Input: Two new ent-3, 4-seco-labdane diterpenoids from Callicarpa nudiflora.

ent-3, 4-seco-labdane diterpenoids


Input: Two new ent-3, 4-seco-labdane diterpenoids, methylcallicarpate (1) and callicarpic acid (2), were isolated from the leaves of Callicarpa nudiflora Hook et Arn.

ent-3, 4-seco-labdane diterpenoids

methylcallicarpate

callicarpic acid


Input: Their structures and relative configurations were established by analysis of spectroscopic data.


Input: Their absolute configurations were assigned by the application of the CD technique for the first time among the ent-3, 4-seco-labdane-type diterpenes.

ent-3, 4-seco-labdane

diterpenes


Input: Paeoniflorin acts as a liver X receptor agonist.

Paeoniflorin


Input: Paeoniflorin is one of the active ingredients of Paeonia lactiflora Pall., a novel traditional herbal medicine exerting pharmacological effects including antihyperlipidemic, neuroprotective, and anti-hepatofibrosis effects.

Paeoniflorin


Input: Liver X receptor (LXR) acts as a ligand-activated transcription factor to exhibit antihyperlipidemic and neuroprotective effects.


Input: In this study, the activity of paeoniflorin against LXR was evaluated by the mammalian one-hybrid and transient transfection reporter assays.

paeoniflorin


Input: The results showed that paeoniflorin transactivated GAL4, rat cholesterol 7 alpha-hydroxylase, phospholipid transfer protein, and ATP-binding cassette A1 gene promoters in dose-dependent manner.

paeoniflorin

cholesterol

ATP


Input: Furthermore, the docking study demonstrated that paeoniflorin resided in the LXR ligand-binding pocket in the similar manner as GSK 3987, a novel LXR agonist.

paeoniflorin

GSK 3987


Input: These results indicated that paeoniflorin might exert pharmacological effects through LXR pathway.

paeoniflorin


Input: Spreading and structuring of water on superhydrophilic polyelectrolyte brush surfaces.


Input: The wetting behavior of superhydrophilic polyelectrolyte brushes was investigated.


Input: Reflection interference contrast microscopy demonstrated that the contact angles of water on the polyelectrolyte brushes were extremely low but remained finite in the range of < 3 degrees.


Input: The presence of water molecules was evident, even outside the macroscopic water droplet.


Input: These water molecules were confined to the thin brush layers and contained a highly ordered hydrogen bond network, which was identified as structural water.

hydrogen


Input: The presence of the thin film and the structural water changed the surface energies, which prevented the complete wetting of the surface.


Input: Design and development of multiple emulsion for enhancement of oral bioavailability of acyclovir.

acyclovir


Input: The objective of this investigation was to design and develop water-in-oil-in-water type multiple emulsions (w/o/w emulsions) entrapping acyclovir for improving its oral bioavailability.

acyclovir


Input: Multiple emulsions (MEs) were prepared and optimized using Span-80 and Span-83 as lipophilic surfactant and Brij-35 as hydrophilic surfactant.


Input: The physio-chemical properties of the w/o/w emulsions-particle size, viscosity, phase separation (centrifugation test) and entrapment efficiency were measured and evaluated along with macroscopic and microscopic observations to confirm multiple nature, homogeneity and globule size.


Input: Stability study, in vitro and ex vivo release studies were performed followed by in vivo studies in rats.


Input: Stable w/o/w emulsions with a particle size of 33. 098 +/- 2. 985 micro m and 85. 25 +/- 4. 865% entrapment efficiency were obtained.


Input: Stability studies showed that the concentration of lipophilic surfactant was very important for stability of MEs.


Input: Drug release from the prepared formulations showed initial rapid release followed by a much slower release.


Input: In vivo studies in rats indicated prolonged release and better oral bioavailability as compared to drug solution.


Input: The overall results of this study show the potential of the w/o/w emulsions as promising drug delivery systems for acyclovir.

acyclovir


Input: Structural studies of mixed glass former 0. 35Na2O + 0. 65 [xB2O3 + (1-x) P2O5] glasses by Raman and 11B and 31P magic angle spinning nuclear magnetic resonance spectroscopies.

[xB2O3 + (1-x) P2O5]


Input: The mixed glass former (MGF) effect (MGFE) is defined as a nonlinear and nonadditive change in the ionic conductivity with changing glass former composition at constant modifier composition.


Input: In this study, sodium borophosphate 0. 35Na (2) O + 0. 65 [xB (2) O (3) + (1-x) P (2) O (5)], 0 <= x <= 1, glasses which have been shown to exhibit a positive MGFE have been prepared and examined using Raman and (11) B and (31) P magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopies.

sodium borophosphate

35Na (2) O

[xB (2) O (3) + (1-x) P (2) O (5)]

(11) B

(31) P


Input: Through examination of the short-range order (SRO) structures found in the ternary glasses, it was determined that the minority glass former, B for 0. 1 <= x <= 0. 7 and P for 0. 7 <= x <= 0. 9, is " overmodified " and contains more Na (+) ions than would be expected from simple linear mixing of the binary sodium borate, x = 1, and sodium phosphate, x = 0, glasses, respectively.

B

P

Na (+)

sodium borate

sodium phosphate


Input: Changes in the intermediate range order (IRO) structures were suggested by changes in the NMR spectral chemical shifts and Raman spectra wavenumber shifts over the full composition range x in the Raman and MAS NMR spectra.


Input: The changes observed in the chemical shifts of (31) P MAS NMR spectra with x are found to be too large to be caused solely by changing sodium modification of the phosphate SRO structural groups, and this indicates that internetwork bonding between phosphorus and boron through bridging oxygens (BOs), P-O-B, must be a major contributor to the IRO structure of these glasses.

(31) P

sodium

phosphorus

boron

oxygens

P-O-B


Input: While not fully developed, a first-order thermodynamic analysis based upon the Gibbs free energies of formation of the various SRO structural units in this system has been developed and can be used to account for the preferential formation of tetrahedral boron groups, B (4), by the reaction of B (3) with P (2) groups to form B (4) and P (3) groups, respectively, where the superscript denotes the number of BOs on these units, in these glasses.

boron

B

B

P

B

P


Input: This preference for B (4) units appears to be a predominate cause of the changing modifier to glass former ratio with composition x in these ternary MGF glasses and appears to be associated with the large negative value of the Gibbs free energy of formation of this group.

B


Input: X-ray absorption near edge structure spectroscopy to resolve the in vivo chemistry of the redox-active indazolium trans-[Tetrachlorobis (1H-indazole) ruthenate (III)] (KP1019).

indazolium trans-[Tetrachlorobis (1H-indazole) ruthenate (III)]


Input: Indazolium trans-[tetrachlorobis (1H-indazole) ruthenate (III)] (1, KP1019) and its analogue sodium trans-[tetrachlorobis (1H-indazole) ruthenate (III)] (2, KP1339) are promising redox-active anticancer drug candidates that were investigated with X-ray absorption near edge structure spectroscopy.

Indazolium trans-[tetrachlorobis (1H-indazole) ruthenate (III)]

sodium trans-[tetrachlorobis (1H-indazole) ruthenate (III)]


Input: The analysis was based on the concept of the coordination charge and ruthenium model compounds representing possible coordinations and oxidation states in vivo.

ruthenium


Input: 1 was investigated in citrate saline buffer (pH 3. 5) and in carbonate buffer (pH 7. 4) at 37 degrees C for different time intervals.

citrate

carbonate


Input: Interaction studies on 1 with glutathione in saline buffer and apo-transferrin in carbonate buffer were undertaken, and the coordination of 1 and 2 in tumor tissues was studied too.

glutathione

carbonate


Input: The most likely coordinations and oxidation states of the compound under the above mentioned conditions were assigned.


Input: Microprobe X-ray fluorescence of tumor thin sections showed the strong penetration of ruthenium into the tumor tissue, with the highest concentrations near blood vessels and in the edge regions of the tissue samples.

ruthenium


Input: Evaluation of animal models for intestinal first-pass metabolism of drug candidates to be metabolized by CYP3A enzymes via in vivo and in vitro oxidation of midazolam and triazolam.

midazolam

triazolam


Input: Abstract 1.


Input: To search an appropriate evaluation methodology for the intestinal first-pass metabolism of new drug candidates, grapefruit juice (GFJ)-and vehicle (tap water)-pretreated mice or rats were orally administered midazolam (MDZ) or triazolam (TRZ), and blood levels of the parent compounds and their metabolites were measured by liquid chromatography/MS/MS.

midazolam

MDZ

triazolam

TRZ


Input: A significant effect of GFJ to elevate the blood levels was observed only for TRZ in mice.

TRZ


Input: In vitro experiments using mouse, rat and human intestinal and hepatic microsomal fractions demonstrated that GFJ suppressed the intestinal microsomal oxidation of MDZ and especially TRZ.

MDZ

TRZ


Input: Substrate inhibition by MDZ caused reduction in 1'-hydroxylation but not 4-hydroxylation in both intestinal and hepatic microsomal fractions.

MDZ


Input: The kinetic profiles of MDZ oxidation and the substrate inhibition in mouse intestinal and hepatic microsomal fractions were very similar to those in human microsomes but were different from those in rat microsomes.

MDZ


Input: Furthermore, MDZ caused mechanism-based inactivation of cytochrome P450 3A-dependent TRZ 1'-hydroxylation in mouse, rat and human intestinal microsomes with similar potencies.

MDZ

TRZ


Input: These results are useful information in the analysis of data obtained in mouse and rat for the evaluation of first-pass effects of drug candidates to be metabolized by CYP3A enzymes.


Input: Catalytic enantioselective cyclization and C3-fluorination of polyenes.

polyenes


Input: (Xylyl-phanephos) Pt (2 +) in combination with XeF (2) mediates the consecutive diastereoselective cation-olefin cyclization/fluorination of polyene substrates.

(Xylyl-phanephos) Pt (2 +)

XeF (2)

olefin

polyene


Input: Isolated yields were typically in the 60-69% range while enantioselectivities reached as high as 87%.


Input: The data are consistent with a stereoretentive fluorination of a P (2) Pt-alkyl cation intermediate.

P (2) Pt-alkyl


Input: A micro-cantilever sensor chip based on contact angle analysis for a label-free troponin I immunoassay.


Input: Cantilever sensors have been extensively explored as a promising technique for real-time and label-free analyses in biological systems.


Input: A major sensing principle utilized by state-of-the-art cantilever sensors is based on analyte-induced surface stress changes, which result in static bending of a cantilever.


Input: The sensor performance, however, suffers from the intrinsically small change in surface stress induced by analytes, especially for molecular recognition such as antigen-antibody binding.


Input: Through the contact angle change on a tailored solid surface, it is possible to convert a tiny surface stress into a capillary force-a much larger physical quantity needed for a practical sensor application.


Input: In this work, a micro-cantilever sensor based on contact angle analysis (CAMCS) was proposed to effectively enhance the sensitivity of a sensor in proportion to the square of the length to thickness ratio of the cantilever structure.


Input: CAMCS chips were fabricated using a standard complementary-metal-oxide-semiconductor (CMOS) process to demonstrate a 1250-fold enhancement in the sensitivity of surface stress to bioanalyte adsorption using a piezoresistive sensing method.

metal-oxide


Input: A real-time and label-free troponin I (cTnI) immunoassay, which is now widely used in clinics and considered a gold standard for the early diagnosis and prognosis of cardiovascular disease, was performed to demonstrate cTnI detection levels as low as 1 pg mL (-1).


Input: The short detection time of this assay was within several minutes, which matches the detection time of commercially available instruments that are based on fluorescence-labeling techniques.


Input: Zinc sulphate and vitamin E alleviate reproductive toxicity caused by aluminium sulphate in male albino rats.

Zinc sulphate

vitamin E

aluminium sulphate


Input: This study was designed to investigate the reproductive toxicity of aluminium sulphate and the therapeutic effects of administration of zinc sulphate and vitamin E individually or in combination against the toxic effect caused by aluminium (Al) in male albino rats.

aluminium sulphate

zinc sulphate

vitamin E

aluminium

Al


Input: The animals were divided into five groups: group 1 received distilled water and served as control; group 2 received only aluminium sulphate (50 mg/kg body weight (b. w.)); group 3 received aluminium sulphate (50 mg/kg b. w.) plus zinc sulphate (50 mg/kg b. w.); group 4 received aluminium sulphate (50 mg/kg b. w.) and vitamin E (15 mg/kg b. w.); group 5 received aluminium sulphate plus a combination of zinc sulphate and vitamin E in similar doses as above.

aluminium sulphate

aluminium sulphate

zinc sulphate

aluminium sulphate

vitamin E

aluminium sulphate

zinc sulphate

vitamin E


Input: Doses were administered orally once daily for 45 consecutive days.


Input: The results revealed that aluminium sulphate induced significant decrease in body weight gain and testis weight and significant increase in Al level in both serum and testes of male rats.

aluminium sulphate

Al


Input: Biochemical analysis showed significant decrease in serum total protein and phospholipids levels, while serum total lipid was significantly elevated post Al treatment.

Al


Input: In addition, significant decrease in total protein, phospholipids and cholesterol levels in the testes of Al-treated rats was recorded.

cholesterol

Al


Input: The data also showed significant decrease in the levels of serum testosterone, leutinizing hormone and follicle stimulating hormone and significant increase in the level of serum prolactin in Al-intoxicated rats.

testosterone

Al


Input: Moreover, histological examination showed that aluminium sulphate caused apparent alterations in the testicular structure of the treated animals.

aluminium sulphate


Input: Treatment with zinc sulphate and vitamin E individually or in combination ameliorated the harmful effects of Al, which was proved histopathologically by the noticeable improvement in the testicular tissues.

zinc sulphate

vitamin E

Al


Input: We can conclude that the tested dose of aluminium sulphate induced toxic effect on the reproductive system of male albino rats and the treatment with zinc sulphate and/or vitamin E alleviated these toxic effects.

aluminium sulphate

zinc sulphate

vitamin E


Input: In some cases, vitamin E exerted a more potent effect, while in other cases, the more potent effect is related to zinc sulphate and the combination of both at most of the recorded data.

vitamin E

zinc sulphate


Input: Trichostatin A inhibits transforming growth factor-beta-induced reactive oxygen species accumulation and myofibroblast differentiation via enhanced NF-E2-related factor 2-antioxidant response element signaling.

Trichostatin A

oxygen


Input: Trichostatin A (TSA) has been shown to prevent fibrosis in vitro and in vivo.

Trichostatin A

TSA


Input: The present study aimed at investigating the role of reactive oxygen species (ROS) scavenging by TSA on transforming growth factor-beta (TGF-beta)-induced myofibroblast differentiation of corneal fibroblasts in vitro.

oxygen

TSA


Input: Human immortalized corneal fibroblasts were treated with TGF-beta in the presence of TSA, the NAD (P) H oxidase inhibitor diphenyleneiodonium (DPI), the antioxidant N-acetyl-cysteine (NAC), the NF-E2-related factor 2-antioxidant response element (Nrf2-ARE) activator sulforaphane, or small interfering RNA.

TSA

NAD (P) H

diphenyleneiodonium

DPI

N-acetyl-cysteine

NAC

sulforaphane


Input: Myofibroblast differentiation was assessed by alpha-smooth muscle actin (alpha-SMA) expression, F-actin bundle formation, and collagen gel contraction.


Input: ROS, H (2) O (2), intracellular glutathione (GSH) level, cellular total antioxidant capacity, and the activation of Nrf2-ARE signaling were determined with various assays.

H (2) O (2)

glutathione

GSH


Input: Treatment with TSA and the Nrf2-ARE activator resulted in increased inhibition of the TGF-beta-induced myofibroblast differentiation as compared with treatment with DPI or NAC.

TSA

DPI

NAC


Input: Furthermore, TSA also decreased cellular ROS and H (2) O (2) accumulation induced by TGF-beta, whereas it elevated intracellular GSH level and cellular total antioxidant capacity.

TSA

H (2) O (2)

GSH


Input: In addition, TSA induced Nrf2 nuclear translocation and up-regulated the expression of Nrf2-ARE downstream antioxidant genes, whereas Nrf2 knockdown by RNA interference blocked the inhibition of TSA on myofibroblast differentiation.

TSA

TSA


Input: In conclusion, this study provides the first evidence implicating that TSA inhibits TGF-beta-induced ROS accumulation and myofibroblast differentiation via enhanced Nrf2-ARE signaling.

TSA


Input: Amide hydrolysis of a novel chemical series of microsomal prostaglandin E synthase-1 inhibitors induces kidney toxicity in the rat.

Amide

prostaglandin E


Input: A novel microsomal prostaglandin E synthase 1 (mPGES-1) inhibitor induced kidney injury at exposures representing less than 4 times the anticipated efficacious exposure in man during a 7-day toxicity study in rats.

prostaglandin E


Input: The findings consisted mainly of tubular lesions and the presence of crystalline material and increases in plasma urea and creatinine.

urea

creatinine


Input: In vitro and in vivo metabolic profiling generated a working hypothesis that a bis-sulfonamide metabolite (determined M1) formed by amide hydrolysis caused this toxicity.

bis-sulfonamide

amide


Input: To test this hypothesis, rats were subjected to a 7-day study and were administered the suspected metabolite and two low-potency mPGES-1 inhibitor analogs, where amide hydrolysis was undetectable in rat hepatocyte experiments.

amide


Input: The results suggested that compounds with a reduced propensity to undergo amide hydrolysis, thus having less ability to form M1, reduced the risk of inducing kidney toxicity.

amide


Input: Rats treated with M1 alone showed no histopathologic change in the kidney, which was likely related to underexposure to M1.


Input: To circumvent rat kidney toxicity, we identified a potent mPGES-1 inhibitor with a low propensity for amide hydrolysis and superior rat pharmacokinetic properties.

amide


Input: A subsequent 14-day rat toxicity study showed that this compound was associated with kidney toxicity at 42, but not 21, times the anticipated efficacious exposure in humans.


Input: In conclusion, by including metabolic profiling and exploratory rat toxicity studies, a new and active mPGES-1 inhibitor with improved margins to chemically induced kidney toxicity in rats has been identified.


Input: Using binary surfactant mixtures to simultaneously improve the dimensional tunability and monodispersity in the seeded growth of gold nanorods.


Input: We report a dramatically improved synthesis of colloidal gold nanorods (NRs) using a binary surfactant mixture composed of hexadecyltrimethylammonium bromide (CTAB) and sodium oleate (NaOL).

hexadecyltrimethylammonium bromide

CTAB

sodium oleate

NaOL


Input: Both thin (diameter < 25 nm) and thicker (diameter > 30 nm) gold NRs with exceptional monodispersity and broadly tunable longitudinal surface plasmon resonance can be synthesized using seeded growth at reduced CTAB concentrations (as low as 0. 037 M).

CTAB


Input: The CTAB-NaOL binary surfactant mixture overcomes the difficulty of growing uniform thick gold NRs often associated with the single-component CTAB system and greatly expands the dimensions of gold NRs that are accessible through a one-pot seeded growth process.

CTAB

NaOL

CTAB


Input: Gold NRs with large overall dimensions and thus high scattering/absorption ratios are ideal for scattering-based applications such as biolabeling as well as the enhancement of optical processes.


Input: Antiproliferative and antiplasmodial dimeric phloroglucinols from Mallotus oppositifolius from the Madagascar Dry Forest (1).

dimeric phloroglucinols


Input: Bioassay-guided fractionation of an ethanol extract of the leaves and inflorescence of Mallotus oppositifolius collected in Madagascar led to the isolation of the two new bioactive dimeric phloroglucinols mallotojaponins B (1) and C (2), together with the known mallotophenone (3).

ethanol

dimeric phloroglucinols mallotojaponins B (1) and C (2)

mallotophenone


Input: The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1D-and 2D-NMR spectra, mass spectrometry, and an X-ray crystal structure.


Input: Compounds 1 and 2 showed potent antimalarial activity against chloroquine-resistant Plasmodium falciparum, with IC50 values of 0. 75 +/- 0. 30 and 0. 14 +/- 0. 04 mu M, while 3 was inactive in this assay.

chloroquine


Input: Compounds 1-3 also displayed strong antiproliferative activity against the A2780 human ovarian cancer cell line (IC50 1. 10 +/- 0. 05, 1. 3 +/- 0. 1 and 6. 3 +/- 0. 4 mu M, respectively).


Input: Delayed frost growth on jumping-drop superhydrophobic surfaces.


Input: Self-propelled jumping drops are continuously removed from a condensing superhydrophobic surface to enable a micrometric steady-state drop size.


Input: Here, we report that subcooled condensate on a chilled superhydrophobic surface are able to repeatedly jump off the surface before heterogeneous ice nucleation occurs.


Input: Frost still forms on the superhydrophobic surface due to ice nucleation at neighboring edge defects, which eventually spreads over the entire surface via an interdrop frost wave.


Input: The growth of this interdrop frost front is shown to be up to 3 times slower on the superhydrophobic surface compared to a control hydrophobic surface, due to the jumping-drop effect dynamically minimizing the average drop size and surface coverage of the condensate.


Input: A simple scaling model is developed to relate the success and speed of interdrop ice bridging to the drop size distribution.


Input: While other reports of condensation frosting on superhydrophobic surfaces have focused exclusively on liquid-solid ice nucleation for isolated drops, these findings reveal that the growth of frost is an interdrop phenomenon that is strongly coupled to the wettability and drop size distribution of the surface.


Input: A jumping-drop superhydrophobic condenser minimized frost formation relative to a conventional dropwise condenser in two respects: preventing heterogeneous ice nucleation by continuously removing subcooled condensate, and delaying frost growth by limiting the success of interdrop ice bridge formation.


Input: Toxicity of copper salts is dependent on solubility profile and cell type tested.

copper salts


Input: Copper (Cu) is considered an essential metal for living organisms.

Copper

Cu


Input: However, disruption of Cu homeostasis is toxic and can lead to disorders such as Menkes and Wilson' s diseases.

Cu


Input: The brain appears to be a vulnerable target organ.


Input: This study investigated the toxicity of Cu based on its solubility profile and cell type tested.

Cu


Input: Human A-172 (glioblastoma), SK-N-SH (neuroblastoma) and CCF-STTG1 (astrocytoma) cells were assessed after exposure to different concentrations (0. 5-500 mu M) of copper sulfate (CuSO4) or copper (II) oxide (CuO).

copper sulfate

copper (II) oxide

CuO


Input: Since Cu is a redox active transition metal, we hypothesized that oxidative stress would be the main mechanism underlying cell toxicity.

Cu

transition metal


Input: Therefore, cell viability was correlated with the extent of reactive oxygen species (ROS) formation.

oxygen


Input: Cell viability decreased at the higher concentrations of the Cu salts and CuO was more toxic compared to CuSO4.

Cu salts

CuO


Input: The astrocytoma and glioblastoma cells were more vulnerable compared to the neuronal cells.


Input: Furthermore, it appears that oxidative stress only partially accounts for Cu-induced cell toxicity.

Cu


Input: Further studies are needed to better understand the unique susceptibility of glial cells and determine the physicochemical properties of insoluble Cu which accounts for its enhanced toxicity.

Cu


Input: Synthesis and biological evaluation of new N-alkylcarbazole derivatives as STAT3 inhibitors: preliminary study.

N-alkylcarbazole


Input: The signalling pathway of Janus tyrosine Kinases-Signal Transducers and Activators of Transcription (JAK-STAT) is activated by a number of cytokines, hormones (GH, erythropoietin and prolactin), and growth factors.

tyrosine


Input: JAK-STAT signalling is involved in regulation of cell proliferation, differentiation and apoptosis.


Input: These activities are due to different members of JAK-STAT family consisting of: JAK1, JAK2, JAK3, Tyk2 and STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6.


Input: Recent studies suggest a key role for STAT family proteins, in particular for STAT3, in selectively inducing and maintaining a pro-carcinogenic inflammatory microenvironment, that promote tumour cells transformation.


Input: Moreover, a striking correlation between cancer development/progression and STAT3 persistent activation exists, probably due to STAT3 promoting of the pro-oncogenic inflammatory pathways, like NF-kB, IL-6 and JAK family kinases.


Input: Recent study demonstrated that carbazoles can inhibit STAT3 mediated transcription.

carbazoles


Input: From these evidences, STAT3 represents a therapeutic target, so we have synthesized a new set of N-alkylcarbazole derivatives substituted in positions 2, 4 and 6, to evaluate their activity on STAT3.

N-alkylcarbazole


Input: Some of these compounds showed an interesting activity as STAT3 selective inhibitors; in particular, compounds 9a 9b and 9c revealed to inhibit the STAT3 activation for the 50%, 90% and 95%, respectively.


Input: Adult dose-dependent behavioral and cognitive disturbances after a single neonatal PFHxS dose.

PFHxS


Input: Perfluoroalkyl acids, including perfluorohexane sulfonate (PFHxS), are fluorinated organic compounds used as surfactants and water and stain repellents in carpets, paper, and textiles, with characteristics to bioaccumulate and biomagnify in the food chain.

Perfluoroalkyl acids

perfluorohexane sulfonate

PFHxS


Input: PFHxS is found in umbilical cord blood, human milk and child serum from all over the world.

PFHxS


Input: We have recently reported that neonatal exposure to certain perfluoroalkyl acids, PFOS and PFOA, can induce persistent aberrations in spontaneous behavior and also affect learning and memory functions in the adult animal.

perfluoroalkyl acids

PFOS

PFOA


Input: The present study indicates that a single exposure to PFHxS on postnatal day 10, during a vulnerable period of brain development can alter adult spontaneous behavior and cognitive function in both male and female mice, effects that are both dose-response related and long-lasting/irreversible.

PFHxS


Input: PFHxS affected the cholinergic system, manifested as altered nicotine-induced behavior in adult animals.

PFHxS

nicotine


Input: This is also in agreement with earlier studies on neonatal exposure to PFOS and PFOA.

PFOS

PFOA


Input: The present findings show that PFHxS, a member of the perfluoroalkyl acid group, can act as a developmental neurotoxicant and affect the cholinergic system and cognitive function and the effects show similarities with effects earlier reported after neonatal exposure to other POPs, such as bisphenol A, PBDEs and PCBs.

PFHxS

perfluoroalkyl acid

bisphenol A

PBDEs

PCBs


Input: Alcohol intoxications during adolescence increase motivation for alcohol in adult rats and induce neuroadaptations in the nucleus accumbens.


Input: Adolescent alcohol binge drinking constitutes a major vulnerability factor to develop alcoholism.


Input: However, mechanisms underlying this susceptibility remain unknown.


Input: We evaluated the effect of adolescent binge-like ethanol intoxication on vulnerability to alcohol abuse in Sprague-Dawley rats.

ethanol


Input: To model binge-like ethanol intoxication, every 2 days, rats received an ethanol injection (3. 0 g/kg) for 2 consecutive days across 14 days either from postnatal day 30 (PND30) to 43 (early adolescence) or from PND 45 to PND 58 (late adolescence).

ethanol

ethanol


Input: In young adult animals, we measured free ethanol consumption in the two-bottle choice paradigm, motivation for ethanol in the operant self-administration task and both ethanol' s rewarding and aversive properties in the conditioned place preference (CPP) and taste aversion (CTA) paradigms.

ethanol

ethanol

ethanol


Input: While intermittent ethanol intoxications (IEI) during late adolescence had no effect on free-choice 10% ethanol consumption, we found that IEI during early adolescence promoted free-choice 10% ethanol consumption, enhanced motivation for ethanol in the self-administration paradigm and induced a loss of both ethanol-induced CPP and CTA in young adults.

ethanol

ethanol

ethanol

ethanol

ethanol


Input: No modification in either sucrose self-administration or amphetamine-induced CPP was observed.

sucrose

amphetamine


Input: As the nucleus accumbens (Nac) is particularly involved in addictive behavior, we analyzed IEI-induced long-term neuroadaptations in the Nac using c-Fos immunohistochemistry and an array of neurotransmission-related genes.


Input: This vulnerability to ethanol abuse was associated with a lower c-Fos immunoreactivity in the Nac and enduring alterations of the expression of Penk and Slc6a4, 2 neurotransmission-related genes that have been shown to play critical roles in the behavioral effects of ethanol and alcoholism.

ethanol

ethanol


Input: Cannabinoid discrimination and antagonism by CB (1) neutral and inverse agonist antagonists.

Cannabinoid


Input: Cannabinoid receptor 1 (CB (1)) inverse agonists (e. g., rimonabant) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications.

Cannabinoid

rimonabant


Input: Recent laboratory studies suggest that the effects of CB (1) neutral antagonists differ from those of such inverse agonists, raising the possibility of improved clinical utility.


Input: However, little is known regarding the antagonist properties of neutral antagonists.


Input: In the present studies, the CB (1) inverse agonist SR141716A (rimonabant) and the CB (1) neutral antagonist AM4113 were compared for their ability to modify CB (1) receptor-mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel CB (1) full agonist AM4054.

rimonabant


Input: Results indicate that AM4054 serves as an effective CB (1) discriminative stimulus, with an onset and time course of action comparable with that of the CB (1) agonist Delta (9)-tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose-related rightward shifts in the AM4054 dose-effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054.

Delta (9)-tetrahydrocannabinol

rimonabant


Input: Schild analyses further show that rimonabant and AM4113 produce highly similar antagonist effects, as evident in comparable pA (2) values (6. 9).

rimonabant


Input: Taken together with previous studies, the present data suggest that the improved safety profile suggested for CB (1) neutral antagonists over inverse agonists is not accompanied by a loss of antagonist action at CB (1) receptors.


Input: Dose dependent molecular effects of acrylamide and glycidamide in human cancer cell lines and human primary hepatocytes.

acrylamide

glycidamide


Input: Recently published studies suggest a weak positive correlation between increased dietary acrylamide intake and the increased risk of endometrial and ovarian cancer.

acrylamide


Input: However, risk assessment of acrylamide remains difficult because the carcinogenic mechanisms are still unknown and in particular the molecular effects of low level acrylamide exposure as seen by dietary intake are not well understood.

acrylamide

acrylamide


Input: Therefore, we analyzed in ovarian and endometrial cancer cell lines as well as in primary hepatocytes the expression of genes involved in cancer development and xenobiotic metabolism after high and low dose exposure (1-0. 001mM) of acrylamide and its metabolite glycidamide.

acrylamide

glycidamide


Input: In conclusion our in vitro results demonstrate that exposure to high doses of glycidamide/acrylamide-exceeding the dietary exposure of the general population by far-can induce genes with growth promoting potential like the oncogene cMYC and genes involved in the MAPK pathway.

glycidamide

acrylamide


Input: However, low-dose exposure seems to activate primarily genes involved in the elimination of the toxicant.


Input: Cloning and characterization of an antibacterial L-amino acid oxidase from Crotalus durissus cumanensis venom.

L-amino acid


Input: An L-amino acid oxidase (LAAO) from Crotalus durissus cumanensis venom (CdcLAAO) was purified to homogeneity using a combination of size-exclusion and ion exchange chromatographies.

L-amino acid


Input: CdcLAAO is a monomeric protein exhibiting an apparent molecular mass of 55 kDa and a calculated pI of 8.


Input: Its complete 498-amino-acid sequence was deduced through cDNA and protein sequencing.

amino-acid


Input: The enzyme oxidized L-Leu with K (m) and a V (Max) of 9. 23 mu M and 0. 46 mu M/min respectively, and exhibited Kcat and a Kcat/K (m) of 1. 8 s (-1) and 195 mM (-1) s (-1).

L-Leu


Input: CdcLAAO inhibited in a dose-dependent manner the growth of Staphylococcus aureus and Acinetobacter baumannii.


Input: The inhibitory effect was more significant on S. aureus, with a Minimal Inhibitory Concentration (MIC) of 8 mu g/mL and Minimal Bactericidal Concentration (MBC) of 16 mu g/mL, than against A. baumannii, with a MIC of 16 mu g/mL and MBC of 32 mu g/mL.


Input: However, against Escherichia coli CdcLAAO did not show inhibitory capacity at the concentrations tested (2-128 mu g/mL).


Input: CdcLAAO did not exhibit cytotoxic activity on the mouse myoblast cell line C (2) C (12) and on peripheral blood mononuclear cell (PBMC).


Input: Toxicity of the flame-retardant BDE-49 on brain mitochondria and neuronal progenitor striatal cells enhanced by a PTEN-deficient background.


Input: Polybrominated diphenyl ethers (PBDEs) represent an important group of flame retardants extensively used, tonnage of which in the environment has been steadily increasing over the past 25 years.

Polybrominated diphenyl ethers

PBDEs


Input: PBDEs or metabolites can induce neurotoxicity and mitochondrial dysfunction (MD) through a variety of mechanisms.

PBDEs


Input: Recently, PBDEs with < 5 Br substitutions (i. e., 2, 2', 4, 4'-tetrabromodiphenyl ether [BDE-47] and 2, 2', 4, 5'-tetrabromodiphenyl ether [BDE-49]) have gained interest because of their high bioaccumulation.

PBDEs

Br

2, 2', 4, 4'-tetrabromodiphenyl ether

2, 2', 4, 5'-tetrabromodiphenyl ether


Input: In particular, congeners such as BDE-49 arise as one of the most biologically active, with concentrations typically lower than those observed for BDE-47 in biological tissues; however, its potential to cause MD at biologically relevant concentrations is unknown.


Input: To this end, the effect of BDE-49 was studied in brain mitochondria and neuronal progenitor striatal cells (NPC).


Input: BDE-49 uncoupled mitochondria at concentrations < 0. 1 nM, whereas at > 1 nM, it inhibited the electron transport at Complex V (mixed type inhibition; IC (50) = 6 nM) and Complex IV (noncompetitive inhibition; IC (50) = 40 nM).


Input: These concentrations are easily achieved in plasma concentrations considering that BDE-49 (this study, 400-fold) and other PBDEs accumulate 1-3 orders of magnitude in the cells, particularly in mitochondria and microsomes.

PBDEs


Input: Similar effects were observed in NPC and exacerbated with PTEN (negative modulator of the PI3K/Akt pathway) deficiency, background associated with autism-like behavior, schizophrenia, and epilepsy.


Input: PBDE-mediated MD per se or enhanced by a background that confers susceptibility to this exposure may have profound implications in the energy balance of brain.

PBDE


Input: Molecular mechanisms of fibrosis-associated promotion of liver carcinogenesis.


Input: Hepatocellular carcinoma (HCC) mostly develops in patients with advanced fibrosis; however, the mechanisms of interaction between a genotoxic insult and fibrogenesis are not well understood.


Input: This study tested a hypothesis that fibrosis promotes HCC via a mechanism that involves activation of liver stem cells.


Input: First, B6C3F1 mice were administered diethylnitrosamine (DEN; single ip injection of 1mg/kg at 14 days of age).

diethylnitrosamine

DEN


Input: Second, carbon tetrachloride (CCl (4); 0. 2ml/kg, 2/week ip starting at 8 weeks of age) was administered for 9 or 14 weeks to develop advanced liver fibrosis.

carbon tetrachloride

CCl (4)


Input: In animals treated with DEN as neonates, presence of liver fibrosis led to more than doubling (to 100%) of the liver tumor incidence as early as 5 months of age.

DEN


Input: This effect was associated with activation of cells with progenitor features in noncancerous liver tissue, including markers of replicative senescence (p16), oncofetal transformation (Afp, H19, and Bex1), and increased " stemness " (Prom1 and Epcam).


Input: In contrast, the dose of DEN used did not modify the extent of liver inflammation, fibrogenesis, oxidative stress, proliferation, or apoptosis induced by subchronic CCl (4) administration.

DEN

CCl (4)


Input: This study demonstrates the potential role of liver stem-like cells in the mechanisms of chemical-induced, fibrosis-promoted HCC.


Input: We posit that the combination of genotoxic and fibrogenic insults is a sensible approach to model liver carcinogenesis in experimental animals.


Input: These results may contribute to identification of cirrhotic patients predisposed to HCC by analyzing the expression of hepatic progenitor cell markers in the noncancerous liver tissue.


Input: Therapeutic drug monitoring of antiepileptic drugs by use of saliva.


Input: Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy.


Input: Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM.


Input: The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly.


Input: For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum.


Input: Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting.


Input: Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide.

carbamazepine

clobazam

ethosuximide

gabapentin

lacosamide

lamotrigine

levetiracetam

oxcarbazepine

phenobarbital

phenytoin

primidone

topiramate

zonisamide


Input: Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent.

valproic acid

clonazepam

eslicarbazepine acetate

felbamate

pregabalin

retigabine

rufinamide

stiripentol

tiagabine

vigabatrin


Input: A new hematite photoanode doping strategy for solar water splitting: oxygen vacancy generation.

hematite

oxygen


Input: The enhancement of the electrical conductivity by doping is important in hematite (alpha-Fe (2) O (3)) photoanodes for efficient solar water oxidation.

hematite

alpha-Fe (2) O (3)


Input: However, in spite of many successful demonstrations using extrinsic dopants, such as Sn, Ti, and Si, the achieved photocurrent is still lower than the practical requirement.

Sn

Ti

Si


Input: There is still lack of our understanding of how intrinsic oxygen defects can change the photocurrent and interact with the extrinsic dopants.

oxygen


Input: In this study, we systematically investigate the interplay of oxygen vacancies and extrinsic Sn dopants in the context of photoanodic properties.

oxygen

Sn


Input: As a result, we demonstrate that the controlled generation of oxygen vacancies can activate the photoactivity of pure hematite remarkably and further enhance the Sn doping effects synergistically.

oxygen

hematite

Sn


Input: Furthermore, the correlated behavior of oxygen vacancies and Sn dopants is closely linked to the variation of electrical conductance and results in the optimum concentration region to show the high photocurrent and low onset voltage.

oxygen

Sn


Input: A popular engagement at the ends.


Input: Three recent studies converged on a specific protein-protein interface between TPP1 and telomerase as being crucial for the regulation of both telomerase recruitment and processivity in mammalian cells.


Input: An equivalent interaction appears to exist in budding yeast, making this a nearly universal means of telomerase regulation.


Input: Electrolyte-gated organic field-effect transistor sensors based on supported biotinylated phospholipid bilayer.


Input: Anchored, biotinylated phospholipids forming the capturing layers in an electrolyte-gated organic field-effect transistor (EGOFET) allow label-free electronic specific detection at a concentration level of 10 nM in a high ionic strength solution.


Input: The sensing mechanism is based on a clear capacitive effect across the PL layers involving the charges of the target molecules.


Input: P-glycoprotein increases portal bioavailability of loperamide in mouse by reducing first-pass intestinal metabolism.

loperamide


Input: P-glycoprotein (P-gp) and CYP3A (cytochrome P450 3A, generally; Cyp3a, rodent enzyme) in the intestine can attenuate absorption of orally administered drugs.


Input: While some suggest that P-gp enhances intestinal metabolism by CYP3A/Cyp3a during absorption of a dual substrate, others suggest that P-gp reduces the metabolism in the intestine when substrates are at subsaturating concentrations.


Input: Hence, to elucidate the cellular mechanisms that can address these divergent reports, we studied intestinal absorption of the dual substrate loperamide in portal vein-cannulated P-gp-competent and P-gp-deficient mice.

loperamide


Input: These studies showed that at low doses of loperamide, which produced intestinal concentrations near the apparent K (m) for oxidative metabolism, the bioavailability across the intestine (F (G)) was 6-fold greater in the P-gp-competent mice than in P-gp-deficient mice.

loperamide


Input: The higher F (G) of loperamide in the presence of P-gp was attributed to lower loperamide intestinal metabolism.

loperamide

loperamide


Input: However, at high doses of loperamide, the sparing of first-pass metabolism by P-gp was balanced against the attenuation of absorption by apical efflux, resulting in no net effect on F (G).

loperamide


Input: In vitro studies with intestinal tissue from P-gp-competent and-deficient mice confirmed that P-gp reduced the metabolic rate of loperamide during absorptive flux at concentrations near K (m) but had little effect on metabolism at higher (saturating) concentrations.

loperamide


Input: Further, studies in which Cyp3a was chemically inactivated by aminobenzotriazole in P-gp-competent and-deficient mice, showed that P-gp and Cyp3a individually attenuated F (G) by 8-fold and 70-fold, respectively.

aminobenzotriazole


Input: These results confirmed that P-gp effectively protects loperamide at low doses from intestinal first-pass metabolism during intestinal absorption.

loperamide


Input: Influence of polyelectrolyte film stiffness on bacterial growth.


Input: Photo-cross-linkable polyelectrolyte films, whose nanomechanical properties can be varied under UV light illumination, were prepared from poly (l-lysine) (PLL) and a hyaluronan derivative modified with photoreactive vinylbenzyl groups (HAVB).

poly (l-lysine)

PLL

vinylbenzyl


Input: The adhesion and the growth of two model bacteria, namely Escherichia coli and Lactococcus lactis, were studied on non-cross-linked and cross-linked films to investigate how the film stiffness influences the bacterial behavior.


Input: While the Gram positive L. lactis was shown to grow slowly on both films, independently of their rigidity, the Gram negative E. coli exhibited a more rapid growth on non-cross-linked softer films compared to the stiffer ones.


Input: Experiments performed on photopatterned films showing both soft and stiff regions, confirmed a faster development of E. coli colonies on softer regions.


Input: Interestingly, this behavior is opposite to the one reported before for mammalian cells.


Input: Therefore, the photo-cross-linked (PLL/HAVB) films are interesting coatings for tissue engineering since they promote the growth of mammalian cells while limiting the bacterial colonization.


Input: Novel 1H-1, 2, 3-, 2H-1, 2, 3-, 1H-1, 2, 4-and 4H-1, 2, 4-triazole derivatives: a patent review (2008-2011).

1H-1, 2, 3-, 2H-1, 2, 3-, 1H-1, 2, 4-and 4H-1, 2, 4-triazole


Input: INTRODUCTION: The triazoles represent a class of five-membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several structural variations with the same numbers of carbon and nitrogen atoms.

triazoles

carbon

nitrogen


Input: Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds.

triazoles


Input: In this review, the authors explored aspects of patents for the 1H-1, 2, 3-, 2H-1, 2, 3-, 1H-1, 2, 4-and 4H-1, 2, 4-triazole families, including prototypes being considered in clinical studies between 2008 and 2011.

1H-1, 2, 3-, 2H-1, 2, 3-, 1H-1, 2, 4-and 4H-1, 2, 4-triazole


Input: AREAS COVERED: The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities.

triazoles


Input: More recently, there has been considerable interest in the development of novel triazoles with anti-inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases.

triazoles


Input: This review emphasizes recent perspective and advances in the therapeutically active 1H-1, 2, 3-, 2H-1, 2, 3-, 1H-1, 2, 4-and 4H-1, 2, 4-triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals.

1H-1, 2, 3-, 2H-1, 2, 3-, 1H-1, 2, 4-and 4H-1, 2, 4-triazole


Input: Many studies have focused on these compounds as target structures and evaluated them in several biological targets.


Input: EXPERT OPINION: The preparation of 1H-1, 2, 3-, 2H-1, 2, 3-, 1H-1, 2, 4-and 4H-1, 2, 4-triazole derivatives brings to light several issues.

1H-1, 2, 3-, 2H-1, 2, 3-, 1H-1, 2, 4-and 4H-1, 2, 4-triazole


Input: There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability.

triazoles


Input: New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these new diseases.


Input: Of great urgency is finding prototypes against bacteria that continue to increase resistance and for neglected diseases that affect a large part of humanity, especially the poor and vulnerable.


Input: Infrared multiple photon dissociation action spectroscopy of deprotonated DNA mononucleotides: gas-phase conformations and energetics.

mononucleotides


Input: The gas phase structures of the deprotonated 2'-deoxymononucleotides including 2'-deoxyadenosine-5'-monophosphate (dA5' p), 2'-deoxycytidine-5'-monophosphate (dC5' p), 2'-deoxyguanosine-5'-monophosphate (dG5' p), and thymidine-5'-monophosphate (T5' p) are examined via infrared multiple photon dissociation (IRMPD) action spectroscopy and theoretical electronic structure calculations.

dA5' p

dC5' p

dG5' p

T5' p


Input: The measured IRMPD action spectra of all four deprotonated DNA mononucleotides exhibit unique spectral features in the region extending from ~ 600 to 1800 cm (-1) such that they can be readily differentiated from one another.

mononucleotides


Input: The measured IRMPD action spectra are compared to the linear IR spectra calculated at the B3LYP/6-311 + G (d, p) level of theory to determine the conformations of these species accessed in the experiments.


Input: On the basis of these comparisons and the computed energetic information, the most stable conformations of the deprotonated forms of dA5' p, dC5' p, and T5' p are conformers where the ribose moiety adopts a C3' endo conformation and the nucleobase is in an anti conformation.

dA5' p

dC5' p

T5' p

ribose

nucleobase


Input: By contrast, the most stable conformations of the deprotonated form of dG5' p are conformers where the ribose adapts a C3' endo conformation and the nucleobase is in a syn conformation.

dG5' p

nucleobase


Input: In addition to the ground-state conformers, several stable low-energy excited conformers that differ slightly in the orientation of the phosphate ester moiety were also accessed in the experiments.

phosphate ester


Input: Freezing continuous-flow self-assembly in a microfluidic device: toward imaging of liposome formation.


Input: A new method is described that combines a microfluidic device for the controlled formation of liposomes with instantaneous immobilization by means of ultrarapid cooling.


Input: The microfluidic device is composed of capillaries to hydrodynamically focus a stream of lipids dissolved in 2-propanol by two adjacent aqueous buffer streams before rapidly cooling by propane jet-freezing.


Input: The capillary containing the frozen sheath-flow is subsequently separated from the flow-focusing unit and trimmed with cryo-ultramicrotomy for imaging with cryo-scanning electron microscopy (SEM).


Input: The emergence of liposomes could be visualized by cryo-SEM without the need for chemical fixation or labeling.


Input: We demonstrate that the method is capable of revealing in more detail the formation of nonequilibrium liposomes.


Input: Partially and completely formed liposomes were observed at the miscible alcohol-buffer interface.

alcohol


Input: The number density of lipid vesicles varied along the focused interface, and we frequently found clusters of liposomes.


Input: Additionally, evidence for the formation of disclike transient intermediates is presented.


Input: The method is not limited to studying self-assembly processes only.


Input: It can be extended to other biochemical reactions, crystallization processes, and even systematic interfacial mixing studies between different solvents.


Input: Distribution and seasonal variation in hypothalamic RF-amide peptides in a semi-desert rodent, the jerboa.

amide


Input: The jerboa is a semi-desert rodent, in which reproductive activity depends on the seasons, being sexually active in the spring-summer.


Input: The present study aimed to determine whether the expression of two RF-amide peptides recently described to regulate gonadotrophin-releasing hormone neurone activity, kisspeptin (Kp) and RF-amide-related peptide (RFRP)-3, displays seasonal variation in jerboa.

amide

amide


Input: Kp and/or RFRP-3 immunoreactivity was investigated in the hypothalamus of jerboas captured in the field of the Middle Atlas mountain (Morocco), either in the spring or autumn.


Input: As in other rodents, the Kp-immunoreactive (-IR) neurones were found in the anteroventro-periventricular and arcuate nuclei.


Input: RFRP-3 neurones were noted within the dorso/ventromedial hypothalamus.


Input: A marked sexual dimorphism in the expression of Kp (but not RFRP-3) was observed.


Input: The number of Kp-IR neurones was nine-fold higher, and the density of Kp-IR fibres and terminal-like elements in the median eminence was two-fold higher in females than in males.


Input: Furthermore, a significant seasonal variation in peptide expression was obtained with an increase in both Kp-and RFRP-3-IR cell bodies in sexually active male jerboas captured in the spring compared to sexually inactive autumn animals.


Input: In the arcuate nucleus, the level of Kp-IR cells and fibres was significant higher during the sexually active period in the spring than during the autumnal sexual quiescence.


Input: Similarly, the number of RFRP-3-IR neurones in the ventro/dorsomedial hypothalamus was approximately three-fold higher in sexually active jerboa captured in the spring compared to sexually inactive autumn animals.


Input: Altogether, the present study reports the distribution of Kp and RFRP-3 neurones in the hypothalamus of a desert species and reveals a seasonal difference in their expression that correlates with sexual activity.


Input: These findings suggest that these two RF-amide peptides may act in concert to synchronise the gonadotrophic activity of jerboas with the seasons.


Input: Living unimodal growth of polyion complex vesicles via two-dimensional supramolecular polymerization.


Input: Understanding the dynamic behavior of molecular self-assemblies with higher-dimensional structures remains a key challenge to obtaining well-controlled and monodispersed structures.


Input: Nonetheless, there exist few systems capable of realizing the mechanism of supramolecular polymerization at higher dimensions.


Input: Herein, we report the unique self-assembling behavior of polyion complexes (PICs) consisting of poly (ethylene glycol)-polyelectrolyte block copolymer as an example of two-dimensional supramolecular living polymerization.

poly (ethylene glycol)


Input: Monodispersed and submicrometer unilamellar PIC vesicles (nano-PICsomes) displayed time-dependent growth while maintaining a narrow size distribution and a unilamellar structure.


Input: Detailed analysis of the system revealed that vesicle growth proceeded through the consumption of unit PICs (uPICs) composed of a single polycation/polyanion pair and was able to restart upon the further addition of isolated uPICs.


Input: Interestingly, the resulting vesicles underwent dissociation into uPICs in response to mechanical stress.


Input: These results clearly frame the growth as a two-dimensional supramolecular living polymerization of uPICs.


Input: Mammalian Trit1 is a tRNA ([Ser] Sec)-isopentenyl transferase required for full selenoprotein expression.

Ser

Sec

isopentenyl


Input: Selenoproteins are proteins carrying the rare amino acid Sec (selenocysteine).

amino acid Sec

selenocysteine


Input: Full expression of selenoproteins requires modification of tRNA ([Ser] Sec), including N (6)-isopentenylation of base A (37).

Ser

Sec


Input: We show that Trit1 is a dimethylallyl: tRNA ([Ser] Sec) transferase.

dimethylallyl

Ser

Sec


Input: Knockdown of Trit1 reduces expression of selenoproteins.


Input: Incubation of in vitro transcribed tRNA [Ser] Sec with recombinant Trit1 transfers [(14) C] dimethylallyl pyrophosphate to tRNA ([Ser] Sec).

Ser

Sec

[(14) C] dimethylallyl pyrophosphate

Ser

Sec


Input: 37A > G tRNA ([Ser] Sec) is resistant to isopentenylation by Trit1.

Ser

Sec


Input: Engagement of CF3 group in N-H... F-C hydrogen bond in the solution state: NMR spectroscopy and MD simulation studies.

N-H

F-C hydrogen


Input: Unambiguous evidence for the engagement of CF (3) group in N-H... F-C hydrogen bond in a low polarity solvent, the first observation of its kind, is reported.

CF (3)

N-H

F-C hydrogen


Input: The presence of such weak molecular interactions in the solution state is convincingly established by one and two-dimensional (1) H, (19) F, and natural abundant (15) N NMR spectroscopic studies.

(1) H

(19) F

(15) N


Input: The strong and direct evidence is derived by the observation of through-space couplings, such as, (1h) J (FH), (1h) J (FN), and (2h) J (FF), where the spin polarization is transmitted through hydrogen bond.

FH

FN

FF

hydrogen


Input: In an interesting example of a molecule containing two CF (3) groups getting simultaneously involved in hydrogen bond, where hydrogen bond mediated couplings are not reflected in the NMR spectrum, (19) F-(19) F NOESY experiment yielded confirmatory evidence.

CF (3)

hydrogen

hydrogen

(19) F

(19) F


Input: Significant deviations in the strengths of (1) J (NH), variable temperature, and the solvent induced perturbations yielded additional support.

NH


Input: The NMR results are corroborated by both DFT calculations and MD simulations, where the quantitative information on different ways of involvement of fluorine in two and three centered hydrogen bonds, their percentage of occurrences, and geometries have been obtained.

fluorine

hydrogen


Input: The hydrogen bond interaction energies have also been calculated.

hydrogen


Input: On the preparation of indoxyl red from indican and some new characteristics.

indoxyl red


Input: An indole compound with a strong purple-red color was produced by boiling a solution of indican under acidic conditions and purified by chromatographies on DEAE-650S Toyopearl TSK-gel and silica-gel columns.

indole

silica


Input: The purple-red compound purified was identified as indoxyl red, on the basis of FAB Mass, (13) C NMR, (1) H NMR, UV-visible spectra, and IR spectra.

indoxyl red

(13) C

(1) H


Input: Although indoxyl red was first synthesized by Seidel (9) 70 years ago, very little information has been available on its characteristics.

indoxyl red


Input: We repot here that the compound was purple-red colored at acidic pH and green at pH 13, and showed antiproliferative and cytotoxic activities to the mouse B cell lymphoma cell line NSF202.


Input: Alkyladenine DNA glycosylase (AAG) localizes to mitochondria and interacts with mitochondrial single-stranded binding protein (mtSSB).

Alkyladenine


Input: Due to a harsh environment mitochondrial genomes accumulate high levels of DNA damage, in particular oxidation, hydrolytic deamination, and alkylation adducts.


Input: While repair of alkylated bases in nuclear DNA has been explored in detail, much less is known about the repair of DNA alkylation damage in mitochondria.


Input: Alkyladenine DNA glycosylase (AAG) recognizes and removes numerous alkylated bases, but to date AAG has only been detected in the nucleus, even though mammalian mitochondria are known to repair DNA lesions that are specific substrates of AAG.

Alkyladenine


Input: Here we use immunofluorescence to show that AAG localizes to mitochondria, and we find that native AAG is present in purified human mitochondrial extracts, as well as that exposure to alkylating agent promotes AAG accumulation in the mitochondria.


Input: We identify mitochondrial single-stranded binding protein (mtSSB) as a novel interacting partner of AAG; interaction between mtSSB and AAG is direct and increases upon methyl methanesulfonate (MMS) treatment.

methyl methanesulfonate

MMS


Input: The consequence of this interaction is specific inhibition of AAG glycosylase activity in the context of a single-stranded DNA (ssDNA), but not a double-stranded DNA (dsDNA) substrate.


Input: By inhibiting AAG-initiated processing of damaged bases, mtSSB potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA.


Input: In summary, our findings suggest the existence of AAG-initiated BER in mitochondria and further support a role for mtSSB in DNA repair.


Input: Zinc drives a tertiary fold in the prion protein with familial disease mutation sites at the interface.

Zinc


Input: The cellular prion protein PrP (C) consists of two domains--a flexible N-terminal domain, which participates in copper and zinc regulation, and a largely helical C-terminal domain that converts to beta sheet in the course of prion disease.

N

copper

zinc

C


Input: These two domains are thought to be fully independent and noninteracting.


Input: Compelling cellular and biophysical studies, however, suggest a higher order structure that is relevant to both PrP (C) function and misfolding in disease.


Input: Here, we identify a Zn (2) +-driven N-terminal to C-terminal tertiary interaction in PrP (C).

Zn (2) +

N

C


Input: The C-terminal surface participating in this interaction carries the majority of the point mutations that confer familial prion disease.

C


Input: Investigation of mutant PrPs finds a systematic relationship between the type of mutation and the apparent strength of this domain structure.


Input: The structural features identified here suggest mechanisms by which physiologic metal ions trigger PrP (C) trafficking and control prion disease.


Input: Syntheses and evaluation of the antioxidant activity of novel methoxypsoralen derivatives.

methoxypsoralen


Input: A series of 5-and 8-methoxypsoralen (MOP) analogs, suitable for structure-antioxidative/anti-inflammatory activity relationship studies, were synthesized using as key-reactions the selective monobromination of MOPs with N-bromosaccharin and either a Heck reaction or a Suzuki coupling or a Suzuki coupling followed by a Wittig reaction to install side-chains of the acrylate-or benzoate-or cinnamate-type, respectively.

5-and 8-methoxypsoralen

MOP

MOPs

N-bromosaccharin

acrylate

benzoate

cinnamate


Input: The 8-MOP analogs 19 and 24, incorporating at position 5 of the psoralen nucleus a butyl acrylate or a tert-butyl cinnamate moiety, were the most powerful inhibitors of soybean LOX and inhibited effectively lipid peroxidation.

psoralen

butyl acrylate

tert-butyl cinnamate


Input: Analog 19 was a more potent anti-inflammatory agent than the reference compound indomethacin and of comparable cytocompatibility to 8-MOP whereas analog 24 was a weaker inhibitor of inflammation than indomethacin and significantly more cytotoxic than 8-MOP.

indomethacin

indomethacin


Input: The results of the biological tests are discussed in terms of structural characteristics.


Input: Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity.

cisplatin


Input: Because of the difficulty in detecting segment-specific response in the kidney, we investigated the molecular events underlying acute kidney injury in the proximal tubules of rats with cisplatin (cis-diamminedichloroplatinum II)-induced nephrotoxicity.

cisplatin

cis-diamminedichloroplatinum II


Input: Microarray analysis revealed that mRNA levels of several cytokines and chemokines, such as interleukin-1beta, chemokine (C-C motif) ligand (CCL) 2, CCL20, chemokine (C-X-C motif) ligand (CXCL) 1, and CXCL10 were significantly increased after cisplatin treatment in both isolated proximal tubules and whole kidney.

cisplatin


Input: Interestingly, tubular CCL2 mRNA levels increased soon after cisplatin administration, whereas CCL2 mRNA levels in whole kidney first decreased and then increased.

cisplatin


Input: Levels of both CCL2 and kidney injury molecule-1 (KIM-1) in the whole kidney increased after cisplatin administration.

cisplatin


Input: Immunofluorescence analysis revealed CCL2 changes in the proximal tubular cells initially and then in the medullary interstitium.


Input: Urinary CCL2 excretion significantly increased approximately 3-fold compared with controls the day after cisplatin administration (5mg/kg), when no changes were observed plasma creatinine and blood urea nitrogen levels.

cisplatin

creatinine

urea nitrogen


Input: Urinary levels of KIM-1 also increased 3-fold after cisplatin administration.

cisplatin


Input: In addition, urinary CCL2 rather than KIM-1 increased in chronic renal failure rats after administration of low-dose cisplatin (2mg/kg), suggesting that urinary CCL2 was selective for cisplatin-induced nephrotoxicity in renal impairment.

cisplatin

cisplatin


Input: These results indicated that the increase in cytokine and chemokine expression in renal epithelial cells might be responsible for kidney deterioration in cisplatin-induced nephrotoxicity, and that urinary CCL2 is associated with tubular injury and serves as a sensitive and noninvasive marker for the early detection of cisplatin-induced tubular injury.

cisplatin

cisplatin


Input: Thyroid disturbance related to chronic hepatitis C infection: role of CXCL10.


Input: Association between autoimmune thyroid diseases (AITD) and hepatitis C is controversial, but may occur or worsen during alpha-interferon treatment.


Input: The mechanism responsible for autoimmune diseases in infected patients has not been fully elucidated.


Input: This study aims to evaluate the frequency of AITD in chronic hepatitis C and the association of CXCL10 and AITD.


Input: One hundred and three patients with chronic hepatitis C and 96 controls were prospectively selected to clinical, hormonal, thyroid autoimmunity and ultrasound exams, besides thyroxine-binding globulin (TBG) and CXCL10 measurements and hepatic biopsies.


Input: The frequency of AITD among infected subjects was similar to controls.


Input: TT3 and TT4 distributions were right shifted, as was TBG, which correlated to both of them.


Input: Thyroid heterogeneity and hypoechogenicity were associated with AITD.


Input: Increased vascularization was more prevalent in chronic hepatitis C. CXCL10 was higher in infected patients (p = 0. 007) but was not related to thyroid dysfunction.


Input: Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity (p = 0. 011).


Input: In summary, no association was found between chronic hepatitis C and AITD.


Input: Infected subjects had higher TT3 and TT4 which were correlated to TBG.


Input: Increased CXCL10 was not associated to thyroid dysfunction in HCV-infected population.


Input: Embryonic stem cell-derived trophoblast differentiation: a comparative review of the biology, function, and signaling mechanisms.


Input: The development of the placenta is imperative for successful pregnancy establishment, yet the earliest differentiation events of the blastocyst-derived trophectoderm that forms the placenta remain difficult to study in humans.


Input: Human embryonic stem cells (hESC) display a unique ability to form trophoblast cells when induced to differentiate either by the addition of exogenous BMP4 or by the formation of cellular aggregates called embryoid bodies.


Input: While mouse trophoblast stem cells (TSC) have been isolated from blastocyst outgrowths, mouse ESC do not spontaneously differentiate into trophoblast cells.


Input: In this review, we focus on addressing the similarities and differences between mouse TSC differentiation and hESC-derived trophoblast differentiation.


Input: We discuss the functional and mechanistic diversity that is found in different species models.


Input: Of central importance are the unique signaling events that trigger downstream gene expression that create specific cellular fate decisions.


Input: We support the idea that we must understand the nuances that hESC differentiation models display so that investigators can choose the appropriate model system to fit experimental needs.


Input: Small-scale heat detection using catalytic microengines irradiated by laser.


Input: We demonstrate a novel approach to modulating the motion speed of catalytic microtubular engines via laser irradiation/heating with regard to small-scale heat detection.


Input: Laser irradiation on the engines leads to a thermal heating effect and thus enhances the engine speed.


Input: During a laser on/off period, the motion behaviour of a microengine can be repeatable and reversible, demonstrating a regulation of motion speeds triggered by laser illumination.


Input: Also, the engine velocity exhibits a linear dependence on laser power in various fuel concentrations, which implies an application potential as local heat sensors.


Input: Our work may hold great promise in applications such as lab on a chip, micro/nano factories, and environmental detection.


Input: The evolution of RuBisCO stability at the thermal limit of photoautotrophy.


Input: A long-standing question in evolutionary biology is how organisms adapt to novel environments.


Input: In North American hot springs, diversification of a clade of the cyanobacterium Synechococcus into hotter environments has resulted in the unique innovation of a light-driven ecosystem at temperatures up to 74 degrees C, and temperature adaptation of photosynthetic carbon fixation with the Calvin cycle contributed to this process.


Input: Here, we investigated the evolution of thermostability of the Calvin cycle enzyme ribulose-1, 5-bisphosphate carboxylase/oxygenase (RuBisCO) during Synechococcus divergence.

ribulose-1, 5-bisphosphate


Input: Circular dichroism thermal scans revealed that the RuBisCO of the most thermotolerant Synechococcus lineage is more stable than those of other lineages or of resurrected ancestral enzymes.


Input: Using site-directed mutagenesis, we next identified four amino acid substitutions that together increased stability and activity of this enzyme at higher temperatures.

amino acid


Input: These are clustered near critical subunit interfaces distant from the active site.


Input: Each of the four amino acids is also observed in a less thermostable Synechococcus RuBisCO, and the impact on stability of three of these appears to be epistatic.

amino acids


Input: Recombination analyses that allow for recurrent mutation as well as patterns of synonymous variation surrounding these sites suggest that the evolution of a more thermostable RuBisCO may have involved homologous recombination.


Input: Our results provide insights on the molecular evolutionary processes that shape niche differentiation and ecosystem function.


Input: New oral anticoagulants: comparative pharmacology with vitamin K antagonists.

vitamin K


Input: New oral anticoagulants (OACs) that directly inhibit Factor Xa (FXa) or thrombin have been developed for the long-term prevention of thromboembolic disorders.


Input: These novel agents provide numerous benefits over older vitamin K antagonists (VKAs) due to major pharmacological differences.

vitamin K


Input: VKAs are economical and very well characterized, but have important limitations that can outweigh these advantages, such as slow onset of action, narrow therapeutic window and unpredictable anticoagulant effect.


Input: VKA-associated dietary precautions, monitoring and dosing adjustments to maintain international normalized ratio (INR) within therapeutic range, and bridging therapy, are inconvenient for patients, expensive, and may result in inappropriate use of VKA therapy.


Input: This may lead to increased bleeding risk or reduced anticoagulation and increased risk of thrombotic events.


Input: The new OACs have rapid onset of action, low potential for food and drug interactions, and predictable anticoagulant effect that removes the need for routine monitoring.


Input: FXa inhibitors, e. g. rivaroxaban and apixaban, are potent, oral direct inhibitors of prothrombinase-bound, clot-associated or free FXa.

rivaroxaban

apixaban


Input: Both agents have a rapid onset of action, a wide therapeutic window, little or no interaction with food and other drugs, minimal inter-patient variability, and display similar pharmacokinetics in different patient populations.


Input: Since both are substrates, co-administration of rivaroxaban and apixaban with strong cytochrome P450 (CYP) 3A4 and permeability glycoprotein (P-gp) inhibitors and inducers can result in substantial changes in plasma concentrations due to altered clearance rates; consequently, their concomitant use is contraindicated and caution is required when used concomitantly with strong CYP3A4 and P-gp inducers.

rivaroxaban

apixaban


Input: Although parenteral oral direct thrombin inhibitors (DTIs), such as argatroban and bivalirudin, have been on the market for years, DTIs such as dabigatran are novel synthetic thrombin antagonists.

argatroban

dabigatran


Input: Dabigatran etexilate is a low-molecular-weight non-active pro-drug that is administered orally and converted rapidly to its active form, dabigatran--a potent, competitive and reversible DTI.

Dabigatran etexilate

dabigatran


Input: Dabigatran has an advantage over the indirect thrombin inhibitors, unfractionated heparin and low-molecular-weight heparin, in that it inhibits free and fibrin-bound thrombin.

Dabigatran


Input: The reversible binding of dabigatran may provide safer and more predictable anticoagulant treatment than seen with irreversible, non-covalent thrombin inhibitors, e. g. hirudin.

dabigatran


Input: Dabigatran shows a very low potential for drug-drug interactions.

Dabigatran


Input: However, co-administration of dabigatran etexilate with other anticoagulants and antiplatelet agents can increase the bleeding risk.

dabigatran etexilate


Input: Although the new agents are pharmacologically better than VKAs--particularly in terms of fixed dosing, rapid onset of action, no INR monitoring and lower risk of drug interactions--there are some differences between them: the bioavailability of dabigatran is lower than rivaroxaban and apixaban, and so the dabigatran dosage required is higher; lower protein binding of dabigatran reduces the variability related to albuminaemia.

dabigatran

rivaroxaban

apixaban

dabigatran

dabigatran


Input: The risk of metabolic drug-drug interactions also appears to differ between OACs: VKAs > rivaroxaban > apixaban > dabigatran.

rivaroxaban

apixaban

dabigatran


Input: The convenience of the new OACs has translated into improvements in efficacy and safety as shown in phase III randomized trials.


Input: The new anticoagulants so far offer the greatest promise and opportunity for the replacement of VKAs.


Input: Fluorescent live-cell imaging of metabolically incorporated unnatural cyclopropene-mannosamine derivatives.

cyclopropene

mannosamine


Input: Sugar coated: We recently developed methylcyclopropenes as low-molecular-weight tetrazine coupling partners.

Sugar

methylcyclopropenes

tetrazine


Input: Here, we demonstrate that methylcyclopropenes can meet the stringent steric demands required for metabolic imaging of unnatural mannosamines on live cells.

methylcyclopropenes

mannosamines


Input: Using sequential azide-alkyne chemistry, we also demonstrate multicolor imaging of two different metabolically incorporated unnatural sugars.

azide

alkyne

sugars


Input: Microwave spectroscopic and atoms in molecules theoretical investigations on the Ar... propargyl alcohol complex: Ar... H-O, Ar... pi, and Ar... C interactions.

propargyl alcohol

H-O

C


Input: The structure of the Ar... propargyl alcohol (Ar... PA) complex is determined from the rotational spectra of the parent complex and its two deuterated isotopologues, namely Ar... PA-D (OD) and Ar... PA-D (CD).

propargyl alcohol

D

OD

D

CD


Input: The spectra confirm a geometry in which PA exists in the gauche form with Ar located in between-OH and-C = C-H groups.

OH

C = C-H


Input: All a, b and c types of transitions show small splitting due to some large-amplitude motion dominated by C-OH torsion, as in the monomer.

C-OH


Input: Splittings in a-and b-type transitions are of the order of a few kilohertz, whereas splitting in the c-type transitions is relatively larger (0. 9-2. 6 MHz) and decreases in the order Ar... PA > Ar... PA-D (CD) > Ar... PA-D (OD).

D

CD

D

OD


Input: The assignments are well supported by ab initio calculations.


Input: Atoms in molecules (AIM) and electrostatic potential calculations are used to explore the nature of the interactions in this complex.


Input: AIM calculations not only reveal the expected O-H... Ar and pi... Ar interactions in the Ar... gauche-PA complex, but also novel C... Ar (of CH2OH group) and O-H... Ar interactions in the Ar... trans-PA complex.

O-H

C

O-H


Input: Similar interactions are also present in the Ar... methanol complex.

methanol


Input: Smoothened is a fully competent activator of the heterotrimeric G protein G (i).


Input: Smoothened (Smo) is a 7-transmembrane protein essential to the activation of Gli transcription factors (Gli) by hedgehog morphogens.


Input: The structure of Smo implies interactions with heterotrimeric G proteins, but the degree to which G proteins participate in the actions of hedgehogs remains controversial.


Input: We posit that the G (i) family of G proteins provides to hedgehogs the ability to expand well beyond the bounds of Gli.


Input: In this regard, we evaluate here the efficacy of Smo as it relates to the activation of G (i), by comparing Smo with the 5-hydroxytryptamine (1A) (5-HT (1A)) receptor, a quintessential G (i)-coupled receptor.


Input: We find that with use of [(35) S] guanosine 5'-(3-O-thio) triphosphate, first, with forms of G (i) endogenous to human embryonic kidney (HEK)-293 cells made to express epitope-tagged receptors and, second, with individual forms of G alpha (i) fused to the C terminus of each receptor, Smo is equivalent to the 5-HT (1A) receptor in the assay as it relates to capacity to activate G (i).

[(35) S] guanosine 5'-(3-O-thio) triphosphate


Input: This finding is true regardless of subtype of G (i) (e. g., G (i2), G (o), and G (z)) tested.


Input: We also find that Smo endogenous to HEK-293 cells, ostensibly through inhibition of adenylyl cyclase, decreases intracellular levels of cAMP.

adenylyl

cAMP


Input: The results indicate that Smo is a receptor that can engage not only Gli but also other more immediate effectors.


Input: 3D nanoscale chemical imaging of the distribution of aluminum coordination environments in zeolites with soft X-ray microscopy.

aluminum

zeolites


Input: Which side are you on?


Input: Scanning transmission X-ray microscopy is used for the first time to elucidate the coordination and distribution of aluminum in industrial-relevant zeolites at the single-particle level.

aluminum

zeolites


Input: Extended regions of a few hundred nanometers, rich in higher aluminum coordination environments, are heterogeneously embedded within the zeolite particle, before and after a steaming post-treatment.

aluminum

zeolite


Input: Structural aspects of gut peptides with therapeutic potential for type 2 diabetes.


Input: Gut hormones represent a niche subset of pharmacologically active agents that are rapidly gaining importance in medicine.


Input: Due to their exceptional specificity for their receptors, these hormones along with their analogues have attracted considerable pharmaceutical interest for the treatment of human disorders including type 2 diabetes.


Input: With the recent advances in the structural biology, a significant amount of structural information for these hormones is now available.


Input: This Minireview presents an overview of the structural aspects of these hormones, which have roles in physiological processes such as insulin secretion, as well as a discussion on the relevant structural modifications used to improve these hormones for the treatment of type 2 diabetes.


Input: Electron doping by charge transfer at LaFeO3/Sm2CuO4 epitaxial interfaces.


Input: Using X-ray absorption spectroscopy and electron energy loss spectroscopy with atomic-scale spatial resolution, experimental evidence for charge transfer at the interface between the Mott insulators Sm2 CuO4 and LaFeO3 is obtained.

Sm2 CuO4


Input: As a consequence of the charge transfer, the Sm2 CuO4 is doped with electrons and thus epitaxial Sm2 CuO4/LaFeO3 heterostructures become metallic.

Sm2 CuO4

Sm2 CuO4


Input: Conformational dynamics of the human propeller telomeric DNA quadruplex on a microsecond time scale.


Input: The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propeller-type topology.


Input: NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal-packing interactions that are effectively equivalent to molecular crowding.


Input: This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state.


Input: Although G-quartet stems have been well characterized, the interactions of the TTA loop with the G-quartets are much less defined.


Input: To better understand the conformational variability and structural dynamics of the propeller-type topology, we performed molecular dynamics simulations in explicit solvent up to 1. 5 mu s.


Input: The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G-quartets including formation of an A: A base pair, triad, pentad and hexad.


Input: The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar-phosphate backbone in formation of unusual architecture within the topology.

sugar

phosphate


Input: Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology.


Input: ParseCNV integrative copy number variation association software with quality tracking.


Input: A number of copy number variation (CNV) calling algorithms exist; however, comprehensive software tools for CNV association studies are lacking.


Input: We describe ParseCNV, unique software that takes CNV calls and creates probe-based statistics for CNV occurrence in both case-control design and in family based studies addressing both de novo and inheritance events, which are then summarized based on CNV regions (CNVRs).


Input: CNVRs are defined in a dynamic manner to allow for a complex CNV overlap while maintaining precise association region.


Input: Using this approach, we avoid failure to converge and non-monotonic curve fitting weaknesses of programs, such as CNVtools and CNVassoc, and although Plink is easy to use, it only provides combined CNV state probe-based statistics, not state-specific CNVRs.


Input: Existing CNV association methods do not provide any quality tracking information to filter confident associations, a key issue which is fully addressed by ParseCNV.


Input: In addition, uncertainty in CNV calls underlying CNV associations is evaluated to verify significant results, including CNV overlap profiles, genomic context, number of probes supporting the CNV and single-probe intensities.


Input: When optimal quality control parameters are followed using ParseCNV, 90% of CNVs validate by polymerase chain reaction, an often problematic stage because of inadequate significant association review.


Input: ParseCNV is freely available at http://parsecnv. sourceforge. net.


Input: Dietary exposure of mink (Mustela vison) to fish from the upper Hudson River, New York, USA: effects on reproduction and offspring growth and mortality.


Input: The effects of feeding farm-raised mink (Mustela vison) diets containing polychlorinated biphenyl (PCB)-contaminated fish from the upper Hudson River (New York, USA) on adult reproductive performance and kit growth and mortality were evaluated.

polychlorinated biphenyl

PCB


Input: Diets contained 2. 5 to 20% Hudson River fish, providing 0. 72 to 6. 1 micro g sum PCBs/g feed (4. 8-38 pg toxic equivalents [TEQWHO 2005]/g feed).


Input: The percentage of stillborn kits per litter was significantly increased by dietary concentrations of 4. 5 micro g sum PCBs/g feed (28 pg TEQWHO 2005/g feed) and greater.


Input: All offspring exposed to dietary concentrations of 4. 5 and 6. 1 micro g sum PCBs/g feed (28 and 38 pg TEQWHO 2005/g feed) died by 10 weeks of age, and all offspring exposed to 1. 5 and 2. 8 micro g sum PCBs/g feed (10 and 18 pg TEQWHO 2005/g feed) died by 31 weeks of age, leaving juveniles in the control and 0. 72 micro g sum PCBs/g feed (0. 41-and 4. 8 pg TEQWHO 2005/g feed) groups only.


Input: The dietary concentration predicted to result in 20% kit mortality (LC20) at six weeks of age was 0. 34 micro g sum PCBs/g feed (2. 6 pg TEQWHO 2005/g feed).


Input: The corresponding maternal hepatic concentration was 0. 80 micro g sum PCBs/g liver, wet weight (13 pg TEQWHO 2005/g liver, wet wt).


Input: Mink residing in the upper Hudson River would be expected to consume species of fish that contain an average of 4. 0 micro g sum PCBs/g tissue.


Input: Thus, a daily diet composed of less than 10% Hudson River fish could provide a dietary concentration of sum PCBs that resulted in 20% kit mortality in the present study.


Input: Clinal variation in colony breeding structure and level of inbreeding in the subterranean termites Reticulitermes flavipes and R. grassei.


Input: Social insects exhibit remarkable variation in their colony breeding structures, both within and among species.


Input: Ecological factors are believed to be important in shaping reproductive traits of social insect colonies, yet there is little information linking specific environmental variables with differences in breeding structure.


Input: Subterranean termites (Rhinotermitidae) show exceptional variation in colony breeding structure, differing in the number of reproductives and degree of inbreeding; colonies can be simple families headed by a single pair of monogamous reproductives (king and queen) or they can be extended families headed by multiple inbreeding neotenic reproductives (wingless individuals).


Input: Using microsatellite markers, we characterized colony breeding structure and levels of inbreeding in populations over large parts of the range of the subterranean termites Reticulitermes flavipes in the USA and R. grassei in Europe.


Input: Combining these new data with previous results on populations of both species, we found that latitude had a strong effect on the proportion of extended-family colonies in R. flavipes and on levels of inbreeding in both species.


Input: We examined the effect of several environmental variables that vary latitudinally; while the degree of inbreeding was greatest in cool, moist habitats in both species, seasonality affected the species differently.


Input: Inbreeding in R. flavipes was most strongly associated with climatic variables (mean annual temperature and seasonality), whereas nonclimatic variables, including the availability of wood substrate and soil composition, were important predictors of inbreeding in R. grassei.


Input: These results are the first showing that termite breeding structure is shaped by local environmental factors and that species can vary in their responses to these factors.


Input: Analytical model for the deformation of a fluid-fluid interface beneath an AFM probe.


Input: We present an analytical solution for the shape of a fluid-fluid interface near a nanoscale solid sphere, which is a configuration motivated by common measurements with an atomic force microscope.


Input: The forces considered are surface tension, gravity, and the van der Waals attraction.


Input: The nonlinear governing equation has been solved previously using the method of matched asymptotic expansions, and this requires that the surface tension forces far exceed those of gravity, i. e., the Bond number is much less than one.


Input: We first present this method using a physically relevant scaling of the equations, then offer a new analytical solution valid for all Bond numbers.


Input: We show that one configuration with a large effective Bond number, and thus one requiring our new solution, is a nanothick liquid film spread over a solid substrate.


Input: The scaling implications of both analytical methods are considered, and both are compared with numerical solutions of the full equation.


Input: Luminescence enhancement of pyrene/dispersant nanoarrays driven by the nanoscale spatial effect on mixing.

pyrene


Input: This work presents a simple method to generate ordered chromophore/dispersant nanoarrays through a pore-filling process for a nanoporous polymer template to enhance chromophore luminescence.


Input: Fluorescence results combining with the morphological evolution examined by scanning probe microscopy reveal that the enhanced luminescence intensity reaches the maximum intensity as the nanopores of the template are completely filled by the chromophore/dispersant mixture.


Input: The variation is attributed to nanoscale spatial effect on the enhanced mixing efficiency of chromophore and dispersant, that is, the alleviation of self-quenching problem, as evidenced by the results of attenuated total reflection Fourier transform IR spectroscopy combining with grazing incident wide-angle X-ray diffraction.


Input: The enhanced luminescence of the chromophore/dispersant nanoarrays driven by the nanoscale spatial effect is highly promising for use in designing luminescent nanodevices.


Input: Hepatocyte growth factor activator inhibitor type 2 (HAI-2) modulates hepcidin expression by inhibiting the cell surface protease matriptase-2.


Input: Matriptase-2, a recently identified cell surface protease, is the key enzyme of iron homoeostasis modulating the expression of the liver peptide hormone hepcidin.

iron


Input: HAI (hepatocyte growth factor activator inhibitor) types 1 and 2 (HAI-1 and HAI-2 respectively) have been shown to inhibit the close homologue, i. e. matriptase.


Input: By co-expressing matriptase-2 and the inhibitor HAI-2 we have identified HAI-2 displaying high inhibitory potential against matriptase-2 at the cell surface as well as in conditioned medium.


Input: Accordingly, complex formation between matriptase-2 and HAI-2 was demonstrated by isolation of the complex via immobilizing either HAI-2 or matriptase-2 from lysates and conditioned medium of co-expressing cells.


Input: Furthermore, HAI-2 indirectly influences the expression of the hepcidin-encoding gene HAMP.


Input: The inhibitor abrogates the matriptase-2-mediated suppression of HAMP expression, presumably by inhibiting the supposed potential of matriptase-2 to cleave membrane-bound HJV (haemojuvelin).


Input: Taken together, the results of the present study have characterized HAI-2 as an inhibitor of matriptase-2 that modulates the synthesis of hepcidin and provides new insights into the regulatory mechanism of iron homoeostasis, with clinical importance for a treatment of iron overload diseases.

iron

iron


Input: Single-molecule force spectroscopy identifies a small cold shock protein as being mechanically robust.


Input: Single-molecule force spectroscopy has emerged as a powerful approach to examine the stability and dynamics of single proteins.


Input: We have completed force extension experiments on the small cold shock protein B from Thermotoga maritima, using a specially constructed chimeric polyprotein.


Input: The protein' s simple topology, which is distinct from the mechanically well-characterized beta-grasp and immunoglobulin (Ig)-like folds, in addition to the wide range of structural homologues resulting from its ancient origin, provides an attractive model protein for single-molecule force spectroscopy studies.


Input: We have determined that the protein has mechanical stability, unfolding at greater than 70 pN at a pulling velocity of 100 nm s (-1).


Input: We reveal features of the unfolding energy landscape by measuring the dependence of the mechanical stability on pulling velocity, in combination with Monte Carlo simulations.


Input: We show that the cold shock protein has mechanically robust, yet malleable, features that may be important in providing the protein with stability and flexibility to function over a range of environmental conditions.


Input: These results provide insights into the relationship between the secondary structure and topology of a protein and its mechanical strength.


Input: This lays the foundation for the investigation of the effects of changes in environmental conditions on the mechanical and dynamic properties of cold shock proteins.


Input: Synthesis and characterization of quarteranthene: elucidating the characteristics of the edge state of graphene nanoribbons at the molecular level.

quarteranthene

graphene


Input: The characteristics of the edge state, which is a peculiar magnetic state in zigzag-edged graphene nanoribbons (ZGNRs) that originates from electron-electron correlation in an edge-localized pi-state, are investigated by preparing and characterizing quarteranthene molecules.

graphene

quarteranthene


Input: The molecular geometry that was determined from the X-ray analysis is consistent with a zigzag-edge-localized structure of unpaired electrons.


Input: The localized electrons are responsible for the peculiar magnetic (room-temperature ferromagnetic correlation), optical (the lowest-lying doubly excited state), and chemical (peroxide bond formation) behaviors.

peroxide


Input: On the basis of these distinguishing properties and a careful consideration of the valence bonding, insight into the edge state of ZGNRs can be gained.


Input: Tobacco smoke modulates ozone-induced toxicity in rat lungs and central nervous system.

ozone


Input: Adult Sprague-Dawley (SD) male rats were exposed for a single 3 h period to air, ozone (O 3) or O 3) followed by tobacco smoke (O 3/TS).

ozone

O 3

O 3

O 3


Input: For pulmonary effects, bronchoalveolar lavage (BAL) cells and fluid were analyzed.


Input: Data revealed a significant increase in polymorphonuclear leukocytes (PMN), total protein and albumin concentrations in the O 3 group, reflecting inflammatory and toxic responses.

O 3


Input: A subsequent exposure to TS attenuated PMN infiltration into the airspaces and their recovery in the BAL.


Input: A similar reduction was observed for BAL protein and albumin in the O 3/TS group, but it was not statistically significant.

O 3


Input: We also observed a significant increase in BAL total antioxidant capacity following O 3 exposure, suggesting development of protective mechanisms for oxidative stress damage from O 3.

O 3

O 3


Input: Exposure to TS attenuated the levels of total antioxidant capacity.


Input: Lung tissue protein analysis showed a significant reduction of extracellular superoxide dismutase (EC-SOD) in the O 3 or O 3/TS group and catalase in the O 3/TS group.

superoxide

O 3

O 3

O 3


Input: TS further altered O 3-induced EC-SOD and catalase protein expression, but the reductions were not significant.

O 3


Input: For effects in the central nervous system (CNS), we measured striatal dopamine levels by HPLC with electrochemical detection.

dopamine


Input: O 3 exposure produced a nonsignificant decrease in the striatal dopamine content.

O 3


Input: The effect was partially reversed in the O 3/TS group.

O 3


Input: Overall, the results show that the toxicity of O 3 in the lung is modulated by TS exposure, and the attenuating trend, though nonsignificant in many cases, is contrary to the synergistic toxicity predicted for TS and O 3, suggesting limited cross-tolerance following such exposures.

O 3

O 3


Input: Comparison of dose-response relations between 4-week inhalation and intratracheal instillation of NiO nanoparticles using polimorphonuclear neutrophils in bronchoalveolar lavage fluid as a biomarker of pulmonary inflammation.

NiO


Input: Inhalation studies and intratracheal instillation studies using laboratory animals are commonly conducted for pulmonary toxicity tests of nanomaterials.


Input: In our study, male Wister rats were exposed to nickel oxide (NiO) particles including a nano-scale, even for aerosols and suspensions, in a 4-week inhalation and intratracheal instillation.

nickel oxide

NiO


Input: Using polymorphonuclear neutrophils (PMNs) in bronchoalveolar lavage fluid as a biomarker of inflammation, we attempted to quantify the relationship between responses to inhalation and intratracheal instillation of the nanoparticles, based on surface area doses.


Input: Four kinds of NiO suspension samples with different specific surface areas were singly injected via the tracheas of the rats.

NiO


Input: The relationship between the instilled doses and PMN production was examined 3 days and 1 month after the instillation.


Input: In parallel, 4-week inhalation studies, using two of the suspensions, were conducted for aerosols generated by a pressurized nebulizer.


Input: NiO samples induced PMN responses 3 days after instillation according to the surface area doses, but not the mass doses, as has been reported in many studies.

NiO


Input: When the same NiO samples were tested in a 4-week inhalation and intratracheal instillation, the amount of pulmonary deposition of the sample after the 4-week inhalation, and an intratracheally instilled dose about ten-times higher, induced similar PMN responses 3 days after termination of inhalation and instillation.

NiO