Input: After controlling for potential confounding factors, the creatinine-adjusted urine NAG concentrations were shown to be influenced by the GG genotype of rs8052394 in exon 3, and were weakly increased with TWICL.

creatinine


Input: Therefore, we concluded that the variations of MT1A SNPs may influence urine UA and NAG excretion in chronic lead-exposed workers, and urine creatinine-adjusted urine UA as a biomarker of lead toxicity should be considered.

creatinine


Input: Reduced Acute Recovery from Alcohol Impairment in Adults with ADHD.

Alcohol


Input: RATIONALE: Prior research has found that adults with attention-deficit/hyperactivity disorder (ADHD) show increased sensitivity to the impairing effects of alcohol (Weafer et al., Exp Clin Psychopharmacol 17: 113-121, 2009).

alcohol


Input: However, these studies have focused exclusively on the ascending limb of the blood alcohol concentration (BAC) curve, and it is unclear whether these adults continue to show increased sensitivity during the later phase of the dose as BAC is declining.

alcohol


Input: OBJECTIVE: This study tested the hypothesis that those with ADHD would display increased response to alcohol during the ascending limb of the BAC curve and less recovery from the impairing effects during the descending limb.

alcohol


Input: METHODS: Adult social drinkers with ADHD and control adults completed measures of motor coordination, reaction time (RT), and subjective intoxication twice following 0. 64 g/kg alcohol and placebo.

alcohol


Input: The measures were administered during the ascending limb of the BAC curve and again during the descending limb.


Input: RESULTS: During the ascending limb, alcohol reduced motor coordination, slowed RT, and increased self-reports of subjective intoxication.

alcohol


Input: Those with ADHD displayed greater impairment of motor coordination compared with controls.


Input: During the descending limb, controls reported diminished subjective intoxication and showed recovery from the impairing effects of alcohol on both their motor coordination and their RT.

alcohol


Input: Those with ADHD showed reduced subjective intoxication and faster RT during this time, but they did not recover motor control.


Input: CONCLUSIONS: The protracted time course of motor impairment in adults with ADHD despite reductions in subjective intoxication may contribute to poor decision making and diminished behavioral control in this group.


Input: Effect of chronic ethanol treatment on mu-opioid receptor function, interacting proteins and morphine-induced place preference.

ethanol

morphine


Input: RATIONALE: Both the acute and chronic consumption of ethanol have been reported to modify several molecular events in the central nervous system, and the endogenous mu-opioid receptor system is involved in the reinforcing/rewarding effects of ethanol.

ethanol

ethanol


Input: OBJECTIVES: The present study was designed to clarify the effects of chronic ethanol treatment on cellular processes involving mu-opioid receptor and the development of morphine-induced rewarding effects.

ethanol

morphine


Input: METHODS: Male C57BL/6J mice were continuously treated with a liquid diet containing 3. 0 w/v ethanol.

ethanol


Input: The direct involvement of mu-opioid receptor functions in the activation of G-proteins and changes in protein levels in the lower midbrain of mice after chronic treatment with ethanol were investigated by a [(35) S] GTP gamma S binding assay and Western blotting, respectively.

ethanol

[(35) S] GTP gamma S


Input: The rewarding effects of morphine (5 mg/kg) under treatment with ethanol were measured by the conditioned place preference paradigm.

morphine

ethanol


Input: RESULTS: The function of mu-opioid receptor was increased by treatment with ethanol in the lower midbrain using [(35) S] GTP gamma S binding assay.

ethanol

[(35) S] GTP gamma S


Input: Furthermore, the GRK2 protein level was significantly increased by treatment with ethanol.

ethanol


Input: Chronic treatment with ethanol enhanced the rewarding effects of morphine.

ethanol

morphine


Input: On the other hand, this enhancement of the rewarding effects of morphine by ethanol treatment was significantly inhibited by the GRK2 inhibitor beta-adrenergic receptor kinase 1 inhibitor.

morphine

ethanol


Input: CONCLUSIONS: The present study demonstrated that chronic treatment with ethanol enhanced the rewarding effects of morphine by up-regulating functional changes in mu-opioid receptor, mediated by GRK2.

ethanol

morphine


Input: Interleukin-10 promoter variants predict HPV-positive tumors and survival of squamous cell carcinoma of the oropharynx.


Input: Interleukin-10 (IL-10) plays an important role in a host' s defense against human papillomavirus (HPV) infection.


Input: IL-10 promoter variants may affect its expression level or functional efficiency and, subsequently, susceptibility to and survival of HPV16-associated squamous cell carcinoma of oropharynx (SCCOP).


Input: We determined tumor HPV16 DNA and genotyped three IL-10 promoter polymorphisms in 309 incident patients with SCCOP.


Input: Compared with the patients with corresponding common homozygous genotypes, patients carrying variant genotypes of IL-10 rs1800871 and rs1800872 were ~ 2. 5 times more likely to have HPV16 (+) tumors among patients with SCCOP.


Input: Among HPV16 (+) patients with SCCOP only, compared to those with the corresponding variant genotypes, the patients with IL-10 rs1800871 and rs1800872 CC genotypes had significantly better survival and ~ 70-80% reduced risk of death/recurrence after multivariable adjustment.


Input: Additionally, functional relevance of these variants was characterized to explore the genotype-phenotype correlation.


Input: Our findings indicate that IL-10 genetic variants may be associated with tumor HPV16 (+) SCCOP and predict survival of HPV16 (+) patients with SCCOP.


Input: Larger studies are needed to validate our findings.-Jin, L., Sturgis, E.


Input: M., Cao, X., Song, X., Salahuddin, T., Wei, Q., Li, G.


Input: Interleukin-10 promoter variants predict HPV-positive tumors and survival of squamous cell carcinoma of the oropharynx.


Input: Effect of Ketoconazole on the Pharmacokinetics of the 11 beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitor ABT-384 and Its Two Active Metabolites in Healthy Volunteers: Population Analysis of Data from a Drug-Drug Interaction Study.

Ketoconazole

11 beta-Hydroxysteroid


Input: ABT-384 [1-piperazineacetamide, N-[5-(aminocarbonyl) tricyclo [3. 3. 1. 13, 7] dec-2-yl]-alpha, alpha-dimethyl-4-[5-(trifluoromethyl)-2-pyridinyl]-, stereoisomer] is a potent and selective inhibitor of 11 beta-hydroxysteroid dehydrogenase type 1 (HSD-1).

1-piperazineacetamide, N-[5-(aminocarbonyl) tricyclo [3. 3. 1. 13, 7] dec-2-yl]-alpha, alpha-dimethyl-4-[5-(trifluoromethyl)-2-pyridinyl]

11 beta-hydroxysteroid


Input: ABT-384 has been shown to be safe and well tolerated in humans at doses up to 100 mg daily, and to fully inhibit both peripheral and brain HSD-1 at a dose of 2 mg daily.


Input: The effect of ketoconazole on the pharmacokinetics of ABT-384 and its two active metabolites, A-1331480 and A-847082, was investigated in healthy volunteers.

ketoconazole


Input: When 10 mg of ABT-384 was coadministered with ketoconazole, ABT-384 exposures increased 18-fold for area under the plasma concentration-time curve from time 0 to infinity and 3. 5-fold for Cmax.

ketoconazole


Input: The results suggest that ABT-384 is a sensitive substrate of CYP3A.


Input: After ketoconazole coadministration, exposures of A-1331480 and A-847082 were also greatly increased.

ketoconazole


Input: A population pharmacokinetic model was constructed for ABT-384 and its metabolites using NonMEM.


Input: A two-compartment model with three transit absorption compartments best described ABT-384 data.


Input: The model predicted a 69. 3% decrease in ABT-384 clearance and 91. 1% increase in the volume of distribution of ABT-384 in the presence of ketoconazole.

ketoconazole


Input: A-1331480 was shown to be formation rate-limited and A-847082 was elimination rate-limited.


Input: Both metabolites were characterized by a one-compartment model with first-order rate constants of formation and elimination.


Input: Overall the model adequately captured the concentration-time profiles of ABT-384, A-1331480, and A-847082 in both ABT-384-alone and ketoconazole-coadministration conditions.

ketoconazole


Input: Although ABT-384 exposures were greatly increased in the presence of ketoconazole, coadministration of ABT-384 with ketoconazole or other strong/moderate CYP3A inhibitors is not expected to contribute to any major clinical safety issues considering the favorable safety profile of ABT-384.

ketoconazole

ketoconazole


Input: Two new sesquiterpenoids from the rhizomes of Nardostachys jatamansi.

sesquiterpenoids


Input: Phytochemical investigation of CHCl (3): MeOH (1: 1) extract from the rhizomes of Nardostachys jatamansi led to the isolation of two new sesquiterpenoids (5 and 6), along with six known compounds (1-4, 7, and 8).

CHCl (3)

MeOH

sesquiterpenoids


Input: The structures of two new compounds were established using IR, MS, 1D, and 2D NMR techniques.


Input: In addition, all the isolates were tested for their cytotoxicities against the A549 (lung cancer), DU-145 (prostate cancer), MCF-7 (breast cancer), and SK-N-SH (neuroblastoma).


Input: Transient Receptor Potential (TRP) Cation Channels in Diabetes.


Input: Transient Receptor Potential (TRP) proteins constitute a family of cation channels with very diverse permeation and gating properties.


Input: Likewise they have a very diverse role in mammalian physiology ranging from sensory nerve endings, the cardiac muscle to immune cells.


Input: Increasing evidence has implicated TRP channels in the pathology of diabetes, both on the level of insulin release from the pancreatic beta cells and in secondary conditions such as diabetic neuropathy, nephropathy and vasculopathy.


Input: In this review we summarize these recent findings, which all together indicate that TRP channels are interesting drug targets for the treatment of patients suffering from diabetes.


Input: Symmetrical Windowing for Quantum States in Quasi-Classical Trajectory Simulations.


Input: A microscopically reversible approach toward computing reaction probabilities via classical trajectory simulation has been developed that bins trajectories symmetrically on the basis of their initial and final classical actions.


Input: The symmetrical quasi-classical (SQC) approach involves defining a classical action window function centered at integer quantum values of the action, choosing a width parameter that is less than unit quantum width, and applying the window function to both initial reactant and final product vibrational states.


Input: Calculations were performed using flat histogram windows and Gaussian windows over a range of width parameters.


Input: Use of the Wigner distribution function was also investigated as a possible choice.


Input: It was demonstrated for collinear H + H2 reactive scattering on the BKMP2 potential energy surface that reaction probabilities computed via the SQC methodology using a Gaussian window function of 1/2 unit width produces good agreement with quantum mechanical results over the 0. 4-0. 6 eV energy range relevant to the ground vibrational state to the ground vibrational state reactive transition.

H


Input: Binding of Diverse Environmental Chemicals with Human Cytochromes P450 2A13, 2A6, and 1B1 and Enzyme Inhibition.


Input: A total of 68 chemicals including derivatives of naphthalene, phenanthrene, fluoranthene, pyrene, biphenyl, and flavone were examined for their abilities to interact with human P450s 2A13 and 2A6.

naphthalene

phenanthrene

fluoranthene

pyrene

biphenyl

flavone


Input: Fifty-one of these 68 chemicals induced stronger Type I binding spectra (iron low-to high-spin state shift) with P450 2A13 than those seen with P450 2A6, i. e., the spectral binding intensities (Delta Amax/Ks ratio) determined with these chemicals were always higher for P450 2A13.

iron


Input: In addition, benzo [c] phenanthrene, fluoranthene, 2, 3-dihydroxy-2, 3-dihydrofluoranthene, pyrene, 1-hydroxypyrene, 1-nitropyrene, 1-acetylpyrene, 2-acetylpyrene, 2, 5, 2', 5'-tetrachlorobiphenyl, 7-hydroxyflavone, chrysin, and galangin were found to induce a Type I spectral change only with P450 2A13.

benzo [c] phenanthrene

fluoranthene

2, 3-dihydroxy-2, 3-dihydrofluoranthene

pyrene

2, 5, 2', 5'-tetrachlorobiphenyl

chrysin

galangin


Input: Coumarin 7-hydroxylation, catalyzed by P450 2A13, was strongly inhibited by 2'-methoxy-5, 7-dihydroxyflavone, 2-ethynylnaphthalene, 2'-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values.

Coumarin

2'-methoxy-5, 7-dihydroxyflavone

2-naphththalene propargyl ether

acenaphthene

acenaphthylene

naphthalene

flavanone

chrysin

flavone


Input: On the basis of the intensities of the spectral changes and inhibition of P450 2A13, we classified the 68 chemicals into eight groups based on the order of affinities for these chemicals and inhibition of P450 2A13.


Input: The metabolism of chemicals by P450 2A13 during the assays explained why some of the chemicals that bound well were poor inhibitors of P450 2A13.


Input: Finally, we compared the 68 chemicals for their abilities to induce Type I spectral changes of P450 2A13 with the Reverse Type I binding spectra observed with P450 1B1: 45 chemicals interacted with both P450s 2A13 and 1B1, indicating that the two enzymes have some similarty of structural features regarding these chemicals.


Input: Molecular docking analyses suggest similarities at the active sites of these P450 enzymes.


Input: These results indicate that P450 2A13, as well as Family 1 P450 enzymes, is able to catalyze many detoxication and activation reactions with chemicals of environmental interest.


Input: ATP synthase: a molecular therapeutic drug target for antimicrobial and antitumor peptides.

ATP


Input: In this review we discuss the role of ATP synthase as a molecular drug target for natural and synthetic antimicrobial/antitumor peptides.

ATP


Input: We start with an introduction of the universal nature of the ATP synthase enzyme and its role as a biological nanomotor.

ATP


Input: Significant structural features required for catalytic activity and motor functions of ATP synthase are described.

ATP


Input: Relevant details regarding the presence of ATP synthase on the surface of several animal cell types, where it is associated with multiple cellular processes making it a potential drug target with respect to antimicrobial peptides and other inhibitors such as dietary polyphenols, is also reviewed.

ATP

polyphenols


Input: ATP synthase is known to have about twelve discrete inhibitor binding sites including peptides and other inhibitors located at the interface of alpha/beta subunits on the F1 sector of the enzyme.

ATP


Input: Molecular interaction of peptides at the beta DEELSEED site on ATP synthase is discussed with specific examples.

ATP


Input: An inhibitory effect of other natural/synthetic inhibitors on ATP is highlighted to explore the therapeutic roles played by peptides and other inhibitors.

ATP


Input: Lastly, the effect of peptides on the inhibition of the Escherichia coli model system through their action on ATP synthase is presented.

ATP


Input: Interlayer breathing and shear modes in few-trilayer MoS2 and WSe2.


Input: Two-dimensional (2D) layered transition metal dichalcogenides (TMDs) have recently attracted tremendous interest as potential valleytronic and nanoelectronic materials, in addition to being well-known as excellent lubricants in the bulk.

transition metal dichalcogenides

TMDs


Input: The interlayer van der Waals (vdW) coupling and low-frequency phonon modes and how they evolve with the number of layers are important for both the mechanical and the electrical properties of 2D TMDs.

TMDs


Input: Here we uncover the ultralow frequency interlayer breathing and shear modes in few-layer MoS2 and WSe2, prototypical layered TMDs, using both Raman spectroscopy and first principles calculations.

TMDs


Input: Remarkably, the frequencies of these modes can be perfectly described using a simple linear chain model with only nearest-neighbor interactions.


Input: We show that the derived in-plane (shear) and out-of-plane (breathing) force constants from experiment remain the same from two-layer 2D crystals to the bulk materials, suggesting that the nanoscale interlayer frictional characteristics of these excellent lubricants should be independent of the number of layers.


Input: Checkpoint protein Rad9 plays an important role in nucleotide excision repair.

nucleotide


Input: Rad9, an evolutionarily conserved checkpoint gene with multiple functions for preserving genomic integrity, has been shown to play important roles in homologous recombination repair, base excision repair and mismatch repair.


Input: However, whether Rad9 has an impact on nucleotide excision repair remains unknown.

nucleotide


Input: Here we demonstrated that Rad9 was involved in nucleotide excision repair and loss of Rad9 led to defective removal of the UV-derived photoproduct 6-4PP (6, 4 pyrimidine-pyrimidone) and the BPDE (anti-benzo (a) pyrene-trans-7, 8-dihydrodiol-9, 10-epoxide)-DNA adducts in mammalian cells.

nucleotide

6, 4 pyrimidine-pyrimidone

BPDE

benzo (a) pyrene-trans-7, 8-dihydrodiol-9, 10-epoxide


Input: We also demonstrated that Rad9 could co-localize with XPC in response to local UV irradiation.


Input: However, our data showed that Rad9 was not required for the photoproducts recognition step of nucleotide excision repair.

nucleotide


Input: Further investigation revealed that reduction of Rad9 reduced the UV-induced transcription of the genes of the nucleotide excision repair factors DDB2, XPC, DDB1 and XPB and DDB2 protein levels in human cells.

nucleotide


Input: Interestingly, knockdown of one subunit of DNA damage recognition complex, hHR23B impaired Rad9-loading onto UV-damaged chromatin.


Input: Based on these results, we suggest that Rad9 plays an important role in nucleotide excision repair through mechanisms including maintaining DDB2 protein level in human cells.

nucleotide


Input: LOX-1 is a novel marker for peripheral artery disease in patients with type 2 diabetes.


Input: OBJECTIVE: The aim of this study was to investigate whether serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), which mediates initiation and progression of atherosclerosis in endothelial cells, could be a novel marker for peripheral artery disease (PAD) in patients with type 2 diabetes.


Input: METHODS: We evaluated relationships of serum sLOX-1 to ankle-brachial index (ABI) and examined the association of serum sLOX-1 with PAD in 410 patients with type 2 diabetes.


Input: RESULTS: Serum sLOX-1 was inversely correlated with ABI (r =-0. 197, P < 0. 0001).


Input: Stepwise regression analysis demonstrated that serum sLOX-1 (beta =-0. 168, F = 5. 571, P < 0. 05) was independently associated with ABI, and multiple logistic regression analysis demonstrated that serum sLOX-1 (16. 254 (1. 237-213. 651), P = 0. 0339) was independently associated with PAD.


Input: CONCLUSIONS: Serum sLOX-1 is associated with ABI and it could be a novel marker for PAD in patients with type 2 diabetes.


Input: Discovery of biological evaluation of pyrazole/imidazole amides as mGlu5 receptor negative allosteric modulators.

pyrazole/imidazole amides


Input: Development of SAR in a 5-aryl-3-acylpyridinyl-pyrazoles and 1-aryl-4-acylpyridinyl imidazoles series of mGlu5 receptor negative allosteric modulators (mGluR5 NAMs) using a functional cell-based assay is described in this Letter.

1-aryl-4-acylpyridinyl imidazoles


Input: Analysis of the Ligand-lipophilic efficiency (LipE) of compounds provided new insight for the design of potent mGluR5 negative allosteric modulators with anti-depressant activities.


Input: Microwave assisted nano (ZnO-TiO2) catalyzed synthesis of some new 4, 5, 6, 7-tetrahydro-6-((5-substituted-1, 3, 4-oxadiazol-2-yl) methyl) thieno [2, 3-c] pyridine as antimicrobial agents.

ZnO

4, 5, 6, 7-tetrahydro-6-((5-substituted-1, 3, 4-oxadiazol-2-yl) methyl) thieno [2, 3-c] pyridine


Input: Combined nano zinc oxide and titanium dioxide [nano (ZnO-TiO (2))] has been reported first time for the synthesis of novel series of 4, 5, 6, 7-tetrahydro-6-((5-substituted-1, 3, 4-oxadiazol-2-yl) methyl) thieno [2, 3-c] pyridine.

zinc oxide

titanium dioxide

ZnO

TiO (2)

4, 5, 6, 7-tetrahydro-6-((5-substituted-1, 3, 4-oxadiazol-2-yl) methyl) thieno [2, 3-c] pyridine


Input: All the synthesized compounds (7a-7m) are novel and were screened for their antimicrobial activity against four different strains like Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis and antifungal activity was determined against two strains Candida albicans and Aspergillus niger.


Input: SAR for the newly synthesised derivatives has been developed by comparing their MIC values with ampicillin, ciprofloxacin and miconazole for antibacterial and antifungal activities, respectively.

ampicillin

ciprofloxacin

miconazole


Input: Among the synthesized compounds, 2, 6 dichlorophenyl analogue (7f), 4 fluorophenyl analogue (7k) and 2, 6 dichlorophenyl analogue (7l) shows promising antibacterial as well as antifungal activity whereas thiophene substituted compound (7j) shows promising antibacterial activity.

2, 6 dichlorophenyl

4 fluorophenyl

2, 6 dichlorophenyl

thiophene


Input: Improved guanide compounds which bind the CXCR4 co-receptor and inhibit HIV-1 infection.

guanide


Input: The G-protein coupled receptor CXCR4 is a co-receptor for HIV-1 infection and is involved in signaling cell migration and proliferation.


Input: In a previous study of non-peptide, guanide-based CXCR4-binding compounds, spermine and spermidine phenylguanides inhibited HIV-1 entry at low micromolar concentrations.

guanide

spermine and spermidine phenylguanides


Input: Subsequently, crystal structures of CXCR4 were used to dock a series of naphthylguanide derivatives of the polyamines spermidine and spermine.

naphthylguanide

polyamines spermidine

spermine


Input: Synthesis and evaluation of the naphthylguanide compounds identified our best compound, spermine tris-1-naphthylguanide, which bound CXCR4 with an IC (50) of 40 nM and inhibited the infection of TZM-bl cells with X4, but not R5, strains of HIV-1 with an IC (50) of 50-100 nM.

naphthylguanide

spermine tris-1-naphthylguanide


Input: Advances in the discovery of kinesin spindle protein (Eg5) inhibitors as antitumor agents.


Input: Cancer is considered as one of the most serious health problems.


Input: Despite the presence of many effective chemotherapeutic agents, their severe side effects together with the appearance of mutant tumors limit the use of these drugs and increase the need for new anticancer agents.


Input: Eg5 represents an attractive target for medicinal chemists since Eg5 is overexpressed in many proliferative tissues while almost no Eg5 is detected in nonproliferative tissues.


Input: Many Eg5 inhibitors displayed potent anticancer activity against some of the mutant tumors with limited side effects.


Input: The present review provides an overview about the progress in the discovery of Eg5 inhibitors especially from 2009 to 2012 as well as the clinical trials conducted on some of these inhibitors.


Input: Synthesis, biological evaluation of new oxazolidino-sulfonamides as potential antimicrobial agents.

oxazolidino-sulfonamides


Input: A number of linezolid-like oxazolidino-sulfonamides (7a-y and 8a-b) were designed and synthesized with a view to develop antimicrobial agents with improved properties.

linezolid

oxazolidino-sulfonamides


Input: Most of the synthesized compounds showed good to moderate activity against a panel of standard Gram-positive and Gram-negative bacteria and fungal strains.


Input: The compounds 7i and 7v exhibited significant activity, with a MIC value of 2. 0-6. 0 mu g/mL against a panel of Gram-positive and Gram-negative bacteria.


Input: These compounds also showed activity against Candida albicans, with a MIC value of 4. 0 mu g/mL.


Input: A correlation of the antimicrobial activity with calculated lipophilicity values (C log P) is also presented.


Input: Synthesis and cytotoxicity of 3-aryl acrylic amide derivatives of the simplified saframycin-ecteinascidin skeleton prepared from l-dopa.

3-aryl acrylic amide

saframycin

ecteinascidin

l-dopa


Input: Twenty four compounds with diversified 3-aryl acrylic amide side chains of the simplified saframycin-ecteinascidin pentacyclic skeleton were synthesized via a 14-step stereospecific route starting from l-dopa.

3-aryl acrylic amide

saframycin

ecteinascidin

l-dopa


Input: The cytotoxicities of these compounds were tested against eight human tumor cell lines including HCT-8, BEL-7402, BGC-803, A549, A2780, MCF-7, MX-1, and MDA-MB-231.


Input: Most of these compounds exhibited potent antitumor activity, and a preliminary structure-activity relationship (SAR) was discussed.


Input: Compound 28 with 3-thiophenyl acrylic amide side chain exhibited selective cytotoxicity against MDA-MB-231 cell line with the IC50 value of 50 nM.

3-thiophenyl acrylic amide


Input: The Interaction of Adrenomedullin and Macrophages Induces Ovarian Cancer Cell Migration via Activation of RhoA Signaling Pathway.


Input: Tumor-associated macrophages (TAMs) are correlated with poor prognosis in many human cancers; however, the mechanism by which TAMs facilitate ovarian cancer cell migration and invasion remains unknown.


Input: This study was aimed to examine the function of adrenomedullin (ADM) in macrophage polarization and their further effects on the migration of ovarian cancer cells.


Input: Exogenous ADM antagonist and small interfering RNA (siRNA) specific for ADM expression were treated to macrophages and EOC cell line HO8910, respectively.


Input: Then macrophages were cocultured with HO8910 cells without direct contact.


Input: Flow cytometry, Western blot and real-time PCR were used to detect macrophage phenotype and cytokine production.


Input: The migration ability and cytoskeleton rearrangement of ovarian cancer cells were determined by Transwell migration assay and phalloidin staining.

phalloidin


Input: Western blot was performed to evaluate the activity status of signaling molecules in the process of ovarian cancer cell migration.


Input: The results showed that ADM induced macrophage phenotype and cytokine production similar to TAMs.


Input: Macrophages polarized by ADM promoted the migration and cytoskeleton rearrangement of HO8910 cells.


Input: The expression of RhoA and its downstream effector, cofilin, were upregulated in macrophage-induced migration of HO8910 cells.


Input: In conclusion, ADM could polarize macrophages similar to TAMs, and then polarized macrophages promote the migration of ovarian cancer cells via activation of RhoA signaling pathway in vitro.


Input: Identification of three genes encoding for the late acyltransferases of lipid A in Cronobacter sakazakii.


Input: Lipid A, the hydrophobic anchor of lipopolysaccharide, is an essential component in the outer membrane of most Gram-negative bacteria.


Input: Food-borne pathogen Cronobacter sakazakii synthesizes two lipid A species, differing by the length of the secondary acyl chain.

acyl


Input: In this work, we identified three genes ESA02293, ESA02951 and ESA01386 encoding for the late acyltransferases of lipid A biosynthesis pathway in C. sakazakii.


Input: Based on the sequence alignment, proteins YP _ 001438378. 1 encoded by ESA02293, YP _ 001439016. 1 encoded by ESA02951, and YP _ 001437482. 1 encoded by ESA01386 are homologous to E. coli LpxL, LpxP and LpxM, respectively.


Input: Functions of the three acyltransferases were confirmed by overexpressing the genes in E. coli, isolating lipid As and analyzing their structures using an ESI/MS.


Input: C. sakazakii LpxL and LpxM transfer a C14: 0 secondary acyl chain to the 2'-and 3'-position of lipid A, respectively.

acyl


Input: C. sakazakii LpxP can transfer either a C16: 1 or a C14: 0 secondary acyl chains to the 2'-position of lipid A.

acyl


Input: A 35kD Phyllanthus niruri protein modulates iron mediated oxidative impairment to hepatocytes via the inhibition of ERKs, p38 MAPKs and activation of PI3k/Akt pathway.

iron


Input: It has been reported that the herb, Phyllanthus niruri, possess antioxidant, anti-infection, anti-asthmatic, anti-diuretic, anti-soresis and many more beneficial activities.


Input: The goal of our present study was to evaluate the protective role of a 35kD protein (PNP) isolated from this herb against iron-induced cytotoxicity in murine hepatocytes.

iron


Input: Exposure of hepatocytes to iron (FeSO4) caused elevation of reactive oxygen species (ROS) production, enhanced lipid peroxidation and protein carbonylation, depleted glutathione levels, decreased the antioxidant power (FRAP) of the cells and reduced cell viability.

iron

oxygen

glutathione


Input: Iron mediated cytotoxicity disrupted mitochondrial membrane potential (Delta psi m) and thereby caused apoptosis mainly by the intrinsic pathway via the down-regulation of I kappa B alpha with a concomitant up-regulation of NF-kB as well as the phosphorylation of ERKs and p38 MAP kinases.

Iron


Input: In addition, iron-induced cytotoxicity disrupted the normal balance of Bcl-2 family proteins in hepatocytes.

iron


Input: Incubation of hepatocytes with PNP, however, protected the cells from apoptosis by stabilizing the mitochondria and arresting the release of cytochrome c.


Input: It also suppressed caspase activation and cleavage of PARP.


Input: Moreover, this protein has strong free radical scavenging activity and thereby scavenged ROS extensively.


Input: Combining all, results suggest that simultaneous treatment with PNP might suppress the iron-induced cytotoxicity in hepatocytes.

iron


Input: Hepatic and renal Bcrp transporter expression in mice treated with perfluorooctanoic acid.

perfluorooctanoic acid


Input: The breast cancer resistance protein (Bcrp) is an efflux transporter that participates in the biliary and renal excretion of drugs and environmental chemicals.


Input: Recent evidence suggests that pharmacological activation of the peroxisome proliferator activated receptor alpha (PPAR alpha) can up-regulate the hepatic expression of Bcrp.


Input: The current study investigated the regulation of hepatic and renal Bcrp mRNA and protein in mice treated with the PPAR alpha agonist perfluorooctanoic acid (PFOA) and the ability of PFOA to alter human BCRP function in vitro.

perfluorooctanoic acid

PFOA

PFOA


Input: Bcrp mRNA and protein expression were quantified in the livers and kidneys of male C57BL/6 mice treated with vehicle or PFOA (1 or 3mg/kg/day oral gavage) for 7 days.

PFOA


Input: PFOA treatment increased liver weights as well as the hepatic mRNA and protein expression of the PPAR alpha target gene, cytochrome P450 4a14.

PFOA


Input: Compared to vehicle-treated control mice, PFOA increased hepatic Bcrp mRNA and protein between 1. 5-and 3-fold.

PFOA


Input: Immunofluorescent staining confirmed enhanced canalicular Bcrp staining in liver sections from PFOA-treated mice.

PFOA


Input: The kidney expression of cytochrome P450 4a14 mRNA, but not Bcrp, was increased in mice treated with PFOA.

PFOA


Input: Micromolar concentrations of PFOA decreased human BCRP ATPase activity and inhibited BCRP-mediated transport in inverted membrane vesicles.

PFOA


Input: Together, these studies demonstrate that PFOA induces hepatic Bcrp expression in mice and may inhibit human BCRP transporter function at concentrations that exceed levels observed in humans.

PFOA


Input: Fluctuating charge-density waves in a cuprate superconductor.

cuprate


Input: Cuprate materials hosting high-temperature superconductivity (HTS) also exhibit various forms of charge and spin ordering whose significance is not fully understood.

Cuprate


Input: So far, static charge-density waves (CDWs) have been detected by diffraction probes only at particular doping levels or in an applied external field.


Input: However, dynamic CDWs may also be present more broadly and their detection, characterization and relationship with HTS remain open problems.


Input: Here we present a method based on ultrafast spectroscopy to detect the presence and measure the lifetimes of CDW fluctuations in cuprates.

cuprates


Input: In an underdoped La1. 9Sr0. 1CuO4 film (Tc = 26 K), we observe collective excitations of CDW that persist up to 100 K.

La1. 9Sr0. 1CuO4


Input: This dynamic CDW fluctuates with a characteristic lifetime of 2 ps at T = 5 K that decreases to 0. 5 ps at T = 100 K.


Input: In contrast, in an optimally doped La1. 84Sr0. 16CuO4 film (Tc = 38. 5 K), we detect no signatures of fluctuating CDWs at any temperature, favouring the competition scenario.

La1. 84Sr0. 16CuO4


Input: This work forges a path for studying fluctuating order parameters in various superconductors and other materials.


Input: Modulation of A-type K (+) channels by the short-chain cobrotoxin through the protein kinase C-delta isoform decreases membrane excitability in dorsal root ganglion neurons.

K (+)


Input: A-type K (+) channels are crucial in controlling neuronal excitability, and their regulation in sensory neurons may alter pain sensation.

K (+)


Input: In this study, we identified the functional role of cobrotoxin, the short-chain alpha-neurotoxin isolated from Naja atra venom, which acts in the regulation of the transient A-type K (+) currents (IA) and membrane excitability in dorsal root ganglion (DRG) neurons via the activation of the muscarinic M3 receptor (M3R).

K (+)


Input: Our results showed that cobrotoxin increased IA in a concentration-dependent manner, whereas the sustained delayed rectifier K (+) currents (IDR) were not affected.

K (+)


Input: Cobrotoxin did not affect the activation of IA markedly, however, it shifted the inactivation curve significantly in the depolarizing direction.


Input: The cobrotoxin-induced IA response was blocked by the M3R-selective antagonists DAU-5884 and 4-DAMP.


Input: An siRNA targeting the M3R in small DRG neurons abolished the cobrotoxin-induced IA increase.


Input: In addition, dialysis of the cells with the novel protein kinase C-delta isoform (PKC-delta) inhibitor delta v1-1 or an siRNA targeting PKC-delta abolished the cobrotoxin-induced IA response, whereas inhibition of PKA or classic PKC activity elicited no such effects.


Input: Moreover, we observed a significant decrease in the firing rate of the neuronal action potential induced by M3R activation.


Input: Pretreatment of the cells with 4-aminopyridine, a selective blocker of IA, abolished this effect.


Input: Taken together, these results suggest that the short-chain cobrotoxin selectively enhances IA via a novel PKC-delta-dependent pathway.


Input: This effect occurred via the activation of M3R and might contribute to its neuronal hypoexcitability in small DRG neurons.


Input: Molecular aspects of cancer cell resistance to chemotherapy.


Input: Cancer cell resistance to chemotherapy is still a heavy burden that impairs treatment of cancer patients.


Input: Both intrinsic and acquired resistance results from the numerous genetic and epigenetic changes occurring in cancer cells.


Input: Most of the hallmarks of cancer cells provide general mechanisms to sustain stresses such as the ones induced by chemotherapeutic drugs.


Input: Moreover, specific changes in the target bring resistance to specific drugs like modification in nucleotide synthesis enzymes upon anti-metabolite exposure, in microtubule composition upon spindle poison treatment, in topoisomerase activity upon topoisomerase inhibitor incubation or in intracellular signaling pathways when targeting tyrosine kinase receptors.

nucleotide

tyrosine


Input: Finally, the stemness properties of a few cancer cells as well as components of the tumor stroma, like fibroblasts and tumor-associated macrophages but also hypoxia, also help tumor to resist to anticancer agents.


Input: These processes provide an additional level of complexity to the understanding of the tumor resistance phenomenon.


Input: This review aims to describe the different general mechanisms as well as some examples of specific on target modifications inducing cancer cell resistance to chemotherapy at the molecular level.


Input: Perspectives to develop more efficient treatment, using genomic signature or more specific biomarkers to characterize putative resistance mechanisms in patients before choosing the more appropriate treatment, will also be discussed.


Input: ATM kinase activity modulates ITCH E3-ubiquitin ligase activity.


Input: Ataxia Telangiectasia Mutated (ATM) kinase, a central regulator of the DNA damage response, regulates the activity of several E3-ubiquitin ligases, and the ubiquitination-proteasome system is a consistent target of ATM.


Input: ITCH is an E3-ubiquitin ligase that modulates the ubiquitination of several targets, therefore participating to the regulation of several cellular responses, such as the DNA damage response, tumor necrosis factor alpha (TNF alpha), Notch and Hedgehog signaling, and the differentiation of' naive' lymphocytes into T helper type 2 cells.


Input: Here we uncover ATM as a novel positive modulator of ITCH E3-ubiquitin ligase activity.


Input: A single residue on ITCH protein, S161, which is part of an ATM SQ consensus motif, is required for ATM-dependent activation of ITCH.


Input: ATM activity enhances ITCH enzymatic activity, which in turn drives the ubiquitination and degradation of c-FLIP-L and c-Jun, previously identified as ITCH substrates.


Input: Importantly, ATM-deficient mice show resistance to hepatocyte cell death, similarly to Itch-deficient animals, providing in vivo genetic evidence for this circuit.


Input: Our data identify ITCH as a novel component of the ATM-dependent signaling pathway and suggest that the impairment of the correct functionality of ITCH caused by Atm deficiency may contribute to the complex clinical features linked to Ataxia Telangiectasia. Oncogene advance online publication, 25 February 2013; doi: 10. 1038/onc. 2013. 52.


Input: Allelic imbalance in sporadic parathyroid carcinoma and evidence for its de novo origins.


Input: Parathyroid cancer is a rare, clinically aggressive cause of primary hyperparathyroidism, and whether these malignancies generally evolve from pre-existing benign adenomas or arise de novo is unclear.


Input: Furthermore, while inactivation of the CDC73 (HRPT2) tumor suppressor gene, encoding parafibromin, is a major contributor, other genes essential to parathyroid carcinogenesis remain unknown.


Input: We sought to identify genomic regions potentially harboring such oncogenes or tumor suppressor genes, and to gain insight into the origins and molecular relationship of malignant versus benign parathyroid tumors.


Input: We performed genome-wide copy-number and loss of heterozygosity analysis using Affymetrix 50K SNP mapping arrays and/or comparative genomic hybridization on 16 primary parathyroid carcinomas, local recurrences or distant metastases, and matched normal controls, from 10 individuals.


Input: Recurrent regions of allelic loss were observed on chromosomes 1p, 3, and 13q suggesting that key parathyroid tumor suppressor genes are located in these chromosomal locations.


Input: Recurrent allelic gains were seen on chromosomes 1q and 16, suggesting the presence of parathyroid oncogenes on these chromosomes.


Input: Importantly, the most common alteration in benign parathyroid adenomas, loss of 11q, was not found as a recurrent change in the malignant parathyroid tissues.


Input: Molecular allelotyping using highly polymorphic microsatellite markers provided further confirmation that the prevalence of 11q loss is markedly and significantly lower in carcinomas as compared with adenomas.


Input: Our observations provide molecular support for the concept that sporadic parathyroid cancer usually arises de novo, rather than evolving from a pre-existing typical benign adenoma.


Input: Furthermore, these results help direct future investigation to ultimately determine which of the candidate genes in these chromosomal locations make significant contributions to the molecular pathogenesis of parathyroid cancer.


Input: Fluorescence spectroscopy of PTCDA molecules on the KCl (100) surface in the limit of low coverages: site selection and diffusion.

PTCDA

KCl


Input: We performed fluorescence (FL) and fluorescence excitation (FLE) spectroscopy on the model molecule perylene-3, 4, 9, 10-tetracarboxyl acid dianhydride (PTCDA) for very low coverages (below 1% of a monolayer) on thin (100) oriented KCl films.

perylene-3, 4, 9, 10-tetracarboxyl acid dianhydride

PTCDA

KCl


Input: Two different states of PTCDA molecules can be distinguished in the spectra: an initial state, which is observed directly after deposition of the molecules onto the cold sample at 20 K, and a final state, which is found after intensive optical excitation or thermal annealing of the sample.

PTCDA


Input: The spectrum of the final state is blue-shifted with respect to that of the initial state by 130 +/- 15 cm (-1) and exhibits lines with significantly reduced widths.


Input: This can be explained by diffusion of molecules from initially populated terrace sites to energetically favoured step edge sites.


Input: Polarization dependent spectroscopy reveals the same azimuthal orientation of the molecules on both adsorption sites and leads to a model of the adsorption geometry of PTCDA at the KCl step sites.

PTCDA

KCl


Input: Our experiment demonstrates how optical spectroscopy can be used to investigate kinetic processes of fluorescent molecules on surfaces.


Input: Avoidance behaviour response and esterase inhibition in the earthworm, Lumbricus terrestris, after exposure to chlorpyrifos.

chlorpyrifos


Input: The avoidance response of earthworms to polluted soils has been standardised using a simple and low-cost test, which facilitates soil toxicity screening.


Input: In this study, the avoidance response of Lumbricus terrestris was quantified in chlorpyrifos-spiked soils, depending on the pesticide concentration and exposure duration.

chlorpyrifos


Input: The inhibition of acetylcholinesterase (AChE) and carboxylesterase (CbE) activities was also determined as indirect measures of pesticide bioavailability.


Input: The effects of different chlorpyrifos concentrations were examined in a standardised test (two-chamber system) with 0. 6, 3 and 15 mg/kg chlorpyrifos.

chlorpyrifos

chlorpyrifos


Input: A modification of the test involved a pre-exposure step (24, 48 or 72 h) in soils spiked with 15 mg/kg.


Input: In both protocols, earthworms were unable to avoid the contaminated soils.


Input: However, the esterase activities showed that all earthworms were exposed to chlorpyrifos.

chlorpyrifos


Input: Acetylcholinesterase activity did not change in earthworms in the standardised behavioural test (0. 58 +/- 0. 20 U/mg protein, mean +/- SD; n = 72), whereas the CbE activity was significantly inhibited (62-87% inhibition) in earthworms exposed to 3 and 15 mg/kg.


Input: In the modified test, earthworms had greatly inhibited AChE activity (0. 088 +/- 0. 034 U/mg protein, n = 72), which was supported by reactivation of the inhibited enzyme activity in the presence of pralidoxime (2-PAM).

pralidoxime


Input: Similarly, the CbE activity was significantly inhibited in earthworms with all treatments.


Input: This study suggests that the avoidance behaviour test for organophosphorus-contaminated soils could be supported by specific biomarkers to facilitate a better understanding of pesticide exposure and toxicity during this test.

organophosphorus


Input: Impact of childhood-onset type 1 diabetes on schooling: a population-based register study.


Input: AIMS/HYPOTHESIS: We investigated the impact of type 1 diabetes on educational achievements in compulsory and upper secondary school, as well as potential long-lasting effects.


Input: METHODS: Altogether 2, 485 individuals with type 1 diabetes, diagnosed at the age of < 15 years and born in 1972-1978, were selected from the Swedish Childhood Diabetes Register, which was linked to national population registers including the Swedish Education Register.


Input: For each individual, four controls from the general population, matched for year of birth and residence at the time of diagnosis, were selected by Statistics Sweden (n = 9, 940).


Input: We analysed the impact of diabetes on final school grades at 16 years (compulsory school) and 19 years (upper secondary school) and on participation in the labour market at 29 years using linear, logistic, ordered logistic and quantile regression analyses, controlling for demographics and socioeconomic background.


Input: RESULTS: Diabetes had a negative effect on mean final grades (scale of 1-5) in compulsory school (-0. 07, p < 0. 001) and theoretical programmes in upper secondary school (-0. 07, p = 0. 001).


Input: Children with early-onset diabetes (0-4 years) suffered a greater disadvantage as a result of the disease (-0. 15, p = 0. 001 in compulsory school).


Input: The strongest effect was seen in the lowest deciles of the conditional distribution on mean final grades.


Input: At age 29, individuals with diabetes were less likely to be gainfully employed (OR 0. 82, 95% CI 0. 73, 0. 91).


Input: CONCLUSIONS/INTERPRETATION: The small but significant negative effect of type 1 diabetes on schooling could affect opportunities for further education and career development.


Input: Attention must be paid in school to the special needs of children with diabetes.


Input: Multiple biological properties of macelignan and its pharmacological implications.

macelignan


Input: Macelignan found in the nutmeg mace of Myristica fragrans obtains increasing attention as a new avenue in treating various diseases.

Macelignan


Input: Macelignan has been shown to possess a spectrum of pharmacological activities, including anti-bacterial, anti-inflammatory, anti-cancer, anti-diabetes, and hepatoprotective activities; recently, it has also been shown to have neuroprotective activities.

Macelignan


Input: This review summarizes the current research on the biological effects of macelignan derived from M. fragrans, with emphasis on the importance in understanding and treating complex diseases such as cancer and Alzheimer' s disease.

macelignan


Input: Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury.

heme


Input: Ischemia/reperfusion (I/R) injury is the main cause of primary graft dysfunction of liver allografts.


Input: Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect the liver from I/R injury.

Cobalt-protoporphyrin

CoPP

heme


Input: This study analyzes the apoptotic mechanisms of HO-1-mediated cytoprotection in mouse liver exposed to I/R injury.


Input: HO-1 induction was achieved by the administration of CoPP (1. 5 mg/kg body weight i. p.).

CoPP


Input: Mice were studied in in vivo model of hepatic segmental (70%) ischemia for 60 min and reperfusion injury.


Input: Mice were randomly allocated to four main experimental groups (n = 10 each): (1) A control group undergoing sham operation.


Input: (2) Similar to group 1 but with the administration of CoPP 72 h before the operation.

CoPP


Input: (3) Mice undergoing in vivo hepatic I/R.


Input: (4) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction.

CoPP


Input: When compared with the I/R mice group, in the I/R + CoPP mice group, the increased hepatic expression of HO-1 was associated with a significant reduction in liver enzyme levels, fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase-3, there was a decreased mean number of proliferating cells (positively stained for Ki67), and a reduced hepatic expression of: C/EBP homologous protein (an index of endoplasmic reticulum stress), the NF-kappa B' s regulated genes (CIAP2, MCP-1 and IL-6), and increased hepatic expression of I kappa Ba (the inhibitory protein of NF-kappa B).

CoPP


Input: HO-1 over-expression plays a pivotal role in reducing the hepatic apoptotic IR injury.


Input: HO-1 may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation.


Input: Myeloperoxidase Activity and Its Corresponding mRNA Expression as well as Gene Polymorphism in the Population Living in the Coal-Burning Endemic Fluorosis Area in Guizhou of China.


Input: The myeloperoxidase (MPO) activity and its corresponding mRNA expression as well as gene polymorphism were investigated in the population who live in the endemic fluorosis area.


Input: In the study, 150 people were selected from the coal-burning endemic fluorosis area and 150 normal persons from the non-fluorosis area in Guizhou province of China.


Input: The blood samples were collected from these people.


Input: The activity of MPO in the plasma was determined by spectrophotometer; the expression of MPO mRNA was measured by employing real-time polymerase chain reaction; DNAs were extracted from the leucocytes in blood and five SNP genotypes of MPO promoter gene detected by a multiplex genotyping method, adapter-ligation-mediated allele-specific amplification.


Input: The results showed that the MPO activity and its corresponding mRNA in blood were significantly increased in the population living in the area of fluorosis.


Input: The different genotype frequencies of MPO, including-1228G/A,-585T/C,-463G/A, and-163C/T, and the three haplotypes with higher frequencies, including-163C-463G-585T-1228G-1276T,-163C-463G-585T-1228G-1276C, and-163C-463G-585T-1228A-1276T, were significantly associated with fluorosis.


Input: The results indicated that the elevated activity of MPO induced by endemic fluorosis may be connected in mechanism to the stimulated expression of MPO mRNA and the changed gene polymorphism.


Input: Microporous carbon nanoplates from regenerated silk proteins for supercapacitors.

carbon


Input: Novel carbon-based microporous nanoplates containing numerous heteroatoms (H-CMNs) are fabricated from regenerated silk fibroin by the carbonization and activation of KOH.

carbon

KOH


Input: The H-CMNs exhibit superior electrochemical performance, displaying a specific capacitance of 264 F/g in aqueous electrolytes, a specific energy of 133 Wh/kg, a specific power of 217 kW/kg, and a stable cycle life over 10000 cycles.


Input: Pharmacokinetic properties of anti-influenza neuraminidase inhibitors.


Input: Neuraminidase inhibitors are the mainstay of anti-influenza treatment.


Input: Oseltamivir is the most widely used drug but is currently available only as an oral formulation.

Oseltamivir


Input: Resistance spreads rapidly in seasonal H1N1 influenza A viruses, which were universally resistant in 2008, because of the H275Y mutation in the neuraminidase (NA) gene.


Input: Oseltamivir is a prodrug for the active carboxylate metabolite.

Oseltamivir

carboxylate


Input: Ex vivo conversion in blood samples may have confounded early pharmacokinetic studies.


Input: Oseltamivir shows dose linear kinetics, and oseltamivir carboxylate has an elimination half-life (t (1/2) beta) after oral administration in healthy individuals of approximately 7. 7 hours.

Oseltamivir

oseltamivir carboxylate


Input: Oseltamivir carboxylate is eliminated primarily by tubular secretion, and both clearance and tissue distribution are reduced by probenecid.

Oseltamivir carboxylate

probenecid


Input: The H275Y mutation in NA confers high-level oseltamivir resistance and intermediate peramivir resistance but does not alter zanamivir susceptibility.

oseltamivir

peramivir

zanamivir


Input: Zanamivir is available as a powder for inhalation, and a parenteral form is under development.

Zanamivir


Input: Zanamivir distributes in an apparent volume of distribution approximating that of extracellular water and is rapidly eliminated (t (1/2) beta of approximately 3. 0 hours).

Zanamivir


Input: Peramivir is slowly eliminated (t (1/2) beta of 7. 7-20. 8 hours) and is prescribed as either a once-daily injection or as a single infusion.

Peramivir


Input: Laninamivir is a recently developed slowly eliminated compound for administration by inhalation.

Laninamivir


Input: Comparison of subcutaneous and intravenous administration of trastuzumab: a phase I/Ib trial in healthy male volunteers and patients with HER2-positive breast cancer.


Input: Trastuzumab is a key component of treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer in both the early and metastatic settings.


Input: It is administered intravenously, with between 17 and 52 infusions in standard regimens over 1 year.


Input: Intravenous administration of trastuzumab requires substantial time commitments for patients and health care professionals and can result in patient discomfort.


Input: A subcutaneous formulation of trastuzumab, containing recombinant human hyaluronidase to overcome subcutaneous absorption barriers, would reduce the administration duration and remove the need to establish intravenous access, thus improving the overall convenience of trastuzumab administration.


Input: This open-label, 2-part, phase I/Ib study (NCT00800436) was undertaken in healthy male volunteers and female patients with HER2-positive early breast cancer to identify the dose of subcutaneous trastuzumab that resulted in exposure comparable with the approved intravenous trastuzumab dose.


Input: A subcutaneous trastuzumab dose of 8 mg/kg was found to result in exposure comparable with the intravenous trastuzumab dose of 6 mg/kg.


Input: The subcutaneous formulation was well tolerated, with a trend toward fewer adverse events versus intravenous administration; most adverse events were mild in intensity.


Input: These results support an ongoing phase III efficacy and safety study comparing a fixed subcutaneous trastuzumab dose with intravenous trastuzumab administration.


Input: Inhibitory effect of ketoconazole on the pharmacokinetics of a multireceptor tyrosine kinase inhibitor BMS-690514 in healthy participants: assessing the mechanism of the interaction with physiologically-based pharmacokinetic simulations.

ketoconazole

tyrosine


Input: BMS-690514, a selective inhibitor of the ErbB and vascular endothelial growth factor receptors, has shown antitumor activity in early clinical development.


Input: The compound is metabolized by multiple enzymes, with CYP3A4 responsible for the largest fraction (34%) of metabolism.


Input: It is also a substrate of P-glycoprotein (P-gp) in vitro.


Input: To assess the effect of ketoconazole on BMS-690514 pharmacokinetics, 17 healthy volunteers received 200 mg BMS-690514 alone followed by 100 mg BMS-690514 with ketoconazole (400 mg once daily for 4 days).

ketoconazole

ketoconazole


Input: The AUC (infinity) of 100 mg BMS-690514 concomitantly administered with ketoconazole was similar to that of 200 mg BMS-690514 alone.

ketoconazole


Input: The dose-normalized C (max) and AUC (infinity) of BMS-690514 from the 100-mg BMS-690514/400-mg ketoconazole treatment increased by 55% and 127%, respectively, relative to those from 200 mg BMS-690514 alone.

ketoconazole


Input: Prediction of the drug-drug interaction (DDI) using a population-based simulator (Simcyp) indicated that, in addition to CYP3A4 inhibition, the inhibition of P-gp by ketoconazole in the intestine, liver, and kidneys must be invoked to fully account for the DDI observed.

ketoconazole


Input: This finding suggests that the inhibition of P-gp by ketoconazole, along with its effect on CYP3A4, needs to be considered when designing a DDI study of ketoconazole with a victim drug that is a dual substrate.

ketoconazole

ketoconazole


Input: Construction of robust enzyme nanocapsules for effective organophosphate decontamination, detoxification, and protection.

organophosphate


Input: Nanocapsules of organophosphorous hydrolase with enhanced enzyme activity and stability are prepared via in situ polymerization, providing a novel class of nanoparticles for the decontamination and detoxification of organophosphates such as chemical warfare agents and pesticides.

organophosphorous

organophosphates


Input: Using the nanocapsules as building blocks, bioactive nanocomposites are also fabricated, enabling their use for organophosphate protection.

organophosphate


Input: Bioactive formulations with sugar-derived surfactants: a new approach for photoprotection and controlled release of promethazine.

sugar

promethazine


Input: Skin deep: A bioactive formulation for dermal delivery of antihistamines is obtained by using the original properties of catanionic associations towards self-assembly in water.


Input: The drug, which participates in its own transport, is preserved from photodegradation when solubilised in the bioactive formulation.


Input: The drug release through the skin is also delayed.


Input: A simple method for fabricating patterned curvilinear microstructures in poly (dimethylsiloxane) by selective wetting.

poly (dimethylsiloxane)


Input: The fabrication of patterned microstructures in poly (dimethylsiloxane) (PDMS) is a prerequisite for soft lithography.

poly (dimethylsiloxane)

PDMS


Input: Herein, curvilinear surface relief microstructures in PDMS are fabricated through a simple three-stage approach combining microcontact printing (mu CP), selective surface wetting/dewetting and replica molding (REM).

PDMS


Input: First, using an original PDMS stamp (first-generation stamp) with linear relief features, a chemical pattern on gold substrate is generated by mu CP using hexadecanethiol (HDT) as an ink.

PDMS

hexadecanethiol

HDT


Input: Then, by a dip-coating process, an ordered polyethylene glycol (PEG) polymer-dot array forms on the HDT-patterned gold substrate.

polyethylene glycol

PEG

HDT


Input: Finally, based on a REM process, the PEG-dot array on gold substrate is used to fabricate a second-generation PDMS stamp with microcavity array, and the second-generation PDMS stamp is used to generate third-generation PDMS stamp with microbump array.

PEG

PDMS

PDMS

PDMS


Input: These fabricated new-generation stamps are utilized in mu CP and in micromolding in capillaries (MIMIC), allowing the generation of surface micropatterns which cannot be obtained using the original PDMS stamp.

PDMS


Input: The method will be useful in producing new-generation PDMS stamps, especially for those who want to use soft lithography in their studies but have no access to the microfabrication facilities.

PDMS


Input: The discovery of novel human androgen receptor antagonist chemotypes using a combined pharmacophore screening procedure.

androgen


Input: Unraveling the mechanisms involved in castration-and therapy-resistant prostate cancer has led to a renewed interest in androgen receptor (AR)-targeted therapeutics.

androgen


Input: Anti-androgens that block the activity of the AR therefore remain a valid therapeutic option.

androgens


Input: However, they must be more effective than, or display a distinct mechanism of action or binding mode from those of bicalutamide and hydroxyflutamide, which are currently in clinical use.

bicalutamide

hydroxyflutamide


Input: For that reason, the second-generation anti-androgen MDV3100 was developed.

androgen MDV3100


Input: MDV3100, however, shares its 4-cyano-3-(trifluoromethyl) phenyl group with bicalutamide and hydroxyflutamide required for binding to the AR.

4-cyano-3-(trifluoromethyl) phenyl

bicalutamide

hydroxyflutamide


Input: In this work, we used a combined strategy to find new antagonist structures distinct from the 4-cyano-3-(trifluoromethyl) phenyl group to avoid cross-resistance for these compounds and to find structures without agonist activity on mutant ARs (AR W741C and AR T877A).

4-cyano-3-(trifluoromethyl) phenyl


Input: We found two novel chemotypes with AR-antagonistic activity (IC (50): 3-6 mu M) by virtual screening and confirmed their biological activity in an androgen-responsive reporter assay.

androgen


Input: The design of our computational approach was validated by the observation of strongly decreased or absence of agonistic activity on the two mutant ARs.


Input: Further structural derivatization to optimize the potency of these compounds can render these chemotypes into very promising, alternative AR antagonists for prostate cancer therapy.


Input: The Overexpression of Hypomethylated miR-663 Induces Chemotherapy Resistance in Human Breast Cancer Cells by Targeting Heparin Sulfate Proteoglycan 2 (HSPG2).

Sulfate


Input: MicroRNAs are involved in regulating the biology of cancer cells, but their involvement in chemoresistance is not fully understood.


Input: We found that miR-663 was up-regulated in our induced multidrug-resistant MDA-MB-231/ADM cell line and that this up-regulation was closely related to chemosensitivity.


Input: In the present study, we aimed to clarify the role of miR-663 in regulating the chemoresistance of breast cancer.


Input: MicroRNA microarray and quantitative RT-PCR assays were used to identify differentially expressed microRNAs.


Input: Cell apoptosis was evaluated by annexin V/propidium iodide staining, TUNEL, and reactive oxygen species generation analysis.

propidium iodide

oxygen


Input: The expression of miR-663 and HSPG2 in breast cancer tissues was detected by in situ hybridization and immunohistochemistry.


Input: The potential targets of miR-663 were defined by a luciferase reporter assay.


Input: Bisulfite sequencing PCR was used to analyze the methylation status.

Bisulfite


Input: We found that miR-663 was significantly elevated in MDA-MB-231/ADM cells, and the down-regulation of miR-663 sensitized MDA-MB-231/ADM cells to both cyclophosphamide and docetaxel.

cyclophosphamide

docetaxel


Input: The overexpression of miR-663 in breast tumor tissues was associated with chemoresistance; in MDA-MB-231 cells, this chemoresistance was accompanied by the down-regulation of HSPG2, which was identified as a target of miR-663.


Input: MDA-MB-231/ADM contained fewer methylated CpG sites than its parental cell line, and miR-663 expression in MDA-MB-231 cells was reactivated by 5-aza-29-deoxycytidine treatment, indicating that DNA methylation may play a functional role in the expression of miR-663.

CpG


Input: Our findings suggest that the overexpression of hypomethylated miR-663 induced chemoresistance in breast cancer cells by down-regulating HSPG2, thus providing a potential target for the development of an microRNA-based approach for breast cancer therapy.


Input: A concise synthesis of pyrazole analogues of combretastatin A1 as potent anti-tubulin agents.

pyrazole

combretastatin A1


Input: Combretastatin A1 (CA1) binds to the beta-subunit at the colchicine binding site of tubulin and inhibits polymerization.

Combretastatin A1

colchicine


Input: As such, it is both an antitumor agent and a vascular disrupting agent.


Input: It has been shown to be at least tenfold more potent than combretastatin A4 (CA4) in terms of vascular shutdown, which correlates with its metabolism to reactive ortho-quinone species that are assumed to be directly cytotoxic in tumor cells.

combretastatin A4

ortho-quinone


Input: A series of 3, 4-diarylpyrazoles were concisely synthesized, one of which, 3-methoxy-6-[4-(3, 4, 5-trimethoxyphenyl)-1H-pyrazol-3-yl] benzene-1, 2-diol (27), proved to be a cytotoxic anti-tubulin agent with low nanomolar potency.

3, 4-diarylpyrazoles

3-methoxy-6-[4-(3, 4, 5-trimethoxyphenyl)-1H-pyrazol-3-yl] benzene-1, 2-diol


Input: We also report that combretastatins, including CA1, CA4, and 27, are effective against mesothelioma cell lines and therefore have significant clinical promise.

combretastatins


Input: Metabolism experiments demonstrate that 27 retains the ability to form ortho-quinone species, while the pyrazole ring shows high metabolic stability, suggesting that this compound might result in better pharmacokinetic profiles than CA1, with similar pharmacodynamic properties and clinical potential.

ortho-quinone

pyrazole


Input: Understanding quantitative structure-property relationships uncertainty in environmental fate modeling.


Input: In cases in which experimental data on chemical-specific input parameters are lacking, chemical regulations allow the use of alternatives to testing, such as in silico predictions based on quantitative structure-property relationships (QSPRs).


Input: Such predictions are often given as point estimates; however, little is known about the extent to which uncertainties associated with QSPR predictions contribute to uncertainty in fate assessments.


Input: In the present study, QSPR-induced uncertainty in overall persistence (POV) and long-range transport potential (LRTP) was studied by integrating QSPRs into probabilistic assessments of five polybrominated diphenyl ethers (PBDEs), using the multimedia fate model Simplebox.

polybrominated diphenyl ethers

PBDEs


Input: The uncertainty analysis considered QSPR predictions of the fate input parameters' melting point, water solubility, vapor pressure, organic carbon-water partition coefficient, hydroxyl radical degradation, biodegradation, and photolytic degradation.

carbon

hydroxyl


Input: Uncertainty in POV and LRTP was dominated by the uncertainty in direct photolysis and the biodegradation half-life in water.


Input: However, the QSPRs developed specifically for PBDEs had a relatively low contribution to uncertainty.

PBDEs


Input: These findings suggest that the reliability of the ranking of PBDEs on the basis of POV and LRTP can be substantially improved by developing better QSPRs to estimate degradation properties.

PBDEs


Input: The present study demonstrates the use of uncertainty and sensitivity analyses in nontesting strategies and highlights the need for guidance when compounds fall outside the applicability domain of a QSPR.


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1069-1076.


Input: (c) 2013 SETAC.


Input: Balance of coordination and hydrophobic interaction in the formation of bilayers in metal-coordinated surfactant mixtures.


Input: Metal-ligand coordination and hydrophobic interaction are two significant driving forces in the aggregation of mixtures of M (n +) surfactants and alkyldimethylamine oxide (CnDMAO) in aqueous solutions.

alkyldimethylamine oxide

CnDMAO


Input: The coordinated systems exhibit rich aggregation behavior.


Input: This study investigated the effect of M (n +) ions (Zn (2 +), Ca (2 +), Ba (2 +), Al (3 +), Fe (3 +), La (3 +), Eu (3 +), and Tb (3 +)) and hydrophobic chains (hydrocarbon and fluorocarbon) on the formation of metal-coordinated bilayers.

Zn (2 +)

Ca (2 +)

Ba (2 +)

Al (3 +)

Fe (3 +)

La (3 +)

Eu (3 +)

Tb (3 +)

hydrocarbon

fluorocarbon


Input: We found that fluorocarbon chains and branched hydrocarbon chains are preferable to the corresponding linear hydrocarbon chains for the formation of an L alpha phase.

fluorocarbon

hydrocarbon

hydrocarbon


Input: Moreover, L alpha phases formed by fluorocarbon chains exhibited higher viscoelasticity than ones formed by the hydrocarbons, and the bilayers formed by branched chains were rather flexible, revealing obvious undulation.

fluorocarbon

hydrocarbons


Input: The construction of bilayers was also strongly affected by metal ions due to their variable coordination ability with CnDMAO.

CnDMAO


Input: Our results contribute to the understanding of the formation of metal-coordinated bilayers, which is driven by the interplay of noncovalent forces.


Input: A natural topological insulator.


Input: The earth' s crust and outer space are rich sources of technologically relevant materials which have found application in a wide range of fields.


Input: Well-established examples are diamond, one of the hardest known materials, or graphite as a suitable precursor of graphene.

diamond

graphite

graphene


Input: The ongoing drive to discover novel materials useful for (opto) electronic applications has recently drawn strong attention to topological insulators.


Input: Here, we report that Kawazulite, a mineral with the approximate composition Bi2 (Te, Se) 2 (Se, S), represents a naturally occurring topological insulator whose electronic properties compete well with those of its synthetic counterparts.

Kawazulite

Bi2 (Te, Se) 2 (Se, S)


Input: Kawazulite flakes with a thickness of a few tens of nanometers were prepared by mechanical exfoliation.


Input: They exhibit a low intrinsic bulk doping level and correspondingly a sizable mobility of surface state carriers of more than 1000 cm (2)/(V s) at low temperature.


Input: Based on these findings, further minerals which due to their minimized defect densities display even better electronic characteristics may be identified in the future.


Input: Robust ordered cubic mesostructured polymer/silica composite films grown at the air/water interface.

silica


Input: Polymer/silica composite films, stable to calcination, were produced using catanionic surfactant mixtures (hexadecyltrimethylammonium bromide (CTAB) and sodium dodecyl sulfate (SDS)) and polymers (polyethylenimine (PEI) or polyacrylamide (PAAm)) at the air/water interface.

silica

hexadecyltrimethylammonium bromide

CTAB

sodium dodecyl sulfate

SDS

polyethylenimine

PEI

polyacrylamide

PAAm


Input: Film formation processes were probed by time-resolved neutron reflectivity measurements.


Input: Grazing incidence X-ray diffraction (GID) measurements indicate that the mesophase geometry of the interfacial films could be controlled to give lamellar, 2D hexagonal, and several cubic phases (Pn3 m, Fm3 m, and Im3 m) by varying the polyelectrolyte molecular weight, polyelectrolyte chemical nature, or the cationic: anionic surfactant molar ratio.


Input: On the basis of GID results, a phase diagram for the catanionic surfactant/polyelectrolyte/TMOS film system was drawn.

TMOS


Input: These films can be easily removed from the interface and mesoporous silica films which retain the film geometry can be obtained after calcination; moreover, this film preparation method provides a simple way to impart polymer functionality into the mesostructured silica wall, which means these films have potential applications in a variety of fields such as catalysis, molecular separation, and drug delivery.

silica

silica


Input: The circadian clock circuitry and the AHR signaling pathway in physiology and pathology.


Input: Life forms populating the Earth must face environmental challenges to assure individual and species survival.


Input: The strategies predisposed to maintain organismal homeostasis and grant selective advantage rely on anticipatory phenomena facing periodic modifications, and compensatory phenomena facing unpredictable changes.


Input: Biological processes bringing about these responses are respectively driven by the circadian timing system, a complex of biological oscillators entrained to the environmental light/dark cycle, and by regulatory and metabolic networks that precisely direct the body' s adjustments to variations of external conditions and internal milieu.


Input: A critical role in organismal homeostatic functions is played by the aryl hydrocarbon receptor (AHR) complex, which senses environmental and endogenous compounds, influences metabolic responses controlling phase I/II gene expression, and modulates vital phenomena such as development, inflammation and adaptive immunity.

aryl hydrocarbon


Input: A physiological cross-talk between circadian and AHR signaling pathways has been evidenced.


Input: The alteration of AHR signaling pathway deriving from genetic damage with polymorphisms or mutations, or produced by exogenous or endogenous AHR activation, and chronodisruption caused by mismatch between the body' s internal clock and geophysical time/social schedules, are capable of triggering pathological mechanisms involved in metabolic, immune-related and neoplastic diseases.


Input: On the other hand, the molecular components of the circadian clock circuitry and AHR signaling pathway may represent useful tools for preventive interventions and valuable targets of therapeutic approaches.


Input: Deficient fear recognition in regular cocaine users is not attributable to elevated impulsivity or conduct disorder prior to cocaine use.

cocaine

cocaine


Input: We previously reported that regular recreational intranasal cocaine users exhibit impaired recognition of facial expressions of fear compared to occasional cocaine users and cocaine-na i ve controls.

cocaine

cocaine

cocaine


Input: The aim of the present study was to re-investigate this phenomenon after controlling for impulsivity, conduct disorder (CD) and anti-social personality disorder (ASPD).


Input: We employed a cross-sectional design to compare 31 cocaine-na i ve participants, 35 occasional cocaine users and 20 regular recreational cocaine users.

cocaine

cocaine

cocaine


Input: An emotional facial expression (EFE) task which comprised a male and a female face expressing six basic emotions morphed to differing degrees of emotional intensity was administered together with questionnaires to assess: CD, ASPD and impulsiveness.


Input: ASPD was not a significant covariate for EFE performance but impulsiveness and CD were significant covariates.


Input: After treating impulsiveness and CD as covariates we again observed a group difference in fear recognition ability attributable to the particularly impaired performance of regular cocaine users.

cocaine


Input: This suggests that, although elevated impulsiveness and CD before the age of 15 years, may predispose a relative inability to recognize facial expressions of fear in adulthood, subsequent regular recreational use of cocaine represents an additional factor that is specifically associated with a selective deficit in fear recognition.

cocaine


Input: Painting by numbers: increasing the parts list for chromatin domains.


Input: In this issue of Molecular Cell, van Bemmel and colleagues (2013) report the genome-wide mapping of 42 novel chromatin factors, systematically identifying new components of the various chromatin domains present in fly cells.


Input: Isolation, identification and antimicrobial activity of propolis-associated fungi.


Input: Propolis is a natural product widely known for its medicinal properties.


Input: In this work, fungi present on propolis samples were isolated, identified and tested for the production of antimicrobial metabolites.


Input: Twenty-two fungal isolates were obtained, some of which were identified as Alternaria alternata, Aspergillus flavus, Bipolaris hawaiiensis, Fusarium merismoides, Lasiodiplodia theobromae, Penicillium citrinum, Penicillium crustosum, Penicillium janthinellum, Penicillium purpurogenum, Pestalotiopsis palustris, Tetracoccosporium paxianum and Trichoderma koningii.


Input: These fungi were grown in liquid media to obtain crude extracts that were evaluated for their antibiotic activity against pathogenic bacteria, yeast and Cladosporium cladosporioides and A. flavus.


Input: The most active extract was obtained from L. theobromae (minimum inhibitory concentration = 64 mu g/mL against Listeria monocitogenes).


Input: Some extracts showed to be more active than the positive control in the inhibition of Staphylococcus aureus and L. monocitogenes.


Input: Therefore, propolis is a promising source of fungi, which produces active agents against relevant food poisoning bacteria and crop-associated fungi.


Input: Long-term potentiation: Peeling the onion.


Input: Since the discovery of long-term potentiation (LTP), thousands of papers have been published on this phenomenon.


Input: With this massive amount of information, it is often difficult, especially for someone not directly involved in the field, not to be overwhelmed.


Input: The goal of this review is to peel away as many layers as possible, and probe the core properties of LTP.


Input: We would argue that the many dozens of proteins that have been implicated in the phenomenon are not essential, but rather modulate, often in indirect ways, the threshold and/or magnitude of LTP.


Input: What is required is NMDA receptor activation followed by CaMKII activation.

NMDA


Input: The consequence of CaMKII activation is the rapid recruitment of AMPA receptors to the synapse.

AMPA


Input: This recruitment is independent of AMPA receptor subunit type, but absolutely requires an adequate pool of surface receptors.

AMPA


Input: An important unresolved issue is how exactly CaMKII activation leads to modifications in the PSD to allow rapid enrichment.


Input: This article is part of a Special Issue entitled' GluR-dep synaptic plasticity'.


Input: Disposition and Metabolism of GSK2251052 in Humans: A Novel Boron-Containing Antibiotic.

Boron


Input: (S)-3-(Aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1, 3-dihydro-2, 1-benzoxaborole (GSK2251052) is a novel boron-containing antibiotic that inhibits bacterial leucyl tRNA synthetase, and that has been in development for the treatment of serious Gram-negative infections.

(S)-3-(Aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1, 3-dihydro-2, 1-benzoxaborole

boron

leucyl


Input: In this study, six healthy adult male subjects received a single i. v. dose of [(14) C] GSK2251052, 1500 mg infused over 1 hour.

[(14) C] GSK2251052


Input: Blood, urine, and feces were collected over an extended period of 14 days, and accelerator mass spectrometry was used to quantify low levels of radioactivity in plasma at later time points to supplement the less-sensitive liquid scintillation counting technique.


Input: An excellent mass balance recovery was achieved representing a mean total of 98. 2% of the dose, including 90. 5% recovered in the urine.


Input: Pharmacokinetic analysis demonstrated that radioactivity was moderately associated with the blood cellular components, and together with GSK2251052, both were highly distributed into tissues.


Input: The parent compound had a much shorter half-life than total radioactivity in plasma, approximately 11. 6 hours compared with 96 hours.


Input: GSK2251052 and its major metabolite M3, which resulted from oxidation of the propanol side chain to the corresponding carboxylic acid, comprised the majority of the plasma radioactivity, 37 and 53% of the area under the plasma versus time concentration curve from time zero to infinity, respectively.

propanol

carboxylic acid


Input: Additionally, M3 was eliminated renally, and was demonstrated to be responsible for the long plasma radioactivity elimination half-life.


Input: A combination of in vitro metabolism experiments and a pharmacokinetic study in monkeys with the inhibitor 4-methylpyrazole provided strong evidence that alcohol dehydrogenase, potentially in association with aldehyde dehydrogenase, is the primary enzyme involved in the formation of the M3 metabolite.

alcohol

aldehyde


Input: Strain-dependent dysregulation of one-carbon metabolism in male mice is associated with choline-and folate-deficient diet-induced liver injury.

carbon

choline

folate


Input: Dysregulation of one-carbon metabolism-related metabolic processes is a major contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD).

carbon


Input: It is well established that genetic and gender-specific variations in one-carbon metabolism contribute to the vulnerability to NAFLD in humans.

carbon


Input: To examine the role of one-carbon metabolism dysregulation in the pathogenesis and individual susceptibility to NAFLD, we used a " population-based " mouse model where male mice from 7 inbred were fed a choline-and folate-deficient (CFD) diet for 12 wk.

carbon

choline

folate


Input: Strain-dependent down-regulation of several key one-carbon metabolism genes, including methionine adenosyltransferase 1 alpha (Mat1a), cystathionine-beta-synthase (Cbs), methylenetetrahydrofolate reductase (Mthfr), adenosyl-homocysteinase (Ahcy), and methylenetetrahydrofolate dehydrogenase 1 (Mthfd1), was observed.

carbon

methionine

cystathionine

methylenetetrahydrofolate

adenosyl

methylenetetrahydrofolate


Input: These changes were strongly associated with interstrain variability in liver injury (steatosis, necrosis, inflammation, and activation of fibrogenesis) and hyperhomocysteinemia.


Input: Mechanistically, the decreased expression of Mat1a, Ahcy, and Mthfd1 was linked to a reduced level and promoter binding of transcription factor CCAAT/enhancer binding protein beta (CEBP beta), which directly regulates their transcription.


Input: The strain specificity of diet-induced dysregulation of one-carbon metabolism suggests that interstrain variation in the regulation of one-carbon metabolism may contribute to the differential vulnerability to NFLD and that correcting the imbalance may be considered as preventive and treatment strategies for NAFLD.-Pogribny, I.

carbon

carbon


Input: P., Kutanzi, K., Melnyk, S., de Conti, A., Tryndyak, V., Montgomery, B., Pogribna, M., Muskhelishvili, L., Latendresse, J.


Input: R., James, S.


Input: J., Beland, F.


Input: A., Rusyn, I.


Input: Strain-dependent dysregulation of one-carbon metabolism in male mice is associated with choline-and folate-deficient diet-induced liver injury.

carbon

choline

folate


Input: Post-synthesis, characterization and catalytic properties of fluorine-planted MWW-type titanosilicate.

fluorine

titanosilicate


Input: F-Ti-MWW was post-synthesized by implanting fluorine species into a Ti-MWW framework through an acid treatment process in the presence of ammonium fluoride.

F-Ti

fluorine

Ti

ammonium fluoride


Input: The effects of NH4F addition amount, acid treatment temperature and precursor Ti content were investigated on the incorporation of F species, the zeolite structure and the coordination sites of Ti.

Ti

F

zeolite

Ti


Input: Fluorine-implanting improved the surface hydrophobicity of the zeolite and altered the electropositivity nearby the tetrahedral Ti sites through forming the SiO3/2F and SiO4/2F (-) units.

Fluorine

zeolite

Ti

2F (-)


Input: The negative effect of SiO4/2F (-) units in F-Ti-MWW was eliminated selectively by convenient anion-exchange with various alkali chlorides.

2F (-)

F-Ti

alkali chlorides


Input: F-Ti-MWW containing the SiO3/2F units possessed better catalytic activity and reusability, and a longer catalyst lifetime than conventional Ti-MWW.

F-Ti

Ti


Input: Mechanism of morphology transformation during annealing of nanostructured gold films on glass.


Input: Nanostructured, just-percolated gold films were prepared by evaporation on bare glass.


Input: Annealing of the films at temperatures close to or higher than the softening temperature of the glass substrate induces morphological transformation to discrete Au islands and gradual embedding of the formed islands in the glass.

Au


Input: The mechanism and kinetics of these processes are studied here using a combination of in situ high-temperature optical spectroscopy; ex situ characterization of the island shape by high-resolution scanning electron microscopy (HRSEM), atomic force microcopy (AFM) and cross-sectional transmission electron microscopy (TEM); and numerical simulations of transmission spectra using the Multiple Multipole Program (MMP) approach.


Input: It is shown that the morphological transformation of just-percolated, 10 nm (nominal thickness) Au films evaporated on glass and annealed at 600 degrees C, i. e., in the vicinity of the substrate glass transition temperature (Tg = 557 degrees C), proceeds via three processes exhibiting different time scales: (i) fast recrystallization and dewetting, leading to formation of single-crystalline islands (minutes); the initial spectrum characteristic of a continuous Au film is transformed to that of an island film, displaying a surface plasmon (SP) absorption band.

Au

Au


Input: (ii) Reshaping and faceting of the single-crystalline islands accompanied by formation of circumferential glass rims around them (first few hours); the overall optical response shows a blue shift of the SP band.


Input: (iii) Gradual island embedding in the glass substrate (tens of hours), seen as a characteristic red shift of the SP band.


Input: The influence of the annealing atmosphere (air, vacuum) on the embedding process is found to be minor.


Input: Numerical modeling of the extinction cross-section corresponding to the morphological transformations during island recrystallization and embedding is in qualitative agreement with the experimental data.


Input: Quality assessment and discrimination of the roots of Cynanchum auriculatum and Cynanchum wilfordii by HPLC-UV analysis.


Input: Cynanchum auriculatum and Cynanchum wilfordii are widely used as folk medicine in Eastern Asia.


Input: However, the indeterminacy in the authentic original plant material has resulted in the same appellative name being given to the two plants, and they are commonly misused.


Input: Therefore, it is necessary to establish an analytical method for discrimination as well as quality control of the two species.


Input: This study was to develop HPLC-UV methods for quality assessment of C. auriculatum and C. wilfordii and discrimination between the two species.


Input: Two HPLC methods to analyze eight marker compounds were established and validated.


Input: The first method analyzed seven marker compounds simultaneously on a reversed-phase column, while the second method analyzed a single marker compound, conduritol F, which exists only in C. wilfordii, on a Si-column.

conduritol F

Si


Input: Thirty-nine batches of C. auriculatum and nineteen batches of C. wilfordii that were collected from different geographical regions of South Korea were analyzed by these methods.


Input: The constructed data matrix was subjected to principal components analysis and hierarchical cluster analysis in order to classify the samples.


Input: The established methods offer a potential strategy for authentication and differentiation of the two species.


Input: Promising new molecular targeted therapies in head and neck cancer.


Input: Despite advances in multimodality therapies for the treatment of squamous cell carcinoma of the head and neck (SCCHN), survival rates, functional outcomes and toxicities of therapy remain poor.


Input: The recognition of the prognostic value of human papillomavirus (HPV) status, and the advent of biologically targeted therapies with potential for decreased toxicities and increased selectivity, represent significant developments in our understanding of SCCHN.


Input: Targeted agents currently approved or under investigation for SCCHN include epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab, nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatanib, dacomitinib), vascular endothelial growth factor receptor (VEGFR) inhibitors (bevacizumab, sorafenib, sunitinib, vandetanib) and various inhibitors of other pathways and targets, including phosphatidylinositol 3' kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), MET and insulin-like growth factor receptor (IGF-1R).

tyrosine

gefitinib

erlotinib

lapatinib

afatanib

dacomitinib

sorafenib

sunitinib

vandetanib

phosphatidylinositol

rapamycin


Input: On-going clinical trials are evaluating these emerging agents and their combinations in the treatment of SCCHN.


Input: Fluorescent probes for G-quadruplex structures.


Input: Mounting evidence supports the presence of biologically relevant G-quadruplexes in single-cell organisms, but the existence of endogenous G-quadruplex structures in mammalian cells remains highly controversial.


Input: This is due, in part, to the common misconception that DNA and RNA molecules are passive information carriers with relatively little structural or functional complexity.


Input: For those working in the field, however, the lack of available tools for characterizing DNA structures in vivo remains a major limitation to addressing fundamental questions about structure-function relationships of nucleic acids.


Input: In this review, we present progress towards the direct detection of G-quadruplex structures by using small molecules and modified oligonucleotides as fluorescent probes.


Input: While most development has focused on cell-permeable probes that selectively bind to G-quadruplex structures with high affinity, these same probes can induce G-quadruplex folding, thereby making the native conformation of the DNA or RNA molecule (i. e., in the absence of probe) uncertain.


Input: For this reason, modified oligonucleotides and fluorescent base analogues that serve as " internal " fluorescent probes are presented as an orthogonal means for detecting conformational changes, without necessarily perturbing the equilibria between G-quadruplex, single-stranded, and duplex DNA.


Input: The major challenges and motivation for the development of fluorescent probes for G-quadruplex structures are presented, along with a summary of the key photophysical, biophysical, and biological properties of reported examples.


Input: The C-terminal extended serine residue is absolutely required in nosiheptide maturation.

C

serine

nosiheptide


Input: Serine qua non: Substitution of the extended Ser13 in the core peptide of nosiheptide by analogous amino acids prevented enamide dealkylation of the terminal residue for nosiheptide maturation.

Serine

nosiheptide

amino acids

enamide

nosiheptide


Input: Carnosine inhibits A beta (42) aggregation by perturbing the H-bond network in and around the central hydrophobic cluster.

Carnosine

H


Input: Aggregation of the amyloid-beta peptide (A beta) into fibrillar structures is a hallmark of Alzheimer' s disease.


Input: Thus, preventing self-assembly of the A beta peptide is an attractive therapeutic strategy.


Input: Here, we used experimental techniques and atomistic simulations to investigate the influence of carnosine, a dipeptide naturally occurring in the brain, on A beta aggregation.

carnosine

dipeptide


Input: Scanning force microscopy, circular dichroism and thioflavin T fluorescence experiments showed that carnosine does not modify the conformational features of A beta 42 but nonetheless inhibits amyloid growth.

thioflavin T

carnosine


Input: Molecular dynamics (MD) simulations indicated that carnosine interacts transiently with monomeric A beta 42 by salt bridges with charged side chains, and van der Waals contacts with residues in and around the central hydrophobic cluster ((17) LVFFA (21)).

carnosine


Input: NMR experiments on the nonaggregative fragment A beta 12-28 did not evidence specific intermolecular interactions between the peptide and carnosine, in agreement with MD simulations.

carnosine


Input: However, a close inspection of the spectra revealed that carnosine interferes with the local propensity of the peptide to form backbone hydrogen bonds close to the central hydrophobic cluster (residues E22, S26 and N27).

carnosine

hydrogen


Input: Finally, MD simulations of aggregation-prone A beta heptapeptide segments show that carnosine reduces the propensity to form intermolecular backbone hydrogen bonds in the region 18-24.

heptapeptide

carnosine

hydrogen


Input: Taken together, the experimental and simulation results (cumulative MD sampling of 0. 2 ms) suggest that, despite the inability of carnosine to form stable contacts with A beta, it might block the pathway toward toxic aggregates by perturbing the hydrogen bond network near residues with key roles in fibrillogenesis.

carnosine

hydrogen


Input: Highly Ordered Hollow Oxide Nanostructures: The Kirkendall Effect at the Nanoscale.

Oxide


Input: Highly ordered ultra-long oxide nanotubes are fabricated by a simple two-step strategy involving the growth of copper nanowires on nanopatterned template substrates by magnetron sputtering, followed by thermal annealing in air.

oxide

copper


Input: The formation of such tubular nanostructures is explained according to the nanoscale Kirkendall effect.


Input: The concept of this new fabrication route is also extendable to create periodic zero-dimensional hollow nanostructures.


Input: Solvatochromic Effect on the Photoluminescence of MoS2 Monolayers.


Input: The effect of surrounding solvents on the photoluminescence (PL) of MoS2 monolayers on Si/SiO2 substrates is studied.

Si


Input: A redshift (up to-60 meV) is observed for MoS2 monolayers with nonhalogenated solvent surroundings.


Input: A blueshift (up to 60 meV) and intensity increase (2-50 times) are observed for monolayers with halogenated solvent surroundings.


Input: Regio-and Stereocontrolled Synthesis of Oligostilbenoids: Theoretical Highlights at the Supramolecular Level.


Input: Oligostilbenoids (e. g., ampelopsin F, viniferin, pallidol) result from homogeneous or heterogeneous coupling of monomeric stilbenoid units, leading to various chemical structures.

ampelopsin F

viniferin

pallidol

stilbenoid


Input: Oligostilbenoid synthesis is regio-and stereocontrolled.


Input: To tackle this regio-and stereocontrol, a supramolecular chemistry approach is required that can be achieved by quantum chemistry.


Input: The stability of noncovalent pi-stacks, formed between two stilbenoid units prior to oxidation, is accurately evaluated with density functional theory (DFT) including dispersive effects (within the DFT-D formalism).

stilbenoid


Input: These noncovalent arrangements drive the regiocontrol.


Input: The rest of the chemical pathway is a succession of dearomatization and rearomatization stages.


Input: The thermodynamics and kinetics of the processes are calculated with classical hybrid functionals.


Input: This study allows discrimination between the two main possible chemical pathways, namely, radical-neutral and radical-radical reactions.


Input: The former appears more likely, thermodynamics and kinetics being in perfect agreement with the experimental 1: 2 ratio obtained for ampelopsin F: pallidol analogues, respectively.

ampelopsin F

pallidol


Input: Molecular interactions between lecithin and bile salts/acids in oils and their effects on reverse micellization.

bile salts/acids


Input: It has been known that the addition of bile salts to lecithin organosols induces the formation of reverse wormlike micelles and that the worms are similar to long polymer chains that entangle each other to form viscoelastic solutions.

bile salts


Input: In this study, we further investigated the effects of different bile salts and bile acids on the growth of lecithin reverse worms in cyclohexane and n-decane.

bile salts

bile acids

cyclohexane

n-decane


Input: We utilized rheological and small-angle scattering techniques to analyze the properties and structures of the reverse micelles.


Input: All of the bile salts can transform the originally spherical lecithin reverse micelles into wormlike micelles and their rheological behaviors can be described by the single-relaxation-time Maxwell model.

bile salts


Input: However, their efficiencies to induce the worms are different.


Input: In contrast, before phase separation, bile acids can induce only short cylindrical micelles that are not long enough to impart viscoelasticity.

bile acids


Input: We used Fourier transform infrared spectroscopy to investigate the interactions between lecithin and bile salts/acids and found that different bile salts/acids employ different functional groups to form hydrogen bonds with lecithin.

bile salts/acids

bile salts/acids

hydrogen


Input: Such effects determine the relative positions of the bile salts/acids in the headgroups of lecithin, thus resulting in varying efficiencies to alter the effective critical packing parameter for the formation of wormlike micelles.

bile salts/acids


Input: This work highlights the importance of intermolecular interactions in molecular self-assembly.


Input: Marine drugs best paper award 2013.


Input: To recognize the most outstanding papers in the area of research, development and production of drugs from the sea, including marine natural product chemistry, that have been published in Marine Drugs, we would like to start an annual " Best Paper Award ".


Input: Cellular imaging demonstrates genetic mosaicism in heterozygous carriers of an X-linked ciliopathy gene.


Input: X-linked retinitis pigmentosa (XLRP) is the least common genetic type of retinitis pigmentosa; however, it has extremely devastating consequences to patients' activities of daily living.


Input: RPGR and RP2 genes expressed in the photoreceptor sensory cilia are predominantly implicated in XLRP; however, the interpretation of genetic mutations and their correlation with clinical phenotypes remain unknown, and the role of these genes in photoreceptor cilia function is not completely elucidated.


Input: Therefore, we evaluated structural characteristics in five female obligate carriers of XLRP by using state-of-the-art non-invasive imaging methods, including adaptive optics (AO) scanning laser ophthalmoscopy (SLO).


Input: In all five carriers examined, qualitative and quantitative analyses by AO SLO imaging revealed a mosaic pattern of cone disruption, even in the absence of visual symptoms, normal visual acuity and normal macular thickness, on optical coherence tomography and mildly subnormal full-field cone electroretinographic findings.


Input: As the technique is sensitive to the level of a single cone, the ability to visualize the cone cells in vivo should be especially useful in other retinal diseases.


Input: In addition, further investigation of XLRP carriers may yield insight into how cone structures change over time and ultimately enable understanding of the role of RPGR and RP2 in cone cell survival. European Journal of Human Genetics advance online publication, 27 February 2013; doi: 10. 1038/ejhg. 2013. 21.


Input: Control of 10 nm scale cylinder orientation in self-organized sugar-based block copolymer thin films.

sugar


Input: The present paper describes the orientational control of 10 nm scale cylinders in sugar-based block copolymer thin films by simply varying the composition of the annealing co-solvent.

sugar


Input: The affinity of the block copolymer to the solvent vapor could be systematically adjusted in this way.