Input: On the basis of these results and docking experiments in both receptor subtypes, a molecular explanation was provided for its different behavior as a full and partial agonist of PPAR alpha and PPAR gamma, respectively.


Input: The effects of (S)-16 on mitochondrial acylcarnitine carrier and carnitine-palmitoyl-transferase 1 gene expression, two key components of the carnitine shuttle system, were also investigated, allowing the hypothesis of a more beneficial pharmacological profile of this compound compared to the less potent PPAR alpha agonist fibrates currently used in therapy.

acylcarnitine

carnitine

palmitoyl

carnitine


Input: Predicting isosteric heats for gas adsorption.


Input: A method for predicting the isosteric heat of gas adsorption on solid materials is developed which requires the measurement of a single isotherm-where previous methods, such as the Clausius-Clapeyron approach, require either multiple isotherms or complex calorimetric measurement.


Input: The T o th potential function, stemming from the Polanyi potential function, is evaluated using the Langmuir and T o th isotherm equations to generate new equations for the isosteric heat.


Input: These new isosteric heat equations share common parameters with the isotherm equations and are determined from isotherm fitting.


Input: This method is demonstrated in the literature for gas adsorption onto solid adsorbates including zeolites of various surface charge character and non-porous rutile phase titanium dioxide.

titanium dioxide


Input: Predictions are made using the new isosteric heat equations and then compared to calorimetric data.


Input: Elastic CNT-polyurethane nanocomposite: synthesis, performance and assessment of fragments released during use.

polyurethane


Input: Intended for use in high performance applications where electrical conductivity is required, we developed a CNT-TPU composite.


Input: Such a composite can be prepared by melt processing (extrusion) on an industrial scale.


Input: Due to the known hazard upon inhalation of CNTs, we assessed three degradation scenarios that may lead to the release of CNTs from the composite: normal use, machining and outdoor weathering.


Input: Unexpectedly, we find that the relative softness of the material actually enhances the embedding of CNTs also in its degradation fragments.


Input: A release of free CNTs was not detected under any condition using several detection methods.


Input: However, since machining may induce a high acute dose of human exposure, we assessed the cytotoxicity potential of released fragments in the in vitro model of precision-cut lung slices, and found no additional toxicity due to the presence of CNTs.


Input: At very low rates over years, weathering degrades the polymer matrix as expected for polyurethanes, thus exposing a network of entangled CNTs.

polyurethanes


Input: In a preliminary risk assessment, we conclude that this material is safe for humans in professional and consumer use.


Input: Cardiolipin-dependent reconstitution of respiratory supercomplexes from purified Saccharomyces cerevisiae complexes III and IV.

Cardiolipin


Input: Here, we report for the first time in vitro reconstitution of the respiratory supercomplexes from individual complexes III and IV.


Input: Complexes III and IV were purified from Saccharomyces cerevisiae mitochondria.


Input: Complex III contained eight molecules of cardiolipin, and complex IV contained two molecules of cardiolipin, as determined by electrospray ionization-mass spectrometry.

cardiolipin

cardiolipin


Input: Complex IV also contained Rcf1p.


Input: No supercomplexes were formed upon mixing of the purified complexes, and low amounts of the supercomplex trimer III (2) IV (1) were formed after reconstitution into proteoliposomes containing only phosphatidylcholine and phosphatidylethanolamine.

phosphatidylcholine

phosphatidylethanolamine


Input: Further addition of cardiolipin to the proteoliposome reconstitution mixture resulted in distinct formation of both the III (2) IV (1) supercomplex trimer and III (2) IV (2) supercomplex tetramer.


Input: No other anionic phospholipid was as effective as cardiolipin in supporting tetramer formation.

cardiolipin


Input: Phospholipase treatment of complex IV prevented trimer formation in the absence of cardiolipin.

cardiolipin


Input: Both trimer and tetramer formations were restored by cardiolipin.

cardiolipin


Input: Analysis of the reconstituted tetramer by single particle electron microscopy confirmed native organization of individual complexes within the supercomplex.


Input: In conclusion, although some trimer formation occurred dependent only on tightly bound cardiolipin, tetramer formation required additional cardiolipin.

cardiolipin

cardiolipin


Input: This is consistent with the high cardiolipin content in the native tetramer.

cardiolipin


Input: The dependence on cardiolipin for supercomplex formation suggests that changes in cardiolipin levels resulting from changes in physiological conditions may control the equilibrium between individual respiratory complexes and supercomplexes in vivo.

cardiolipin

cardiolipin


Input: Osteopetrosis, osteopetrorickets and hypophosphatemic rickets differentially affect dentin and enamel mineralization.


Input: Osteopetrosis (OP) is an inherited disorder of defective bone resorption, which can be accompanied by impaired skeletal mineralization, a phenotype termed osteopetrorickets (OPR).


Input: Since individuals with dysfunctional osteoclasts often develop osteomyelitis of the jaw, we have analyzed, if dentin and enamel mineralization are differentially affected in OP and OPR.


Input: Therefore, we have applied non-decalcified histology and quantitative backscattered electron imaging (qBEI) to compare the dental phenotypes of Src (-/-), oc/oc and Hyp (-/0) mice, which serve as models for OP, OPR and hypophosphatemic rickets, respectively.


Input: While both, Src (-/-) and oc/oc mice, were characterized by defects of molar root formation, only oc/oc mice displayed a severe defect of dentin mineralization, similar to Hyp (-/0) mice.


Input: Most importantly, while enamel thickness was not affected in either mouse model, the calcium content within the enamel phase was significantly reduced in oc/oc, but not in Src (-/-) or Hyp (-/0) mice.

calcium


Input: Taken together, these data demonstrate that dentin and enamel mineralization are differentially affected in Src (-/-) and oc/oc mice.


Input: Moreover, since defects of dental mineralization may trigger premature tooth decay and thereby osteomyelitis of the jaw, they further underscore the importance of discriminating between OP and OPR in the respective individuals.


Input: Mn (2 +) modulates the kinetic properties of an archaeal member of the PLL family.

Mn (2 +)


Input: Recently we reported on the characterization of an archaeal member of the amidohydrolase superfamily, namely Sulfolobus acidocaldarius lactonase, showing low but significant and extremely thermostable paraoxonase activity.


Input: This enzyme, that we have named SacPox, is a member of the new described family of phosphotriesterase-like lactonases (PLLs).


Input: In this family the binuclear metal centre, which is involved in the catalytic machinery, has been poorly studied up to now.


Input: In this work we describe the expression of the protein in presence of different metals showing Mn (2 +) to support the higher activity.

Mn (2 +)


Input: The enzyme has been over-expressed, purified and characterized as a Mn (2 +)-containing enzyme by inductive plasma coupled mass spectrometry (ICP-MS), showing also surprising kinetic differences in comparison with the cadmium-containing enzyme.

Mn (2 +)

cadmium


Input: The Mn (2 +) containing enzyme was about 30-fold more efficient with paraoxon as substrate and more stable than the Cd (2 +) counterpart, even though the Mn (2 +) affinity for the binuclear metal centre is apparently lower.

Mn (2 +)

paraoxon

Cd (2 +)

Mn (2 +)


Input: These results increase our knowledge of the biochemical characteristics of SacPox mainly with regard to the metal-ions modulation of function.


Input: Usage patterns of personal care products: important factors for exposure assessment.


Input: Complete information regarding the use of personal care products (PCPs) by consumers is limited, but such information is crucial for realistic consumer exposure assessment.


Input: To fill this gap, a database was created with person-oriented information regarding usage patterns and circumstances of use for 32 different PCPs.


Input: Out of 2700 potential participants from the Netherlands, 516 men and women completed a digital questionnaire.


Input: The prevalence of use varied by gender, age, level of education and skin type.


Input: A high frequency of use was observed for some products (e. g. lip care products), while toothpaste, deodorant and day cream were generally used once or twice a day.


Input: The frequency of use for other PCPs varied over a wide range.


Input: The amounts of use varied largely between and within different product groups.


Input: Body lotion, sunscreen and after sun lotion were often applied on adjacent body parts.


Input: The majority of PCPs were applied in the morning, but some products, such as night cream and after sun, were predominantly applied in the evening or night.


Input: As expected, the participants used several PCPs simultaneously.


Input: The database yields important personalized exposure factors which can be used in aggregate consumer exposure assessment for substances that are components of PCPs.


Input: An unusual marine envenomation following a rope contact: a report on nine cases of dermatitis caused by Pennaria disticha.


Input: We would like to present the clinical course of nine patients who had an acute, painful dermatitis following contact with a rope used as a swimming area liner in the sea.


Input: The macroscopic and microscopic analysis of the fouling on the rope retrospectively, revealed Pennaria disticha as the causative organism.


Input: To our knowledge, there is no previous report on P. disticha envenomation in medical literature.


Input: P. disticha is a benthic hydrozoa belonging to Cnidaria phylum.


Input: Cnidaria are well known for their envenomation with their venomous organelle, " cnidocyst ".


Input: The contact with cnidaria can result in a wide range of cytotoxic or anaphylactic reactions.


Input: While there is a large body of data in the literature from studies at molecular and cellular levels, there is limited data about the in vivo effects of cnidaria toxins.


Input: We think the clinical aspects of the dermatologic reactions caused by P. disticha and the diagnostic work-up to reveal the contamination on this unusual medium would be of interest to the readers.


Input: Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats.

permethrin

monoamine


Input: Pesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases.


Input: Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats.

permethrin

PERM


Input: Despite the PERM dose did not elicited overt signs of toxicity (i. e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase).

PERM

dopamine


Input: The present study was designed to characterize the cognitive deficits in the current animal model.


Input: When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls.

PERM


Input: No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task.


Input: Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus.

PERM


Input: The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area.

dopamine

serotonin

noradrenaline


Input: In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls.

PERM


Input: The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41. 50 mu g/L and it was completely eliminated after 96 h.

pyrethroid

3-phenoxybenzoic acid


Input: Orofacial dyskinesia induced by nasal Ritalin (R) (methylphenidate) sniffing: a rare case report from Switzerland.

Ritalin

methylphenidate


Input: Ritalin (R) (methylphenidate) is an amphetamine-like prescription stimulant commonly used in the treatment of attention deficit hyperactivity disorder in children and adults.

Ritalin

methylphenidate

amphetamine


Input: Recently, the recreational use of Ritalin has increased, particularly among young adults.

Ritalin


Input: Well-known symptoms of intoxication include signs of sympathetic nervous stimulation, such as agitation, anxiety, tachycardia, hypertension, headache, tremor, and dizziness.


Input: This case report describes oral dyskinesia as a rare presentation of Ritalin intoxication, with the review of pathophysiology and some epidemiological data.

Ritalin


Input: Oncogenic FGFR3 gene fusions in bladder cancer.


Input: FGF receptor 3 (FGFR3) is activated by mutation or over-expression in many bladder cancers.


Input: Here, we identify an additional mechanism of activation via chromosomal re-arrangement to generate constitutively activated fusion genes.


Input: FGFR3-transforming acid coiled coil 3 (TACC3) fusions resulting from 4p16. 3 re-arrangements and a t (4; 7) that generates a FGFR3-BAI1-associated protein 2-like 1 (BAIAP2L1) fusion were identified in 4 of 43 bladder tumour cell lines and 2 of 32 selected tissue samples including the tumour from which one of the cell lines was derived.


Input: These are highly activated and transform NIH-3T3 cells.


Input: The FGFR3 component is identical in all cases and lacks the final exon that includes the phospholipase C gamma 1 (PLC gamma 1) binding site.


Input: Expression of the fusions in immortalized normal human urothelial cells (NHUC) induced activation of the mitogen-activated protein kinase pathway but not PLC gamma 1.


Input: A protein with loss of the terminal region alone was not as highly activated as the fusion proteins, indicating that the fusion partners are essential.


Input: The TACC3 fusions retain the TACC domain that mediates microtubule binding and the BAIAP2L1 fusion retains the IRSp53/MIM domain (IMD) that mediates actin binding and Rac interaction.


Input: As urothelial cell lines with FGFR3 fusions are extremely sensitive to FGFR-selective agents, the presence of a fusion gene may aid in selection of patients for FGFR-targeted therapy.


Input: Design, synthesis and biological evaluation of glucose-containing scutellarein derivatives as neuroprotective agents based on metabolic mechanism of scutellarin in vivo.

glucose

scutellarein

scutellarin


Input: Based on metabolic mechanism of scutellarin in vivo that scutellarin could be hydrolyzed into scutellarein by beta-glucuronide enzyme, some glucose-containing scutellarein derivatives were designed and synthesized through the introduction of glucose moiety at C-7 position of scutellarein via a glucosidic bond.

scutellarin

scutellarin

scutellarein

glucose

scutellarein

glucose

scutellarein


Input: Biological activity evaluation showed that these glucose-containing scutellarein derivatives exhibited potent DPPH radical scavenging activities.

glucose

scutellarein

DPPH


Input: Furthermore, the improvement of physicochemical properties such as anticoagulant and neuroprotective activities alongside with the water solubility was achieved by introducing glucose.

glucose


Input: These findings suggest that the introduction of the glucose moiety to scutellarein wattants further development of this kind of compounds as neuroprotective agents.

glucose

scutellarein


Input: Pharmacophore identification of c-Myc inhibitor 10074-G5.


Input: A structure-activity relationship (SAR) study of the c-Myc (Myc) inhibitor 10074-G5 (N-([1, 1'-biphenyl]-2-yl)-7-nitrobenzo [c] [1, 2, 5] oxadiazol-4-amine, 1)-which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues-was executed in order to determine its pharmacophore.

N-([1, 1'-biphenyl]-2-yl)-7-nitrobenzo [c] [1, 2, 5] oxadiazol-4-amine

arginine


Input: Whilst the 7-nitrobenzofurazan was found to be critical for inhibitory activity, the ortho-biphenyl could be replaced with a para-carboxyphenyl group to furnish the new inhibitor JY-3-094 (3q).

ortho-biphenyl

para-carboxyphenyl


Input: Around five times as potent as the lead with an IC (50) of 33 mu M for disruption of the Myc-Max heterodimer, JY-3-094 demonstrated excellent selectivity over Max-Max homodimers, with no apparent effect at 100 mu M.


Input: Importantly, the carboxylic acid of JY-3-094 improves the physicochemical properties of the lead compound, which will facilitate the incorporation of additional hydrophobicity that might enhance Myc inhibitory activity further still.


Input: Rigid 5'-6-locked phenanthroline-derived nucleosides chelated to ruthenium and europium ions.

phenanthroline

nucleosides

ruthenium

europium


Input: We describe complexes of ruthenium and europium with rigid, 5'-6-locked 1, 10-phenanthroline-containing nucleosides.

ruthenium

europium

1, 10-phenanthroline

nucleosides


Input: Both nucleosides were synthesized from condensation of 5-amino-2'-deoxycytidine with the corresponding diketone.

diketone


Input: The ruthenium nucleoside displayed fluorescence characteristic of polypyridine ruthenium complexes with a maximum at 616 nm and a quantum yield of 0. 011.

ruthenium

polypyridine ruthenium


Input: Binding of europium to the 1, 10-phenanthroline-2, 9-diacid moiety of the lanthanide binding nucleoside showed formation of a 1: 1 complex with emission at 570-630 nm, whose emission was enhanced by addition of two phenanthroline ligands.

europium

1, 10-phenanthroline-2, 9-diacid

lanthanide

nucleoside

phenanthroline


Input: The lanthanide-binding nucleoside was incorporated into DNA oligonucleotides and shown to selectively bind one equivalent of europium ions.

lanthanide

nucleoside

europium


Input: Structure of a Ca (2 +)/CaM: Kv7. 4 (KCNQ4) B-helix complex provides insight into M current modulation.

Ca (2 +)


Input: Calmodulin (CaM) is an important regulator of Kv7. x (KCNQx) voltage-gated potassium channels.

potassium


Input: Channels from this family produce neuronal M currents and cardiac and auditory I (KS) currents and harbor mutations that cause arrhythmias, epilepsy, and deafness.


Input: Despite extensive functional characterization, biochemical and structural details of the interaction between CaM and the channel have remained elusive.


Input: Here, we show that both apo-CaM and Ca (2 +)/CaM bind to the C-terminal tail of the neuronal channel Kv7. 4 (KCNQ4), which is involved in both hearing and mechanosensation.

Ca (2 +)

CaM


Input: Interactions between apo-CaM and the Kv7. 4 tail involve two C-terminal tail segments, known as the A and B segments, whereas the interaction between Ca (2 +)/CaM and the Kv7. 4 C-terminal tail requires only the B segment.

CaM

Ca (2 +)

CaM


Input: Biochemical studies show that the calcium dependence of the CaM: B segment interaction is conserved in all Kv7 subtypes.

calcium


Input: X-ray crystallographic determination of the structure of the Ca (2 +)/CaM: Kv7. 4 B segment complex shows that Ca (2 +)/CaM wraps around the Kv7. 4 B segment, which forms an alpha-helix, in an antiparallel orientation that embodies a variation of the classic 1-14 Ca (2 +)/CaM interaction motif.

Ca (2 +)

Ca (2 +)

Ca (2 +)


Input: Taken together with the context of prior studies, our data suggest a model for modulation of neuronal Kv7 channels involving a calcium-dependent conformational switch from an apo-CaM form that bridges the A and B segments to a Ca (2 +)/CaM form bound to the B-helix.

calcium

Ca (2 +)


Input: The structure presented here also provides a context for a number of disease-causing mutations and for further dissection of the mechanisms by which CaM controls Kv7 function.


Input: Subtle alterations in swimming speed distributions of rainbow trout exposed to titanium dioxide nanoparticles are associated with gill rather than brain injury.

titanium dioxide


Input: The effects of engineered nanomaterials on fish behaviours are poorly understood.


Input: The present study aimed to determine the locomotor behaviours of trout during waterborne exposure to titanium dioxide nanoparticles (TiO (2) NPs) as well as inform on the underlying physiological mechanisms involved.

titanium dioxide

TiO (2)


Input: Trout were exposed to either control (without TiO (2)), 1 mg l (-1) TiO (2) NPs or 1 mg l (-1) bulk TiO (2) for 14 days.

TiO (2)

TiO (2)

TiO (2)


Input: Titanium dioxide exposure resulted in 31 (bulk) and 22 fold (nano) increases in the Ti concentrations of gill tissue compared to controls, but there were no measurable increases of Ti in the internal organs including the brain.

Titanium dioxide

Ti

Ti


Input: Gill pathologies were observed in both TiO (2) treatments.

TiO (2)


Input: Locomotor behaviours were quantified using video tracking software and the proportion of time spent swimming at high speed (> 20 cms (-1)) was significantly decreased in fish exposed to TiO (2) NPs, compared to controls, but not fish exposed to bulk TiO (2).

TiO (2)

TiO (2)


Input: The shift in swimming speed distribution in the TiO (2) NP-exposed fish was associated with decreased area of red pulp in the spleen, increases in haematocrit and whole blood haemoglobin, all consistent with a compensation for respiratory hypoxia without the accumulation of plasma lactate.

TiO (2)

lactate


Input: Fish exposed to TiO (2) NPs also retained competitive abilities when paired with controls in aggressive social encounters.

TiO (2)


Input: The duration of competitive contests, the level of aggression and contest outcome were not affected by NP exposure.


Input: Neurological injury did not explain the changes in locomotor behaviour, although there was some apparent enlargement of the blood vessels on the brain.


Input: Whole brain homogenates showed a statistically significant increase in oxidative stress defences such as the total glutathione pool, but without loss of Na (+) K (+)-ATPase or acetylcholinesterase activities.

glutathione

Na (+) K (+)


Input: Inhibition of the thyroid hormone pathway in Xenopus laevis by 2-mercaptobenzothiazole.


Input: Determining the effects of chemicals on the thyroid system is an important aspect of evaluating chemical safety from an endocrine disrupter perspective.


Input: Since there are numerous chemicals to test and limited resources, prioritizing chemicals for subsequent in vivo testing is critical.


Input: 2-Mercaptobenzothiazole (MBT), a high production volume chemical, was tested and shown to inhibit thyroid peroxidase (TPO) enzyme activity in vitro, a key enzyme necessary for the synthesis of thyroid hormone.

MBT


Input: To determine the thyroid disrupting activity of MBT in vivo, Xenopus laevis larvae were exposed using 7-and 21-day protocols.

MBT


Input: The 7-day protocol used 18-357 mu g/L MBT concentrations and evaluated: metamorphic development, thyroid histology, circulating T4, circulating thyroid stimulating hormone, thyroidal sodium-iodide symporter gene expression, and thyroidal T4, T3, and related iodo-amino acids.

MBT

sodium-iodide

iodo-amino acids


Input: The 21-day protocol used 23-435 mu g/L MBT concentrations and evaluated metamorphic development and thyroid histology.

MBT


Input: Both protocols demonstrated that MBT is a thyroid disrupting chemical at the lowest concentrations tested.

MBT


Input: These studies complement the in vitro study used to identify MBT as a high priority for in vivo testing, supporting the utility/predictive potential of a tiered approach to testing chemicals for TPO activity inhibition.

MBT


Input: The 7-day study, with more comprehensive, sensitive, and diagnostic endpoints, provides information at intermediate biological levels that enables linking various endpoints in a robust and integrated pathway for thyroid hormone disruption associated with TPO inhibition.


Input: UCCB01-125, a dimeric inhibitor of PSD-95, reduces inflammatory pain without disrupting cognitive or motor performance: comparison with the NMDA receptor antagonist MK-801.

NMDA


Input: Excessive N-Methyl-d-aspartate receptor (NMDAR)-dependent production of nitric oxide (NO) is involved in the development and maintenance of chronic pain states, and is mediated by postsynaptic density protein-95 (PSD-95).

N-Methyl-d-aspartate

nitric oxide

NO


Input: By binding to both the NMDAR and neuronal NO synthase (nNOS), PSD-95 mediates a specific coupling between NMDAR activation and NO production.

NO


Input: NMDAR antagonism shows anti-nociceptive action in humans and animal models of chronic pain but is associated with severe disturbances of cognitive and motor functions.


Input: An alternative approach to modulate the NMDAR-related activity is to perturb the NMDAR/PSD-95/nNOS complex by targeting PSD-95, thereby decreasing NO production without interfering with the NMDAR ion channel function.


Input: Here, we compared the effects of a dimeric PSD-95 inhibitor, UCCB01-125, and the NMDAR antagonist, MK-801, on mechanical hypersensitivity in the complete Freund' s adjuvant (CFA) model of inflammatory pain.


Input: To examine side-effect profiles we also compared the effects of UCCB01-125 and MK-801 in tests of attention, long-term memory, and motor performance.


Input: When administered concurrently with CFA, both MK-801 and UCCB01-125 prevented the development of CFA-induced mechanical hypersensitivity 1 and 24 h after treatment.


Input: Moreover, UCCB01-125 was found to reverse CFA-induced hypersensitivity when administered 24 h after CFA treatment, an effect lasting for at least 3 days.


Input: At the dose reducing hypersensitivity, MK-801 disrupted attention, long-term memory, and motor performance.


Input: By contrast, even high doses of UCCB01-125 were devoid of side-effects in these tests.


Input: The data suggest that PSD-95 inhibition is a feasible strategy to prevent both development and maintenance of chronic inflammatory pain, while avoiding NMDAR antagonism-related side-effects.


Input: Highly regioselective glycosylation of xylosyl-containing taxanes by Enterobacter cloaceae.

xylosyl-containing taxanes


Input: Three new diglycoside taxanes (4-6) containing an additional alpha-d-glucose unit were obtained via Enterobacter cloaceae-mediated, highly regioselective glycosylations at OH-4 of the xylosyl moieties in 7-xylosyl taxanes (1-3).

diglycoside taxanes

alpha-d-glucose

OH

xylosyl

7-xylosyl taxanes


Input: Their structures were determined on the basis of extensive spectroscopic analysis and chemical reactivity.


Input: This is the first report of an enzymatic elongation of the saccharide chain in taxanes, and the glycosylation reaction is the first described example of a transformation effected by E. cloaceae.


Input: Evaluation of immunohistochemical markers to detect the genotoxic mode of action of fine and ultrafine dusts in rat lungs.


Input: Data on local genotoxicity after particle exposure are crucial to resolve mechanistic aspects such as the impact of chronic inflammation, types of DNA damage, and their role in lung carcinogenesis.


Input: We established immunohistochemical methods to quantify the DNA damage markers poly (ADP-ribose) (PAR), phosphorylated H2AX (gamma-H2AX), 8-hydroxyguanosine (8-OH-dG), and 8-oxoguanine DNA glycosylase (OGG1) in paraffin-embedded tissue from particle-exposed rats.

poly (ADP-ribose)

PAR

paraffin


Input: The study was based on lungs from a subchronic study that was part of an already published carcinogenicity study where rats had been intratracheally instilled with saline, quartz DQ12, amorphous silica (Aerosil ((R)) 150), or carbon black (Printex ((R)) 90) at monthly intervals for 3 months.

silica

Aerosil

carbon black

Printex


Input: Lung sections were stained immunohistochemically and markers were quantified in alveolar lining cells.


Input: Local genotoxicity was then correlated with already defined endpoints, i. e. mean inflammation score, bronchoalveolar lavage parameters, and carcinogenicity.


Input: Genotoxicity was most pronounced in quartz DQ12-treated rats, where all genotoxicity markers gave statistically significant positive results, indicating considerable genotoxic stress such as occurrence of DNA double-strand breaks (DSB), and oxidative damage with subsequent repair activity.


Input: Genotoxicity was less pronounced for Printex ((R)) 90, but significant increases in gamma-H2AX-and 8-OH-dG-positive nuclei and OGG1-positive cytoplasm were nevertheless detected.

Printex


Input: In contrast, Aerosil ((R)) 150 significantly enhanced only 8-OH-dG-positive nuclei and oxidative damage-related repair activity (OGG1) in cytoplasm.

Aerosil


Input: In the present study, gamma-H2AX was the most sensitive genotoxicity marker, differentiating best between the three types of particles.


Input: The mean number of 8-OH-dG-positive nuclei, however, correlated best with the mean inflammation score at the same time point.


Input: This methodological approach enables integration of local genotoxicity testing in subchronic inhalation studies and makes immunohistochemical detection, in particular of gamma-H2AX and 8-hydroxyguanine, a very promising approach for local genotoxicity testing in lungs, with prognostic value for the long-term outcome of particle exposure.


Input: Glucocorticoid receptor concentration and the ability to dimerize influence nuclear translocation and distribution.


Input: Glucocorticoid receptor (GR) concentrations and the ability of the GR to dimerize are factors which influence sensitivity to glucocorticoids.


Input: Upon glucocorticoid binding, the GR is actively transported into the nucleus, a crucial step in determining GR function.


Input: We examined the effects of GR concentration and the ability to dimerize on GR nuclear import, export and nuclear distribution using both live cell microscopy of GFP-tagged GR and immunofluorescence of untagged GR, with both wild type GR (GRwt) and dimerization deficient GR (GRdim).


Input: We found that the observed rate of GR nuclear import increases significantly at higher GR concentrations, at saturating concentrations of dexamethasone (10 (-6) M) using GFP-tagged GR, while with untagged GR it is only discernable at sub-saturating ligand concentrations (10 (-10)-10 (-9) M).

dexamethasone


Input: Loss of dimerization results in a slower observed rate of nuclear import (2. 5-to 3. 3-fold decrease for GFP-GRdim) as well as a decreased extent of GR nuclear localization (18-27% decrease for untagged GRdim).


Input: These results were linked to an increased rate of GR export at low GR concentrations (1. 4-to 1. 6-fold increase for untagged GR) and where GR dimerization is abrogated (1. 5-to 1. 7-fold increase for GFP-GRdim).


Input: Furthermore, GR dimerization was shown to be required for the appearance of discrete GC-dependent GR nuclear foci, the loss of which may explain the increased rate of GR export for the GRdim.


Input: The reduction in the observed rate of nuclear import and increased rate of nuclear export displayed at low GR concentrations and by the GRdim could explain the lowered glucocorticoid response under these conditions.


Input: New approach to improve encapsulation and antitumor activity of doxorubicin loaded in solid lipid nanoparticles.

doxorubicin


Input: This work aimed to develop solid lipid nanoparticles (SLNs) loaded with doxorubicin evaluating the influence of docosahexaenoic acid (DHA), a polyunsaturated fatty acid that enhances the activity of anticancer drugs, on drug encapsulation efficiency (EE).

doxorubicin

docosahexaenoic acid

DHA

polyunsaturated fatty acid


Input: The SLN were characterized for size, zeta potential, entrapment efficiency (EE) and drug release.


Input: Studies of in vitro antitumor activity and cellular uptake were also conducted.


Input: The reduction in particle size (from 127 +/- 14 to 94 +/- 1 nm) and negative charges were obtained for SLN loaded with DHA and triethanolamine (TEA), amine used to increase the solubility of doxorubicin in melted lipid.

DHA

triethanolamine

TEA

amine

doxorubicin


Input: The EE was significantly improved from 36 +/- 4% to 99 +/- 2% for SLN without and with DHA at 0. 4%, respectively.

DHA


Input: The doxorubicin release in a slightly acid medium (pH 5. 0) was higher than that observed at physiological pH.

doxorubicin


Input: The in vitro studies clearly showed the higher cytotoxicity of doxorubicin-DHA-loaded SLN than free doxorubicin + DHA on human lung tumor cell line (A549) and the improved cellular uptake achieved with the drug encapsulation can be an explanation.

doxorubicin

DHA

doxorubicin

DHA


Input: These findings suggest that DHA-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer.

DHA

doxorubicin


Input: A novel recombinant fibrinogenase of Agkistrodon acutus venom protects against hyperacute rejection via degradation of complements.


Input: Hyperacute rejection (HAR) is a main barrier in xenotransplantation, which is mediated by the combination of natural antibody to the xenograft and complement activation.


Input: Current therapies have focus on the inhibition of complement by development of complement inhibitor and transgenic animal organ.


Input: Here, we investigated the effects of rFII, a recombinant fibrinogenase from Agkistrodon acutus venom, on complement and HAR.


Input: The degradation effect of rFII on complement was tested by SDS-PAGE, CH50 examination, ELISA Kit and cofocal immunofluorescence microscopy in vitro and in vivo.


Input: An ex-vivo rat-to-human perfusion model and a vivo guinea-pig-to-rat heat HAR model were used to determine the protection of rFII against HAR.


Input: Our investigation indicated that rFII could significantly degrade human C5, C6, and C9, decrease the activity of complement, and inhibit the MAC deposition on HUVECs membrane in vitro.


Input: In addition, serum levels of C1q, C3 and C4 in rat were gradually reduced after infusion of rFII.


Input: Importantly, in an ex vivo rat-to-human perfusion model, the survival of rat hearts perfused with human serum treated with rFII (83. 36 +/- 16. 63 min) were significantly longer than that of hearts perfused with fresh human serum (15. 94 +/- 4. 75 min).


Input: At the time of 15 minutes after perfusion, functions of hearts added with 50 ug/ml rFII sustained well with heart rates at 283 +/- 65. 32 beats/minute and LVDP at 13. 70 +/- 5. 45 Kpa, while that of hearts perfused with fresh human serum were severely damaged by HAR with heart rates at 107. 77 +/- 40. 31 beats/minute and LVDP at 1. 01 +/- 0. 83 Kpa.


Input: We also found that rFII significantly decreased the levels of C1q, C3 and C4 in human fresh serum perfusate.


Input: In a vivo guinea-pig-to-rat heat HAR model, the survival of rat hearts treated with rFII were significantly longer than that of hearts perfused with normal saline; and relieved heart damage by complete activation.


Input: Our finding demonstrates the anti-complement property of rFII and its protection against HAR, indicating that rFII might be as a potential therapeutic agent for xenotransplantation.


Input: Pocketed microneedles for rapid delivery of a liquid-state botulinum toxin A formulation into human skin.


Input: Botulinum toxin A (BT) is used therapeutically for the treatment of primary focal hyperhidrosis, a chronic debilitating condition characterised by over-activity of the eccrine sweat glands.


Input: Systemic toxicity concerns require BT to be administered by local injection, which in the case of hyperhidrosis means multiple painful intradermal injections by a skilled clinician at 6-monthly intervals.


Input: This study investigates the potential of a liquid-loaded pocketed microneedle device to deliver botulinum toxin A into the human dermis with the aim of reducing patient pain, improving therapeutic targeting and simplifying the administration procedure.


Input: Initially, beta-galactosidase was employed as a detectable model for BT to (i) visualise liquid loading of the microneedles, (ii) determine residence time of a liquid formulation on the device and (iii) quantify loaded doses.


Input: An array of five stainless steel pocketed microneedles was shown to possess sufficient capacity to deliver therapeutic doses of the potent BT protein.


Input: Microneedle-mediated intradermal delivery of beta-galactosidase and formaldehyde-inactivated botulinum toxoid revealed effective deposition and subsequent diffusion within the dermis.

formaldehyde


Input: This study is the first to characterise pocketed microneedle delivery of a liquid formulation into human skin and illustrates the potential of such systems for the cutaneous administration of potent proteins such as BT.


Input: A clinically appropriate microneedle delivery system for BT could have a significant impact in both the medical and cosmetic industries.


Input: Changes of the serum cytokine contents in broilers fed on diets supplemented with nickel chloride.

nickel chloride


Input: Cytokines are immunoregulatory proteins which play an important role in the immune system.


Input: The purpose of this study was to examine the serum cytokine contents including interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) induced by dietary nickel chloride in broilers by enzyme-linked immunospecific assay.

nickel chloride


Input: A total of 240 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet or the same basal diet supplemented with 300, 600, and 900 mg/kg of nickel chloride.

nickel chloride


Input: During the experimental period of 42 days, the results showed that the serum IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha contents were lower (p < 0. 05 or p < 0. 01) in the 300, 600, 900 mg/kg groups than those in the control group.


Input: It was concluded that dietary nickel chloride in the range of 300 to 900 mg/kg could reduce the serum cytokine contents, which could finally impact the immune function in broilers.

nickel chloride


Input: Natures of benzene-water and pyrrole-water interactions in the forms of sigma and pi types: theoretical studies from clusters to liquid mixture.

benzene

pyrrole


Input: A combined and sequential use of quantum mechanical (QM) calculations and classical molecular dynamics (MD) simulations was made to investigate the sigma and pi types of hydrogen bond (HB) in benzene-water and pyrrole-water as clusters and as their liquid mixture, respectively.

hydrogen

benzene

pyrrole


Input: This paper aims at analyzing similarities and differences of these HBs resulted from QM and MD on an equal footing.


Input: Based on the optimized geometry at omega b97xD/aug-cc-pVTZ level of theory, the nature and property of sigma and pi types of HBs are unveiled by means of atoms in molecules (AIM), natural bond orbital (NBO) and energy decomposition analysis (EDA).


Input: In light of the above findings, MD simulation with OPLS-AA and SPC model was applied to study the liquid mixture at different temperatures.


Input: The MD results further characterize the behavior and structural properties of sigma and pi types HBs, which are somewhat different but reasonable for the clusters by QM.


Input: Finally, we provide a reasonable explanation for the different solubility between benzene/water and pyrrole/water.

benzene

pyrrole


Input: Serotonin-glutamate and serotonin-dopamine reciprocal interactions as putative molecular targets for novel antipsychotic treatments: from receptor heterodimers to postsynaptic scaffolding and effector proteins.

Serotonin

glutamate

serotonin

dopamine


Input: The physical and functional interactions between serotonin-glutamate and serotonin-dopamine signaling have been suggested to be involved in psychosis pathophysiology and are supposed to be relevant for antipsychotic treatment.

serotonin

glutamate

serotonin

dopamine


Input: Type II metabotropic glutamate receptors (mGluRs) and serotonin 5-HT (2A) receptors have been reported to form heterodimers that modulate G-protein-mediated intracellular signaling differentially compared to mGluR2 and 5-HT (2A) homomers.

glutamate

serotonin 5-HT


Input: Additionally, direct evidence has been provided that D (2) and 5-HT (2A) receptors form physical heterocomplexes which exert a functional cross-talk, as demonstrated by studies on hallucinogen-induced signaling.


Input: Moving from receptors to postsynaptic density (PSD) scenario, the scaffolding protein PSD-95 is known to interact with N-methyl-D-aspartate (NMDA), D (2) and 5-HT (2) receptors, regulating their activation state.

N-methyl-D-aspartate

NMDA


Input: Homer1a, the inducible member of the Homer family of PSD proteins that is implicated in glutamatergic signal transduction, is induced in striatum by antipsychotics with high dopamine receptor affinity and in the cortex by antipsychotics with mixed serotonergic/dopaminergic profile.

dopamine


Input: Signaling molecules, such as Akt and glycogen-synthase-kinase-3 (GSK-3), could be involved in the mechanism of action of antipsychotics, targeting dopamine, serotonin, and glutamate neurotransmission.

dopamine

serotonin

glutamate


Input: Altogether, these proteins stand at the crossroad of glutamate-dopamine-serotonin signaling pathways and may be considered as valuable molecular targets for current and new antipsychotics.

glutamate

dopamine

serotonin


Input: The aim of this review is to provide a critical appraisal on serotonin-glutamate and serotonin-dopamine interplay to support the idea that next generation schizophrenia pharmacotherapy should not exclusively rely on receptor targeting strategies.

serotonin

glutamate

serotonin

dopamine


Input: Pocket-based drug design: exploring pocket space.


Input: The identification and application of druggable pockets of targets play a key role in in silico drug design, which is a fundamental step in structure-based drug design.


Input: Herein, some recent progresses and developments of the computational analysis of pockets have been covered.


Input: Also, the pockets at the protein-protein interfaces (PPI) have been considered to further explore the pocket space for drug discovery.


Input: We have presented two case studies targeting the kinetic pockets generated by normal mode analysis and molecular dynamics method, respectively, in which we focus upon incorporating the pocket flexibility into the two-dimensional virtual screening with both affinity and specificity.


Input: We applied the specificity and affinity (SPA) score to quantitatively estimate affinity and evaluate specificity using the intrinsic specificity ratio (ISR) as a quantitative criterion.


Input: In one of two cases, we also included some applications of pockets located at the dimer interfaces to emphasize the role of PPI in drug discovery.


Input: This review will attempt to summarize the current status of this pocket issue and will present some prospective avenues of further inquiry.


Input: Assessing the sublethal effects of in-river concentrations of parameters contributing to cumulative effects in the athabasca river basin using a fathead minnow bioassay.


Input: The Athabasca River basin, located in Alberta, Canada, covers 157, 000 km (2) and holds significant cultural and economic importance.


Input: Recent research assessed changes in several water quality and quantity parameters that have changed both spatially (along the river continuum) and temporally (pre-development and present day) in the Athabasca River Basin.


Input: In particular, parameters such as salinity and dissolved sulphate have changed significantly across the Athabasca River mainstem over the past five decades.

sulphate


Input: Further laboratory testing has linked concentrations of these parameters to changes in fathead minnow reproduction.


Input: Research is required to determine whether these changes observed in the laboratory can be applied to actual in-river conditions.


Input: The objectives of the present study were to twofold: assess changes in fathead minnow response metrics (i. e., condition, liver and gonad size, egg production, and gill histology) associated with increasing concentrations of salinity and dissolved sulphate and determine whether sublethal effect thresholds established in laboratory experiments correspond to actual in-river concentrations using water from the mouth and headwaters of the Athabasca River.

sulphate


Input: Three dose-response experiments (NaCl, SO4, and water sampled from the mouth of the Athabasca River) were conducted at Jasper National Park, Alberta, Canada.

NaCl


Input: Significant increases in mean eggs per female per day occurred at the 50% treatment for the mouth experiment and thresholds previously developed in the laboratory were verified.


Input: Solvated graphenes: an emerging class of functional soft materials.

graphenes


Input: From a materials science point of view, graphene is essentially a polymer having a giant, two-dimensional molecular configuration.

graphene


Input: In this Progress Report, solvated graphene and its derivatives are illustrated from the perspective of soft matter.

graphene


Input: Firstly, the key appealing features of graphene as a molecular building block for assembling bulk soft materials are highlighed.

graphene


Input: It is then demonstrated how the intersheet interactions in solution are correlated with the molecular structure of graphene, and how a combination of the unique molecular structure and colloidal interactions can lead to simple, solution-phase approaches for assembling graphenes into a variety of macroscopic nanoarchitectures.

graphene

graphenes


Input: A number of new exciting functions and applications are also highlighted, which are enabled by the solvation effect and in particular, it is discussed why and how solvated graphenes can offer exciting functions that are unattainable with the dried, hard counterpart.

graphenes


Input: The discussion is concluded with some personal perspectives on the future directions in which this emerging class of functional soft materials could be pursued.


Input: Stability of pharmaceuticals and other polar organic compounds stored on polar organic chemical integrative samplers and solid-phase extraction cartridges.


Input: The stability of 24 chemicals, including pharmaceuticals and personal care products, and some agrochemicals on extraction media was evaluated by preloading them onto Oasis hydrophilic lipophilic balanced solid-phase extraction (SPE) cartridges and polar organic chemical integrative samplers (POCIS) followed by storage at-20 degrees C over time.


Input: After 20 months, the average loss was 11% on POCIS, with only 2, 4-dichlorophenoxyacetic acid, atrazine, chlorpyrifos, and gemfibrozil showing a statistically significant decline compared with initial concentrations.

2, 4-dichlorophenoxyacetic acid

atrazine

chlorpyrifos

gemfibrozil


Input: Losses on SPE cartridges were below 19%, with an average loss of 9%.


Input: In addition to laboratory spiked samples, multiple POCIS deployed in wastewater-impacted surface waters and SPE extracts of these waters were stored in their original coextracted matrix for nearly two years with minimal observed losses.


Input: Errors from typical sampling, handling, and concentration estimates from POCIS sampling rates were typically +/- 15 to 30% relative standard deviation, so observed storage losses are minimal for most POCIS applications.


Input: While losses during storage on SPE cartridges for 20 months were small but statistically significant for many compounds, addition of labeled internal standards prior to freezing should correct for such losses.


Input: Thus, storage of processed water samples for analysis of polar organic pollutants is viable for archival purposes or studies for which samples cannot be analyzed in the short term.


Input: Mitigating with macrophytes: submersed plants reduce the toxicity of pesticide-contaminated water to zooplankton.


Input: In ecotoxicology, appreciation is growing for the influence that ecological interactions have on the toxicity of contaminants, such as insecticides, to sensitive species.


Input: Most previous studies, however, have focused on factors that exacerbate insecticide effects on species, while factors that may mitigate these effects have been relatively ignored.


Input: In aquatic habitats, a small number of studies have shown that submersed macrophytes can remove some insecticides from the water column via sorption.


Input: Although examining sorption dynamics is important for understanding the environmental fate of insecticides, whether and to what extent macrophytes actually mitigate insecticide effects on aquatic species remains unknown.


Input: In the present study, the authors examined how much and how quickly several realistic densities of the macrophyte Elodea canadensis decreased the toxicity of the insecticide malathion to Daphnia magna, a keystone aquatic herbivore.

malathion


Input: To do this, the authors quantified Daphnia survival in outdoor test systems (0. 95 L) exposed to a factorial combination of five Elodea densities crossed with five malathion concentrations.

malathion


Input: The authors discovered that malathion' s lethality to Daphnia decreased with increasing Elodea density.

malathion


Input: Furthermore, the rate at which Elodea reduced malathion' s toxicity in the water column increased with macrophyte density.

malathion


Input: These results provide strong evidence that submersed macrophytes can mitigate the ecological impacts of a popular insecticide and further support that ecological interactions can strongly influence contaminant environmental effects.


Input: The nucleoid-associated protein Dan organizes chromosomal DNA through rigid nucleoprotein filament formation in E. coli during anoxia.


Input: Dan is a transcription factor that regulates the ttd operon encoding tartrate dehydratase.

tartrate


Input: During anaerobic conditions, its copy number increases by 100-fold, making Dan an abundant nucleoid-associated protein.


Input: However, little is known about the mode of Dan-DNA interaction.


Input: To understand its cellular functions, we used single-molecule manipulation and imaging techniques to show that Dan binds cooperatively along DNA, resulting in formation of a rigid periodic nucleoprotein filament that strongly restricts accessibility to DNA.


Input: Furthermore, in the presence of physiologic levels of magnesium, these filaments interact with each other to cause global DNA condensation.

magnesium


Input: Overall, these results shed light on the architectural role of Dan in the compaction of Escherichia coli chromosomal DNA under anaerobic conditions.


Input: Formation of the nucleoprotein filament provides a basis in understanding how Dan may play roles in both chromosomal DNA protection and gene regulation.


Input: Animal QTLdb: an improved database tool for livestock animal QTL/association data dissemination in the post-genome era.


Input: The Animal QTL database (QTLdb; http://www. animalgenome. org/QTLdb) is designed to house all publicly available QTL and single-nucleotide polymorphism/gene association data on livestock animal species.


Input: An earlier version was published in the Nucleic Acids Research Database issue in 2007.


Input: Since then, we have continued our efforts to develop new and improved database tools to allow more data types, parameters and functions.


Input: Our efforts have transformed the Animal QTLdb into a tool that actively serves the research community as a quality data repository and more importantly, a provider of easily accessible tools and functions to disseminate QTL and gene association information.


Input: The QTLdb has been heavily used by the livestock genomics community since its first public release in 2004.


Input: To date, there are 5920 cattle, 3442 chicken, 7451 pigs, 753 sheep and 88 rainbow trout data points in the database, and at least 290 publications that cite use of the database.


Input: The rapid advancement in genomic studies of cattle, chicken, pigs, sheep and other livestock animals has presented us with challenges, as well as opportunities for the QTLdb to meet the evolving needs of the research community.


Input: Here, we report our progress over the recent years and highlight new functions and services available to the general public.


Input: Versican 3'-untranslated region (3'-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity.


Input: This study was designed to explore the role of versican in the development of hepatocellular carcinoma (HCC).


Input: Ectopic expression of the versican 3'-untranslated region (3'-UTR) was studied as a competitive endogenous RNA for regulating miRNA functions.


Input: We used this approach to modulate the expression of versican and its related proteins in 3'-UTR transgenic mice and in the liver cancer cell line HepG2, stably transfected with the 3'-UTR or a control vector.


Input: We demonstrated that transgenic mice expressing the versican 3'-UTR developed HCC and increased expression of versican isoforms V0 and V1.


Input: HepG2 cells transfected with versican 3'-UTR displayed increased proliferation, survival, migration, invasion, colony formation, and enhanced endothelial cell growth, but decreased apoptosis.


Input: We found that versican 3'-UTR could bind to miRNAs miR-133a, miR-199a *, miR-144, and miR-431 and also interacted with CD34 and fibronectin.


Input: As a consequence, expression of versican, CD34, and fibronectin was up-regulated by ectopic transfection of the versican 3'-UTR, which was confirmed in HepG2 cells and in transgenic mice as compared with wild-type controls.


Input: Transfection with siRNAs targeting the versican 3'-UTR abolished the effects of the 3'-UTR.


Input: Taken together, these results demonstrate that versican V0 and V1 isoforms play important roles in HCC development and that versican mRNAs compete with endogenous RNAs in regulating miRNA functions.


Input: Conformational landscape of diisopropyl ketone: quantum chemical calculations validated by microwave spectroscopy.

diisopropyl ketone


Input: We report on the gas-phase structure of the most abundant conformer of diisopropyl ketone, (CH (3)) (2) HC-CO-CH (CH (3)) (2), as observed by molecular beam Fourier transform microwave spectroscopy.

diisopropyl ketone

(CH (3)) (2) HC-CO-CH (CH (3)) (2)


Input: The gas-phase structures of five conformers of diisopropyl ketone were optimized using ab initio calculations at the MP2/6-311 + + G (d, p) level of theory.

diisopropyl ketone


Input: The natures of the stationary points were verified using harmonic frequency calculations.


Input: The only conformer observed in the supersonic jet possesses C (2) symmetry and appears as an enantiomeric pair.


Input: From the microwave spectrum, a set of three highly accurate rotational constants, five centrifugal distortion constants, and three sextic centrifugal distortion constants were determined.


Input: The structure of the observed conformer was optimized again at different levels of theory using the HF, MP2, and B3LYP methods.


Input: The theoretical constants of the C (2) conformer were subsequently validated using the experimental constants.


Input: To understand the transitions of one conformer to the others, the isopropyl groups were rotated against each other.

isopropyl


Input: The resulting two-dimensional potential energy surface shows nicely the symmetry of the conformational landscape and also indicates the enantiomeric pairs of the conformers.


Input: The barriers to internal rotation of the methyl groups were determined to be 1052 and 905 cm (-1) at the MP2/6-311 + + G (d, p) and the B3LYP/6-311 + + G (d, p) levels, respectively.

methyl


Input: In agreement with the theoretical predictions, no internal rotation patterns could be observed in the microwave spectrum.


Input: Progestin effects on expression of AKR1C1-AKR1C3, SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line.

Progestin


Input: Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity.


Input: This disease is associated with diminished protective effects of progesterone, which are usually explained by inadequate activation of progesterone receptors and also enhanced pre-receptor metabolism of progesterone.

progesterone

progesterone

progesterone


Input: Endometriosis is often treated with progestins, which act as progesterone receptor agonists, although their exact mechanisms of action are not completely understood.

progestins

progesterone


Input: The aim of the present study was to investigate how the progestins medroxyprogesterone acetate, dydrogesterone and dienogest, as well as progesterone, impact on the expression of genes of pre-receptor progesterone metabolism in Z-12 epithelial cell line, a model system of peritoneal endometriosis.

progestins medroxyprogesterone acetate

dydrogesterone

dienogest

progesterone

progesterone


Input: Our data demonstrate that these progestins affect local pre-receptor metabolism to a different extent.

progestins


Input: The most favorable effects were seen for dydrogesterone and dienogest, where the first, dydrogesterone, significantly reduced SRD5A1, AKR1C2 and AKR1C3 expression, and additionally had a nonsignificant impact on progesterone receptor B (PR-B) protein levels.

dydrogesterone

dienogest

dydrogesterone

progesterone


Input: This might slow down the first step of pre-receptor metabolism, the conversion of progesterone to 5 alpha-dihydroprogestrone by SRD5A1, and it might also affect further reduction of 3-keto and 20-keto groups catalyzed by AKR1C2 and AKR1C3.

progesterone

5 alpha-dihydroprogestrone


Input: Similarly favorable effects were seen for dienogest, which promoted significant reduction of AKR1C1 and AKR1C2 expression and also showed no effect on PR-B protein levels.

dienogest


Input: Different effects were seen for progesterone, which significantly decreased SRD5A1, PR-B and HSD17B2 protein levels.

progesterone


Input: In contrast, treatment with medroxyprogesterone acetate resulted in increased AKR1C1 expression and decreased levels of PR-B, which might lead to enhanced progesterone metabolism and reduced signaling through progesterone receptors.

medroxyprogesterone acetate

progesterone

progesterone


Input: Altogether, our data in this Z-12 cell model suggest that the beneficial effects of treatment with progestin observed in endometriosis patients might arise from decreased pre-receptor metabolism of the protective progesterone by the SRD5A1 and AKR1C enzymes.

progestin

progesterone


Input: Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss-of-function studies.


Input: Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP), and their receptor, guanylyl cyclase (GC)-A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions.


Input: In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses.


Input: Medaka has two ligands, BNP and C-type NP3 (CNP3) (but not ANP), that have greater affinity for the two O. latipes GC-A receptors (OLGC), OLGC7 and OLGC2, respectively.


Input: CNP3 is the ancestral molecule of cardiac NPs.


Input: Initially, we examined developmental expression of cardiac NP/receptor combinations, BNP/OLGC7 and CNP3/OLGC2, using quantitative real-time PCR and in situ hybridization.


Input: BNP and CNP3 mRNA increased at stages 25 (onset of ventricular formation) and 22 (appearance of heart anlage), respectively, whereas both receptor mRNAs increased at as early as stage 12.


Input: BNP/OLGC7 transcripts were found in arterial/ventricular tissues and CNP3/OLGC2 transcripts in venous/atrial tissues by in situ hybridization.


Input: Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine/autocrine fashion.


Input: Double knockdown of BNP/OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation.


Input: CNP3 knockdown induced hypertrophy of atria and activated the renin-angiotensin system.


Input: Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates.


Input: The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates.


Input: P21-activated protein kinase 1 (Pak1) mediates the cross talk between insulin and beta-catenin on proglucagon gene expression and its ablation affects glucose homeostasis in male C57BL/6 mice.

glucose


Input: In gut endocrine L cells, the Wnt signaling pathway effector beta-catenin (beta-cat)/transcription factor 7-like 2 mediates the stimulatory effect of insulin on proglucagon (gcg) expression and glucagon-like peptide-1 (GLP-1) production.


Input: In several other cell lineages, insulin is able to stimulate p21-activated protein kinase 1 (Pak1).


Input: Here we determined the role of Pak1 in gcg expression and the effect of Pak1 deletion on glucose homeostasis.

glucose


Input: Insulin stimulated Pak1 activation through increasing its Thr423 phosphorylation in gut gcg-expressing cell lines, associated with increased gcg mRNA levels.


Input: This stimulation was attenuated by the Pak inhibitor 2, 2'-dihydroxy-1, 1'-dinaphthyldisulfide (IPA3) or dominant-negative Pak1.

2, 2'-dihydroxy-1, 1'-dinaphthyldisulfide


Input: Both insulin and cAMP-promoting agents activated beta-cat Ser675 phosphorylation, which was attenuated by IPA3 or protein kinase A inhibition, respectively.

cAMP


Input: Gut gcg levels were reduced in male Pak1 (-/-) mice, associated with impaired glucose tolerance after an ip or oral glucose challenge.

glucose

glucose


Input: These mice had lower circulating active GLP-1 levels after a glucose challenge as well as reduced distal ileum GLP-1 content after insulin treatment.

glucose


Input: Finally, the Pak1 (-/-) mice exhibited reduced brainstem gcg level and abolished beta-cat Ser675 phosphorylation in brain neurons after insulin treatment.


Input: We suggest that Pak1 mediates the cross talk between insulin and Wnt signaling pathways on gut and brain gcg expression, and its ablation impairs glucose homeostasis.

glucose


Input: Mortality, bioaccumulation and physiological responses in juvenile freshwater mussels (Lampsilis siliquoidea) chronically exposed to copper.

copper


Input: Several studies have indicated that the early life stages of freshwater mussels are among the most sensitive aquatic organisms to inorganic chemicals, including copper.

copper


Input: However, little is known about the toxic mode of action and sub-lethal effects of copper exposure in this group of imperiled animals.

copper


Input: In this study, the physiological effects of long-term copper exposure (survival, growth, copper bioaccumulation, whole-body ion content, oxygen consumption, filtration rate, ATPase activities, and biomarkers of oxidative stress) were evaluated in juvenile (6 month old) mussels (Lampsilis siliquoidea).

copper

copper

oxygen


Input: The mussels' recovery capacity and their ability to withstand further acute copper challenge were also evaluated in secondary experiments following the 28 day exposure by assessing survival, copper bioaccumulation and whole-body ion content.

copper

copper


Input: Mussels chronically exposed to 2 and 12 mu g Cu/L showed significantly higher mortality than those held under control conditions (mortality 20. 9, 69. 9 and 12. 5%, respectively), indicating that juvenile L. siliquoidea is underprotected by the U. S.


Input: Environmental Protection Agency (USEPA) biotic ligand model (BLM)-derived chronic water quality criteria (WQC) (2. 18 mu g Cu/L) and the hardness-derived USEPA WQC (12. 16 mu g Cu/L).


Input: Soft tissue copper burden increased equally for both copper exposures, suggesting that chronic toxicity is not associated with copper bioaccumulation.

copper

copper

copper


Input: Several physiological disturbances were also observed during chronic copper exposure.

copper


Input: Most relevant was a decrease in whole-body sodium content paralleled by an inhibition of Na (+) K (+)-ATPase activity, indicating a metal-induced ionoregulatory disturbance.

sodium

Na (+) K (+)


Input: Filtration and oxygen consumption rates were also affected.

oxygen


Input: Redox parameters (reactive oxygen production, antioxidant capacity against peroxyl radicals, glutathione-S-transferase (GST) activity, and glutathione (GSH) concentration) did not show clear responses, but membrane damage as lipid peroxidation (LPO) was observed in both copper exposures.

oxygen

peroxyl

glutathione

S

glutathione

GSH

copper


Input: Mussels previously held in control conditions or pre-exposed to 2 mu g dissolved Cu/L were able to maintain their ionic homeostasis and did not experience mortality after the 4-d recovery period.

Cu


Input: In contrast, those previously exposed to 12 mu g dissolved Cu/L exhibited 50% mortality indicating that they had already reached a' point of no return'.

Cu


Input: Pre-exposure to copper did not influence mussel response to the copper challenge test.

copper

copper


Input: As observed for the chronic exposure, mortality of mussels held in the absence of copper and submitted to the challenge test was also associated with an ionoregulatory disturbance.

copper


Input: These results indicate that ionoregulatory disruption in freshwater mussels chronically exposed to copper is the main mechanism of toxicity and that redox parameters do not appear to be useful as indicators of sub-lethal copper toxicity in these animals.

copper

copper


Input: Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host.

nitrogen


Input: Alimentary and endogenous proteins are mixed in the small intestinal lumen with the microbiota.


Input: Although experimental evidences suggest that the intestinal microbiota is able to incorporate and degrade some of the available amino acids, it appears that the microbiota is also able to synthesize amino acids raising the view that amino acid exchange between the microbiota and host can proceed in both directions.

amino acids

amino acids

amino acid


Input: Although the net result of such exchanges remains to be determined, it is likely that a significant part of the amino acids recovered from the alimentary proteins are used by the microbiota.

amino acids


Input: In the large intestine, where the density of bacteria is much higher than in the small intestine and the transit time much longer, the residual undigested luminal proteins and peptides can be degraded in amino acids by the microbiota.

amino acids


Input: These amino acids cannot be absorbed to a significant extent by the colonic epithelium, but are precursors for the synthesis of numerous metabolic end products in reactions made by the microbiota.

amino acids


Input: Among these products, some like short-chain fatty acids and organic acids are energy substrates for the colonic mucosa and several peripheral tissues while others like sulfide and ammonia can affect the energy metabolism of colonic epithelial cells.

fatty acids

sulfide

ammonia


Input: More work is needed to clarify the overall effects of the intestinal microbiota on nitrogenous compound metabolism and consequences on gut and more generally host health.


Input: Interactions of the intact FsrC membrane histidine kinase with the tricyclic peptide inhibitor siamycin I revealed through synchrotron radiation circular dichroism.


Input: The suitability of synchrotron radiation circular dichroism spectroscopy (SRCD) for studying interactions between the tricyclic peptide inhibitor siamycin I and the intact FsrC membrane sensor kinase in detergent micelles has been established.


Input: In the present study, tertiary structural changes demonstrate that inhibitor binding occurs at a different, non-overlapping site to the native ligand, GBAP.


Input: Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both?


Input: Many members of the nudix hydrolase family exhibit considerable substrate multispecificity and ambiguity, which raises significant issues when assessing their functions in vivo and gives rise to errors in database annotation.


Input: Several display low antimutator activity when expressed in bacterial tester strains as well as some degree of activity in vitro towards mutagenic, oxidized nucleotides such as 8-oxo-dGTP.

oxidized nucleotides


Input: However, many of these show greater activity towards other nucleotides such as ADP-ribose or diadenosine tetraphosphate (Ap (4) A).

nucleotides

ADP

ribose

diadenosine tetraphosphate

Ap (4) A


Input: The antimutator activities have tended to gain prominence in the literature, whereas they may in fact represent the residual activity of an ancestral antimutator enzyme that has become secondary to the more recently evolved major activity after gene duplication.


Input: Whether any meaningful antimutagenic function has also been retained in vivo requires very careful assessment.


Input: Then again, other examples of substrate ambiguity may indicate as yet unexplored regulatory systems.


Input: For example, bacterial Ap (4) A hydrolases also efficiently remove pyrophosphate from the 5' termini of mRNAs, suggesting a potential role for Ap (4) A in the control of bacterial mRNA turnover, while the ability of some eukaryotic mRNA decapping enzymes to degrade IDP and dIDP or diphosphoinositol polyphosphates (DIPs) may also be indicative of new regulatory networks in RNA metabolism.

Ap (4) A

pyrophosphate

Ap (4) A

IDP

dIDP

diphosphoinositol polyphosphates

DIPs


Input: DIP phosphohydrolases also degrade diadenosine polyphosphates and inorganic polyphosphates, suggesting further avenues for investigation.

DIP

diadenosine polyphosphates

polyphosphates


Input: This article uses these and other examples to highlight the need for a greater awareness of the possible significance of substrate ambiguity among the nudix hydrolases as well as the need to exert caution when interpreting incomplete analyses.


Input: ATP hydrolysis enhances RNA recognition and antiviral signal transduction by the innate immune sensor, laboratory of genetics and physiology 2 (LGP2).

ATP


Input: Laboratory of genetics and physiology 2 (LGP2) is a member of the RIG-I-like receptor family of cytoplasmic pattern recognition receptors that detect molecular signatures of virus infection and initiate antiviral signal transduction cascades.


Input: The ATP hydrolysis activity of LGP2 is essential for antiviral signaling, but it has been unclear how the enzymatic properties of LGP2 regulate its biological response.

ATP


Input: Quantitative analysis of the dsRNA binding and enzymatic activities of LGP2 revealed high dsRNA-independent ATP hydrolysis activity.

ATP


Input: Biochemical assays and single-molecule analysis of LGP2 and mutant variants that dissociate basal from dsRNA-stimulated ATP hydrolysis demonstrate that LGP2 utilizes basal ATP hydrolysis to enhance and diversify its RNA recognition capacity, enabling the protein to associate with intrinsically poor substrates.

ATP

ATP


Input: This property is required for LGP2 to synergize with another RIG-I-like receptor, MDA5, to potentiate IFN beta transcription in vivo during infection with encephalomyocarditis virus or transfection with poly (I: C).


Input: These results demonstrate previously unrecognized properties of LGP2 ATP hydrolysis and RNA interaction and provide a mechanistic basis for a positive regulatory role for LGP2 in antiviral signaling.


Input: Aminoacyl-tRNA Substrate and Enzyme Backbone Atoms Contribute to Translational Quality Control by YbaK.

Aminoacyl


Input: Amino acids are covalently attached to their corresponding transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases.

Amino acids

aminoacyl


Input: Proofreading mechanisms exist to ensure that high fidelity is maintained in this key step in protein synthesis.


Input: Prolyl-tRNA synthetase (ProRS) can misacylate cognate tRNA (Pro) with Ala and Cys.

Prolyl

ProRS

Ala

Cys


Input: The cis-editing domain of ProRS (INS) hydrolyzes Ala-tRNA (Pro), whereas Cys-tRNA (Pro) is hydrolyzed by a single domain editing protein, YbaK, in trans.

Ala

Cys

Pro


Input: Previous studies have proposed a model of substrate-binding by bacterial YbaK and elucidated a substrate-assisted mechanism of catalysis.


Input: However, the microscopic steps in this mechanism have not been investigated.


Input: In this work, we carried out biochemical experiments together with a detailed hybrid quantum mechanics/molecular mechanics study to investigate the mechanism of catalysis by Escherichia coli YbaK.


Input: The results support a mechanism wherein cyclization of the substrate Cys results in cleavage of the Cys-tRNA ester bond.

Cys

Cys

ester


Input: Protein side chains do not play a significant role in YbaK catalysis.


Input: Instead, protein backbone atoms play crucial roles in stabilizing the transition state, while the product is stabilized by the 2'-OH of the tRNA.


Input: Maturation-associated changes in the internal distribution of tetrodotoxin in the female goby Yongeichthys criniger.

tetrodotoxin


Input: Maturation-associated changes in the internal distribution of tetrodotoxin (TTX) in the goby Yongeichthys criniger were investigated in 29 and 40 female specimens collected from Okinawa, Japan, from August 2008 to June 2009 (Group I), and from November 2009 to August 2010 (Group II), respectively.

tetrodotoxin

TTX


Input: In Group I, based on changes in the gonadosomatic index (GSI) and histologic observation of the ovary, the period from October 2008 through January 2009 was estimated to be the' previtelline-forming period', February through March 2009 the' vitelline-forming period', April through June 2009 the' spawning period', and August 2008 the' end of spawning period' of the preceding year.


Input: The TTX content (mouse unit [MU] per gram tissue) of each Y. criniger tissue (skin, muscle, liver, and ovary) quantified by liquid chromatography/mass spectrometry (LC/MS) was generally high during the spawning period and continued to rise until the end of spawning period, especially in the ovary.

TTX


Input: Total TTX per individual increased considerably during the spawning period, most of which located in the ovary, indicating that Y. criniger obtains a high amount of TTX during the spawning period, and accumulates most of it in the ovary.

TTX

TTX


Input: In contrast, the TTX content of the skin was highest at the end of spawning period, and most of the total TTX located in the skin during this period as well as during the previtelline-forming period.

TTX

TTX


Input: In Group II, the maturation stage of the ovaries of all specimens was determined, and the specimens were grouped accordingly.


Input: In the perinucleolus stage, yolk vesicle stage, and yolk globule stage I, most of the TTX was localized in the skin, but the TTX in the ovary greatly increased as the maturation stage advanced from yolk globule stage I to yolk globule stage III.

TTX

TTX


Input: Effect of clonidine in mice injected with Tityus discrepans scorpion venom.

clonidine


Input: A study was conducted to assess the effect of clonidine (alpha (2)-adrenoceptor selective agonist) on glycemia, serum and urine alpha-amylase, blood urea nitrogen (BUN), serum creatinine, white blood cell count, kidney histology and zymogen granule content in pancreatic acini, in mice under the effect of Tityus discrepans (Td) scorpion venom.

clonidine

urea nitrogen

creatinine


Input: BALB/c male mice (20 +/- 2 g, n = 7-11) were intraperitoneally (ip) injected with a sublethal dose (1 mu g/g) of Td venom, and were treated (ip) with 0. 1 mu g/g of clonidine (Catapresan ((R))) or 0. 9% NaCl 30 min after the venom injection, and then every 2 h.

clonidine

Catapresan

NaCl


Input: Six hours later, mice were anesthetized with diethylether and urine and blood samples were withdrawn by cystocentesis and cardiocentesis, respectively.

diethylether


Input: Tissue samples were obtained and fixed immediately in buffered formalin (2%, pH 7. 4) and then processed for stain H & E.

formalin


Input: Td venom did not cause hyperglycemia by itself.


Input: However, clonidine induced hyperglycemia, which was synergized by Td venom.

clonidine


Input: Although the venom did not produce hyperamylasemia, clonidine significantly diminished serum alpha-amylase activity in envenomed mice.

clonidine


Input: Td venom did not significantly increase urinary alpha-amylase activity, which was unaffected by clonidine.

clonidine


Input: Morphometric analysis using microphotographs of pancreata from mice injected with Td venom showed a reduced zymogen granule content as judged by the acidophilic bidimensional area of acini.


Input: This effect was significantly reduced by clonidine.

clonidine


Input: Kidney samples showed histological changes which were partially affected by the drug.


Input: Clonidine reduced the increase in BUN and serum creatinine concentration in envenomed mice.

Clonidine

creatinine


Input: Td venom produced neutrophilia and lymphopenia, which were clonidine-resistant at the assayed dose.

clonidine


Input: These results suggest that alpha (2)-adrenoceptor selective agonists would be able to reduce some scorpion venom-induced renal and pancreatic disturbances, possibly through the inhibition of neurotransmitter release from presynaptic cholinergic and noradrenergic terminals, as well as from adrenal medulla.


Input: Pyrimidine salvage in Trypanosoma brucei bloodstream forms and the trypanocidal action of halogenated pyrimidines.

Pyrimidine

halogenated pyrimidines


Input: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host.

pyrimidine

pyrimidines


Input: However, uptake of pyrimidines in bloodstream form trypanosomes has not been investigated, making it difficult to judge the relative importance of salvage and synthesis or to design a pyrimidine-based chemotherapy.

pyrimidines

pyrimidine


Input: Detailed characterization of pyrimidine transport activities in bloodstream form Trypanosoma brucei brucei found that these cells express a high-affinity uracil transporter (designated TbU3) that is clearly distinct from the procyclic pyrimidine transporters.

pyrimidine

uracil

pyrimidine


Input: This transporter had low affinity for uridine and 2' deoxyuridine and was the sole pyrimidine transporter expressed in these cells.

uridine

2' deoxyuridine

pyrimidine


Input: In addition, thymidine was taken up inefficiently through a P1-type nucleoside transporter.

thymidine

nucleoside


Input: Of importance, the anticancer drug 5-fluorouracil was an excellent substrate for TbU3, and several 5-fluoropyrimidine analogs were investigated for uptake and trypanocidal activity; 5F-orotic acid, 5F-2' deoxyuridine displayed activity in the low micromolar range.

5F-orotic acid

5F-2' deoxyuridine


Input: The metabolism and mode of action of these analogs was determined using metabolomic assessments of T. brucei clonal lines adapted to high levels of these pyrimidine analogs, and of the sensitive parental strains.

pyrimidine


Input: The analysis showed that 5-fluorouracil is incorporated into a large number of metabolites but likely exerts toxicity through incorporation into RNA.


Input: 5F-2' dUrd and 5F-2' dCtd are not incorporated into nucleic acids but act as prodrugs by inhibiting thymidylate synthase as 5F-dUMP.

5F-2' dUrd

5F-2' dCtd


Input: We present the most complete model of pyrimidine salvage in T. brucei to date, supported by genome-wide profiling of the predicted pyrimidine biosynthesis and conversion enzymes.

pyrimidine

pyrimidine


Input: Impact of thyroid dysfunction on erythropoietin dosage in hemodialysis patients.


Input: Background: Although thyroid diseases exist in patients with renal failure, thyroid function tests are not routine tests in patients on chronic hemodialysis (HD).


Input: Therefore, the impact of thyroid diseases on erythropoietin (EPO) dosage in HD patients is not well defined.


Input: This study evaluated the relationship between the dose of EPO and the presence or absence of thyroid dysfunction in HD patients.


Input: Methods: This study included 1013 adult patients on HD who did not have a malignancy, liver cirrhosis, thalassemia, iron deficiency, gastrointestinal bleeding, or a major operation within 6 months.

iron


Input: Patients were characterized as being euthyroid, or having the sick euthyroid syndrome, primary hypothyroidism, subclinical hypothyroidism, hyperthyroidism, or subclinical hyperthyroidism based on thyroid function tests.


Input: Routine biochemistry profiles including an index of the efficiency of HD, along with clinical data over the previous 6-month period, were collected and analyzed.


Input: Multiple regression models were employed to assess the relationship between the dose of EPO and the presence or absence of thyroid status.


Input: Results: The mean monthly EPO dosages were 77. 7 +/- 37. 0, 70. 2 +/- 40. 6, 90. 8 +/- 68. 4, 78. 5 +/- 46. 7, and 82. 3 +/- 41. 2 mu g, respectively, in the sick euthyroid syndrome, euthyroid patients, hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism groups (p < 0. 05).


Input: After adjustment of all other variables in multiple regression, the mean monthly EPO dosage was 19. 00 +/- 8. 59 mu g more in hypothyroid patients compared with euthyroid patients (p = 0. 027).


Input: Further, considering an interaction with the presence of diabetes, the mean monthly EPO dosage in patients with either hypothyroidism or subclinical hypothyroidism and diabetes was 54. 66 +/- 17. 12 mu g (p = 0. 001) and 31. 51 +/- 10. 38 mu g more than that of euthyroid patients, respectively (p = 0. 002).


Input: Conclusions: In HD patients, the EPO dosage required to maintain the target hemoglobin level is significantly higher in patients having both hypothyroidism or subclinical hypothyroidism and diabetes than in euthyroid patients.


Input: Phenolic compounds: the role of redox regulation in neurodegenerative disease and cancer.

Phenolic


Input: Much work has been carried out in the last two decades on the role of oxidative stress and antioxidants deficiency in the pathophysiology of civilization diseases.


Input: A considerable amount of chemical, biochemical, epidemiological and clinical evidence indicates that (poly) phenolic compounds widely distributed in the plant kingdom, exhibit a wide range effects on biomolecules.

(poly) phenolic


Input: The beneficial effects on human health, many of phenolics have been described to their reactive oxygen (ROS) and nitrogen species (RNS) scavenging and antioxidant capacity.

oxygen

nitrogen


Input: The consumption of vegetables, fruits and flavonoid-rich beverages has been reported to prevent against neurodegenerative diseases, cancer, and ageing.

flavonoid


Input: This paper reviews the recent data on (1) the role oxidative stress in the pathology of civilization diseases; (2) the protection against oxidative damage due to the toxicity of ROS/RNS; (3) the cellular and molecular interactions of the (poly) phenolic compounds relevant to the prevention of neurodegenerative diseases and cancer, and (4) the methods for assessing antioxidant capacity.

(poly) phenolic


Input: 17 beta-Oestradiol anti-inflammatory effects in primary astrocytes require oestrogen receptor beta-mediated neuroglobin up-regulation.

17 beta-Oestradiol

oestrogen


Input: Neuroglobin (Ngb), so named after its initial discovery in brain neurones, has received great attention as a result of its neuroprotective effects both in vitro and in vivo.


Input: Recently, we demonstrated that, in neurones, Ngb is a 17 beta-oestradiol (E (2)) inducible protein that is pivotal for hormone-induced anti-apoptotic effects against H (2) O (2) toxicity.

17 beta-oestradiol

H (2) O (2)


Input: The involvement of Ngb in other brain cell populations, as well as in other neuroprotective effects of E (2), is completely unknown at present.


Input: We demonstrate Ngb immunoreactivity in reactive astrocytes located in the proximity of a penetrating cortical injury in vivo and the involvement of Ngb in the E (2)-mediated anti-inflammatory effect in primary cortical astrocytes.


Input: Upon binding to oestrogen receptor (ER) beta, E (2) enhances Ngb levels in a dose-dependent manner.

oestrogen


Input: Although with a lesser degree than E (2), the pro-inflammatory stimulation with lipopolysaccharide (LPS) also induces the increase of Ngb protein levels via nuclear factor-(NF) kappa B signal (s).


Input: Moreover, a negative cross-talk between ER subtypes and NF kappa B signal (s) has been demonstrated.


Input: In particular, ER alpha-activated signals prevent the NF kappa B-mediated Ngb increase, whereas LPS impairs the ER beta-induced up-regulation of Ngb.


Input: Therefore, the co-expression of both ER alpha and ER beta is pivotal for mediating E (2)-induced Ngb expression in the presence of NF kappa B-activated signals.


Input: Interestingly, Ngb silencing prevents the effect of E (2) on the expression of inflammatory markers (i. e. interleukin 6 and interferon gamma-inducible protein 10).


Input: Ngb can be regarded as a key mediator of the different protective effects of E (2) in the brain, including protection against oxidative stress and the control of inflammation, both of which are at the root of several neurodegenerative diseases.


Input: Synthesis and thermal decomposition behaviors of magnesium borohydride ammoniates with controllable composition as hydrogen storage materials.

magnesium borohydride ammoniates

hydrogen


Input: An ammonia-redistribution strategy for synthesizing metal borohydride ammoniates with controllable coordination number of NH (3) was proposed, and a series of magnesium borohydride ammoniates were easily synthesized by a mechanochemical reaction between Mg (BH (4)) (2) and its hexaammoniate.

ammonia

metal borohydride ammoniates

NH (3)

magnesium borohydride ammoniates

Mg (BH (4)) (2)

hexaammoniate


Input: A strong dependence of the dehydrogenation temperature and purity of the released hydrogen upon heating on the coordination number of NH (3) was elaborated for Mg (BH (4)) (2). xNH (3) owing to the change in the molar ratio of H (delta +) and H (delta-), the charge distribution on H (delta +) and H (delta-), and the strength of the coordinate bond N: --> Mg (2 +).

NH (3)

Mg (BH (4)) (2). xNH (3)

H (delta +)

H (delta-)

H (delta +)

H (delta-)

N: --> Mg (2 +)


Input: The monoammoniate of magnesium borohydride (Mg (BH (4)) (2). NH (3)) was obtained for the first time.

magnesium borohydride

Mg (BH (4)) (2). NH (3)


Input: It can release 6. 5% pure hydrogen within 50 minutes at 180 degrees C.

hydrogen


Input: The role of prolactin receptor in GH signaling in breast cancer cells.


Input: GH and prolactin (PRL) are structurally related hormones that exert important effects in disparate target tissues.


Input: Their receptors (GHR and PRLR) reside in the cytokine receptor superfamily and share signaling pathways.


Input: In humans, GH binds both GHR and PRLR, whereas PRL binds only PRLR.


Input: Both hormones and their receptors may be relevant in certain human and rodent cancers, including breast cancer.


Input: GH and PRL promote signaling in human T47D breast cancer cells that express both GHR and PRLR.


Input: Furthermore, GHR and PRLR associate in a fashion augmented acutely by GH, even though GH primarily activates PRLR, rather than GHR, in these cells.


Input: To better understand PRLR' s impact, we examined the effects of PRLR knockdown on GHR availability and GH sensitivity in T47D cells.


Input: T47D-ShPRLR cells, in which PRLR expression was reduced by stable short hairpin RNA (shRNA) expression, were compared with T47D-SCR control cells.


Input: PRLR knockdown decreased the rate of GHR proteolytic turnover, yielding GHR protein increase and ensuing sensitization of these cells to GHR signaling events including phosphorylation of GHR, Janus kinase 2, and signal transducer and activator of transcription 5 (STAT5).


Input: Unlike in T47D-SCR cells, acute GH signaling in T47D-ShPRLR cells was not blocked by the PRLR antagonist G129R but was inhibited by the GHR-specific antagonist, anti-GHR (ext-mAb).


Input: Thus, GH' s use of GHR rather than PRLR was manifested when PRLR was reduced.


Input: In contrast to acute effects, GH incubation for 2 h or longer yielded diminished STAT5 phosphorylation in T47D-ShPRLR cells compared with T47D-SCR, a finding perhaps explained by markedly greater GH-induced GHR down-regulation in cells with diminished PRLR.


Input: However, when stimulated with repeated 1-h pulses of GH separated by 3-h washout periods to more faithfully mimic physiological GH pulsatility, T47D-ShPRLR cells exhibited greater transactivation of a STAT5-responsive luciferase reporter than did T47D-SCR cells.


Input: Our data suggest that PRLR' s presence meaningfully affects GHR use in breast cancer cells.


Input: MLL histone methylases regulate expression of HDLR-SR-B1 in presence of estrogen and control plasma cholesterol in vivo.

estrogen

cholesterol


Input: High-density lipoprotein receptors scavenger receptor class B type I [HDLR-SR-B1 (SR-B1)] is a key player in reverse cholesterol transport and maintaining blood cholesterol.

cholesterol

cholesterol


Input: We demonstrated that human SR-B1 is transcriptionally activated by 17 beta-estradiol (E2) in HEPG2 and JAR cells.

17 beta-estradiol


Input: SR-B1 promoter contains multiple estrogen response elements (ERE half-sites) along with some Sp1 binding sites.

estrogen


Input: Knockdown of estrogen receptor (ER) alpha and ER beta down-regulated E2-induced SR-B1 expression.

estrogen


Input: ERs were bound to SR-B1 promoter EREs in an E2-dependent manner.


Input: Along with ERs, mixed-lineage leukemia (MLL) histone methylases, especially MLL1 and MLL2, play key roles in E2-mediated SR-B1 activation.


Input: MLL1 and MLL2 bind to SR-B1 promoter in an E2-dependent manner and control the assembly of transcription pre-initiation complex and RNA polymerase II (RNAPII) recruitment.


Input: ERs and MLLs play critical roles in determining the cholesterol uptake by steroidogenic tissues/cells, and their knockdown suppressed the E2-induced cholesterol uptake efficiencies of the cells.

cholesterol

cholesterol


Input: Intriguingly, MLL2 knockdown in mice resulted in a 33% increase in plasma cholesterol level and also reduced SR-B1 expression in mice liver, demonstrating its crucial functions in controlling plasma cholesterol in vivo.

cholesterol

cholesterol


Input: Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study.


Input: Type 2 diabetes (T2D) disproportionally affects African Americans (AfA) but, to date, genetic variants identified from genome-wide association studies (GWAS) are primarily from European and Asian populations.


Input: We examined the single nucleotide polymorphism (SNP) and locus transferability of 40 reported T2D loci in six AfA GWAS consisting of 2, 806 T2D case subjects with or without end-stage renal disease and 4, 265 control subjects from the Candidate Gene Association Resource Plus Study.


Input: Our results revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loci were significantly associated with T2D (P < 0. 05).


Input: The strongest association was observed at TCF7L2 rs7903146 (odds ratio [OR] 1. 30; P = 6. 86 x 10-8).


Input: Locus-wide analysis demonstrated significant associations (P (emp) < 0. 05) at regional best SNPs in the TCF7L2, KLF14, and HMGA2 loci as well as suggestive signals in KCNQ1 after correction for the effective number of SNPs at each locus.


Input: Of these loci, the regional best SNPs were in differential linkage disequilibrium (LD) with the index and adjacent SNPs.


Input: Our findings suggest that some loci discovered in prior reports affect T2D susceptibility in AfA with similar effect sizes.


Input: The reduced and differential LD pattern in AfA compared with European and Asian populations may facilitate fine mapping of causal variants at loci shared across populations.


Input: Clone DB: an integrated NCBI resource for clone-associated data.


Input: The National Center for Biotechnology Information (NCBI) Clone DB (http://www. ncbi. nlm. nih. gov/clone/) is an integrated resource providing information about and facilitating access to clones, which serve as valuable research reagents in many fields, including genome sequencing and variation analysis.


Input: Clone DB represents an expansion and replacement of the former NCBI Clone Registry and has records for genomic and cell-based libraries and clones representing more than 100 different eukaryotic taxa.


Input: Records provide details of library construction, associated sequences, map positions and information about resource distribution.


Input: Clone DB is indexed in the NCBI Entrez system and can be queried by fields that include organism, clone name, gene name and sequence identifier.


Input: Whenever possible, genomic clones are mapped to reference assemblies and their map positions provided in clone records.


Input: Clones mapping to specific genomic regions can also be searched for using the NCBI Clone Finder tool, which accepts queries based on sequence coordinates or features such as gene or transcript names.


Input: Clone DB makes reports of library, clone and placement data on its FTP site available for download.


Input: With Clone DB, users now have available to them a centralized resource that provides them with the tools they will need to make use of these important research reagents.


Input: KEGG OC: a large-scale automatic construction of taxonomy-based ortholog clusters.


Input: The identification of orthologous genes in an increasing number of fully sequenced genomes is a challenging issue in recent genome science.


Input: Here we present KEGG OC (http://www. genome. jp/tools/oc/), a novel database of ortholog clusters (OCs).


Input: The current version of KEGG OC contains 1 176 030 OCs, obtained by clustering 8 357 175 genes in 2112 complete genomes (153 eukaryotes, 1830 bacteria and 129 archaea).


Input: The OCs were constructed by applying the quasi-clique-based clustering method to all possible protein coding genes in all complete genomes, based on their amino acid sequence similarities.

amino acid


Input: It is computationally efficient to calculate OCs, which enables to regularly update the contents.


Input: KEGG OC has the following two features: (i) It consists of all complete genomes of a wide variety of organisms from three domains of life, and the number of organisms is the largest among the existing databases; and (ii) It is compatible with the KEGG database by sharing the same sets of genes and identifiers, which leads to seamless integration of OCs with useful components in KEGG such as biological pathways, pathway modules, functional hierarchy, diseases and drugs.


Input: The KEGG OC resources are accessible via OC Viewer that provides an interactive visualization of OCs at different taxonomic levels.


Input: An isoquinoline alkaloid from the Chinese herbal plant Corydalis yanhusuo W. T.

isoquinoline alkaloid


Input: Wang inhibits P-glycoprotein and multidrug resistance-associate protein 1.


Input: Overexpression of P-glycoprotein (P-gp) and multidrug resistance-associate protein 1 (MRP1) is a major mechanism leading to multidrug resistance (MDR) of cancer cells.


Input: These transporters expel anti-cancer drugs and greatly impair therapeutic efficacy of chemotherapy.


Input: A Chinese herbal plant Yanhusuo (Corydalis yanhusuo W. T. Wang, YHS) is frequently used in functional food and traditional Chinese medicine to improve the efficacy of chemotherapy.


Input: The objective of this work was to study effects of glaucine, an alkaloid component of YHS, on P-gp and MRP1 in resistant cancer cells.

glaucine


Input: The resistant cancer cell line, MCF-7/ADR and corresponding parental sensitive cells were employed to determine reversal properties of glaucine.

glaucine


Input: Glaucine inhibits P-gp and MRP1-mediated efflux and activates ATPase activities of the transporters, indicating that it is a substrate and inhibits P-gp and MRP1 competitively.

Glaucine


Input: Furthermore, glaucine suppresses expression of ABC transporter genes.


Input: It reverses the resistance of MCF-7/ADR to adriamycin and mitoxantrone effectively.

adriamycin

mitoxantrone


Input: Antioxidant activity and effective compounds of immature calamondin peel.


Input: The antioxidant activity and the flavonoids of mature and immature calamondin (Citrus mitis Blanco) peel were investigated.

flavonoids


Input: The hot water extract of immature calamondin peel exhibited the highest oxygen radical absorbance capacity (ORAC), reducing power, and superoxide scavenging effect.

oxygen

superoxide