Input: Intergrowth of two partially miscible phases of BiFeO (3) and BiMnO (3) gives a new class of room-temperature multiferroic phase, Bi (3) Fe (2) Mn (2) O (10 + delta), which has a unique supercell (SC) structure.

BiFeO (3)

BiMnO (3)

Bi (3) Fe (2) Mn (2) O (10 + delta)


Input: The SC heterostructures exhibit simultaneously room-temperature ferrimagnetism and remanent polarization.


Input: These results open up a new avenue for exploring room-temperature single-phase multiferroic thin films by controlling the phase mixing of two perovskite BiRO (3) (R = Cr, Mn, Fe, Co, Ni) materials.

perovskite BiRO (3)

Cr

Mn

Fe

Co

Ni


Input: DDBJ new system and service refactoring.


Input: The DNA data bank of Japan (DDBJ, http://www. ddbj. nig. ac. jp) maintains a primary nucleotide sequence database and provides analytical resources for biological information to researchers.


Input: This database content is exchanged with the US National Center for Biotechnology Information (NCBI) and the European Bioinformatics Institute (EBI) within the framework of the International Nucleotide Sequence Database Collaboration (INSDC).


Input: Resources provided by the DDBJ include traditional nucleotide sequence data released in the form of 27 316 452 entries or 16 876 791 557 base pairs (as of June 2012), and raw reads of new generation sequencers in the sequence read archive (SRA).


Input: A Japanese researcher published his own genome sequence via DDBJ-SRA on 31 July 2012.


Input: To cope with the ongoing genomic data deluge, in March 2012, our computer previous system was totally replaced by a commodity cluster-based system that boasts 122. 5 TFlops of CPU capacity and 5 PB of storage space.


Input: During this upgrade, it was considered crucial to replace and refactor substantial portions of the DDBJ software systems as well.


Input: As a result of the replacement process, which took more than 2 years to perform, we have achieved significant improvements in system performance.


Input: Synthesis and anti-angiogenic activity of benzothiazole, benzimidazole containing phthalimide derivatives.

benzothiazole

benzimidazole

phthalimide


Input: Benzothiazole and benzimidazole containing phthalimide derivatives (NK037, NK041, NK042, NK0139A and NK0148) have been synthesized and their anti-angiogenic activity was evaluated using ex vivo egg yolk angiogenesis model.

Benzothiazole

benzimidazole

phthalimide


Input: A comparative study with pure thalidomide (NKTA) has also been performed to describe the efficacy of these derivatives in blocking angiogenesis.

thalidomide


Input: NK037, NK041 and NK042 were equally potent in blocking egg yolk angiogenesis and the anti-angiogenesis effect was higher than NKTA suggesting the efficacy of these three derivatives in blocking angiogenesis when compare to control.

NKTA


Input: Other two derivatives NK0139A and NK0148 showed effect less than NKTA and stronger than control in ex vivo angiogenesis.

NKTA


Input: Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA. TTC) associated with Friedreich' s ataxia.


Input: Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells.


Input: Below, we show that long (230 repeats) tracts of the trinucleotide associated with Friedreich' s ataxia (GAA. TTC) stimulate both large (> 50 bp) deletions and point mutations in a reporter gene located more than 1 kb from the repetitive tract.


Input: Sequence analysis of deletion breakpoints indicates that the deletions reflect non-homologous end joining of double-stranded DNA breaks (DSBs) initiated in the tract.


Input: The tract-induced point mutations appear to reflect a different mechanism involving single-strand annealing of DNA molecules generated by DSBs within the tract, followed by filling-in of single-stranded gaps by the error-prone DNA polymerase zeta.


Input: Cytotoxicity, antioxidant activity and an effect on CYP3A4 and CYP2D6 of Mutellina purpurea L. extracts.


Input: Mutellina purpurea is an aromatic Apiaceae plant known as Alpine lovage.


Input: Its polar extracts consist of phenolic acids, tannins and flavonoids.

phenolic acids

tannins

flavonoids


Input: The cytotoxic effect of methanolic and aqueous extracts from M. purpurea was studied on the most frequently used cell lines: HeLa and BHK-21.


Input: Taking into account that the natural products are often used with other medicines there is a risk of reciprocal interaction on the metabolic level.


Input: Thus, the influence of M. purpurea extracts was investigated on the activity of CYP2D6 and CYP3A4, which are the most important P450 isoenzymes from the pharmacological and toxicological points of view.


Input: Additionally, because M. purpurea contains phenolic compounds, the antioxidative properties of this plant extracts were also studied and compared.

phenolic


Input: Control of hypercholesterolemia and atherosclerosis using the cholesterol recognition/interaction amino acid sequence of the translocator protein TSPO.

amino acid


Input: The translocator protein (18-kDa) TSPO is an ubiquitous high affinity cholesterol-binding protein reported to be present in the endothelial and smooth muscle cells of the blood vessels; its expression dramatically increased in macrophages found in atherosclerotic plaques.

cholesterol


Input: A domain in the carboxy-terminus of TSPO was identified and characterized as the cholesterol recognition/interaction amino acid consensus (CRAC).

carboxy

cholesterol

amino acid


Input: The ability of the CRAC domain to bind to cholesterol led us to hypothesize that this peptide could be used as an hypocholesterolemic, with potential anti-atherogenic properties, agent.

cholesterol


Input: We report herein the therapeutic benefit that resulted for the administration of the VLNYYVWR human CRAC sequence to guinea pigs fed with a high cholesterol diet and ApoE knock-out B6. 129P2-Apoetm1Unc/J mice.

cholesterol


Input: CRAC treatment (3 and 30mg/kg once daily for 6 weeks) resulted in reduced circulating cholesterol levels in guinea pigs fed with 2% high cholesterol diet and ApoE knock-out B6. 129P2-Apoetm1Unc/J mice.

cholesterol

cholesterol


Input: In high cholesterol fed guinea pigs, CRAC treatment administered once daily induced an increase in circulating HDL, decreased total, free and LDL cholesterol, and removed atheroma deposits in the aorta in a dose-dependent manner.

cholesterol

cholesterol


Input: The treatment also prevented the high cholesterol diet-induced increase in serum creatine kinase, total and isoforms, markers of neurological, cardiac and muscular damage.

cholesterol

creatine


Input: No toxicity was observed.


Input: Taken together these results support a role of TSPO in lipid homeostasis and atherosclerosis and indicate that CRAC may constitute a novel and safe treatment of hypercholesterolemia and atherosclerosis.


Input: Disrupted cytoskeletal homeostasis, astrogliosis and apoptotic cell death in the cerebellum of preweaning rats injected with diphenyl ditelluride.

diphenyl ditelluride


Input: In the present report 15 day-old rats were injected with 0. 3 mu mol of diphenyl ditelluride (PhTe) (2)/kg body weight and parameters of neurodegeneration were analyzed in slices from cerebellum 3 and 6 days afterwards.

diphenyl ditelluride (PhTe) (2)


Input: The earlier responses, at day 3 after injection, included hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein-GFAP-and vimentin) and neuron (low-, medium-and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H); increased mitogen-activated protein kinase (MAPK) (Erk and p38MAPK) and cAMP-dependent protein kinase (PKA) activities.

cAMP


Input: Also, reactive astrogliosis takes part of the early responses to the insult with (PhTe) (2), evidenced by upregulated GFAP in Western blot, PCR and immunofluorescence analysis.

(PhTe) (2)


Input: Six days after (PhTe) (2) injection we found persistent astrogliosis, increased propidium iodide (PI) positive cells in NeuN positive population evidenced by flow cytometry and reduced immunofluorescence for NeuN, suggesting that the in vivo exposure to (PhTe) (2) progressed to neuronal death.

(PhTe) (2)

propidium iodide

(PhTe) (2)


Input: Moreover, activated caspase 3 suggested apoptotic neuronal death.


Input: Neurodegeneration was related with decreased [(3) H] glutamate uptake and decreased Akt immunoreactivity, however phospho-GSK-3-beta (Ser9) was not altered in (PhTe) (2) injected rat.

[(3) H] glutamate

(PhTe) (2)


Input: Therefore, the present results show that the earlier cerebellar responses to (PhTe) (2) include disruption of cytoskeletal homeostasis that could be related with MAPK and PKA activation and reactive astrogliosis.

(PhTe) (2)


Input: Akt inhibition observed at this time could also play a role in the neuronal death evidenced afterwards.


Input: The later events of the neurodegenerative process are characterized by persistent astrogliosis and activation of apoptotic neuronal death through caspase 3 mediated mechanisms, which could be related with glutamate excitotoxicity.

glutamate


Input: The progression of these responses are therefore likely to be critical for the outcome of the neurodegeneration provoked by (PhTe) (2) in rat cerebellum.

(PhTe) (2)


Input: The microsomal enzyme 17 beta-hydroxysteroid dehydrogenase 3 faces the cytoplasm and uses NADPH generated by glucose-6-phosphate dehydrogenase.

17 beta-hydroxysteroid

NADPH


Input: Recent studies proposed a functional coupling between 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3)-dependent testosterone formation and 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1)-mediated interconversion of glucocorticoids through competition for the luminal pyridine nucleotide pool.

17 beta-hydroxysteroid

11 beta-hydroxysteroid

pyridine nucleotide


Input: To test this hypothesis, we used human embryonic kidney-293 cells transfected with 17 beta-HSD3 and/or 11 beta-HSD1, in the absence or presence of hexose-6-phosphate dehydrogenase that generates reduced nicotinamide adenine dinucleotide phosphate (NADPH) in the endoplasmic reticulum and determined enzyme activities.

nicotinamide adenine dinucleotide phosphate

NADPH


Input: As an endogenous cell model, mouse MA-10 Leydig cells were used.


Input: 17 beta-HSD3-dependent reduction of Delta 4-androstene-3, 17-dione was affected by neither coexpression with 11 beta-HSD1 nor overexpression or knockdown of hexose-6-phosphate dehydrogenase.

Delta 4-androstene-3, 17-dione


Input: In contrast, knockdown of glucose-6-phosphate dehydrogenase decreased 17 beta-HSD3 activity, indicating dependence on cytoplasmic NADPH.

NADPH


Input: Upon selective permeabilization of the plasma membrane by digitonin, 17 beta-HSD3 but not 11 beta-HSD1 was detected by antibodies against C-terminal epitope tags, suggesting a cytoplasmic orientation of 17 beta-HSD3.

digitonin

C


Input: The cytoplasmic orientation was confirmed using proteinase K digestion of microsomal preparations and by analysis of glycosylation of wild-type 17 beta-HSD3 and chimera in which the N-terminal anchor sequences between 17 beta-HSD3 and 11 beta-HSD1 were exchanged.

N


Input: In conclusion, the results demonstrate a cytoplasmic orientation of 17 beta-HSD3 and dependence on glucose-6-phosphate dehydrogenase-generated NADPH, explaining the lack of a direct functional coupling with the luminal 11 beta-HSD1-mediated glucocorticoid metabolism.

NADPH


Input: A combined nuclear and nucleolar localization motif in activation-induced cytidine deaminase (AID) controls immunoglobulin class switching.

cytidine


Input: Activation-induced cytidine deaminase (AID) is a DNA mutator enzyme essential for adaptive immunity.

cytidine


Input: AID initiates somatic hypermutation and class switch recombination (CSR) by deaminating cytosine to uracil in specific immunoglobulin (Ig) gene regions.

cytosine

uracil


Input: However, other loci, including cancer-related genes, are also targeted.


Input: Thus, tight regulation of AID is crucial to balance immunity versus disease such as cancer.


Input: AID is regulated by several mechanisms including nucleocytoplasmic shuttling.


Input: Here we have studied nuclear import kinetics and subnuclear trafficking of AID in live cells and characterized in detail its nuclear localization signal.


Input: Importantly, we find that the nuclear localization signal motif also directs AID to nucleoli where it colocalizes with its interaction partner, catenin-beta-like 1 (CTNNBL1), and physically associates with nucleolin and nucleophosmin.


Input: Moreover, we demonstrate that release of AID from nucleoli is dependent on its C-terminal motif.

C


Input: Finally, we find that CSR efficiency correlates strongly with the arithmetic product of AID nuclear import rate and DNA deamination activity.


Input: Our findings suggest that directional nucleolar transit is important for the physiological function of AID and demonstrate that nuclear/nucleolar import and DNA cytosine deamination together define the biological activity of AID.

cytosine


Input: This is the first study on subnuclear trafficking of AID and demonstrates a new level in its complex regulation.


Input: In addition, our results resolve the problem related to dissociation of deamination activity and CSR activity of AID mutants.


Input: One pot synthesis and biological activity evaluation of novel Schiff bases derived from 2-hydrazinyl-1, 3, 4-thiadiazole.

Schiff bases

2-hydrazinyl-1, 3, 4-thiadiazole


Input: Considering the structural features of a group of known potent inhibitors of human platelet aggregation containing hydrazone structural backbone, a series of novel hydrazone derivatives of 2-hydrazinyl-1, 3, 4-thiadiazole were synthesized using a one-pot process and tested for their inhibitory activity against platelet aggregation induced by arachidonic acid and ADP.

hydrazone

hydrazone

2-hydrazinyl-1, 3, 4-thiadiazole

arachidonic acid

ADP


Input: Among the derivatives, compounds 3l, 3o and 3p exhibited the highest antiplatelet aggregation activity.


Input: The derivatives were also screened for their potential antimycobacterial activity and compounds 3g, 3k, 3p and 3q were among the most active compounds.


Input: Inhibition of ice nucleation by slippery liquid-infused porous surfaces (SLIPS).


Input: Ice repellent coatings have been studied and keenly sought after for many years, where any advances in the durability of such coatings will result in huge energy savings across many fields.


Input: Progress in creating anti-ice and anti-frost surfaces has been particularly rapid since the discovery and development of slippery, liquid infused porous surfaces (SLIPS).


Input: Here we use SLIPS-coated differential scanning calorimeter (DSC) pans to investigate the effects of the surface modification on the nucleation of supercooled water.


Input: This investigation is inherently different from previous studies which looked at the adhesion of ice to SLIPS surfaces, or the formation of ice under high humidity conditions.


Input: Given the stochastic nature of nucleation of ice from supercooled water, multiple runs on the same sample are needed to determine if a given surface coating has a real and statistically significant effect on the nucleation temperature.


Input: We have cycled supercooling to freezing and then thawing of deionized water in hydrophilic (untreated aluminum), hydrophobic, superhydrophobic, and SLIPS-treated DSC pans multiple times to determine the effects of surface treatment on the nucleation and subsequent growth of ice.

aluminum


Input: We find that SLIPS coatings lower the nucleation temperature of supercooled water in contact with statistical significance and show no deterioration or change in the coating performance even after 150 freeze-thaw cycles.


Input: X-linked dystonia parkinsonism syndrome (XDP, lubag): disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism.

dopamine


Input: X-chromosomal dystonia parkinsonism syndrome (XDP,' lubag') is associated with sequence changes within the TAF1/DYT3 multiple transcript system.


Input: Although most sequence changes are intronic, one, disease-specific single-nucleotide change 3 (DSC3), is located within an exon (d4).

nucleotide


Input: Transcribed exon d4 occurs as part of multiple splice variants.


Input: These variants include exons d3 and d4 spliced to exons of TAF1, and an independent transcript composed of exons d2-d4.


Input: Location of DSC3 in exon d4 and utilization of this exon in multiple splice variants suggest an important role of DSC3 in the XDP pathogenesis.


Input: To test this hypothesis, we transfected neuroblastoma cells with four expression constructs, including exons d2-d4 [d2-d4/wild-type (wt) and d2-d4/DSC3] and d3-d4 (d3-d4/wt and d3-d4/DSC3).


Input: Expression profiling revealed a dramatic effect of DSC3 on overall gene expression.


Input: Three hundred and sixty-two genes differed between cells containing d2-d4/wt and d2-d4/DSC3.


Input: Annotation clustering revealed enrichment of genes related to vesicular transport, dopamine metabolism, synapse function, Ca (2 +) metabolism and oxidative stress.

dopamine

Ca (2 +)


Input: Two hundred and eleven genes were differentially expressed in d3-d4/wt versus d3-d4/DSC3.


Input: Annotation clustering highlighted genes in signal transduction and cell-cell interaction.


Input: The data show an important role of physiologically occurring transcript d2-d4 in normal brain function.


Input: Interference with this role by DSC3 is a likely pathological mechanism in XDP.


Input: Disturbance of dopamine function and of Ca (2 +) metabolism can explain abnormal movement; loss of protection against reactive oxygen species may account for the neurodegenerative changes in XDP.

Ca (2 +)

oxygen


Input: Although d3-d4 also affect genes potentially related to neurodegenerative processes, their physiologic role as splice variants of TAF1 awaits further exploration.


Input: An artificial neural network approach to improving the correlation between protein energetics and the backbone structure.


Input: Computational approaches to modeling protein structures have made significant advances over the past decade.


Input: However, the current limitation in modeling protein structures is to produce protein structures consistently below the limit of 6 A compared to their native structure.


Input: Therefore, improvement of protein structures consistently below the 6 A limit using simulation of biophysical forces is of significant interest.


Input: Current protein force fields such as those implemented in CHARMM, AMBER, and NAMD have been deemed complete, yet their use in ab initio approaches to protein structure determination has been unsuccessful.


Input: Here, we introduce a new approach in evaluation of protein structures based on analysis of energy profiles produced by the SCOPE software package.


Input: The latest version of SCOPE produces a hydrogen bond profile that is substantially more informative than a single hydrogen bond energy value.

hydrogen

hydrogen


Input: We demonstrate how analysis of SCOPE' s energy profile by an artificial neural network shows a significant improvement compared to the traditional force-based approaches to evaluation of structures.


Input: The artificial neural network based analysis of SCOPE' s energy profile showed identification of structures to within the range of 1. 5-3. 0 A of the native structure.


Input: These results have been obtained by testing structures in the same Homology, Topology, Architecture, or Class of the CATH family.


Input: Electronic transition moments of 6-methyl isoxanthopterin--a fluorescent analogue of the nucleic acid base guanine.

6-methyl isoxanthopterin

guanine


Input: Fluorescent nucleic acid base analogues are important spectroscopic tools for understanding local structure and dynamics of DNA and RNA.


Input: We studied the orientations and magnitudes of the electric dipole transition moments (EDTMs) of 6-methyl isoxanthopterin (6-MI), a fluorescent analogue of guanine that has been particularly useful in biological studies.

6-methyl isoxanthopterin

guanine


Input: Using a combination of absorption spectroscopy, linear dichroism (LD) and quantum chemical calculations, we identified six electronic transitions that occur within the 25, 000-50, 000 cm (-1) spectral range.


Input: Our results indicate that the two experimentally observed lowest-energy transitions, which occur at 29, 687 cm (-1) (337 nm) and 34, 596 cm (-1) (289 nm), are each polarized within the plane of the 6-MI base.


Input: A third in-plane polarized transition is experimentally observed at 47, 547 cm (-1) (210 nm).


Input: The theoretically predicted orientation of the lowest-energy transition moment agrees well with experiment.


Input: Based on these results, we constructed an exciton model to describe the absorption spectra of a 6-MI dinucleotide-substituted double-stranded DNA construct.


Input: This model is in good agreement with the experimental data.


Input: The orientations and intensities of the low-energy electronic transitions of 6-MI reported here should be useful for studying local conformations of DNA and RNA in biologically important complexes.


Input: Evaluation of romidepsin for clinical activity and radioactive iodine reuptake in radioactive iodine-refractory thyroid carcinoma.

romidepsin

radioactive iodine

radioactive iodine


Input: Background: Historically, systemic therapy for radioactive iodine (RAI)-refractory thyroid cancer has been understudied.

radioactive iodine

RAI


Input: Available drugs have modest efficacy.


Input: Romidepsin is a histone deacetylase inhibitor with potent antitumor effects both in vitro and in vivo.

Romidepsin


Input: In thyroid cancer cell lines, romidepsin increases expression of both thyroglobulin and the sodium iodide symporter messenger RNAs, suggesting the possibility of improved iodine concentrating ability of RAI-resistant tumors.

sodium iodide

iodine

RAI


Input: Methods: This was a single-institution Simon 2-stage phase II clinical study.


Input: Eligible patients had progressive, RAI-refractory, recurrent/metastatic, nonmedullary, nonanaplastic thyroid cancer.

RAI


Input: Response Evaluation Criteria in Solid Tumors (RECIST) 1. 0 measurable disease and adequate organ/marrow function were required.


Input: Romidepsin 13 mg/m (2) was administered intravenously on days 1, 8, and 15, in cycles of 28 days.

Romidepsin


Input: The primary endpoint was the response rate by RECIST; change in RAI avidity was a secondary endpoint.

RAI


Input: The study closed after the first stage due to the lack of response.


Input: Results: Twenty patients were enrolled: female, 50%; median age, 64 years; histology, 8 papillary/1 follicular/11 H u rthle.


Input: Grade 4-5 adverse events (AEs) possibly related to the drug: grade 5, 1 sudden death; grade 4, 1 pulmonary embolus.


Input: Twelve of 20 subjects had a reported adverse event.


Input: No RECIST major responses have been seen.


Input: Response per protocol: stable disease, 13; disease progression, 7.


Input: Restoration of RAI avidity was documented in two patients.

RAI


Input: Median overall survival and time on study was 33. 2 (1-71 +) and 1. 7 (0. 46-12) months, respectively.


Input: Conclusions: We observed preliminary signs of in vivo reversal of RAI resistance after treatment with romidepsin.

RAI

romidepsin


Input: However, no major responses were observed and accrual was poor after the grade 5 AE.


Input: Neuronal P2X3 receptor activation is essential to the hyperalgesia induced by prostaglandins and sympathomimetic amines released during inflammation.

prostaglandins

amines


Input: We have demonstrated that the activation of P2X3 receptor on peripheral afferent neurons is critical to development of inflammatory hyperalgesia in peripheral tissue, although pharmacological administration of prostaglandin E (2) or sympathomimetic amines is enough to sensitize primary afferent neurons by acting directly in neuronal receptors.

prostaglandin E (2)

amines


Input: Therefore, to clarify this ambiguity this study verifies whether P2X3 receptor activation on primary afferent neurons enables the sensitization induced by prostaglandin E (2) or sympathomimetic amine.

prostaglandin E (2)

amine


Input: Initially, this study confirmed that co-administration of A317491 (60 mu g/paw), a selective P2X3 receptor antagonist, or pre-treatment with dexamethasone (1 mg/mL/kg) prevents the mechanical hyperalgesia induced by carrageenan (300 mu g/paw) in the rat' s hind paw.

dexamethasone


Input: Sub-threshold doses of PGE (2) (4 ng/paw) or dopamine (0. 4 mu g/paw), that do not induce hyperalgesia by themselves, when injected just following alpha beta meATP or carrageenan in rats treated with dexamethasone induced hyperalgesia, which is prevented by A317491 or treatment with periganglionar (DRG-L5) injections of ODN-antisense, against P2X3 receptor.

PGE (2)

dopamine

alpha beta meATP

dexamethasone


Input: Furthermore, because PKC epsilon translocation induces an increase of neuronal susceptibility to inflammatory mediators, this study demonstrates that alpha beta meATP in peripheral tissue increases the expression of PKC epsilon in cell membranes of DRG-L5, and in contrast, the administration of PKC epsilon translocation inhibitor (1 mu g/paw) in peripheral tissue 45 min before alpha beta meATP, prevented the hyperalgesia induced by sub-threshold dose of PGE (2) (4 ng/paw).

alpha beta meATP

alpha beta meATP

PGE (2)


Input: In conclusion, this study suggests that neuronal P2X3 receptor activation and the consequent PKC epsilon translocation increase the susceptibility of nociceptor to inflammatory mediators allowing the development of inflammatory hyperalgesia.


Input: An ultrasonic-accelerated oxidation method for determining the oxidative stability of biodiesel.


Input: Biodiesel is considered an alternative energy because it is produced from fats and vegetable oils by means of transesterification.


Input: Furthermore, it consists of fatty acid alkyl esters (FAAS) which have a great influence on biodiesel fuel properties and in the storage lifetime of biodiesel itself.

fatty acid alkyl esters

FAAS


Input: The biodiesel storage stability is directly related to the oxidative stability parameter (Induction Time-IT) which is determined by means of the Rancimat (R) method.


Input: This method uses condutimetric monitoring and induces the degradation of FAAS by heating the sample at a constant temperature.

FAAS


Input: The European Committee for Standardization established a standard (EN 14214) to determine the oxidative stability of biodiesel, which requires it to reach a minimum induction period of 6h as tested by Rancimat (R) method at 110 degrees C.


Input: In this research, we aimed at developing a fast and simple alternative method to determine the induction time (IT) based on the FAAS ultrasonic-accelerated oxidation.

FAAS


Input: The sonodegradation of biodiesel samples was induced by means of an ultrasonic homogenizer fitted with an immersible horn at 480Watts of power and 20 duty cycles.


Input: The UV-Vis spectrometry was used to monitor the FAAS sonodegradation by measuring the absorbance at 270nm every 2.

FAAS


Input: Biodiesel samples from different feedstock were studied in this work.


Input: In all cases, IT was established as the inflection point of the absorbance versus time curve.


Input: The induction time values of all biodiesel samples determined using the proposed method was in accordance with those measured through the Rancimat (R) reference method by showing a R (2) = 0. 998.


Input: Quantification of silanol sites for the most common mesoporous ordered silicas and organosilicas: total versus accessible silanols.

silanol

silicas

organosilicas

silanols


Input: IR and NMR spectroscopy were used to determine the silanol content in the most common mesoporous ordered silicas: MCM-41, MCM-48, SBA-15 and SBA-16.

silanol

silicas


Input: In addition, a spray dried MCM-41 and an ethene bridged PMO are investigated.

ethene

PMO


Input: The results are compared with a commercial chromatographic silica (Nucleosil).

silica

Nucleosil


Input: The complete distribution of surface and bulk silanols, and of isolated, geminal and vicinal silanols for all these materials is presented.

silanols

geminal and vicinal silanols


Input: A distinction is made between the total silanol number and the reachable or surface silanol content.

silanol

silanol


Input: The latter is determined by controlled reactions with simple silanes.

silanes


Input: All mesoporous ordered silicas, and especially the thick walled SBA-type materials and the PMO contain a surprisingly high amount of total silanol sites, albeit that up to 90% of these silanols are buried inside the walls and are not reachable for small silanes.

silicas

PMO

silanol

silanols


Input: Effect of structural defects and chemical functionalisation on the intrinsic mechanical properties of graphene.

graphene


Input: Due to its unique mechanical properties, graphene can be applied for reinforcement in nanocomposites.

graphene


Input: We analyse the Young' s modulus of graphene at the semi-empirical PM6 level of theory.

graphene


Input: The internal forces are calculated and the Young' s modulus is predicted for a finite graphene sheet when external strain is applied on the system.

graphene


Input: These results are in a good agreement with theoretical and experimental results from the literature giving values of about 1 TPa for the Young' s modulus.


Input: Stress-strain curves are computed for elongation up to 20%.


Input: In addition, the influence of the presence of a single vacancy, as well as for oxygenation of a vacancy, on the mechanical properties of graphene has been analysed.

graphene


Input: Our results indicate that when applying the deformation locally onto the system, higher local stress can be induced, as confirmed by Finite Element Analysis.


Input: Also, the presence of structural defects in the system will stiffen the system upon low strain, but reduces the elastic limit from more than 20% strain for pristine graphene to less than 10% strain when defects are present.

pristine graphene


Input: The role of natriuretic peptides as biomarkers for guiding the management of chronic heart failure.


Input: The current standard treatment of chronic heart failure (HF) is based on clinical judgment, with the goal of achieving the maximally tolerated therapeutic program.


Input: The complexity of this approach may contribute to the well-established treatment gaps that exist in HF management; consequently, the risks for morbidity and mortality in this population remain extremely high.


Input: Alternative means are needed to improve the outcomes of patients with HF.


Input: Natriuretic peptides are biological markers for HF disease--its presence, severity, and prognosis--and show unique interactions with therapeutics known to have benefit in HF.


Input: Accordingly, interest has recently developed in " biomarker-guided " care for HF.


Input: This approach involves applying these assays to identify patients in need of therapy intensification and to provide an objective " monitor " of disease status.


Input: This review examines the biology of natriuretic peptides, discusses the rationale for their use in HF, and details the aggregate experience gained thus far in biomarker-guided care.


Input: Lipotoxicity impairs incretin signalling.


Input: The incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic peptide are secreted by enteroendocrine cells and augment glucose-induced insulin secretion in response to food ingestion in a glucose-dependent manner.

glucose

glucose

glucose


Input: This mechanism forms the basis for incretin-based therapies in type 2 diabetes.


Input: However, the insulinotropic effect of incretins is diminished in type 2 diabetic patients, due in part to reduced expression of incretin receptors as a consequence of glucotoxicity.


Input: In this issue of Diabetologia, Kang et al (DOI: 10. 1007/s00125-012-2776-x) provide evidence that in addition to glucotoxicity, lipotoxicity also affects incretin receptor expression and signalling in insulin-secreting cells and isolated islets.


Input: In animal models of diabetes, the authors show that co-administration of a lipid-lowering drug with a dipeptidyl peptidase-4 inhibitor or a glucagon-like peptide-1 agonist improved glucose tolerance and beta cell mass.

glucose


Input: These novel findings provide convincing support for the notion that restoring normal circulating lipid levels in type 2 diabetes might help improve the efficacy of incretin-based therapies.


Input: Mechanism of the antiproliferative activity of some naphthalene diimide G-quadruplex ligands.

naphthalene diimide


Input: G-quadruplexes are higher-order nucleic acid structures that can form in G-rich telomeres and promoter regions of oncogenes.


Input: Telomeric quadruplex stabilization by small molecules can lead to telomere uncapping, followed by DNA damage response and senescence, as well as chromosomal fusions leading to deregulation of mitosis, followed by apoptosis and downregulation of oncogene expression.


Input: We report here on investigations into the mechanism of action of tetra-substituted naphthalene diimide ligands on the basis of cell biologic data together with a National Cancer Institute COMPARE study.

naphthalene diimide


Input: We conclude that four principal mechanisms of action are implicated for these compounds: 1) telomere uncapping with subsequent DNA damage response and senescence; 2) inhibition of transcription/translation of oncogenes; 3) genomic instability through telomeric DNA end fusions, resulting in mitotic catastrophe and apoptosis; and 4) induction of chromosomal instability by telomere aggregate formation.


Input: Insulin-degrading enzyme (IDE): a novel heat shock-like protein.


Input: Insulin-degrading enzyme (IDE) is a highly conserved zinc metallopeptidase that is ubiquitously distributed in human tissues, and particularly abundant in the brain, liver, and muscles.

zinc


Input: IDE activity has been historically associated with insulin and beta-amyloid catabolism.


Input: However, over the last decade, several experimental findings have established that IDE is also involved in a wide variety of physiopathological processes, including ubiquitin clearance and Varicella Zoster Virus infection.


Input: In this study, we demonstrate that normal and malignant cells exposed to different stresses markedly up-regulate IDE in a heat shock protein (HSP)-like fashion.


Input: Additionally, we focused our attention on tumor cells and report that (i) IDE is overexpressed in vivo in tumors of the central nervous system (CNS); (ii) IDE-silencing inhibits neuroblastoma (SHSY5Y) cell proliferation and triggers cell death; (iii) IDE inhibition is accompanied by a decrease of the poly-ubiquitinated protein content and co-immunoprecipitates with proteasome and ubiquitin in SHSY5Y cells.


Input: In this work, we propose a novel role for IDE as a heat shock protein with implications in cell growth regulation and cancer progression, thus opening up an intriguing hypothesis of IDE as an anticancer target.


Input: Mangiferin-a bioactive xanthonoid, not only from mango and not just antioxidant.

Mangiferin

xanthonoid


Input: Mangiferin is a plant natural polyphenol of C-glycosylxanthone structure and various pharmacological activities.

Mangiferin

polyphenol

C-glycosylxanthone


Input: It can be found in many plant species, among which the mango tree (Mangifera indica) is one of the primary sources.


Input: Mangiferin is also present in some medicinal herbs, influencing their therapeutic and preventive properties, and in honeybush (Cyclopia sp.), a popular South African herbal tea.

Mangiferin


Input: Mangiferin dissolves well in water, so it can be easily extracted into infusions and decoctions.

Mangiferin


Input: In the mangiferin molecule, four aromatic hydroxyl groups determine its strong antiradical and antioxidant properties.

mangiferin

aromatic hydroxyl


Input: Mangiferin is also an efficient iron chelator, therefore preventing the generation of hydroxyl radical in Fenton-type reactions.

Mangiferin

iron

hydroxyl


Input: Numerous published in vitro and in vivo pharmacological studies, demonstrated many other activities of mangiferin: analgesic, antidiabetic, antisclerotic, atimicrobial and antiviral, cardio-, hepato-, and neuroprotective, antiinflammatory, antiallergic, MAO inhibiting and memory improving, as well as radioprotective against X-ray, gamma, and UV radiation.

mangiferin


Input: Several studies indicated also its ability to inhibit cancerogenesis and cancer cells growth by apoptosis induction in vitro and in vivo.


Input: It is also used in cosmetics, due to antioxidant and UV-protecting properties.


Input: Phenolic compounds as antioxidants: carbonic anhydrase isoenzymes inhibitors.

Phenolic


Input: Antioxidant compounds can scavenge free radicals and increase shelf life by retarding the process of lipid peroxidation, which is one of the major reasons for deterioration of food, medicine and pharmaceutical products during processing and storage.


Input: An antioxidant molecule has been defined as any substance when found in low concentrations compared to that of an oxidizable substrate significantly delays or inhibits the oxidation.


Input: The major antioxidant compounds are especially phenolics and flavonoids, which are responsible for their health benefits.

phenolics

flavonoids


Input: Carbonic anhydrase (EC 4. 2. 1. 1., CA) is a pH regulatory/metabolic enzyme in all life kingdoms, being found in organisms all over the phylogenetic tree.


Input: It catalyzes the hydration of carbon dioxide (CO (2)) to bicarbonate (HCO (3)-) and the corresponding dehydration of HCO (3)-in acidic medium with regeneration of CO (2).

carbon dioxide

CO (2)

bicarbonate

HCO (3)-

HCO (3)-

CO (2)


Input: Also, CA isoforms are found in a variety of tissues where they participate in several important biological processes such as acid-base balance, respiration, carbon dioxide and ion transport, bone resorption, ureagenesis, gluconeogenesis, lipogenesis and electrolyte secretion.

carbon dioxide


Input: On the other hand, the phenyl moiety of phenol was found to lay in the hydrophobic part of the CA active site, where CO (2), the physiologic substrate of the CAs, binds in the precatalytic complex, explaining thus the behavior of phenol as a unique CO (2) competitive inhibitor.

phenyl

phenol

CO (2)

phenol

CO (2)


Input: This review consists of two main sections.


Input: The first section is devoted to main phenolic antioxidant compounds in the foodstuffs and beverages.

phenolic


Input: The second general section is about some definitions of CA inhibitory effects of the main phenolic compounds used for antioxidant activity.

phenolic


Input: The phenolic compounds and acids had marked especially CA I and CA II inhibitory effects and might be used as leads for generating CA isoenzyme inhibitors.

phenolic


Input: This class of compounds may lead to isoform-selective inhibitors targeting just one or few of the medicinally relevant CAs.


Input: In addition, there are given some chemical and kinetic basis and technical details related to phenolic antioxidant compounds and carbonic anhydrase isoenzymes.

phenolic


Input: Recent studies of antioxidant quinoline derivatives.

quinoline


Input: Quinoline derivatives constitute an important class of compounds for new drug development.

Quinoline


Input: As a large number of experimental and theoretical studies have shown that the quinoline ring system is an important structural unit widely existing in alkaloids, therapeutics and synthetic analogues with exciting biological activities.

quinoline


Input: The present review provides recent antioxidant activities covering in vivo and in vitro studies of natural and synthetic analogues, as well as the proposed mechanisms of action and structure-activity relationships.


Input: Supramolecular hydrogels with reverse thermal gelation properties from (oligo) tyrosine containing block copolymers.

(oligo) tyrosine


Input: Novel block copolymers comprising poly (ethylene glycol) (PEG) and an oligo (tyrosine) block were synthesized in different compositions by N-carboxyanhydride (NCA) polymerization.

poly (ethylene glycol)

PEG

oligo (tyrosine)

N-carboxyanhydride

NCA


Input: It was shown that PEG2000-Tyr (6) undergoes thermoresponsive hydrogelation at a low concentration range of 0. 25-3. 0 wt% within a temperature range of 25-50 degrees C.

PEG2000-Tyr (6)


Input: Cryogenic transmission electron microscopy (Cryo-TEM) revealed a continuous network of fibers throughout the hydrogel sample, even at concentrations as low as 0. 25 wt%.


Input: Circular dichroism (CD) results suggest that better packing of the beta-sheet tyrosine block at increasing temperature induces the reverse thermogelation.

tyrosine


Input: A preliminary assessment of the potential of the hydrogel for in vitro application confirmed the hydrogel is not cytotoxic, is biodegradable, and produced a sustained release of a small-molecule drug.


Input: 2, 5-Dihydroxy-4-methoxybenzophenone: a novel major in vitro metabolite of benzophenone-3 formed by rat and human liver microsomes.

2, 5-Dihydroxy-4-methoxybenzophenone


Input: 1. When benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) was incubated with liver microsomes of untreated rats in the presence of NADPH, the 5-hydroxylated metabolite, 2, 5-dihydroxy-4-methoxybenzophenone (5-OH-BP-3), was formed as a major novel metabolite of BP-3.

NADPH

2, 5-dihydroxy-4-methoxybenzophenone


Input: The 4-desmethylated metabolite, 2, 4-dihydroxybenzophenone (2, 4-diOH-BP), previously reported as the major in vivo metabolite of BP-3, was also detected.

2, 4-dihydroxybenzophenone

2, 4-diOH-BP


Input: However, the amount of 5-OH-BP-3 formed in vitro was about the same as that of 2, 4-diOH-BP.

2, 4-diOH-BP


Input: 2. The oxidase activity affording 5-OH-BP-3 was inhibited by SKF 525-A and ketoconazole, and partly by quinidine and sulfaphenazole.

SKF 525-A

ketoconazole

quinidine

sulfaphenazole


Input: The oxidase activity affording 2, 4-diOH-BP was inhibited by SKF 525-A, ketoconazole and alpha-naphthoflavone, and partly by sulfaphenazole.

2, 4-diOH-BP

SKF 525-A

ketoconazole

alpha-naphthoflavone

sulfaphenazole


Input: 3. The oxidase activity affording 5-OH-BP-3 was enhanced in liver microsomes of dexamethasone-, phenobarbital-and 3-methylcholanthrene-treated rats.

dexamethasone

phenobarbital


Input: The activity affording 2, 4-diOH-BP was enhanced in liver microsomes of 3-methylcholanthrene-and phenobarbital-treated rats.

2, 4-diOH-BP

phenobarbital


Input: 4. When examined recombinant rat cytochrome P450 isoforms catalyzing the metabolism of BP-3, 5-hydroxylation was catalyzed by P450 3A2, 1A1, 2B1, 2C6 and 2D1, while 4-desmethylation was catalyzed by P450 2C6 and 1A1.


Input: Identifying biases at different spatial and temporal scales of diversification: a case study in the Neotropical parrotlet genus Forpus.


Input: The temporal origins of the extraordinary biodiversity of the Neotropical region are highly debated.


Input: Recent empirical work has found support for alternative models on the tempo of speciation in Neotropical species further fuelling the debate.


Input: However, relationships within many Neotropical lineages are poorly understood, and it is unclear how this uncertainty impacts inferences on the evolution of taxa in the region.


Input: We examined the robustness of diversification patterns in the avian genus Forpus by testing whether the use of different units of biodiversity (i. e. biological species and statistically inferred species) impacted diversification rates and inferences regarding important biogeographic breaks in the genus.


Input: We found that the best-fit model of diversification for the biological species data set was a declining rate of diversification; whereas a model of constant diversification was the best-fit model for statistically inferred species or subspecies.


Input: Moreover, the relative importance of different landscape features in delimiting genetic structure across the landscape varied across data sets with differing units of biodiversity.


Input: Patterns based on divergence times among biological species indicated old speciation events across major geographic and river barriers.


Input: In contrast, data sets more inclusive of the diversity in Forpus illustrate the role of both old divergence across major landscape features and more recent divergences that are possibly attributed to Pleistocene climatic changes.


Input: Overall, these results indicate that conflicting models on the temporal origins of Neotropical birds may be attributable to sampling biases.


Input: Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity.


Input: Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K-cells in response to nutrient ingestion.


Input: GIP potentiates glucose-stimulated insulin secretion and induces energy accumulation into adipose tissue, resulting in obesity.

glucose


Input: Plasma GIP levels are reported to be increased in the obese state.


Input: However, the molecular mechanisms of GIP secretion and high fat diet (HFD)-induced GIP hypersecretion remain unclear, primarily due to difficulties in separating K-cells from other intestinal epithelial cells in vivo.


Input: In this study, GIP-GFP knock-in mice that enable us to visualize K-cells by enhanced GFP were established.


Input: Microarray analysis of isolated K-cells from these mice revealed that transcriptional regulatory factor X6 (Rfx6) is expressed exclusively in K-cells.


Input: In vitro experiments using the mouse intestinal cell line STC-1 showed that knockdown of Rfx6 decreased mRNA expression, cellular content, and secretion of GIP.


Input: Rfx6 bound to the region in the gip promoter that regulates gip promoter activity, and overexpression of Rfx6 increased GIP mRNA expression.


Input: HFD induced obesity and GIP hypersecretion in GIP-GFP heterozygous mice in vivo.


Input: Immunohistochemical and flow cytometry analysis showed no significant difference in K-cell number between control fat diet-fed (CFD) and HFD-fed mice.


Input: However, GIP content in the upper small intestine and GIP mRNA expression in K-cells were significantly increased in HFD-fed mice compared with those in CFD-fed mice.


Input: Furthermore, expression levels of Rfx6 mRNA were increased in K-cells of HFD-fed mice.


Input: These results suggest that Rfx6 increases GIP expression and content in K-cells and is involved in GIP hypersecretion in HFD-induced obesity.


Input: The crystal structure of the protein-disulfide isomerase family member ERp27 provides insights into its substrate binding capabilities.

disulfide


Input: About one-third of all cellular proteins pass through the secretory pathway and hence undergo oxidative folding in the endoplasmic reticulum (ER).


Input: Protein-disulfide isomerase (PDI) and related members of the PDI family assist in the folding of substrates by catalyzing the oxidation of two cysteines and isomerization of disulfide bonds as well as by acting as chaperones.

disulfide

cysteines

disulfide


Input: In this study, we present the crystal structure of ERp27, a redox-inactive member of the PDI family.


Input: The structure reveals its substrate-binding cleft, which is homologous to PDI, but is able to adapt in size and hydrophobicity.


Input: Isothermal titration calorimetry experiments demonstrate that ERp27 is able to distinguish between folded and unfolded substrates, only interacting with the latter.


Input: ERp27 is up-regulated during ER stress, thus presumably allowing it to bind accumulating misfolded substrates and present them to ERp57 for catalysis.


Input: Silencing alpha 1, 3-fucosyltransferases in human leukocytes reveals a role for FUT9 enzyme during E-selectin-mediated cell adhesion.


Input: Leukocyte adhesion during inflammation is initiated by the binding of sialofucosylated carbohydrates expressed on leukocytes to endothelial E/P-selectin.

carbohydrates


Input: Although the glycosyltransferases (glycoTs) constructing selectin-ligands have largely been identified using knock-out mice, important differences may exist between humans and mice.


Input: To address this, we developed a systematic lentivirus-based shRNA delivery workflow to create human leukocytic HL-60 cell lines that lack up to three glycoTs.


Input: Using this, the contributions of all three myeloid alpha 1, 3-fucosyltransferases (FUT4, FUT7, and FUT9) to selectin-ligand biosynthesis were evaluated.


Input: The cell adhesion properties of these modified cells to L-, E-, and P-selectin under hydrodynamic shear were compared with bone marrow-derived neutrophils from Fut4 (-/-) Fut7 (-/-) dual knock-out mice.


Input: Results demonstrate that predominantly FUT7, and to a lesser extent FUT4, forms the selectin-ligand at the N terminus of leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) in humans and mice.

N


Input: Here, 85% reduction in leukocyte interaction was observed in human FUT4 (-) 7 (-) dual knockdowns on P/L-selectin substrates.


Input: Unlike Fut4 (-/-) Fut7 (-/-) mouse neutrophils, however, human knockdowns lacking FUT4 and FUT7 only exhibited partial reduction in rolling interaction on E-selectin.


Input: In this case, the third alpha 1, 3-fucosyltransferase FUT9 played an important role because leukocyte adhesion was reduced by 50-60% in FUT9-HL-60, 70-80% in dual knockdown FUT7 (-) 9 (-) cells, and ~ 85% in FUT4 (-) 7 (-) 9 (-) triple knockdowns.


Input: Gene silencing results are in agreement with gain-of-function experiments where all three fucosyltransferases conferred E-selectin-mediated rolling in HEK293T cells.


Input: This study advances new tools to study human glycoT function.


Input: It suggests a species-specific role for FUT9 during the biosynthesis of human E-selectin ligands.


Input: Forkhead box M1 is regulated by heat shock factor 1 and promotes glioma cells survival under heat shock stress.


Input: The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology.


Input: Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression.


Input: In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines.


Input: Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1.


Input: Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression.


Input: Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity.


Input: Furthermore, we demonstrated that FoxM1 was required for the G (2)-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition.


Input: Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression.


Input: Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response.


Input: We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance.


Input: Green asymmetric synthesis: beta-amino alcohol-catalyzed direct asymmetric aldol reactions in aqueous micelles.

beta-amino alcohol

aldol


Input: The ability of chiral beta-amino alcohols to catalyze the direct asymmetric aldol reaction was evaluated for the first time in aqueous micellar media.

chiral beta-amino alcohols

aldol


Input: A family of cheap and easily accessible beta-amino alcohols, obtained in one step from naturally occurring amino acids, was shown to successfully catalyze the asymmetric aldol reaction between a series of ketones and aromatic aldehydes.

beta-amino alcohols

amino acids

aldol

ketones

aromatic aldehydes


Input: These aldol reactions furnished the corresponding beta-hydroxy ketones with up to 93% isolated yield and 89% ee.

aldol

beta-hydroxy ketones


Input: (S)-2-phenylglycinol and Triton X-100 proved to be the best organocatalyst and surfactant, respectively.

Triton X-100


Input: Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system.


Input: The Allen Brain Atlas (http://www. brain-map. org) provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate.


Input: Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization (ISH) and supporting histology, microarray, RNA sequencing, reference atlases, projection mapping and magnetic resonance imaging].


Input: In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets.


Input: Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent ISH image viewers, graphical displays of ISH, microarray and RNA sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer.


Input: In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously.


Input: All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal.


Input: Diet, physical exercise and Orlistat administration increase serum Anti-M u llerian Hormone (AMH) levels in women with polycystic ovary syndrome (PCOS).

Orlistat


Input: The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum Anti-M u llerian Hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls.

Orlistat


Input: Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks.

Orlistat


Input: At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated.

androgens

glucose

Androgen


Input: In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment.


Input: After 12 weeks LH and SHBG were increased, while Testosterone decreased.

Testosterone


Input: After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved.


Input: We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

Orlistat


Input: Growth and differentiation of prechondrogenic cells on bioactive self-assembled peptide nanofibers.


Input: Restoration of cartilage defect remains a challenge, as the current treatments are ineffective to return tissue to its health.


Input: Thus, developing therapies for treatment of cartilage tissue damage caused by common joint diseases including osteoarthritis, rheumatoid arthritis, and accidents is crucial.


Input: Sulfated glycosaminoglycan molecules are vital constituents of both developing and mature cartilage extracellular matrix.


Input: The interplay between regulator proteins and glycosaminoglycan molecules has an essential role in coordinating differentiation, expansion, and patterning during cartilage development.


Input: In this study, we exploited the functional role of an extracellular matrix on chondrogenic differentiation by imitating extracellular matrix both chemically by imparting functional groups of native glycosaminoglycans and structurally through peptide nanofiber network.


Input: For this purpose, sulfonate, carboxylate, and hydroxyl groups were incorporated on self-assembled peptide nanofibers.

sulfonate

carboxylate

hydroxyl


Input: We observed that when ATDC5 cells were cultured on functional peptide nanofibers, they rapidly aggregated in insulin-free medium and formed cartilage-like nodules and deposited sulfated glycosaminoglycans shown by Safranin-O staining.

Safranin-O


Input: Moreover, collagen II and aggrecan gene expressions revealed by qRT-PCR were significantly enhanced, which indicated the remarkable bioactive role of this nanofiber system on chondrogenic differentiation.


Input: Overall, these results show that glycosaminoglycan mimetic peptide nanofiber system provides a promising platform for cartilage regeneration.


Input: Experimentally engineering the edge termination of graphene nanoribbons.

graphene


Input: The edges of graphene nanoribbons (GNRs) have attracted much interest due to their potentially strong influence on GNR electronic and magnetic properties.

graphene


Input: Here we report the ability to engineer the microscopic edge termination of high-quality GNRs via hydrogen plasma etching.

hydrogen


Input: Using a combination of high-resolution scanning tunneling microscopy and first-principles calculations, we have determined the exact atomic structure of plasma-etched GNR edges and established the chemical nature of terminating functional groups for zigzag, armchair, and chiral edge orientations.


Input: We find that the edges of hydrogen-plasma-etched GNRs are generally flat, free of structural reconstructions, and terminated by hydrogen atoms with no rehybridization of the outermost carbon edge atoms.

hydrogen

hydrogen

carbon


Input: Both zigzag and chiral edges show the presence of edge states.


Input: Arcuate nucleus homeostatic systems are not altered immediately prior to the scheduled consumption of large, binge-type meals of palatable solid or liquid diet in rats and Mice.


Input: Meal feeding is a critical issue in the over-consumption of calories leading to human obesity.


Input: To investigate the mechanisms involved in the regulation of meal feeding in rodents, we studied a scheduled feeding regime that induces substantial food intake over short periods of time.


Input: Male Sprague-Dawley rats and C57BL6 mice were fed one of four palatable diets [45% fat pellet, 60% fat pellet or standard pellet supplemented with Ensure (EN; Abbott Laboratories, Maidenhead, UK) or 12. 5% sucrose (SUC)] either ad lib. or with daily 2-h scheduled access and standard pellet available for 22 h.


Input: Energy balance gene expression in the hypothalamic arcuate nucleus (ARC) and nucleus accumbens (NAcc) reward gene expression were assessed by in situ hybridisation.


Input: Rats fed ad lib. on 45% or 60% fat diet were heavier and fatter than controls, and had reduced neuropeptide Y (NPY) gene expression in the ARC.


Input: Mice fed ad lib. on any of the palatable diets were heavier, fatter and had higher blood leptin than controls, and had reduced NPY and increased cocaine-and-amphetamine-regulated transcript mRNA in the ARC.

cocaine

amphetamine


Input: Schedule-fed rats and mice quickly adapted their feeding behaviour to 2-h access on palatable food.


Input: Three schedule-fed groups binged: the percentage of daily calories consumed in 2 h on 45% fat diet, 60% fat diet or EN, respectively, was 55%, 63% and 49% in rats, and 86%, 86% and 45% in mice.


Input: However, changed feeding behaviour was not reflected in an induction of orexigenic neuropeptide or suppression of anorexigenic neuropeptide gene expression in the ARC, in the 2-h period prior to scheduled feeding.


Input: The mechanisms underlying large meal/binge-type eating may be regulated by nonhomeostatic processes involving other genes in the hypothalamus or other brain areas.


Input: However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of the involvement of these genes in driving large meals, at least at the investigated time point.

dopamine


Input: A potential practical approach to reduce Ara h 6 allergenicity by gamma irradiation.


Input: Peanut allergen Ara h 6 was isolated and irradiated at 1, 3, 5, or 10 kGy, and a whole peanut protein extract (WPPE) was also treated by irradiation.


Input: Alteration in structure of Ara h 6 was characterised by circular dichroism (CD) spectroscopy, ultraviolet (UV) absorption spectroscopy, fluorescence spectroscopy and SDS-PAGE, and antigenicity was evaluated by immunoblotting and indirect ELISA with anti-Ara h 6 polyclonal antibody.

SDS


Input: Irradiation induced significant changes in the secondary and tertiary structures of Ara h 6, and the antigenicity of both purified Ara h 6 and WPPE were reduced upon increasing the irradiation doses.


Input: Moreover, a good correlation between the loss in alpha-helix and IgG binding to Ara h 6 was observed.


Input: This indicated that irradiation might be an efficient approach to reduce or eliminate peanut allergenicity.


Input: Analysis of total polyphenols in wines by FIA with highly stable amperometric detection using carbon nanotube-modified electrodes.

polyphenols

carbon


Input: The use of glassy carbon electrodes (GCEs) modified with multi-walled carbon nanotube (CNT) films for the continuous monitoring of polyphenols in flow systems has been examined.

carbon

carbon

polyphenols


Input: The performance of these modified electrodes was evaluated and compared to bare GCE by cyclic voltammetry experiments and by flow injection analysis (FIA) with amperometric detection monitoring the response of gallic, caffeic, ferulic and p-coumaric acids in 0. 050 M acetate buffer pH 4. 5 containing 100 mM NaCl.

gallic, caffeic, ferulic and p-coumaric acids

acetate

NaCl


Input: The GCE modified with CNT dispersions in polyethyleneimine (PEI) provided lower overpotentials, higher sensitivity and much higher signal stability under a dynamic regime than bare GCEs.

polyethyleneimine

PEI


Input: These properties allowed the estimation of the total polyphenol content in red and white wines with a remarkable long-term stability in the measurements despite the presence of potential fouling substances in the wine matrix.

polyphenol


Input: In addition, the versatility of the electrochemical methodology allowed the selective estimation of the easily oxidisable polyphenol fraction as well as the total polyphenol content just by tuning the detection potential at + 0. 30 or 0. 70 V, respectively.

polyphenol

polyphenol


Input: The significance of the electrochemical results was demonstrated through correlation studies with the results obtained with conventional spectrophotometric assays for polyphenols (Folin-Ciocalteu, absorbance at 280 nm index and colour intensity index).

polyphenols


Input: Use of an electrodialytic reactor for the simultaneous beta-lactoglobulin enzymatic hydrolysis and fractionation of generated bioactive peptides.


Input: The enzymatic hydrolysis of beta-lactoglobulin and the fractionation of peptides were performed in one step in an electrodialysis cell with ultrafiltration membranes stacked.


Input: After 240 min of treatment, 15 anionic and 4 cationic peptides were detected in the anionic and cationic peptide recovery compartments.


Input: Amongst these 15 anionic peptides, 2 hypocholesterolemic, 3 antihypertensive and 1 antibacterial peptides were recovered and concentrated with migration rates ranging from 5. 5% and 81. 7%.


Input: Amongst the 4 cationic peptides, the peptide sequence ALPMHIR, identified as lactokinin and known to exert an important antihypertensive effect, was recovered with an estimated 66% migration rate.

lactokinin


Input: To our knowledge, it was the first attempt to perform hydrolysis under an electric field and to simultaneously separate anionic and cationic peptides produced.


Input: The heat treatment and the gelation are strong determinants of the kinetics of milk proteins digestion and of the peripheral availability of amino acids.

amino acids


Input: This study aimed to determine the kinetics of milk protein digestion and amino acid absorption after ingestion of four dairy matrices by six minipigs: unheated or heated skim milk and corresponding rennet gels.

amino acid


Input: Digestive contents and plasma samples were collected over a 7 h-period after meal ingestion.


Input: Gelation of milk slowed down the outflow of the meal from the stomach and the subsequent absorption of amino acids, and decreased their bioavailability in peripheral blood.

amino acids


Input: The gelled rennet matrices also led to low levels of milk proteins at the duodenum.


Input: Caseins and beta-lactoglobulin, respectively, were sensitive and resistant to hydrolysis in the stomach with the unheated matrices, but showed similar digestion with the heated matrices, with a heat-induced susceptibility to hydrolysis for beta-lactoglobulin.


Input: These results suggest a significant influence of the meal microstructure (resulting from heat treatment) and macrostructure (resulting from gelation process) on the different steps of milk proteins digestion.


Input: The presence of D-fagomine in the human diet from buckwheat-based foodstuffs.

D-fagomine


Input: Buckwheat (Fagopyrum esculentum Moench) groats contain the iminosugar D-fagomine as a minor component that might contribute to the alleged health benefits of this pseudo-cereal.

D-fagomine


Input: This study presents analysis of D-fagomine in buckwheat-based foodstuffs by liquid chromatography coupled to mass spectrometry and an estimation of its presence in the human diet based on a published population-based cross-sectional nutrition survey.

D-fagomine


Input: D-fagomine is present in common buckwheat-based foodstuffs in amounts ranging from 1 to 25 mg/kg or mg/L, it is stable during boiling, baking, frying and fermentation, and it is biosynthesised upon sprouting.

D-fagomine


Input: The estimated total intake of D-fagomine resulting from a diet that includes such foodstuffs would be between 3 and 17 mg per day (mean for both genders; range from P5 to P95).

D-fagomine


Input: A diet rich in buckwheat products would provide a daily amount of D-fagomine that may in part explain the beneficial properties traditionally attributed to buckwheat consumption.

D-fagomine


Input: The in vivo antioxidant and antifibrotic properties of green tea (Camellia sinensis, Theaceae).


Input: The in vivo antioxidant and antifibrotic properties of green tea (Camellia sinensis, Theaceae) were investigated with a study of carbon tetrachloride (CCl (4))-induced oxidative stress and hepatic fibrosis in male ICR mice.

carbon tetrachloride

CCl (4)


Input: Oral administration of green tea extract at doses of 125, 625 and 1250 mg/kg for 8 weeks significantly reduced (p < 0. 05) the levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyls in the liver by at least 28% compared with that was induced by CCl (4) (1 mL/kg) in mice.

thiobarbituric acid

carbonyls

CCl (4)


Input: Moreover, green tea extract administration significantly increased (p < 0. 05) the activities of catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) in the liver.

glutathione

GSH

glutathione

GSH


Input: Our study found that oral administration of green tea extract prevented CCl (4)-induced hepatic fibrosis, as evidenced by a decreased hydroxyproline level in the liver and a reduced incidence of hepatic fibrosis by histological observations.

CCl (4)

hydroxyproline


Input: These results indicate that green tea exhibits potent protective effects against CCl (4)-induced oxidative stress and hepatic fibrosis in mice by inhibiting oxidative damage and increasing antioxidant enzyme activities.

CCl (4)


Input: Whey protein hydrolysate enhances the exercise-induced heat shock protein (HSP70) response in rats.


Input: Whey protein has been suggested to be potential protective agent against various forms of stress.


Input: The heat shock protein HSP70 confers greater cellular tolerance against stressors.


Input: The present study evaluated the effects of whey protein intake on HSP70 expression.


Input: Forty-eight male Wistar rats were divided into sedentary and exercised groups, and each group was fed as a protein source casein (CAS), whey protein (WP) or whey protein hydrolysate (WPH) for 3weeks.


Input: Exercise on a treadmill was used as the source of stress in the animals from the exercised group.


Input: The results showed a larger increase in HSP70 expression in the soleus, gastrocnemius and lung of the WPH-fed rats than WP or casein-fed rats.


Input: HSP70 expression in the sedentary rats was very low, independent of the diet or tissue.


Input: Protein carbonyls were lower in the group that consumed WPH.

carbonyls


Input: These data suggest that the consumption of WPH enhances HSP70 expression.


Input: A new QSAR model, for angiotensin I-converting enzyme inhibitory oligopeptides.

angiotensin I


Input: A new quantitative structure activity relationship (QSAR) model is established for oligopeptides that inhibit angiotensin I-converting enzyme (ACE).

angiotensin I


Input: Information concerning the C-terminal pentapeptide is considered to describe the peptide structure in the model.

C


Input: A database is constructed, with 263 ACE inhibitory peptides and 38 physicochemical descriptors, abstracted from the published literature.


Input: The model is generated through a generalised linear model, with a gamma distribution that yields a coefficient of determination of 94. 4%.


Input: The whole C-terminal pentapeptide information is a determinant for modelling the ACE inhibition activity of oligopeptides.

C


Input: Starting from the C-terminus, the C-1 position is the most relevant position in the model; this is followed by position C-4.

C


Input: In C-1, there is a preference for aliphatic and tiny residues.


Input: However, in the C-4 position, the model indicates a clear preference for bulky hydrophobic amino acids and for sulphur-containing amino acids.

amino acids

sulphur

amino acids


Input: Due to its good predictive capability, this model could be used as a tool for identifying and prioritizing the potential ACE inhibitory peptides present in a complex matrix.


Input: Total polyphenols, catechin profiles and antioxidant activity of tea products from purple leaf coloured tea cultivars.

polyphenols

catechin


Input: Black (aerated) and green (unaerated) tea products, processed from 10 green and 18 purple leaf coloured cultivars of Kenyan origin, and two tea products, from the Japanese cultivars, Yabukita and Yutakamidori, were assayed for total polyphenols (TP) content, individual catechin profiles and in vitro antioxidant capacity (AA).

polyphenols

catechin


Input: In addition, the phenolic content of the tea products was determined using the Folin-Ciocalteu phenol reagent.

phenolic

Folin-Ciocalteu phenol


Input: Catechin fractions were identified using reverse phase high performance liquid chromatography (HPLC) with a binary gradient elution system.

Catechin


Input: The AA% of the tea products was determined using a 2, 2'-diphenyl picrylhydrazyl (DPPH) radical assay method.

2, 2'-diphenyl picrylhydrazyl

DPPH


Input: The results showed that TPs, catechin profiles and antioxidant activities were significantly (p <= 0. 05) higher in unaerated than in aerated teas.

catechin


Input: Tea products from the purple leaf coloured tea cultivars had levels of TPs, total catechin (TC) and antioxidant activities similar to those from the green leaf coloured cultivars, except for teas from the Japanese cultivars that were very low in the assayed parameters.

catechin


Input: Caffeine content was significantly (p <= 0. 05) lower in products from the purple leaf coloured cultivars than in those from the green leaf coloured tea cultivars.

Caffeine


Input: Antioxidant activity (%) was higher in tea products from the Kenyan germplasm than in those from the Japanese cultivars.


Input: Antioxidant potency of tea products was significantly (r = 0. 789 (* *), p <= 0. 01) influenced by the total anthocyanin content of the purple leaf coloured cultivars.

anthocyanin


Input: Cyanidin-3-O-glucoside was the anthocyanin most highly correlated with AA% (r = 0. 843 (* *), p <= 0. 01 in unaerated tea).

anthocyanin


Input: Total catechins in the unaerated products from the green leaf coloured tea cultivars were also significantly correlated with antioxidant capacity (r = 0. 818 (* *), p <= 0. 01).

catechins


Input: Results from this study suggest that the antioxidant potency of teas is dependent on the predominant flavonoid compound, the type of tea cultivar and the processing method.

flavonoid


Input: Simple multiresidue extraction method for the determination of fungicides and plant growth regulator in bean sprouts using low temperature partitioning and tandem mass spectrometry.


Input: A simple multiresidue analytical method is developed for the simultaneous determination of carbendazim (CB), thiabendazole (TB), and 6-benzyl aminopurine (6-BA) in bean sprouts.

carbendazim

thiabendazole

6-benzyl aminopurine


Input: The samples were extracted with acetonitrile followed by partitioning at-80 degrees C for 5-10 min.

acetonitrile


Input: A YMC C (8) column was used to separate the analytes before being qualitatively and quantitatively determined by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) in positive ion mode using multiple reaction monitoring (MRM).


Input: The matrix-matched calibration curves showed good linearity in the range 0. 01-1. 0 mg/kg with correlation coefficients in excess of 0. 998.


Input: The mean recoveries were in the range of 80. 4-96. 3% at 0. 1 and 0. 5 spiked levels, and the relative standard deviations (RSDs) were in the range of 0. 5-7. 6%.


Input: The limits of quantifications (LOQ) were in the range of 0. 005-0. 01 mg/kg.


Input: The method was successfully applied to 90 samples (among which 45 were organic) collected from a commercial bean sprout production house throughout the city.


Input: Except for 6-BA, the rest of the analytes had values lower than their LOQs.


Input: In sum, carbendazim, thiabendazole, and 6-BA were extracted in a single step, and no steps for clean-up or concentration of the extracts were needed.

carbendazim

thiabendazole


Input: The current method can be used for sensitive and accurate determination and confirmation of residues in bean sprout samples.


Input: Screening of whey protein isolate hydrolysates for their dual functionality: influence of heat pre-treatment and enzyme specificity.


Input: Heat pre-treated and non heat pre-treated whey protein isolate (WPI) were hydrolysed using alpha-chymotrypsin (chymotrypsin), pepsin and trypsin.


Input: The in vitro antioxidant activity, ACE-inhibition activity and surface hydrophobicities of the hydrolysates were measured in order to determine if peptides with dual functionalities were present.


Input: Dual functional peptides have both biological (e. g. antioxidant, ACE-inhibition, opioid activities) and technological (e. g. nanoemulsification abilities) functions in food systems.


Input: Heat pre-treatment marginally enhanced the hydrolysis of WPI by pepsin and trypsin but had no effect on WPI hydrolysis with chymotrypsin.


Input: With the exception of the hydrolysis by trypsin, heat pre-treatment did not affect the peptide profile of the hydrolysates as analysed using size exclusion chromatography, or the antioxidant activity (P > 0. 05).


Input: Heat pre-treatment significantly affected the ACE-inhibition activities and the surface hydrophobicities of the hydrolysates (P < 0. 05), which was a function of the specificity of the hydrolysing enzyme.


Input: Extended hydrolysis (up to 24 h) had no significant effect on the DH and the molecular weight profiles (P > 0. 05) but in some instances caused a reduction in the antioxidant activity of WPI hydrolysates.


Input: The chymotrypsin hydrolysate showed a broad MW size range, and was followed by pepsin and then trypsin.


Input: The bioactivities of the hydrolysates generally decreased in the order; chymotrypsin > trypsin > pepsin.


Input: This study showed that by manipulating protein conformation with pre-hydrolysis heat treatment, combined with careful enzyme selection, peptides with dual functionalities can be produced from WPI for use as functional ingredients in the manufacture of functional foods.


Input: Purification, physicochemical characterisation and anticancer activity of a polysaccharide from Cyclocarya paliurus leaves.


Input: A Cyclocarya paliurus (Batal.) Iljinskaja polysaccharide (CPP) was isolated and purified by hot water extraction, ethanol precipitation, deproteinisation and anion-exchange chromatography.

ethanol


Input: Its physicochemical properties were characterised by gel permeation chromatography (GPC), gas chromatography-mass spectrometry (GC-MS), thermal gravimetric analysis (TGA), Fourier transform infrared spectrometry (FTIR), UV-visible spectrophotometry, dynamic light scattering (DLS) and viscometry analysis.


Input: The anticancer effect of CPP in human gastric cancer HeLa cells was also evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.

3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide

MTT


Input: The results showed that the molecular weight of CPP was 900 kDa, and it contained 64. 8% total sugar, 23. 5% uronic acid, 9. 26% protein, and six kinds of monosaccharides, including glucose, rhamnose, arabinose, xylose, mannose and galactose, with molar percentages of 32. 7%, 9. 33%, 30. 6%, 3. 48%, 10. 4%, and 13. 5%, respectively.

uronic acid

monosaccharides

glucose

rhamnose

arabinose

xylose

mannose

galactose


Input: Furthermore, the results showed that CPP exhibited a strong inhibition effect on the growth of human gastric cancer HeLa cells.


Input: Field application of farm-food safety risk assessment (FRAMp) tool for small and medium fresh produce farms.


Input: The objective of this study was to develop a farm food safety-risk assessment tool (FRAMp) which serves as a self-assessment and educational tool for fresh produce farms.


Input: FRAMp was developed in Microsoft (R) Excel spreadsheet software using standard mathematical and logical functions and utilised a qualitative risk assessment approach for farmers to evaluate their food safety practices.


Input: The FRAMp tool has since been tested on 12 fresh produce farms throughout UK.


Input: All the farms determined that FRAMp was interesting but 17% found it too long while 25% of the farms felt the tool was too complicated.


Input: The instructions on FRAMp usage were revised and farmers were given the options to skip and select specific steps in the farm risk assessment.


Input: The end users (farmers/farm managers) determined that developing their own action plans and using it as proof of assessment for future third-party audits were most useful to them.


Input: FRAMp tool can be described as an illustrative risk ranking tool to facilitate farms to identify potential risk factors during their crop production.


Input: Long term compulsivity on the 5-choice serial reaction time task after acute Chlorpyrifos exposure.

Chlorpyrifos


Input: Pesticide exposure has been associated with neuropsychological and psychiatric impairments and neurodegenerative disorders.


Input: Pesticide exposure commonly causes a deficit in inhibitory control behaviours.


Input: In the present study, we investigated whether acute exposure to organophosphate (OP) chlorpyrifos (CPF) is related to long-term lack of inhibitory control; we also examined the possible neurochemical basis of this association.

organophosphate

chlorpyrifos

CPF


Input: Lister Hooded rats were exposed to an acute dose of CPF (250 mg/kg).

CPF


Input: Seven months later, we tested inhibitory control with the 5-choice serial reaction time task (5-CSRTT).


Input: We manipulated the baseline conditions of this task and also systemically pre-administered d-amphetamine, quinpirole, dizocilpine (MK-801) or ketanserin.

d-amphetamine

quinpirole

dizocilpine

ketanserin


Input: We also analysed the post-mortem baseline levels of monoamines and amino acids in different brain regions.

monoamines

amino acids


Input: On the 5-CSRT task, CPF-exposed rats showed elevated perseverative responses that persisted across manipulation of baseline conditions of the task and under most of the pharmacological challenges tested.

CPF


Input: Only D-amphetamine induced a dose-dependent amelioration of the increased perseverative responses in the CPF group.

D-amphetamine

CPF


Input: The CPF group also exhibited increased levels of dopamine metabolism in the hippocampus and decreased levels of gamma-aminobutyric acid (GABA) and glutamate in the striatum compared to the vehicle group.

CPF

dopamine

gamma-aminobutyric acid

GABA

glutamate


Input: These findings suggest that CPF induced a long-term compulsivity that was apparent in the 5-CSRT task and associated with changes in monoaminergic and amino acid brain systems of inhibitory control function.

CPF

amino acid


Input: Exposure to high doses of OP should be taken into account in studies of environmental causes for neurodegenerative, neuropsychological and neuropsychiatric disorders.


Input: Chronic autoimmune-mediated inflammation: a senescent immune response to injury.


Input: The increasing prevalence of chronic autoimmune-mediated inflammatory diseases (AIMIDs) in ageing western societies is a major challenge for the drug development industry.


Input: The current high medical need for more-effective treatments is at least in part caused by our limited understanding of the mechanisms that drive chronic inflammation.


Input: Here, we postulate a role for immunosenescence in the progression of acute to chronic inflammation via a dysregulated response to primary injury at the level of the damaged target organ.


Input: A corollary to this notion is that treatment of acute versus chronic phases of disease might require differential targeting strategies.


Input: Synthesis and antiplasmodial evaluation of novel (4-aminobutyloxy) quinolines.

(4-aminobutyloxy) quinolines


Input: A variety of 5-, 6-and 8-(4-aminobutyloxy) quinolines as novel oxygen analogues of known 4-and 8-(4-aminobutylamino) quinoline antimalarial drugs was generated from hydroxyquinolines through a three-step approach with a rhodium-catalyzed hydroformylation as the key step.

5-, 6-and 8-(4-aminobutyloxy) quinolines

oxygen

4-and 8-(4-aminobutylamino) quinoline

hydroxyquinolines

rhodium


Input: Antiplasmodial assays of these new quinolines revealed micromolar potency for all representatives against a chloroquine-sensitive strain of Plasmodium falciparum, and three compounds showed submicromolar activity against a chloroquine-resistant strain of P. falciparum with IC (50)-values ranging between 150 and 680 nM.

quinolines

chloroquine

chloroquine


Input: Reproductive experience modifies the effects of estradiol on learning and memory bias in female rats.

estradiol


Input: Previous studies have shown that estrogen affects whether a hippocampus-mediated place (allocentric) or a striatum-mediated response (egocentric) memory system is employed by female rats when searching for a food reward in a maze.

estrogen


Input: Because it has been suggested that reproductive experience alters some of the responses to E in the brain, two experiments were carried out to investigate whether reproductive experience would also alter the effect of E on place and response learning.


Input: In experiment 1, 152 ovariectomized nulliparous (n = 77; no reproductive experience) and primiparous (n = 74; having had and raised one litter of pups) Wistar rats were trained on an ambiguous t-maze task and tested for memory system bias.


Input: In experiment 2, 35 ovariectomized nulliparous (n = 16) and primiparous (n = 19) Wistar rats were trained on place and response plus-maze tasks.


Input: All rats were exposed to no, chronic low or chronic low with pulsatile high 17 beta-estradiol (E2) replacement.

17 beta-estradiol


Input: Congruent with previous findings, low E2 nulliparous rats showed predominant use of response memory and faster response learning, whereas high E2 nulliparous rats showed a trend towards predominant place memory use.


Input: Interestingly, the facilitatory effect of low E2 on response task learning and memory seen in nulliparous rats was not observed in low E2 primiparous rats in either experiment.


Input: In conclusion, E2 levels do dictate the rate at which female rats learn a response task and utilize response memory, but only in those with no reproductive experience.


Input: Ubiquitin-dependent regulation of phospho-AKT dynamics by the ubiquitin E3 ligase, NEDD4-1, in the insulin-like growth factor-1 response.

phospho


Input: AKT is a critical effector kinase downstream of the PI3K pathway that regulates a plethora of cellular processes including cell growth, death, differentiation, and migration.


Input: Mechanisms underlying activated phospho-AKT (pAKT) translocation to its action sites remain unclear.

phospho


Input: Here we show that NEDD4-1 is a novel E3 ligase that specifically regulates ubiquitin-dependent trafficking of pAKT in insulin-like growth factor (IGF)-1 signaling.


Input: NEDD4-1 physically interacts with AKT and promotes HECT domain-dependent ubiquitination of exogenous and endogenous AKT.


Input: NEDD4-1 catalyzes K63-type polyubiquitin chain formation on AKT in vitro.


Input: Plasma membrane binding is the key step for AKT ubiquitination by NEDD4-1 in vivo.


Input: Ubiquitinated pAKT translocates to perinuclear regions, where it is released into the cytoplasm, imported into the nucleus, or coupled with proteasomal degradation.


Input: IGF-1 signaling specifically stimulates NEDD4-1-mediated ubiquitination of pAKT, without altering total AKT ubiquitination.


Input: A cancer-derived plasma membrane-philic mutant AKT (E17K) is more effectively ubiquitinated by NEDD4-1 and more efficiently trafficked into the nucleus compared with wild type AKT.


Input: This study reveals a novel mechanism by which a specific E3 ligase is required for ubiquitin-dependent control of pAKT dynamics in a ligand-specific manner.


Input: AhR-mediated changes in global gene expression in rat liver progenitor cells.


Input: Although the tumor-promoting effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), coplanar polychlorinated biphenyls (PCBs), and related compounds in liver tissue are primarily attributed to the activation of the aryl hydrocarbon receptor (AhR), the underlying molecular mechanisms are still unclear.

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

TCDD

polychlorinated biphenyls

PCBs

aryl hydrocarbon


Input: Liver progenitor (oval) cells have been suggested to constitute a potential target for hepatocarcinogenic chemicals.


Input: To better understand AhR-driven pathways, we analyzed the transcriptional program in response to coplanar PCB 126 in contact-inhibited rat liver progenitor WB-F344 cells using high-density microarrays.

PCB 126


Input: After 6-h treatment, we identified 145 significantly deregulated genes considered to be direct AhR-dependent target genes.


Input: The number of differentially regulated genes increased to 658 and 968 genes after 24 and 72 h, respectively.


Input: Gene ontology analysis revealed that these genes were primarily involved in drug and lipid metabolism, cell cycle and growth control, cancer developmental processes, cell-cell communication, and adhesion.


Input: Interestingly, the Wnt and TGF-beta signaling pathways, both being involved in developmental and tumorigenic processes, belonged to the most affected pathways.


Input: AhR-and ARNT-dependent regulation of selected target genes of interest was then confirmed using TCDD as a model AhR agonist, together with pharmacological inhibition of the AhR and by RNA-interference techniques.

TCDD


Input: We demonstrated AhR-dependent regulation of emerging and novel AhR target genes, such as Fst, Areg, Hbegf, Ctgf, Btg2, and Foxq1.


Input: Among them, the transcription factor Foxq1, recently suggested to contribute to tumor promotion and/or progression, was found to be regulated at both mRNA and protein levels by AhR/ARNT activation.


Input: Mechanistic models describing active renal reabsorption and secretion: a simulation-based study.


Input: The objective of the present study was to evaluate mechanistic pharmacokinetic models describing active renal secretion and reabsorption over a range of Michaelis-Menten parameter estimates and doses.


Input: Plasma concentration and urinary excretion profiles were simulated and renal clearance (CL (r)) was calculated for two pharmacokinetic models describing active renal reabsorption (R1/R2), two models describing active secretion (S1/S2), and a model containing both processes.


Input: A range of doses (1-1, 000 mg/kg) was evaluated, and V (max) and K (m) parameter estimates were varied over a 100-fold range.


Input: Similar CL (r) values were predicted for reabsorption models (R1/R2) with variations in V (max) and K (m).


Input: Tubular secretion models (S1/S2) yielded similar relationships between Michaelis-Menten parameter perturbations and CL (r), but the predicted CL (r) values were threefold higher for model S1.


Input: For both reabsorption and secretion models, the greatest changes in CL (r) were observed with perturbations in V (max), suggesting the need for an accurate estimate of this parameter.


Input: When intrinsic clearance was substituted for Michaelis-Menten parameters, it failed to predict similar CL (r) values even within the linear range.


Input: For models S1 and S2, renal secretion was predominant at low doses, whereas renal clearance was driven by fraction unbound in plasma at high doses.


Input: Simulations demonstrated the importance of Michaelis-Menten parameter estimates (especially V (max)) for determining CL (r).


Input: K (m) estimates can easily be obtained directly from in vitro studies.


Input: However, additional scaling of in vitro V (max) estimates using in vitro/in vivo extrapolation methods are required to incorporate these parameters into pharmacokinetic models.


Input: Diagnostic accuracy of fine needle aspiration biopsy cytology and ultrasonography in patients with thyroid nodules diagnosed as benign or indeterminate before thyroidectomy.


Input: Fine-needle aspiration biopsy cytology (FNABC) and ultrasonography (US) play an important role in differentiating benign thyroid nodules from malignant nodules.


Input: We retrospectively investigated the prevalence of follicular thyroid carcinoma (FTC) in patients with thyroid nodules whose FNABC and US readings were not malignant before thyroidectomy.


Input: Between 2007 and 2008, 3333 patients underwent thyroidectomy at our institution, and the 737 of them who had thyroid nodule that had been diagnosed as hyperplastic nodule or follicular tumor by FNABC and US preoperatively were the subjects in this study.


Input: Postoperative histopathology showed hyperplastic nodule in 416 patients, follicular adenoma in 200 patients, FTC in 99 patients, and other disease in 22 patients.


Input: By FNABC, 34 (6. 7%) of the 505 patients with diagnosis as benign and 65 (28%) of the 232 patients with diagnosis as indeterminate, were diagnosed as having FTC.


Input: The diagnosis was FTC in 56 (9. 6%) of the 582 patients with a preoperative diagnosis of hyperplastic nodule by US and 43 (27. 7%) of the 155 patients with a diagnosis of follicular tumor by US.


Input: The diagnosis of FTC was made in 21 (4. 8%) of 438 patients who were concurrently diagnosed as benign by FNABC and as hyperplastic nodule by US, and in 30 (34. 1%) of 88 patients who were diagnosed as indeterminate by FNABC and follicular tumor by US.


Input: FNABC has been the mainstay for the preoperative evaluation of thyroid nodule.


Input: The results of this study showed that US can also be a useful tool for diagnosing FTC.


Input: New pockets in dengue virus 2 surface identified by molecular dynamics simulation.


Input: One of the factors limiting the search of new compounds based on the structure of target proteins involved in diseases is the limited amount of target structural information.


Input: Great advances in the search for lead compounds could be achieved to find new cavities in protein structures that are generated using well established computational chemistry tools.


Input: In the case of dengue, the discovery of pockets in the crystallographic structure of the E protein has contributed to the search for lead compounds aimed at interfering in conformational transitions involved in the pH-dependent fusion process.


Input: This is a complex mechanism triggered by the acid pH of the endosomes that leads to the initial changes in the E protein assembly at the virus surface.


Input: In the present work, an arrangement of three ectodomain portions of the E protein present on the surface of the mature dengue virus was studied through long all-atom molecular dynamics simulations with explicit solvent.


Input: In order to identify new pockets and to evaluate the influence of the acid pH on these pockets, the physiological neutral pH conditions and the acid pH of the endosomes that trigger the fusion process were modeled.


Input: Several pockets presenting pH-dependent characteristics were found in the contact regions between the chains.


Input: Pockets at the protein-protein interfaces induced by a monomer in another monomer were also found.


Input: Some of the pockets are good candidates for the design of lead compounds that could interfere in the rearrangements in E proteins along the fusion process contributing to the development of specific inhibitors of the dengue disease.


Input: Photochemical properties and activity of water-soluble polymer/c (60) nanohybrids for photodynamic therapy.

c (60)


Input: Water-soluble star-like poly (vinyl alcohol)/C (60) and poly {[poly (ethylene glycol) acrylate]-co-(vinyl acetate)}/C (60) nanohybrids are prepared by grafting macroradicals onto C (60) and are assessed as photosensitizers for photodynamic therapy.

poly (vinyl alcohol)

C (60)

poly {[poly (ethylene glycol) acrylate]-co-(vinyl acetate)}

C (60)

C (60)


Input: The photophysical and biological properties of both nanohybrids highlight key characteristics influencing their overall efficiency.


Input: The macromolecular structure (linear/graft) and nature (presence/absence of hydroxyl groups) of the polymeric arms respectively impact the photodynamic activity and the stealthiness of the nanohybrids.

hydroxyl


Input: The advantages of both nanohybrids are encountered in a third one, poly [(N-vinylpyrrolidone)-co-(vinyl acetate)]/C (60), which has linear grafts without hydroxyl groups, and shows a better photodynamic activity.

poly [(N-vinylpyrrolidone)-co-(vinyl acetate)]

C (60)

hydroxyl


Input: Identification of transporters associated with Etoposide sensitivity of stomach cancer cell lines and methotrexate sensitivity of breast cancer cell lines by quantitative targeted absolute proteomics.

Etoposide

methotrexate


Input: Membrane transporter proteins may influence the sensitivity of cancer cells to anticancer drugs that can be recognized as substrates.


Input: The purpose of this study was to identify proteins that play a key role in the drug sensitivity of stomach and breast cancer cell lines by measuring the absolute protein expression levels of multiple transporters and other membrane proteins and examining their correlation to drug sensitivity.


Input: Absolute protein expression levels of 90 membrane proteins were examined by quantitative targeted absolute proteomics using liquid chromatography-linked tandem mass spectrometry.


Input: Among them, 11 and 14 membrane proteins, including transporters, were present in quantifiable amounts in membrane fraction of stomach cancer and breast cancer cell lines, respectively.


Input: In stomach cancer cell lines, the protein expression level of multidrug resistance-associated protein 1 (MRP1) was inversely correlated with etoposide sensitivity.

etoposide


Input: MK571, an MRP inhibitor, increased both the cell-to-medium ratio of etoposide and the etoposide sensitivity of MRP1-expressing stomach cancer cell lines.


Input: In breast cancer cell lines, the protein expression level of reduced folate carrier 1 (RFC1) was directly correlated with methotrexate (MTX) sensitivity.

methotrexate

MTX


Input: Initial uptake rate and steady-state cell-to-medium ratio of [(3) H] MTX were correlated with both RFC1 expression level and MTX sensitivity.

[(3) H] MTX

MTX


Input: These results suggest that MRP1 modulates the etoposide sensitivity of stomach cancer cell lines and RFC1 modulates the MTX sensitivity of breast cancer cell lines.

etoposide

MTX


Input: Our results indicate that absolute quantification of multiple membrane proteins could be a useful strategy for identification of candidate proteins involved in drug sensitivity.


Input: Analysis of tolerance and behavioral/physical dependence during chronic CB1 agonist treatment: effects of CB1 agonists, antagonists, and noncannabinoid drugs.


Input: Behavioral studies of chronic CB (1) receptor activation may provide a pharmacological approach to understanding efficacy-related differences among CB (1) ligands as well as mechanistic commonalities between cannabinoid and noncannabinoid drugs.