk of venous thromboembolism (VTE).


Input: Anticoagulants are recommended to prevent VTE, and recently an oral direct factor Xa inhibitor (FXaI) was approved for this indication.


Input: We compared the cost-effectiveness of FXaIs with low-molecular-weight heparin (LMWH) in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery.


Input: DESIGN: A decision-tree model was developed to compare the cost-effectiveness of oral direct FXaIs (rivaroxaban, apixaban, and edoxaban) to subcutaneous LMWHs (enoxaparin and dalteparin), with separate models for THR and TKR.

rivaroxaban

apixaban

edoxaban


Input: The analysis was conducted over a 180-day postoperative time horizon from the U. S.


Input: Medicare perspective.


Input: The model was developed using TreeAge Pro 2011 (TreeAge Software Inc., Williamstown, MA, USA).


Input: METHODS: Efficacy and safety data (probabilities of distal and proximal deep vein thrombosis, symptomatic pulmonary embolism, and major bleeding) were derived from a systematic review and meta-analysis of phase II and III clinical trials.


Input: Costs and quality-adjusted life-years (QALYs) are reported.


Input: One-way and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty.


Input: RESULTS: In the THR model, the average costs per patient for FXaIs and LMWHs were $18, 762 and $18, 897, respectively, and the QALYs were 0. 938 and 0. 932.


Input: In the TKR model, the average cost per patient for FXaIs and LMWHs were $18, 804 and $18, 991, respectively, and the QALYs were 0. 935 and 0. 931.


Input: In both models, FXaIs dominated LMWH (less costly and more efficacious).


Input: Neither model was sensitive to changes in any of the variables in the one-way sensitivity analyses.


Input: Probabilistic sensitivity analysis indicated that FXaIs were cost-effective in more than 99% of iterations in the THR population and in 98% of iterations in the TKR population assuming a willingness-to-pay threshold of $50, 000/QALY.


Input: CONCLUSION: Oral direct FXaIs may be an economically dominant strategy compared with LMWHs for VTE prophylaxis in patients undergoing either THR or TKR surgery.


Input: Psychologic Disorders and Statin Use: A Propensity Score-Matched Analysis.


Input: STUDY OBJECTIVE: To evaluate the association between statin therapy and the risk of psychologic disorders including schizophrenia, psychosis, major depression, and bipolar disorder in a military population.


Input: DESIGN: Retrospective, observational, population-based, propensity score-matched, cohort study.


Input: SETTING: Database of a patient population enrolled in the San Antonio Military Multi-Market Area as Tricare Prime or Plus.


Input: PATIENTS: Medical records were reviewed from 46, 249 patients aged 30-85 years who were continuously enrolled in the San Antonio Military Multi-Market Area as Tricare Prime or Plus from October 1, 2003-March 1, 2010.


Input: Data were obtained from the Military Health System Management Analysis and Reporting Tool (M2).


Input: Based on drug fills during fiscal year 2005, patients were stratified as statin users (13, 626 patients received at least 90-days supply of statin) or nonusers (32, 623 patients never received a statin during the study period).


Input: A propensity score-matched cohort of 6972 statin users and 6972 nonusers from this population was created.


Input: MEASUREMENTS AND MAIN RESULTS: The occurrence of psychologic disorders between October 1, 2005, and March 1, 2010, was determined using prespecified groups of ICD-9-CM, Psych1: schizophrenia, schizoaffective disorders, and other psychosis; Psych2: major depression and bipolar disorder; Psych3: all psychologic disorders as identified by the Agency for Health Research and Quality-Clinical Classifications (except for categories of childhood or developmental psychiatric disorders).


Input: Between matched pairs of statin users and nonusers, the odds ratios and 95% confidence intervals were as follows: Psych1 (0. 9, 0. 75-1. 05), Psych2 (1. 02, 0. 94-1. 11), and Psych3 (1. 02, 0. 96-1. 1), respectively.


Input: CONCLUSION: The risk of developing psychologic disorders was similar in this cohort of propensity score-matched statin users and nonusers.


Input: Exciton Dynamics in Semiconductor Nanocrystals.


Input: This review article provides an overview of recent advances in the study and understanding of dynamics of excitons in semiconductor nanocrystals (NCs) or quantum dots (QDs).


Input: Emphasis is placed on the relationship between exciton dynamics and optical properties, both linear and nonlinear.


Input: We also focus on the unique aspects of exciton dynamics in semiconductor NCs as compared to those in bulk crystals.


Input: Various experimental techniques for probing exciton dynamics, particularly time-resolved laser methods, are reviewed.


Input: Relevant models and computational studies are also briefly presented.


Input: By comparing different materials systems, a unifying picture is proposed to account for the major dynamic features of excitons in semiconductor QDs.


Input: While the specific dynamic processes involved are material-dependent, key processes can be identified for all the materials that include electronic dephasing, intraband relaxation, trapping, and interband recombination of free and trapped charge carriers (electron and hole).


Input: Exciton dynamics play a critical role in the fundamental properties and functionalities of nanomaterials of interest for a variety of applications including optical detectors, solar energy conversion, lasers, and sensors.


Input: A better understanding of exciton dynamics in nanomaterials is thus important both fundamentally and technologically.


Input: Mechanistic Aspects of hSOD1 Maturation from the Solution Structure of Cu (I)-Loaded hCCS Domain 1 and Analysis of Disulfide-Free hSOD1 Mutants.

Cu (I)

Disulfide


Input: Superoxide dismutase 1 (SOD1) maturation within the cell is mainly accomplished with the SOD1-specific chaperone, CCS, a dimeric protein with three distinct domains in each monomer.

Superoxide


Input: We recently showed that the first domain of human CCS (hCCSD1) is responsible for copper transfer to its protein partner, human SOD1 (hSOD1).

copper


Input: The NMR solution structure of the copper (I)-loaded form of hCCSD1 reported here contributes further to characterization of the copper-transfer mechanism to hSOD1.

copper (I)


Input: NMR spectroscopy was also used to examine the hSOD1 mutants C57A, C146A, and C57A/C146A, which are unable to form the structurally conserved disulfide bond in SOD1, in order to investigate the role of these cysteines during hSOD1 copper acquisition.

disulfide

cysteines


Input: Together, the information on both hCCS and hSOD1, along with a sequence analysis of eukaryotic CCSD1, allows us to propose important mechanistic aspects regarding the copper-transfer process from hCCS to hSOD1.

copper


Input: Metoprolol and diltiazem ameliorate ziprasidone-induced prolonged corrected QT interval in rats.

Metoprolol

diltiazem

ziprasidone


Input: Ziprasidone, an atypical antipsychotic agent, has been shown to increase the corrected QT (QTc) interval in some patients.

Ziprasidone


Input: The aim of this study was to reveal the effects of metoprolol and diltiazem on ziprasidone drug-induced prolonged QTc interval.

metoprolol

diltiazem

ziprasidone


Input: A total of 24 rats were equally divided into the following four groups: the first group was used as the control and received 1 mL/kg saline; 3 mg/kg ziprasidone and saline were administered to the second group; 3 mg/kg ziprasidone and 1 mg/kg metoprolol were administered to the third group and 3 mg/kg ziprasidone and 2 mg/kg diltiazem were administered to the fourth group.

ziprasidone

ziprasidone

metoprolol

ziprasidone

diltiazem


Input: Two hours following application of the drugs, the QTc was calculated by performing electrocardiography in derivation (D) I.


Input: The duration of QTc interval was compared among the four groups.


Input: The mean QTc intervals were significantly increased in the third and fourth groups compared with the second group (p < 0. 0005 and p < 0. 0001, respectively).


Input: The study demonstrated the effectiveness of metoprolol and diltiazem in the prevention of ziprasidone-induced elongation in the QTc interval.

metoprolol

diltiazem

ziprasidone


Input: Both metoprolol and diltiazem may be considered in the prophylactic therapy of high-risk patients who are using ziprasidone.

metoprolol

diltiazem

ziprasidone


Input: Store-operated Ca2 + Entry (SOCE) Induced by Protease-activated Receptor-1 mediates STIM1 Phosphorylation to inhibit SOCE in Endothelial Cells through AMP-activated Protein Kinase and p38beta Mitogen-activated Protein Kinase.

Ca2 +

AMP


Input: The Ca2 + sensor STIM1 is crucial for activation of store-operated Ca2 + entry (SOCE) through TRPC and Orai channels.

Ca2 +

Ca2 +


Input: STIM1 phosphorylation serves as an off-switch for SOCE.


Input: However, the signaling pathway for STIM1 phosphorylation is unknown.


Input: Here we show that SOCE activates AMP-activated protein kinase (AMPK); its effector p38 beta mitogen-activated protein kinase (p38 beta MAPK) phosphorylates STIM1, thus inhibiting SOCE in human lung microvascular endothelial cells (ECs).

AMP


Input: Activation of AMPK using AICAR resulted in STIM1 phosphorylation on serine residues and prevented PAR-1-induced Ca2 + entry.

AICAR

serine

Ca2 +


Input: Further, AICAR pretreatment blocked PAR-1-induced increase in permeability of mouse-lung microvessels.

AICAR


Input: Activation of SOCE with thrombin caused phosphorylation of isoform alpha 1, but not alpha 2 of the AMPK catalytic subunit.


Input: Moreover, knockdown of AMPK alpha 1 augmented SOCE induced by thrombin.


Input: Interestingly, SB203580, a selective inhibitor of p38 MAPK, blocked STIM1 phosphorylation and led to sustained STIM1-puncta formation and Ca2 + entry.

Ca2 +


Input: Of the three p38 MAPK isoforms expressed in ECs, p38 beta knockdown prevented PAR-1-mediated STIM1 phosphorylation and potentiated SOCE.


Input: In addition, inhibition of the SOCE downstream target CaMKK beta or knockdown of AMPK alpha 1 suppressed PAR-1-mediated phosphorylation of p38 beta and hence STIM1.


Input: Thus, our findings demonstrate that SOCE activates CaMKK beta-AMPK alpha 1-p38 beta MAPK signaling to phosphorylate STIM1, thereby suppressing endothelial SOCE and permeability responses.


Input: Novel pentablock copolymer (PLA-PCL-PEG-PCL-PLA) based nanoparticles for controlled drug delivery: Effect of copolymer compositions on the crystallinity of copolymers and in vitro drug release profile from nanoparticles.

PLA

PCL

PEG

PCL

PLA


Input: The purpose of this investigation was to design novel pentablock copolymers (polylatide-polycaprolactone-polyethylene glycol-polycaprolactone-polylatide) (PLA-PCL-PEG-PCL-PLA) to prepare nanoparticle formulations which provide continuous delivery of steroids over a longer duration with minimal burst effect.

polylatide

polycaprolactone

polyethylene glycol

polycaprolactone

polylatide

PLA

PCL

PEG

PCL

PLA

steroids


Input: Another purpose was to evaluate the effect of poly (L-lactide) (PLLA) or poly (D, L-lactide) (PDLLA) incorporation on crystallinity of pentablock copolymers and in vitro release profile of triamcinolone acetonide (selected as model drug) from nanoparticles.

poly (L-lactide)

PLLA

poly (D, L-lactide)

PDLLA

triamcinolone acetonide


Input: PLA-PCL-PEG-PCL-PLA copolymers with different block ratio of PCL/PLA segment were synthesized.

PLA

PCL

PEG

PCL

PLA

PCL

PLA


Input: Release of triamcinolone acetonide from nanoparticles was significantly affected by crystallinity of the copolymers.

triamcinolone acetonide


Input: Burst release of triamcinolone acetonide from nanoparticles was significantly minimized with incorporation of proper ratio of PDLLA in the existing triblock (PCL-PEG-PCL) copolymer.

triamcinolone acetonide

PDLLA

PCL

PEG

PCL


Input: Moreover, pentablock copolymer based nanoparticles exhibited continuous release of triamcinolone acetonide.

triamcinolone acetonide


Input: Pentablock copolymer based nanoparticles can be utilized to achieve continuous near zero-order delivery of corticosteroids from nanoparticles without any burst effect.


Input: Synthesis and Structure Activity Relationship of Tetrahydroisoquinoline-based Potentiators of GluN2C and GluN2D Containing N-Methyl-D-Aspartate Receptors.

Tetrahydroisoquinoline

N-Methyl-D-Aspartate


Input: We describe here the synthesis and evaluation of a series of tetrahydroisoquinolines that show subunit-selective potentiation of NMDA receptors containing the GluN2C or GluN2D subunits.

tetrahydroisoquinolines

NMDA


Input: Bischler-Napieralski conditions were employed in the key step for the conversion of acyclic amides to the corresponding tetrahydroisoquinoline containing analogs.

acyclic amides

tetrahydroisoquinoline


Input: Compounds were evaluated using both two electrode voltage clamp recordings from Xenopus laevis oocytes and imaging of mammalian BHK cells loaded with Ca (2 +)-sensitive dyes.

Ca (2 +)


Input: The most potent analogues had EC50 values of 300 nM and showed over 2-fold potentiation of the response to maximally effective concentrations of glutamate and glycine, but had no effect on responses from NMDA receptors containing the GluN2A or GluN2B subunits, AMPA, kainate, GABA, or glycine receptors or a variety of other potential targets.

glutamate

glycine

NMDA

AMPA

kainate

GABA

glycine


Input: These compounds represent a potent class of small molecule subunit-selective potentiators of NMDA receptors.

NMDA


Input: Design, synthesis and molecular modeling of novel pyrido [2, 3-d] pyrimidine analogs as antifolates: Application of Buchwald-Hartwig aminations of heterocycles.

pyrido [2, 3-d] pyrimidine


Input: Opportunistic infections caused by Pneumocystis jirovecii (P. jirovecii, pj), Toxoplasma gondii (T. gondii, tg) and Mycobacterium avium (M. avium, ma) are the principal causes of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS).


Input: The absence of any animal models for human Pneumocystis jirovecii pneumonia and the lack of crystal structures of pjDHFR and tgDHFR make the design of inhibitors challenging.


Input: A novel series of pyrido [2, 3-d] pyrimidines as selective and potent DHFR inhibitors against these opportunistic infections are presented.

pyrido [2, 3-d] pyrimidines


Input: Buchwald-Hartwig coupling reaction of substituted anilines with pivaloyl protected 2, 4-diamino-6-bromo-pyrido [2, 3-d] pyrimidine was successfully explored to synthesize these analogs.

pivaloyl

2, 4-diamino-6-bromo-pyrido [2, 3-d] pyrimidine


Input: Compound 26 was the most selective inhibitor with excellent potency against pjDHFR.


Input: Molecular modeling studies with a pjDHFR homology model explained the potency and selectivity of 26.


Input: Structural data are also reported for 26 with pcDHFR and 16 and 22 with variants of pcDHFR.


Input: Towards Understanding the Bonding Character in Complexes of Coinage Metals with Lone-Pair Ligands.


Input: CCSD (T) and DFT Computations.


Input: We present CCSD (T) interaction energies and the bonding analysis for complexes of Cu, Ag, and Au with the lone-pair ligands, H2O, OF2, OMe2, NH3, NF3, NMe3, H2S, SF2, SMe2, PH3, PF3, PCl3, PMe3 (ML complexes).

Cu

Ag

Au


Input: Both, electron correlation and relativistic effects, are crucial in the bonding of all complexes.


Input: AuPH3, AuPF3 and AuPCl3 (MPX3) complexes exhibit particularly large relativistic effects, 30-46 kJ/mol.


Input: Upon neglecting relativistic effects the Au-P bonds almost vanish aside from weak long-range van der Waals interactions.

Au

P


Input: Highest binding energies are computed for complexes with Au, followed by Cu and Ag.

Au

Cu

Ag


Input: For all coinage metals the strongest interactions are computed for PX3 ligands followed by SX2 and NX3 OX2 ligands.

NX3 OX2


Input: Upon methylation the interaction energy rises significantly.


Input: Metal-thiol complexes, particularly AuSCH3, form a separate class.

Metal-thiol


Input: Exceptional stability of gold complexes is due to large relativistic enhancement of the electron affinity of Au.

Au


Input: Along with the electron affinity of a metal we link the pattern of interaction energies in ML complexes with ionization potentials (IPs) of ligands.


Input: Strong interaction with P containing ligands is attributed to their lower IP and the lone pair --> metal electron donation accompanied with the back-donation characteristic for P containing ligand.

P


Input: Energy data are accompanied with the Natural Bond Orbital (NBO) analysis.


Input: Computationally less demanding DFT computations with the PBE0 functional provide correct pattern of interaction energies when compared with benchmark CCSD (T) results.


Input: Broad-Range Modulation of Light Emission in Two-Dimensional Semiconductors by Molecular Physisorption Gating.


Input: In the monolayer limit, transition metal dichalcogenides become direct-bandgap, light-emitting semiconductors.

transition metal dichalcogenides


Input: The quantum yield of light emission is low and extremely sensitive to the substrate used, while the underlying physics remains elusive.


Input: In this work, we report over 100 times modulation of light emission efficiency of these two-dimensional semiconductors by physical adsorption of O2 and/or H2O molecules, while inert gases do not cause such effect.


Input: The O2 and/or H2O pressure acts quantitatively as an instantaneously reversible " molecular gating " force, providing orders of magnitude broader control of carrier density and light emission than conventional electric field gating.


Input: Physi-sorbed O2 and/or H2O molecules electronically deplete n-type materials such as MoS2 and MoSe2, which weakens electrostatic screening that would otherwise destabilize excitons, leading to the drastic enhancement in photoluminescence.


Input: In p-type materials such as WSe2, the molecular physisorption results in the opposite effect.


Input: Unique and universal in two-dimensional semiconductors, the effect offers a new mechanism for modulating electronic interactions and implementing optical devices.


Input: Combinatorial Growth and Anisotropy Control of Self-Assembled Epitaxial Ultrathin Alloy Nanowires.


Input: Self-assembled vertical epitaxial nanostructures form a new class of heterostructured materials that has emerged in recent years.


Input: Interestingly, such kind of architectures can be grown using combinatorial processes, implying sequential deposition of distinct materials.


Input: Although opening many perspectives, this combinatorial nature has not been fully exploited yet.


Input: This work demonstrates that the combinatorial character of the growth can be further exploited in order to obtain alloy nanowires coherently embedded in a matrix.


Input: This issue is illustrated in the case of a fully epitaxial system: CoxNi1-x nanowires in CeO2/SrTiO3 (001).


Input: The advantage brought by the ability to grow alloys is illustrated by the control of the magnetic anisotropy of the nanowires when passing from pure Ni wires to CoxNi1-x alloys.

Ni


Input: Further exploitation of this combinatorial approach may pave the way toward full three-dimensional heteroepitaxial architectures through axial structuring of the wires.


Input: Conformational determinants of the activity of Antiproliferative factor glycopeptide.


Input: The antiproliferative factor (APF) involved in interstitial cystitis is a glycosylated nonapeptide (TVPAAVVVA) containing a sialylated core alpha-O-disaccharide linked to the N-terminal threonine.

nonapeptide

alpha-O-disaccharide

N

threonine


Input: The chemical structure of APF was deduced using spectroscopic techniques and confirmed using total syn-thesis.


Input: The synthetic APF provided a platform to study amino acid modifications and their effect on APF activity, based on which a structure-activity relationship (SAR) for APF activity was previously proposed.

amino acid


Input: However, this SAR model could not explain the change in activity associated with minor al-terations in the peptide sequence.


Input: Presented is computational analysis of 14 APF derivatives to identify structural trends from which a more detailed SAR is obtained.


Input: The APF activity is found to be dictated by the close interplay between carbohydrate-peptide and peptide-peptide interactions.

carbohydrate


Input: The former in-volves hydrogen bond and hydrophobic interactions and the latter is dominated by hydrophobic interac-tions.

hydrogen


Input: The highly flexible hydrophobic peptide adopts collapsed conformations separated by low energy barriers.


Input: APF activity correlates with hydrophobic clustering associated with amino acids 4A, 6V and 8V.

amino acids


Input: Peptide conformations are highly sensitive to single point mutations, which explain the experi-mental trends.


Input: The presented SAR will act as a guide for lead optimization of more potent APF ana-logues of potential therapeutic utility.


Input: Active Layer-Incorporated, Spectrally-Tuned Au/SiO2 Core/Shell Nanorod-Based Light Trapping for Organic Photovoltaics.

Au


Input: We demonstrated that incorporation of octadecyltrimethoxysilane (OTMS) functionalized, spectrally tuned, gold/silica (Au/SiO2) core/shell nanospheres and nanorods into the active layer of an organic photovoltaic (OPV) device led to an in increase photo conversion efficiency (PCE).

octadecyltrimethoxysilane

OTMS

silica

Au


Input: A silica shell layer was added onto Au core nanospheres and nanorods in order to provide an electrically insulating surface that does not interfere with carrier generation and transport inside the active layer.

silica

Au


Input: Functionalization of the Au/SiO2 core/shell nanoparticles with the OTMS organic ligand was then necessary in order to transfer the Au/SiO2 core/shell nanoparticles from an ethanol solution into an OPV polymer-compatible solvent, such as dichlorobenzene (DCB).

Au

OTMS

Au

ethanol

dichlorobenzene

DCB


Input: The OTMS-functionalized Au/SiO2 core/shell nanorods and nanospheres were then incorporated into the active layers of two OPV polymer systems: a poly (3-hexylthiophene): [6, 6]-phenyl-C61-butyric acid methyl ester (P3HT: PCB60M) OPV device and a poly [2, 6-4, 8-di (5-ethylhexylthienyl) benzo [1, 2-b; 3, 4-b] dithiophene-alt-5-dibutyloctyl-3, 6-bis (5-bromothiophen-2-yl) pyrrolo [3, 4-c] pyrrole-1, 4-dione] (PBDTT-DPP: PC60BM) OPV device.

OTMS

Au

poly (3-hexylthiophene)

[6, 6]-phenyl-C61-butyric acid methyl ester

poly [2, 6-4, 8-di (5-ethylhexylthienyl) benzo [1, 2-b; 3, 4-b] dithiophene-alt-5-dibutyloctyl-3, 6-bis (5-bromothiophen-2-yl) pyrrolo [3, 4-c] pyrrole-1, 4-dione]

PBDTT-DPP


Input: For the P3HT: PC60BM polymer with a band edge of ~ 700 nm, the addition of the core/shell nanorods with an aspect ratio (AR) of ~ 2. 5 (extinction peak ~ 670 nm) resulted in a 7. 1% improvement in PCE, while for the PBDTT-DPP: PC60BM polymer with a band edge ~ 860 nm, the addition of core/shell nanorods with an AR of ~ 4 (extinction peak ~ 830 nm) resulted in a 14. 4% improvement in PCE.

PBDTT-DPP


Input: The addition of Au/SiO2 core/shell nanospheres to the P3HT: PC60BM-polymer resulted in a 2. 7% improvement in PCE, while their addition to a PBDTT-DPP: PC60BM polymer resulted in a 9. 1% improvement.

Au

PBDTT-DPP


Input: The PCE and Jsc enhancements were consistent with external quantum efficiency (EQE) measurements and the EQE enhancements spectrally matched the extinction spectra of Au/SiO2 nanospheres and nanorods in both OPV polymer systems.

Au


Input: Interactions between solid surfaces with pre-adsorbed poly (ethylenimine) (PEI) layers: effect of unadsorbed free PEI chains.

poly (ethylenimine)

PEI

PEI


Input: Poly (ethylenimine) (PEI) polyelectrolytes have been widely used to tune the stability, rheology, or adhesion properties of colloidal suspensions due to their strong tendency to adsorb to solid surfaces.

Poly (ethylenimine)

PEI


Input: They have also gained importance as gene carriers in biomedical applications, in which the anionic DNA chains are complexed and condensed to form PEI/DNA polyplexes.

PEI


Input: Some reported literatures have recently shown that the overdosed PEI chains, which are free in the solution mixture, also play a vital role in promoting the gene transfection, but the reason is unclear.

PEI


Input: In this work, we present the results of using total internal reflection microscopy (TIRM) to measure the interaction forces between a Brownian colloidal sphere and a flat glass plate in the presence of overdosed free PEI cationic chains, when both surfaces were saturated adsorbed with the PEI chains.

PEI

PEI


Input: The colloidal sphere pre-adsorbed with PEI chains was chosen to mimic the PEI/DNA polyplex.

PEI

PEI


Input: Results for the potential energy of interaction measured for model polyplex (e. g., PEI-coated sphere) interacting with a PEI-coated glass surface in the presence of overdosed free PEI chains at various pH values and salt concentrations were presented.

PEI

PEI

PEI


Input: As can be shown by direct force measurements, the interaction potentials in NaCl salt solution are dominated by repulsive forces originating from diffuse layer overlap and gravitational attraction.

NaCl


Input: However, the presence of free PEI chains in the solution mixture produces a long-ranged (> 60 nm) attractive force between two PEI-coated surfaces with the range and magnitude tunable by pH value, PEI and salt concentrations.

PEI

PEI

PEI


Input: The possible mechanisms of this long-ranged attractive force are discussed.


Input: A better understanding of this free PEI-induced attractive force will be useful in the development of improved PEI/DNA polyplexes systems for biomedical applications.

PEI

PEI


Input: Evaluation of the In Vitro Cytotoxicity of Cross-Linked Biomaterials.


Input: This study evaluated the in vitro cytotoxicity of poly (propylene fumarate) (PPF).

poly (propylene fumarate)

PPF


Input: PPF is an aliphatic biodegradable polymer that has been well characterized for use in bone tissue engineering scaffolds.

PPF


Input: Four different cell types, human mesenchymal stem cells (hMSC), fibroblasts (L929), preosteoblasts (MC3T3), and canine mesenchymal stem cells (cMSC), were used to evaluate the cytotoxicity of PPF.

PPF


Input: These cell types represent the tissues that PPF would interact with in vivo as a bone tissue scaffold.

PPF


Input: The sol fraction of the PPF films was measured and then utilized to estimate cross-linking density.

PPF


Input: Cytotoxicity was evaluated using XTT assay and fluorescence imaging.

XTT


Input: Results showed that PPF supported similar cell metabolic activities of hMSC, L929, MC3T3, and cMSC compared to the noncytotoxic control, high-density polyethylene (HDPE) and were statistically different than those cultured with the cytotoxic control, a polyurethane film containing 0. 1% zinc diethyldithiocarbamate (ZCF).

PPF

polyethylene

polyurethane

zinc diethyldithiocarbamate

ZCF


Input: Results showed differing cellular responses to ZCF, the cytotoxic control.

ZCF


Input: The L929 cells had the lowest cell metabolic activity levels after exposure to ZCF compared to the cell metabolic activity levels of the MC3T3, hMSC, or cMSC cells.

ZCF


Input: Qualitative verification of the results using fluorescence imaging demonstrated no change in cell morphology, vacuolization, or detachment when cultured with PPF compared to HDPE or blank media cultures.

PPF


Input: Overall, the cytotoxicity response of the cells to PPF was demonstrated to be similar to the cytotoxic response of cells to known noncytotoxic materials (HDPE).

PPF


Input: Fas receptor-deficient lpr mice are protected against acetaminophen hepatotoxicity due to higher glutathione synthesis and enhanced detoxification of oxidant stress.

acetaminophen

glutathione


Input: Acetaminophen (APAP) overdose is a classical model of hepatocellular necrosis; however, the involvement of the Fas receptor in the pathophysiology remains controversial.

Acetaminophen

APAP


Input: Fas receptor-deficient (lpr) and C57BL/6 mice were treated with APAP to compare the mechanisms of hepatotoxicity.

APAP


Input: Lpr mice were partially protected against APAP hepatotoxicity as indicated by reduced plasma ALT and GDH levels and liver necrosis.

APAP


Input: Hepatic Cyp2e1 protein, adduct formation and hepatic glutathione (GSH) depletion were similar, demonstrating equivalent reactive metabolite generation.

glutathione

GSH


Input: There was no difference in cytokine formation or hepatic neutrophil recruitment.


Input: Interestingly, hepatic GSH recovered faster in lpr mice than in wild type animals resulting in enhanced detoxification of reactive oxygen species.

GSH

oxygen


Input: Driving the increased GSH levels, mRNA induction and protein expression of glutamate-cysteine ligase (gclc) were higher in lpr mice.

GSH

glutamate

cysteine


Input: Inducible nitric oxide synthase (iNOS) mRNA and protein levels at 6h were significantly lower in lpr mice, which correlated with reduced nitrotyrosine staining.

nitric oxide

nitrotyrosine


Input: Heat shock protein 70 (Hsp70) mRNA levels were substantially higher in lpr mice after APAP.

APAP


Input: Conclusion: Our data suggest that the faster recovery of hepatic GSH levels during oxidant stress and peroxynitrite formation, reduced iNOS expression and enhanced induction of Hsp70 attenuated the susceptibility to APAP-induced cell death in lpr mice.

GSH

peroxynitrite

APAP


Input: A proteome-wide visual screen identifies fission yeast proteins localizing to DNA double-strand breaks.


Input: DNA double-strand breaks (DSBs) are a major threat to genome integrity.


Input: Proteins involved in DNA damage checkpoint signaling and DSB repair often relocalize and concentrate at DSBs.


Input: Here, we used an ORFeome library of the fission yeast Schizosaccharomyces pombe to systematically identify proteins targeted to DSBs.


Input: We found 51 proteins that, when expressed from a strong exogenous promoter on the ORFeome plasmids, were able to form a distinct nuclear focus at an HO endonuclease-induced DSB.


Input: The majority of these proteins have known connections to DNA damage response, but few have been visualized at a specific DSB before.


Input: Among the screen hits, 37 can be detected at DSBs when expressed from native promoters.


Input: We classified them according to the focus emergence timing of the endogenously tagged proteins.


Input: Eight of these 37 proteins are yet unnamed.


Input: We named these eight proteins DNA-break-localizing proteins (Dbls) and performed preliminary functional analysis on two of them, Dbl1 (SPCC2H8. 05c) and Dbl2 (SPCC553. 01c).


Input: We found that Dbl1 and Dbl2 contribute to the normal DSB targeting of checkpoint protein Rad26 (homolog of human ATRIP) and DNA repair helicase Fml1 (homolog of human FANCM), respectively.


Input: As the first proteome-wide inventory of DSB-localizing proteins, our screen result will be a useful resource for understanding the mechanisms of eukaryotic DSB response.


Input: Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission.


Input: Mitochondria and peroxisomes can be fragmented by the process of fission.


Input: The fission machineries of both organelles share a set of proteins.


Input: GDAP1 is a tail-anchored protein of mitochondria and induces mitochondrial fragmentation.


Input: Mutations in GDAP1 lead to Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy, and affect mitochondrial dynamics.


Input: Here, we show that GDAP1 is also targeted to peroxisomes mediated by the import receptor Pex19.


Input: Knockdown of GDAP1 leads to peroxisomal elongation that can be rescued by re-expressing GDAP1 and by missense mutated forms found in CMT patients.


Input: GDAP1-induced peroxisomal fission is dependent on the integrity of its hydrophobic domain 1, and on Drp1 and Mff, as is mitochondrial fission.


Input: Thus, GDAP1 regulates mitochondrial and peroxisomal fission by a similar mechanism.


Input: However, our results reveal also a more critical role of the amino-terminal GDAP1 domains, carrying most CMT-causing mutations, in the regulation of mitochondrial compared to peroxisomal fission.

amino


Input: Down-regulation of LRRK2 in control and DAT transfected HEK cells increases manganese-induced oxidative stress and cell toxicity.

manganese


Input: The extra-pyramidal symptoms associated with manganism often overlap with that seen in Parkinsonism suggesting a common link between the two disorders.

manganism


Input: Since wide deviations are observed in susceptibility and characteristics of the symptoms observed in manganism, these differences may be due to underlying genetic variability.

manganism


Input: Genes linked to early onset of Parkinsonism which includes ATP13A2 and parkin have already been suggested to promote development of Mn toxicity.

Mn


Input: Of the other Parkinson-linked genes, mutations in LRRK2, an autosomal dominant gene, represent another likely candidate involved in the development of manganism.

manganism


Input: In this paper the effect of shRNA LRRK2 knock-down on Mn toxicity was examined in control and DAT transfected HEK293 cells.

Mn


Input: Results demonstrate that LRRK2 down-regulation potentiates Mn toxicity in both control and DAT-transfected cell as well as potentiates DA toxicity.

Mn


Input: Combined treatment of Mn and DA further augments cell toxicity, ROS production and JNK phosphorylation in LRRK2 deficient cells compared to controls.

Mn


Input: Consistent with studies demonstrating that LRRK2 plays a role in the phosphorylation of p38, our results similarly demonstrate a decrease in p38 activation in LRRK2 knock-down cells.


Input: Our findings suggest that null mutations in LRRK2 which cause Parkinsonism potentiate Mn toxicity and increase susceptibility to develop manganism.

Mn

manganism


Input: Dendritic architectures based on bis-MPA: functional polymeric scaffolds for application-driven research.

bis-MPA


Input: Dendritic polymers are highly branched, globular architectures with multiple representations of functional groups.


Input: These nanoscale organic frameworks continue to fascinate researchers worldwide and are today under intensive investigation in application-driven research.


Input: A large number of potential application areas have been suggested for dendritic polymers, including theranostics, biosensors, optics, adhesives and coatings.


Input: The transition from potential to real applications is strongly dictated by their commercial accessibility, scaffolding ability as well as biocompatibility.


Input: A dendritic family that fulfills these requirements is based on the 2, 2-bismethylolpropionic acid (bis-MPA) monomer.

2, 2-bismethylolpropionic acid

bis-MPA


Input: This critical review is the first of its kind to cover most of the research activities generated on aliphatic polyester dendritic architectures based on bis-MPA.

bis-MPA


Input: It is apparent that these scaffolds will continue to be in the forefront of cutting-edge research as their structural variations are endless including dendrons, dendrimers, hyperbranched polymers, dendritic-linear hybrids and their hybridization with inorganic surfaces.


Input: Differential Activity of Plasma and Vacuolar Membrane Transporters Contributes to Genotypic Differences in Salinity Tolerance in a Halophyte Species, Chenopodium quinoa.


Input: Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants.


Input: Earlier, we reported that quinoa (Chenopodium quinoa Willd.), a facultative C3 halophyte species, can efficiently control the activity of slow (SV) and fast (FV) tonoplast channels to match specific growth conditions by ensuring that most of accumulated Na + is safely locked in the vacuole (Bonales-Alatorre et al. (2013) Plant Physiology).

Na +


Input: This work extends these finding by comparing the properties of tonoplast FV and SV channels in two quinoa genotypes contrasting in their salinity tolerance.


Input: The work is complemented by studies of the kinetics of net ion fluxes across the plasma membrane of quinoa leaf mesophyll tissue.


Input: Our results suggest that multiple mechanisms contribute towards genotypic differences in salinity tolerance in quinoa.


Input: These include: (i) a higher rate of Na + exclusion from leaf mesophyll; (ii) maintenance of low cytosolic Na + levels; (iii) better K + retention in the leaf mesophyll; (iv) a high rate of H + pumping, which increases the ability of mesophyll cells to restore their membrane potential; and (v) the ability to reduce the activity of SV and FV channels under saline conditions.

Na +

Na +

K +

H +


Input: These mechanisms appear to be highly orchestrated, thus enabling the remarkable overall salinity tolerance of quinoa species.


Input: Basic evidence for epidermal H2O2/ONOO--mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB-UVB-activated pseudocatalase PC-KUS.

ONOO


Input: Nonsegmental vitiligo (NSV) is characterized by loss of inherited skin color.


Input: The cause of the disease is still unknown despite accumulating in vivo and in vitro evidence of massive epidermal oxidative stress via H2O2 and peroxynitrite (ONOO (-)) in affected individuals.

peroxynitrite

ONOO (-)


Input: The most favored hypothesis is based on autoimmune mechanisms.


Input: Strictly segmental vitiligo (SSV) with dermatomal distribution is a rare entity, often associated with stable outcome.


Input: Recently, it was documented that this form can be associated with NSV (mixed vitiligo).


Input: We here asked the question whether ROS and possibly ONOO (-) could be players in the pathogenesis of SSV.

ONOO (-)


Input: Our in situ results demonstrate for the first time epidermal biopterin accumulation together with significantly decreased epidermal catalase, thioredoxin/thioreoxin reductase, and MSRA/MSRB expression.


Input: Moreover, we show epidermal ONOO (-) accumulation.

ONOO (-)


Input: In vivo FT-Raman spectroscopy reveals the presence of H2O2, methionine sulfoxide, and tryptophan metabolites; i. e., N-formylkynurenine and kynurenine, implying Fenton chemistry in the cascade (n = 10).

methionine sulfoxide

tryptophan

N-formylkynurenine

kynurenine


Input: Validation of the basic data stems from successful repigmentation of skin and eyelashes in affected individuals, regardless of SSV or segmental vitiligo in association with NSV after reduction of epidermal H2O2 (n = 5).


Input: Taken together, our contribution strongly supports H2O2/ONOO-mediated stress in the pathogenesis of SSV.

ONOO-


Input: Our findings offer new treatment intervention for lost skin and hair color.-Schallreuter, K.


Input: U., Salem, M.


Input: A.


Input: E.


Input: L., Holtz, S., Panske, A.


Input: Basic evidence for epidermal H2O2/ONOO (-)-mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB-UVB-activated pseudocatalase PC-KUS.

ONOO (-)


Input: Caveolae-Mediated Endocytosis of Conjugated Polymer Nanoparticles.


Input: Understanding the cellular entry pathways of synthetic biomaterials is highly important to improve overall labeling and delivery efficiency.


Input: Herein, cellular entry mechanisms of conjugated polymer nanoparticles (CPNs) are presented.


Input: CPNs are intrinsic fluorescent materials used for various biological applications.


Input: While CPNs cause no toxicity, decreased CPN uptake is observed from cancer cells pretreated with genistein, which is an inhibitor of caveolae-mediated endocytosis (CvME).

genistein


Input: CvME is further confirmed by high co-localization with caveolin-1 proteins found in the caveolae and caveosomes.


Input: Excellent photophysical properties, non-toxicity, and non-destructive delivery pathways support that CPNs are promising multifunctional carriers minimizing degradation of contents during delivery.


Input: Identification of an Inhibitory Mechanism of Luteolin on the Insulin-Like Growth Factor-1 Ligand-Receptor Interaction.

Luteolin


Input: Using single-molecule force measurement and fluorescence imaging, we have demonstrated that luteolin has an inhibitory effect on IGF-1 ligand-receptor binding, the initial step in IGF-1 signaling.

luteolin


Input: This inhibition mechanism, which was confirmed by flow cytometry and molecular docking, could play a role in cancer therapy.


Input: Strong Parent-of-Origin Effects in the Association of KCNQ1 Variants with Type 2 Diabetes Mellitus in American Indians.


Input: Parent-of-origin effects were observed in an Icelandic population for several genetic variants associated with type 2 diabetes, including those in KLF14 (rs4731702), MOB2 (rs2334499) and KCNQ1 (rs2237892, rs231362).


Input: We analyzed parent-of-origin effects for these variants, along with two others in KCNQ1 identified in previous genome-wide association studies (rs2237895, rs2299620), in 7351 Pima Indians from 4549 nuclear families; 34% of participants had diabetes.


Input: In a subset of 287 normoglycemic individuals, acute insulin secretion was measured by an intravenous glucose tolerance test.

glucose


Input: Statistically significant (P < 0. 05) parent-of-origin effects were seen for association with type 2 diabetes for all variants.


Input: The strongest effect was seen at rs2299620 in KCNQ1: the C allele was associated with increased diabetes when maternally-derived (odds ratio = 1. 92, P = 4. 1x10 (-12)), but not when paternally-derived (odds ratio = 0. 93, P = 0. 47; P = 9. 9x10 (-6) for difference in maternal and paternal effects).


Input: A maternally-derived C allele was also associated with a 28% decrease in insulin secretion (P = 0. 002).


Input: This study confirms parent-of-origin effects in the association with type 2 diabetes for variants in KLF14, MOB2 and KCNQ1.


Input: In Pima Indians the effect of maternally-derived KCNQ1 variants appears to be mediated through decreased insulin secretion, and is particularly strong, accounting for 4% of the variance in liability to diabetes.


Input: Matrix Metalloproteinase Inhibitors Based on the 3-Mercaptopyrrolidine Core.


Input: New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamido pyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated.

pyrrolidine mercaptosulfide

2-mercaptocyclopentane arylsulfonamide

3-mercapto-4-arylsulfonamido pyrrolidine


Input: Exhibiting unique properties over other MMPIs (e. g., hydroxamates), these newly reported compounds are capable of modulating activities of several MMPs in the low nanomolar range, including MMP-2 (~ 2 to 50 nM), MMP-13 (~ 2 to 50 nM), and MMP-14 (~ 4 to 60 nM).

hydroxamates


Input: Additionally these compounds are selective to intermediate-and deep-pocket MMPs but not shallow-pocketed MMPs (e. g., MMP-1, ~ 850 to > 50, 000 nM; MMP-7, ~ 4, 000 to > 25, 000 nM).


Input: Our previous work with the mercaptosulfide functionality attached to both cyclopentane and pyrrolidine frameworks demonstrated that the cis-(3S, 4R)-stereochemistry was optimal for all of the MMPs tested.

mercaptosulfide

cyclopentane

pyrrolidine


Input: However, in our newest compounds an interesting shift of preference to the trans-form of the mercaptosulfonamides was observed with increased oxidative stability and biological compatibility.

mercaptosulfonamides


Input: We also report several kinetic and biological characteristics showing that these compounds may be used to probe the mechanistic activities of MMPs in disease.


Input: Design, Synthesis and Biological Evaluation of Aminoalkylindole Derivatives as Cannabinoid Receptor Ligands with Potential for Treatment of Alcohol Abuse.

Aminoalkylindole

Alcohol


Input: Attenuation of increased endocannabinoid signaling with a CB1R neutral antagonist might offer a new therapeutic direction for treatment of alcohol abuse.

alcohol


Input: We have recently reported that a mono-hydroxylated metabolite of the synthetic aminoalkylindole cannabinoid JHW-073 (3) exhibits neutral antagonist activity at CB1Rs and thus may serve as a promising lead for the development of novel alcohol abuse therapies.

aminoalkylindole

alcohol


Input: In the current study, we show that systematic modification of an aminoalkylindole scaffold identifies two new compounds with dual CB1R antagonist/CB2R agonist activity.

aminoalkylindole


Input: Similar to the CB1R antagonist/inverse agonist rimonabant, analogues 27 and 30 decrease oral alcohol self-administration, without affecting total fluid intake and block the development of alcohol-conditioned place preference.

alcohol

alcohol


Input: Collectively, these initial findings suggest that design and systematic modification of aminoalkylindoles such as 3 may lead to development of novel cannabinoid ligands with dual CB1R antagonist/CB2R agonist activity with potential for use as treatments of alcohol abuse.

aminoalkylindoles

alcohol


Input: Milk-Derived Peptides, Val-Pro-Pro and Ile-Pro-Pro, Attenuate Atherosclerosis Development in Apolipoprotein E-Deficient Mice: A Preliminary Study.

Val-Pro-Pro

Ile-Pro-Pro


Input: Abstract Milk-derived peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), have angiotensin I-converting enzyme inhibitory activities and blood pressure-lowering effects.

Val-Pro-Pro

Ile-Pro-Pro


Input: We examined the effects of these peptides on the development of atherosclerosis in apolipoprotein E-deficient [apoE (-/-)] mice.


Input: For 31 weeks, six-week-old male apoE (-/-) mice received a diet that included one of the following: fermented milk containing both VPP and IPP; casein hydrolysate containing both of these peptides; synthesized VPP; synthesized IPP; enalapril; captopril; or control diet.

enalapril

captopril


Input: At the end of feeding, blood biochemistry, aortic atherogenesis, and gene expression by DNA microarray analysis were evaluated.


Input: There were no significant changes in the plasma lipid levels and 8-isoprostane, a marker of oxidative stress.


Input: The area ratio of intima to media in the aortic arch was significantly lower in the fermented milk, casein hydrolysate, synthesized VPP, enalapril, and captopril groups than in the control group.

enalapril

captopril


Input: As is common with diets containing VPP and/or IPP, we observed reductions in mRNA expression of inflammatory cytokines, such as interleukin (IL)-6 and IL-1 beta, oxidized low-density lipoprotein receptor, and transcription regulators.


Input: These results suggest that a continuous intake of VPP and IPP might be beneficial for preventing atherosclerosis caused by hypercholesterolemia.


Input: Inhibition of Foodborne Pathogens by Pomegranate Juice.


Input: Abstract Pomegranates have health-promoting benefits because of their polyphenol constituents.

polyphenol


Input: Previous studies have demonstrated the antimicrobial activity of aqueous and organic extracts of pomegranate components and by-products.


Input: We sought to determine the antimicrobial activity against 40 foodborne pathogens representing eight bacterial species using juice itself.


Input: In addition, we sought to determine the synergistic antimicrobial activity between pomegranate juice and other plant products displaying antimicrobial activity.


Input: The antimicrobial activity of pomegranate juice was dependent on the test organism, which varied to highly susceptible (four Gram-positive species) to unaffected (Salmonella and Escherichia coli O157: H7).


Input: Two Gram-negative species, which were inhibited were Helicobacter pylori and Vibrio parahemolyticus.


Input: No synergistic antimicrobial activity was seen between pomegranate and either barberry, oregano, or cranberry.


Input: The antimicrobial activity of pomegranate juice is dependent on the test organism and extraction method.


Input: The sensitivity of H. pylori suggests that pomegranate juice may be an alternative or supplemental treatment for gastric ulcers caused by this organism.


Input: Designed amphiphilic beta-sheet peptides as templates for paraoxon adsorption and detection.

paraoxon


Input: Amphiphilic peptides were designed to fold into a beta-sheet monolayer structure while presenting the catalytic triad residues of the enzyme, acetylcholinesterase (Glu, His and Ser), to a solution containing the organophosphate, paraoxon.

Glu

His

Ser

organophosphate

paraoxon


Input: Three peptides, in which the catalytic triad residues were arranged in different orders along the strand, were generated to reveal potential differences in interactions with paraoxon as a function of the order of these amino acids.

paraoxon

amino acids


Input: One additional peptide with amino acids introduced in random order was studied to highlight the contribution of the beta-sheet secondary structure to any interactions with paraoxon.

amino acids

paraoxon


Input: Langmuir isotherms, Brewster angle microscope at interfaces and circular dichroism measurements in bulk showed that both the beta-sheet conformation and the order of the amino acids along the strand influenced the interactions of paraoxon with the peptides.

amino acids

paraoxon


Input: Compression isotherm curves, as well as Brewster-angle microscopy images, provided evidence for enhanced adsorption of the paraoxon to the monolayers of peptides which present neighboring Glu and Ser residues along the hydrophilic face of the beta-strand.

paraoxon

Glu

Ser


Input: Circular dichroism revealed that the peptide most sensitive to interactions with paraoxon was that with the triad residues in the order Glu, Ser and His, which appears to be appropriate for supporting a catalytic mechanism similar to that in acetylcholinesterase enzyme.

paraoxon

Glu

Ser

His


Input: These rationally designed peptides may be further utilized for the development of technologies for organophosphate adsorption and detection.

organophosphate


Input: Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing.


Input: Abstract A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available.


Input: The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane.


Input: The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear.


Input: Four formulations and a control were examined in this study using cidofovir as the model drug.

cidofovir


Input: Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system.


Input: The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system.


Input: Among the formulations investigated, poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions.

poly (lactic-co-glycolic acid)

poly (ethylene glycol)

poly (lactic-co-glycolic acid)

cidofovir


Input: Membrane fusion-competent virus-like proteoliposomes and proteinaceous supported bilayers made directly from cell plasma membranes.


Input: Virus-like particles are useful materials for studying virus-host interactions in a safe manner.


Input: However, the standard production of pseudovirus based on the Vesicular Stomatitis Virus (VSV) backbone is an intricate procedure that requires trained laboratory personnel.


Input: In this work, a new strategy for creating virus-like proteoliposomes (VLPLs) and virus-like supported bilayers (VLSBs) is presented.


Input: This strategy uses a cell blebbing technique to induce the formation of nanoscale vesicles from the plasma membrane of BHK cells expressing the hemagglutinin (HA) fusion protein of influenza X-31.


Input: These vesicles and supported bilayers contain HA and are used to carry out single particle membrane fusion events, monitored using total internal reflection fluorescence microscopy.


Input: The results of these studies show that the VLPLs and VLSBs contain HA proteins that are fully competent to carry out membrane fusion, including the formation of a fusion pore and the release of fluorophores loaded into vesicles.


Input: This new strategy for creating spherical and planar geometry virus-like membranes has many potential applications.


Input: VLPLs could be used to study fusion proteins of virulent viruses in a safe manner, or they could be used as therapeutic delivery particles to transport beneficial proteins co-expressed in the cells to a target cell.


Input: VLSBs could facilitate high throughput screening of antiviral drugs or pathogen-host cell interactions.


Input: Synthesis of Amylose-Polystyrene Inclusion Complexes by a Facile Preparation Route.

Polystyrene


Input: The formation of amylose-polystyrene inclusion complexes via a novel two-step approach is described.

polystyrene


Input: In the first-step, styrene was inserted inside the amylose helical cavity, followed by free radical polymerization in the second step.


Input: The inclusion complexes were characterized by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), Ultraviolet Spectroscopy (UV), X-ray Diffraction (XRD), Atomic Force Microscopy (AFM), and Differential Scanning Calorimetry (DSC).


Input: The formation of polystyrene was confirmed by gel Permeation Chromatography (GPC).

polystyrene


Input: The molecular weight of polystyrene can be varied by using amylose bearing different molar masses.

polystyrene


Input: The approach described here is general and could be used to synthesis other host-polymer inclusion complexes for which long chains of polymeric guests are difficult to insert into the host cavity.


Input: Synthesis of Silver Octahedra with Controlled Sizes and Optical Properties via Seed-Mediated Growth.

Silver


Input: Silver octahedra with edge lengths controlled in the range of 20-72 nm were synthesized via seed-mediated growth.

Silver


Input: The key to the success of this synthesis is the use of single-crystal Ag seeds with uniform and precisely controlled sizes to direct the growth and the use of citrate as a selective capping agent for the {111} facets.

Ag

citrate


Input: Our mechanistic studies demonstrated that Ag seeds with both cubic and quasi-spherical shapes could evolve into octahedra.

Ag


Input: For the first time, we were able to precisely control the edge lengths of Ag octahedra below 100 nm, and the lower limit of size could even be pushed down to 20 nm.

Ag


Input: Using the as-obtained Ag octahedra as sacrificial templates, Au nanocages with an octahedral shape and precisely tunable optical properties were synthesized through a galvanic replacement reaction.

Ag

Au


Input: Such hollow nanostructures are promising candidates for a broad range of applications related to optics, catalysis, and biomedicine.


Input: Highly Enantioselective Zirconium-Catalyzed Cyclization of Aminoalkenes.

Zirconium

Aminoalkenes


Input: Aminoalkenes are catalytically cyclized in the presence of cyclopentadienylbis (oxazolinyl) borato group 4 complexes {PhB (C5H4) (Ox (R)) 2} M (NMe2) 2 (M = Ti, Zr, Hf; Ox (R) = 4, 4-dimethyl-2-oxazoline, 4S-isopropyl-5, 5-dimethyl-2-oxazoline, 4S-tert-butyl-2-oxazoline) at room temperature and below, affording five-, six-, and seven-membered N-heterocyclic amines with enantiomeric excesses of > 90% in many cases and up to 99%.

Aminoalkenes

cyclopentadienylbis (oxazolinyl) borato

{PhB (C5H4) (Ox (R)) 2} M (NMe2) 2

Ti

Zr

Hf

Ox (R)

4, 4-dimethyl-2-oxazoline

4S-isopropyl-5, 5-dimethyl-2-oxazoline

N-heterocyclic amines


Input: Mechanistic investigations of this highly selective system employed synthetic tests, kinetics, and stereochemistry.


Input: Secondary aminopentene cyclizations require a primary amine (1-2 equiv vs catalyst).

Secondary aminopentene

primary amine


Input: Aminoalkenes are unchanged in the presence of a zirconium monoamido complex {PhB (C5H4) (Ox (4S-iPr, Me2)) 2} Zr (NMe2) Cl or a cyclopentadienylmono (oxazolinyl) borato zirconium diamide {Ph2B (C5H4) (Ox (4S-iPr, Me2))} Zr (NMe2) 2.

Aminoalkenes

zirconium monoamido

{PhB (C5H4) (Ox (4S-iPr, Me2)) 2} Zr (NMe2) Cl

cyclopentadienylmono (oxazolinyl) borato zirconium diamide {Ph2B (C5H4) (Ox (4S-iPr, Me2))} Zr (NMe2) 2


Input: Plots of initial rate versus [substrate] show a rate dependence that evolves from first-order at low concentration to zero-order at high concentration, and this is consistent with a reversible substrate-catalyst interaction preceding an irreversible step.


Input: Primary kinetic isotope effects from substrate conversion measurements (k' obs ((H))/k' obs ((D)) = 3. 3 +/- 0. 3) and from initial rate analysis (k2 ((H))/k2 ((D)) = 2. 3 +/- 0. 4) indicate that a N-H bond is broken in the turnover-limiting and irreversible step of the catalytic cycle.

N-H


Input: Asymmetric hydroamination/cyclization of N-deutero-aminoalkenes provides products with higher optical purities than obtained with N-proteo-aminoalkenes.

N-deutero-aminoalkenes

N-proteo-aminoalkenes


Input: Transition state theory, applied to the rate constant k2 that characterizes the irreversible step, provides activation parameters consistent with a highly organized transition state (Delta S (|=) =-43 (7) cal. mol (-1) K (-1)) and a remarkably low enthalpic barrier (Delta H (|=) = 6. 7 (2) kcal. mol (-1)).


Input: A six-centered, concerted transition state for C-N and C-H bond formation and N-H bond cleavage involving two amidoalkene ligands is proposed as most consistent with the current data.

C-N

C-H

N-H

amidoalkene


Input: Elucidation of the biochemical basis for a clinical drug-drug interaction between atorvastatin and 5-(N-(4-((4-ethylbenzyl) thio) phenyl) sulfamoyl)-2-methyl benzoic acid (CP-778 875), a subtype selective agonist of the peroxisome proliferator-activated receptor alpha.

atorvastatin

5-(N-(4-((4-ethylbenzyl) thio) phenyl) sulfamoyl)-2-methyl benzoic acid

CP-778 875


Input: Abstract 1. 5-(N-(4-((4-ethylbenzyl) thio) phenyl) sulfamoyl)-2-methyl benzoic acid (CP-778 875), an agonist of the peroxisome proliferator-activated receptor alpha, has been evaluated in the clinic to treat dyslipidemia and type 2 diabetes mellitus.

5-(N-(4-((4-ethylbenzyl) thio) phenyl) sulfamoyl)-2-methyl benzoic acid

CP-778 875


Input: Herein, we investigate the effect of CP-778 875 on the pharmacokinetics of atorvastatin acid and its metabolites in humans.

CP-778 875

atorvastatin acid


Input: 2. The study incorporated a fixed-sequence design conducted in two groups.


Input: Group A was designed to estimate the effects of multiple doses of CP-778 875 on the single dose pharmacokinetics of atorvastatin.

CP-778 875

atorvastatin


Input: Subjects in group A (n = 26) received atorvastatin (40 mg) on days 1 and 9 and CP-778 875 (1. 0 mg QD) on days 5-12.

atorvastatin

CP-778 875


Input: Group B was designed to examine the effects of multiple doses of atorvastatin on the single dose pharmacokinetics of CP-778 875.

atorvastatin

CP-778 875


Input: Subjects in group B (n = 29) received CP-778 875 (0. 3 mg) on days 1 and 9 and atorvastatin (40 mg QD) on days 5-12.

CP-778 875

atorvastatin


Input: 3. Mean maximum serum concentration (Cmax) and area under the curve of atorvastatin were increased by 45% and 20%, respectively, upon co-administration with CP-778 875.

atorvastatin

CP-778 875


Input: Statistically significant increases in the systemic exposure of ortho-and para-hydroxyatorvastatin were also observed upon concomitant dosing with CP-778 875.

ortho-and para-hydroxyatorvastatin

CP-778 875


Input: CP-778 875 pharmacokinetics, however, were not impacted upon concomitant dosing with atorvastatin.

CP-778 875

atorvastatin


Input: 4. Inhibition of organic anion transporting polypeptide 1B1 by CP-778 875 (IC50 = 2. 14 +/- 0. 40 mu M) could be the dominant cause of the pharmacokinetic interaction as CP-778 875 did not exhibit significant inhibition of cytochrome P450 3A4/3A5, multidrug resistant protein 1 or breast cancer resistant protein, which are also involved in the hepatobiliary disposition of atorvastatin.

CP-778 875

CP-778 875

atorvastatin


Input: Simultaneous determination by LC-MS/MS of 25-methoxydammarane-3 beta, 12 beta, 20-triol epimers and active metabolites in rat plasma after intravenous administration.

25-methoxydammarane-3 beta, 12 beta, 20-triol


Input: Abstract 1.


Input: The pharmacokinetics of the 25-OCH3-PPD epimers and active metabolites in rat plasma after a single intravenous (i. v.) administration were studied by a rapid, selective and sensitive UPLC-MS/MS method.


Input: Chromatographic separation was performed on an Acquity UPLC with Agela C18 column, and the solvents of 5 mM ammonium acetate (pH 7. 8)-acetonitrile (65: 35, v/v) were used as mobile phase for elution.

ammonium acetate

acetonitrile


Input: The quantification was performed with the transitions of m/z 493. 5 --> 475. 5 for 20 (R, S)-25-OCH3-PPD, m/z 479. 5 --> 461. 5 for 20 (R, S)-25-OH-PPD.

20 (R, S)-25-OCH3-PPD

20 (R, S)-25-OH-PPD


Input: The Lower Limit Of Quantitation (LLOQ) was 20. 0 ng mL (-1) for 20 (R, S)-25-OCH3-PPD, 2. 0 ng mL (-1) for 20 (R, S)-25-OH-PPD in the plasma samples assay.

20 (R, S)-25-OCH3-PPD

20 (R, S)-25-OH-PPD


Input: The pharmacokinetic parameters of AUC, t1/2 and MRT had no difference between 20 (R)-and (S)-25-OCH3-PPD, but S-epimer has a lower plasma clearance compared to the R-isomer.

20 (R)-and (S)-25-OCH3-PPD


Input: The active metabolite 20 (S)-25-OH-PPD showed significantly higher AUC, MRT and a longer half-life than that of 20 (R)-25-OH-PPD.

20 (S)-25-OH-PPD

20 (R)-25-OH-PPD


Input: These assay results are necessary for the evaluation of the pharmacokinetic behavior of 25-methoxydammarane-3 beta, 12 beta, 20-triol in vivo.

25-methoxydammarane-3 beta, 12 beta, 20-triol


Input: Spatial memory deficits in maternal iron deficiency paradigms are associated with altered glucocorticoid levels.

iron


Input: " The goal of this study was to examine the effect of maternal iron deficiency on the developing hippocampus in order to define a developmental window for this effect, and to see whether iron deficiency causes changes in glucocorticoid levels.

iron

iron


Input: The study was carried out using pre-natal, post-natal, and pre + post-natal iron deficiency paradigm.

iron


Input: Iron deficient pregnant dams and their pups displayed elevated corticosterone which, in turn, differentially affected glucocorticoid receptor (GR) expression in the CA1 and the dentate gyrus.

Iron

corticosterone


Input: Brain Derived Neurotrophic Factor (BDNF) was reduced in the hippocampi of pups following elevated corticosterone levels.

corticosterone


Input: Reduced neurogenesis at P7 was seen in pups born to iron deficient mothers, and these pups had reduced numbers of hippocampal pyramidal and granule cells as adults.

iron


Input: Hippocampal subdivision volumes also were altered.


Input: The structural and molecular defects in the pups were correlated with radial arm maze performance; reference memory function was especially affected.


Input: Pups from dams that were iron deficient throughout pregnancy and lactation displayed the complete spectrum of defects, while pups from dams that were iron deficient only during pregnancy or during lactation displayed subsets of defects.

iron

iron


Input: These findings show that maternal iron deficiency is associated with altered levels of corticosterone and GR expression, and with spatial memory deficits in their pups. "

iron

corticosterone


Input: An investigation of the effect of thiamine pyrophosphate on cisplatin-induced oxidative stress and DNA damage in rat brain tissue compared with thiamine: Thiamine and thiamine pyrophosphate effects on cisplatin neurotoxicity.

thiamine pyrophosphate

cisplatin

thiamine

Thiamine

thiamine pyrophosphate

cisplatin


Input: This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine.

thiamine pyrophosphate

TPP

cisplatin

thiamine


Input: Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses.

Cisplatin


Input: Oxidative stress is considered responsible for cisplatin toxicity.

cisplatin


Input: Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD).

cisplatin

thio barbituric acid

glutathione

GSH

superoxide


Input: TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels.

TPP

cisplatin

thiamine

TPP

GSH


Input: In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1. 7 +/- 0. 12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0. 97 +/- 0. 03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1. 55 +/- 0. 11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group.

guanine

8-hydroxyl guanine

8-OH Gua

Gua

cisplatin

Gua

Gua

thiamine pyrophosphate

8-OH Gua

Gua

thiamine


Input: These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.

thiamine pyrophosphate

cisplatin

thiamine


Input: Effect of subacute exposure to silver nanoparticle on some hematological and plasma biochemical indices in silver carp (Hypophthalmichthys molitrix).

silver

silver


Input: The use of silver nanoparticles (Ag-NPs) is rapidly increasing, but there are limited data on their effects on the aquatic environment.

silver

Ag


Input: The present study aimed to determine the acute toxicity and evaluate the effect of subacute concentrations of Ag-NPs (Nanocid (R): average particle size of 61 nm) on hematological and plasma biochemical indices of silver carp, Hypophthalmichthys molitrix, after 3, 7 and 14 days.

Ag

Nanocid

silver


Input: The 24-, 48-, 72-and 96-h median lethal concentration (LC50) values of Nanocid for silver carp were estimated at 0. 810, 0. 648, 0. 383 and 0. 202 mg/L, respectively; 20% and 10% of the 96-h LC50 values (0. 04 and 0. 02 mg/L) were selected for subacute study.

Nanocid

silver


Input: Red blood cell (RBC) count, hemoglobin (Hb) count and hematocrit (Hct) level were significantly reduced at both concentrations tested (p < 0. 05).


Input: White blood cell (WBC), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), cortisol and glucose levels in Nanocid-treated groups were significantly higher than the controlled group at experimental periods (p < 0. 05).

cortisol

glucose

Nanocid


Input: In conclusion, Ag-NPs intoxication resulted in erythrocyte reduction, hematological disturbances, leucocytosis and stress response in silver carp and offered a simple tool to evaluate toxicity-derived alterations.

Ag

silver


Input: Non-classic congenital adrenal hyperplasia.


Input: Non-classic or late-onset congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders.


Input: Reported prevalence is approximately 1 in 1000.


Input: Affected individuals typically present due to signs and symptoms of androgen excess.

androgen


Input: The purpose of this review is to provide current information regarding the pathophysiology, molecular genetics, and management of this common disorder.


Input: The treatment of NCAH needs to be directed towards the symptoms.


Input: For affected children, goals of treatment include normal linear growth velocity, normal rate of skeletal maturation, " on-time " puberty.


Input: For affected adolescent and adult women, goals of treatment include regular menstrual cycles, prevention or progression of hirsutism and acne, and fertility.


Input: Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations.


Input: Calcium pathways such as cAMP modulate clothianidin action through activation of alpha-bungarotoxin-sensitive and-insensitive nicotinic acetylcholine receptors.

Calcium

cAMP

clothianidin

acetylcholine


Input: Clothianidin is a neonicotinoid insecticide developed in the early 2000s.

Clothianidin


Input: We have recently demonstrated that it was a full agonist of alpha-bungarotoxin-sensitive and-insensitive nicotinic acetylcholine receptors expressed in the cockroach dorsal unpaired median neurons.

acetylcholine


Input: Clothianidin was able to act as an agonist of imidacloprid-insensitive nAChR2 receptor and internal regulation of cAMP concentration modulated nAChR2 sensitivity to clothianidin.

Clothianidin

imidacloprid

cAMP

clothianidin


Input: In the present study, we demonstrated that cAMP modulated the agonist action of clothianidin via alpha-bungarotoxin-sensitive and insensitive receptors.

cAMP

clothianidin


Input: Clothianidin-induced current-voltage curves were dependent to clothianidin concentrations.

Clothianidin

clothianidin


Input: At 10 mu M clothianidin, increasing cAMP concentration induced a linear current-voltage curve.

clothianidin

cAMP


Input: Clothianidin effects were blocked by 0. 5 mu M alpha-bungarotoxin suggesting that cAMP modulation occurred through alpha-bungarotoxin-sensitive receptors.

Clothianidin

cAMP


Input: At 1mM clothianidin, cAMP effects were associated to alpha-bungarotoxin-insensitive receptors because clothianidin-induced currents were blocked by 5 mu M mecamylamine and 20 mu M d-tubocurarine.

clothianidin

cAMP

clothianidin

mecamylamine

d-tubocurarine


Input: In addition, we found that application of 1mM clothianidin induced a strong increase of intracellular calcium concentration.

clothianidin

calcium


Input: These data reinforced the finding that calcium pathways including cAMP modulated clothianidin action on insect nicotinic acetylcholine receptors.

calcium

cAMP

clothianidin

acetylcholine


Input: We proposed that intracellular calcium pathways such as cAMP could be a target to modulate the mode of action of neonicotinoid insecticides.

calcium

cAMP


Input: Immunoregulatory effects of Glycyrrhizic acid exerts anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4 (+) CD25 (+) Foxp3 (+) regulatory T cells in ovalbumin-sensitized mice.

Glycyrrhizic acid


Input: ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhizic acid (GA) is the main bioactive ingredient of licorice (Glycyrrhiza glabra), and has been found to be associated with multiple therapeutic properties.

Glycyrrhizic acid


Input: AIM OF THE STUDY: In this study, we investigated immunoregulatory effects of glycyrrhizic acid on anti-asthmatic effects and underlying mechanisms.

glycyrrhizic acid


Input: MATERIALS AND METHODS: Asthma model was established by ovalbumin-induced.


Input: A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2mg/kg) and GA (10mg/kg, 20mg/kg, 40mg/kg).

dexamethasone


Input: Airway resistance (Raw) were measured by the forced oscillation technique, histological studies were evaluated by The hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and CD4 (+) CD25 (+) Foxp3 (+) regulatory T cells (Tregs) was evaluated by Flow Cytometry (FCM), the forkhead/winged helix transcription factor (Foxp3) was evaluated by western blotting.

hematoxylin

eosin


Input: RESULTS: Our study demonstrated that, compared with model group, GA inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4, IL-5, IL-13 levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-gamma level in bronchoalveolar lavage fluid; histological studies demonstrated that GA substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue compared with model group.


Input: Flow cytometry studies demonstrated that GA substantially enhanced Tregs compared with model group.


Input: CONCLUSION: These findings suggest that GA may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.


Input: Electronic structure analysis of multistate reactivity in transition metal catalyzed reactions: the case of C-H bond activation by non-heme iron (iv)-oxo cores.

C-H


Input: This perspective discusses the principles of the multistate scenario often encountered in transition metal catalyzed reactions, and is organized as follows.


Input: First, several important theoretical concepts (physical versus formal oxidation states, orbital interactions, use of (spin) natural and corresponding orbitals, exchange enhanced reactivity and the connection between valence bond and molecular orbital based electronic structure analysis) are presented.


Input: These concepts are then used to analyze the electronic structure changes occurring in the reaction of C-H bond oxidation by Fe (IV) oxo species.

C-H

Fe (IV) oxo


Input: The analysis reveals that the energy separation and the overlap between the electron donating orbitals and electron accepting orbitals of the Fe (IV) oxo complexes dictate the reaction stereochemistry, and that the manner in which the exchange interaction changes depends on the identity of these orbitals.

Fe (IV) oxo


Input: The electronic reorganization of the Fe (IV) oxo species during the reaction is thoroughly analyzed and it is shown that the Fe (IV) oxo reactant develops oxyl radical character, which interacts effectively with the sigma CH orbital of the alkane.

Fe (IV) oxo

Fe (IV) oxo

oxyl

CH

alkane


Input: The factors that determine the energy barrier for the reaction are discussed in terms of molecular orbital and valence bond concepts.


Input: First principles intensity calculations of the methane rovibrational spectra in the infrared up to 9300 cm (-1.)

methane


Input: We report global calculations of rovibrational spectra and dipole transition intensities of methane using our recent ab initio dipole moment and potential surfaces [Nikitin et al., Chem. Phys. Lett., 2011, 501, 179; 2013, 565, 5].

methane


Input: For the full symmetry account, a recently published variational tensor formalism in normal modes [Rey et al., J. Chem. Phys., 2012, 136, 244106] is applied, the convergence of high-J calculations being improved by the use of vibrational eigenfunctions to make a compressed basis set for solving the rovibrational problem.


Input: Comparisons of theoretical predictions up to J = 25 for various complex polyads of methane involving strongly coupled vibration-rotation bands support the validity of this new approach.

methane


Input: For the first time, positions and line intensities at 80 K and 296 K are shown to be in excellent agreement with raw experimental data, even for high energy ranges.


Input: The theoretical predictions also correctly describe the isotopic effects in line positions and intensities due to the CH4 --> CD4 substitution which is considered as the test for the method.


Input: This work is a first step toward the theoretical interpretation of numerous methane bands which remain still unassigned and detailed line-by-line absorption/emission spectra analyses for atmospheric and planetological applications.

methane


Input: A Structural Snapshot of Cytochrome P450 2B4 in Complex with Paroxetine Provides Insights into Ligand Binding and Clusters of Conformational States.

Paroxetine


Input: An X-ray crystal structure of cytochrome P450 2B4 in complex with the drug paroxetine was solved at 2. 14 A resolution.

paroxetine


Input: The structure revealed a conformation intermediate to that of the recently solved complex with amlodipine and of the more compact complex with 4-(4-chlorophenyl) imidazole in terms of the placement of the F-G cassette.

amlodipine

4-(4-chlorophenyl) imidazole


Input: Moreover, the comparison of the new structure with 15 previously solved structures of P450 2B4 revealed some new insights into determinants of active site size and shape.


Input: The 2B4-paroxetine structure is nearly superimposable on a previously solved closed structure in a ligand free state.

paroxetine


Input: Despite the overall conformational similarity among multiple closed structures, the active site cavity volume of the paroxetine complex is enlarged.

paroxetine


Input: Further analysis of the accessible space and binding pocket near the heme reveals a new sub-chamber that resulted from the movement of secondary structural elements and rearrangements of active site side chains.


Input: Overall, the results from the comparison of all the 16 structures of P450 2B4 demonstrate a cluster of protein conformations that were observed in the presence or absence of various ligands.


Input: Pyridinylquinazolines Selectively Inhibit Human Methionine Aminopeptidase-1 in Cells.

Pyridinylquinazolines

Methionine


Input: Methionine aminopeptidases (MetAPs), which remove the initiator methionine from nascent peptides, are essential in all organisms.

Methionine

methionine


Input: While MetAP2 has been demonstrated to be a therapeutic target for inhibiting angiogenesis in mammals, MetAP1 seems to be vital for cell proliferation.


Input: Our earlier efforts identified two structural classes of human MetAP1 (HsMetAP1)-selective inhibitors (1-4), but all of them failed to inhibit cellular HsMetAP1.


Input: Using Mn (II) or Zn (II) to activate HsMetAP1, we found that 1-4 could only effectively inhibit purified HsMetAP1 in the presence of physiologically unachievable concentrations of Co (II).

Mn (II)

Zn (II)

Co (II)


Input: In an effort to seek Co (II)-independent inhibitors, a novel structural class containing a 2-(pyridin-2-yl) quinazoline core has been discovered.

Co (II)

2-(pyridin-2-yl) quinazoline


Input: Many compounds in this class potently and selectively inhibited HsMetAP1 without Co (II).

Co (II)


Input: Subsequently, we demonstrated that 11j, an auxiliary metal-dependent inhibitor, effectively inhibited HsMetAP1 in primary cells.


Input: This is the first report that an HsMetAP1-selective inhibitor is effective against its target in cells.


Input: Single Ion Channel Recordings with CMOS-Anchored Lipid Membranes.


Input: We present single-ion-channel recordings performed with biomimetic lipid membranes which are directly attached to the surface of a complementary metal-oxide-semiconductor (CMOS) preamplifier chip.

metal-oxide


Input: With this system we resolve single-channel currents from several types of bacterial ion channels, including fluctuations of a single alamethicin channel at a bandwidth of 1 MHz which represent the fastest single-ion-channel recordings reported to date.


Input: The platform is also used for high-resolution alpha-hemolysin nanopore recordings.


Input: These results illustrate the high signal fidelity, fine temporal resolution, small geometry, and multiplexed integration which can be achieved by leveraging integrated semiconductor platforms for advanced ion channel interfaces.


Input: Indazole-based Potent and Cell-Active Mps1 Kinase Inhibitors: Rational Design from Pan-Kinase Inhibitor Anthrapyrazolone (SP600125).

Indazole

Anthrapyrazolone


Input: Monopolar spindle 1 (Mps1) is essential for centrosome duplication, the spindle assembly check point, and the maintenance of chromosomal instability.


Input: Mps1 is highly expressed in cancer cells, and its expression levels correlate with the histological grades of cancers.


Input: Thus, selective Mps1 inhibitors offer an attractive opportunity for the development of novel cancer therapies.


Input: To design novel Mps1 inhibitors, we utilized the pan-kinase inhibitor anthrapyrazolone (4, SP600125) and its crystal structure bound to JNK1.

anthrapyrazolone


Input: Our design efforts led to the identification of indazole-based lead 6 with an Mps1 IC50 value of 498 nM.

indazole


Input: Optimization of the 3-and 6-positions on the indazole core of 6 resulted in 23c with improved Mps1 activity (IC50 = 3. 06 nM).

indazole


Input: Finally, application of structure-based design using the X-ray structure of 23d bound to Mps1 culminated in the discovery of 32a and 32b with improved potency for cellular Mps1 and A549 lung cancer cells.


Input: Moreover, 32a and 32b exhibited reasonable selectivities over 120 and 166 kinases, respectively.


Input: 3D Printed Bionic Ears.


Input: The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts.


Input: Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different.


Input: Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements.


Input: As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles.

silver


Input: This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes.


Input: The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music.


Input: Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing.


Input: Synthesis and biological evaluation of (68) Ga labeled bis-DOTA-3, 3'-(benzylidene)-bis-(1H-indole-2-carbohydrazide) as a PET tracer for in vivo visualization of necrosis.

(68) Ga labeled bis-DOTA

3, 3'-(benzylidene)-bis-(1H-indole-2-carbohydrazide)


Input: The aim of the present study was to develop a (68) Ga labeled bis-DOTA derivative of benzylidene-bis-indole and compare the in vivo stability and biodistribution with that of the previously reported bis-DTPA derivate for in vivo imaging of necrosis using PET.

(68) Ga labeled bis-DOTA

benzylidene-bis-indole

bis-DTPA


Input: Uptake of the tracer was evaluated in a mouse model of Fas-mediated hepatic apoptosis in correlation with histochemical stainings.


Input: The novel (68) Ga labeled tracer showed an improved in vivo stability and could therefore be used for selective non-invasive imaging of necrotic cell death using PET.

(68) Ga


Input: Cigarette craving and withdrawal symptoms during temporary abstinence and the effect of nicotine gum.

nicotine


Input: RATIONALE: It is widely believed that nicotine withdrawal symptoms appear within a few hours of stopping smoking, but few data exist documenting their emergence in naturalistic settings.

nicotine


Input: In several countries, nicotine replacement products are licensed for relief of withdrawal symptoms during temporary abstinence, but again, there are no data supporting this from naturalistic settings.

nicotine


Input: OBJECTIVES: To examine the emergence of cigarette craving and withdrawal symptoms during temporary abstinence in a naturalistic setting while using either nicotine or placebo gum.

nicotine


Input: METHODS: Double-blind, randomised, placebo-controlled study in which 132 dependent smokers abstained for 6 h with the assistance of either nicotine (2 mg, n = 42 or 4 mg, n = 24) or placebo (n = 66) gum while travelling on a non-smoking train.

nicotine


Input: Outcome measures were ratings of craving and mood withdrawal symptoms prior to treatment and at regular intervals during abstinence.


Input: RESULTS: In a multivariate analysis of all symptoms, there was no interaction between treatment and time [F (21, 110) = 1. 28, p = 0. 20, [Formula: see text] = 0. 20] nor an effect of treatment [F (7, 124) = 0. 45, p = 0. 87, [Formula: see text] = 0. 03].


Input: There was an effect of time [F (21, 110) = 11. 59, p < 0. 001, [Formula: see text] = 0. 69) and univariate analyses revealed that the majority of symptoms increased linearly throughout the period of abstinence with detectable onsets typically between the first 60 and 180 min of abstinence.


Input: CONCLUSIONS: Smokers who temporarily abstain in naturalistic settings experience craving and withdrawal symptoms that emerge linearly over the first 6 h of abstinence.


Input: Changes in craving and several mood withdrawal symptoms can be detected within the first 3 h.


Input: Nicotine gum may not have an acute effect on the development of these symptoms.

Nicotine


Input: Enhanced beta cell function and anti-inflammatory effect after chronic treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin in an advanced-aged diet-induced obesity mouse model.

vildagliptin


Input: AIMS/HYPOTHESIS: Studies have shown that dipeptidyl peptidase-4 (DPP4) inhibitors stimulate insulin secretion and increase beta cell mass in rodents.


Input: However, in these models hyperglycaemia has been induced early on in life and the treatment periods have been short.


Input: To explore the long-term effects of DPP4 inhibition on insulin secretion and beta cell mass, we have generated a high-fat diet (HFD)-induced-obesity model in mice of advanced age (10 months old).


Input: METHODS: After 1 month of HFD alone, the mice were given the DPP4 inhibitor vildagliptin for a further 11 months.

vildagliptin


Input: At multiple time points throughout the study, OGTTs were performed and beta cell area and long-term survival were evaluated.


Input: RESULTS: Beta cell function and glucose tolerance were significantly improved by vildagliptin with both diets.

glucose

vildagliptin


Input: In contrast, in spite of the long treatment period, beta cell area was not significantly different between vildagliptin-treated mice and controls.

vildagliptin


Input: Mice of advanced age chronically fed an HFD displayed clear and extensive pancreatic inflammation and peri-insulitis, mainly formed by CD3-positive T cells, which were completely prevented by vildagliptin treatment.

vildagliptin


Input: Chronic vildagliptin treatment also improved survival rates for HFD-fed mice.

vildagliptin


Input: CONCLUSIONS/INTERPRETATION: In a unique advanced-aged HFD-induced-obesity mouse model, insulin secretion was improved and the extensive peri-insulitis prevented by chronic DPP4 inhibition.


Input: The improved survival rates for obese mice chronically treated with vildagliptin suggest that chronic DPP4 inhibition potentially results in additional quality-adjusted life-years for individuals with type 2 diabetes, which is the primary goal of any diabetes therapy.

vildagliptin


Input: PT-ACRAMTU, A Platinum-Acridine Anticancer Agent, Lengthens and Aggregates, but does not Stiffen or Soften DNA.

Platinum

Acridine


Input: We used atomic force microscopy (AFM) to study the dose-dependent change in conformational and mechanical properties of DNA treated with PT-ACRAMTU ([PtCl (en) (ACRAMTU-S)] (NO3) 2, (en = ethane-1, 2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino) ethyl]-1, 3-dimethylthiourea.

PT-ACRAMTU ([PtCl (en) (ACRAMTU-S)] (NO3) 2

ethane-1, 2-diamine

ACRAMTU

1-[2-(acridin-9-ylamino) ethyl]-1, 3-dimethylthiourea


Input: PT-ACRAMTU is the parent drug of a family of non-classical platinum-based agents that show potent activity in non-small cell lung cancer in vitro and in vivo.

PT-ACRAMTU

platinum


Input: Its acridine moiety intercalates between DNA bases, while the platinum group forms mono-adducts with DNA bases.

acridine

platinum


Input: AFM images show that PT-ACRAMTU causes some DNA looping and aggregation at drug-to-base pair ratio (r b) of 0. 1 and higher.

PT-ACRAMTU


Input: Very significant lengthening of the DNA was observed with increasing doses of PT-ACRAMTU, and reached saturation at an r b of 0. 15.

PT-ACRAMTU


Input: At r b of 0. 1, lengthening was 0. 6 nm per drug molecule, which is more than one fully stretched base pair stack can accommodate, indicating that ACRAMTU also disturbs the stacking of neighboring base pair stacks.

ACRAMTU


Input: Analysis of the AFM images based on the worm-like chain (WLC) model showed that PT-ACRAMTU did not change the flexibility of (non-aggregated) DNA, despite the extreme lengthening.

PT-ACRAMTU


Input: The persistence length of untreated DNA and DNA treated with PT-ACRAMTU was in the range of 49-65 nm.

PT-ACRAMTU


Input: Potential consequences of the perturbations caused by this agent for the recognition and processing of the DNA adducts it forms are discussed.


Input: The Atrial Natriuretic Peptide Genetic Variant Rs5068 Is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population.


Input: OBJECTIVEWe hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population. RESEARCH DESIGN AND METHODSWe genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068. RESULTSGenotype frequencies of rs5068 are AA, 93. 5%; AG, 6. 4%; and GG, 0. 1%.


Input: All subsequent analyses are AA versus AG + GG.


Input: After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]:-1. 7 kg/m (2) [0. 8], P = 0. 04).


Input: In the AG + GG group, males with HDL cholesterol levels < 40 mg/dL are less frequent (P = 0. 05) and obesity tends to be less prevalent (P = 0. 07).

cholesterol


Input: Importantly, the G allele is associated with a lower prevalence of metabolic syndrome (P = 0. 02).


Input: After adjusting for BMI, the above associations were attenuated.


Input: Independently of age, sex, and BMI, the minor allele is also associated with lower systolic blood pressure (-6. 0 mmHg [2. 5], P = 0. 02) and lower prevalence of hypertension (odds ratio 0. 41 [95% CI 0. 20-0. 83], P = 0. 01). CONCLUSIONSThe association between the minor allele of rs5068 and a favorable cardiometabolic phenotype that we previously reported in a U. S. population is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure, BMI, and prevalence of hypertension and metabolic syndrome.


Input: These findings may lead to a diagnostic strategy to assess cardiometabolic risk and lay the foundation for the future development of an ANP or ANP-like therapy for metabolic syndrome.


Input: Diabetes Prevention and Treatment Strategies: Are we doing enough?


Input: OBJECTIVEEffective interventions to prevent, delay, or remit diabetes are currently available.


Input: However, their impact on the prevalence of diabetes at the population level is unknown.