Input: The phage attachment site attP is located within the phage repressor gene such that chromosomal integration results in removal of a C-terminal tag that destabilizes the virally encoded form of the repressor.

C


Input: Integration thus not only confers prophage stability but also is a requirement for lysogenic establishment.


Input: The variety of these self-contained integration-dependent immunity systems in different genomic contexts suggests that these represent ancestral states in switch evolution from which more-complex switches have evolved.


Input: They also provide a powerful toolkit for building synthetic biological circuits.


Input: The novel delta opioid receptor agonist KNT-127 produces distinct anxiolytic-like effects in rats without producing the adverse effects associated with benzodiazepines.

benzodiazepines


Input: We previously reported that a delta opioid receptor agonist SNC80 produced potent anxiolytic-like effects in rodents.


Input: Recently, we succeeded in synthesizing a novel delta opioid receptor agonist KNT-127.


Input: In this study, we investigated the anxiolytic-like effects of KNT-127 using three different rat models of innate anxiety.


Input: In an elevated plus-maze test, KNT-127 (0. 3, 1, and 3. 0 mg/kg, s. c.) significantly and dose-dependently increased the time rats spent in the open arms 30 min after administration.


Input: The magnitude of the KNT-127 (3. 0 mg/kg, s. c.)-induced anxiolytic-like effects was similar to that produced by diazepam (1. 0 mg/kg, s. c.), a benzodiazepine anxiolytic.

diazepam

benzodiazepine


Input: The anxiolytic-like effects of KNT-127 (3. 0 mg/kg, s. c.) were abolished by pretreatment with naltrindole (0. 1 mg/kg, s. c.), a selective delta opioid receptor antagonist, suggesting that KNT-127-induced anxiolytic-like effects are mediated by delta opioid receptors.

naltrindole


Input: These findings were supported by results obtained from light/dark and open-field tests.


Input: Interestingly, in contrast to diazepam (1. 0 mg/kg, s. c.), KNT-127 (3. 0 mg/kg, s. c.) caused no significant performance changes in the Y-maze test, the ethanol-induced sleeping test, and footprint test.

diazepam

ethanol


Input: This is the first study to demonstrate that the novel delta opioid receptor agonist KNT-127 produces distinct anxiolytic-like effects in rats, without producing the adverse effects associated with benzodiazepines.

benzodiazepines


Input: Effect of monospecific antibodies against baltergin in myotoxicity induced by Bothrops alternatus venom from northeast of Argentina.


Input: Role of metalloproteinases in muscle damage.


Input: Myotoxicity, one of the most relevant local manifestations in envenomation by Bothrops genus, may result from a direct action of myotoxins or be due to an indirect vascular degeneration and ischemia.


Input: Baltergin, a snake venom metalloproteinase (SVMP), isolated from Bothrops alternatus venom has been used to obtain monospecific IgG, in order to determine the relative role of toxin in myotoxicity induced by whole venom.


Input: Bothrops diporus venom, another medical relevant genus of the northeastern region of Argentina, was also studied.


Input: Anti-baltergin IgG was able to neutralize completely the hemorrhagic activity of B. alternatus venom at an antibodies: venom ratio of 30: 1 (w: w).


Input: However, mice injected with B. diporus venom showed a small spot remaining even at the highest ratio of IgG: venom assayed (50: 1; w: w).


Input: Specific antibodies were efficient to neutralize the myotoxicity of B. alternatus venom at ratio 30: 1 (w: w) but did not neutralize the same effects in B. diporus venom.


Input: Anti-baltergin polyclonal antibodies were useful tools for revealing the central role of SVMPs in the development of myotoxicity of B. alternatus venom, as well as, helping to suggest indirectly presence of potent myotoxic phospholipases A2 (PLA2s) in B. diporus venom.


Input: Phthalate and di-(2-ethylhexyl) adipate (DEHA) intake by German infants based on the results of a duplicate diet study and biomonitoring data (INES 2).

Phthalate

di-(2-ethylhexyl) adipate

DEHA


Input: Phthalates as well as di-(2-ethylhexyl) adipate (DEHA) are used as plasticizers in diverse applications and are of toxicological concern.

Phthalates

di-(2-ethylhexyl) adipate

DEHA


Input: The study was conducted with a study population of 25 German subjects aged between 15 and 21 months.


Input: Overall, 16 phthalates and DEHA were measured by gas chromatography-mass spectrometry in a total of 171 duplicate diet samples collected over 7 consecutive days, and 20 phthalate metabolites were analyzed in the urine samples collected over 7 consecutive days using a liquid chromatography-tandem mass spectrometry method.

phthalates

DEHA

phthalate


Input: The median " high " daily dietary intake based on 95th percentiles was 4. 66 mu g/kg b. w. for di-2-ethylhexyl phthalate (DEHP), 1. 03 mu g/kg b. w. for di-isobutyl phthalate (DiBP), and 0. 70 mu g/kg b. w. for di-n-butyl phthalate (DnBP), and 1. 0 mu g/kg b. w. for DEHA.

di-2-ethylhexyl phthalate

DEHP

di-isobutyl phthalate

DiBP

di-n-butyl phthalate

DnBP

DEHA


Input: The " high " daily total intake from biomonitoring data was 4. 9 mu g/kg b. w. for DEHP, 2. 2 mu g/kg b. w. for DnBP, 3. 9 mu g/kg b. w. for DiBP, and 2. 6 mu g/kg b. w. for di-isononyl phthalate.

DEHP

DnBP

DiBP

di-isononyl phthalate


Input: The comparison of the two intake estimates indicates that the dominant intake source of DEHP was food ingestion, whereas other sources considerably contributed to the total intake of other phthalates.

DEHP

phthalates


Input: Using our " high " intake scenario, none of the analyzed phthalates reached the recommended tolerable daily intake levels.

phthalates


Input: The protective role of curcumin on perfluorooctane sulfonate-induced genotoxicity: single cell gel electrophoresis and micronucleus test.

curcumin

perfluorooctane sulfonate


Input: Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant and global pollutant.

Perfluorooctane sulfonate

PFOS


Input: PFOS a persistent and bioaccumulative compound, is widely distributed in humans and wildlife.

PFOS


Input: Therefore, it was added to Annex B of the Stockholm Convention on Persistent Organic Pollutants in May 2009.


Input: Curcumin is a natural polyphenolic compound abundant in the rhizome of the perennial herb turmeric.

Curcumin

polyphenolic


Input: It is commonly used as a dietary spice and coloring agent in cooking and anecdotally as an herb in traditional Asian medicine.


Input: In this study, male rats were treated with three different PFOS doses (0. 6, 1. 25 and 2. 5 mg/kg) and one dose of curcumin, from Curcuma longa (80 mg/kg) and combined three doses of PFOS with 80 mg/kg dose of curcumin by gavage for 30 days at 48 h intervals.

PFOS

curcumin


Input: Here, we evaluated the DNA damage via single cell gel electrophoresis or comet assay and micronucleus test in bone marrow in vivo.


Input: PFOS induced micronucleus frequency and decreased the ratio of polychromatic erythrocyte to normochromatic erythrocyte in bone marrow.

PFOS


Input: Using the alkaline comet assay, we showed that all doses of the PFOS strongly induced DNA damage in rat bone marrow and curcumin prevented the formation of DNA damage induced by PFOS.

PFOS

curcumin

PFOS


Input: Lead-induced neurodegenerative events and abnormal behaviors occur via ORXRergic/GABA (A) Rergic mechanisms in a marine teleost.

GABA


Input: The hindering effects of metals and in particular lead (Pb) are representing a growing threat to aquatic organisms such as fish.

Pb


Input: This observation derives from toxic concentrations of Pb accounting for altered neurophysiological activities of some interesting teleost models like Thalassoma pavo, a fish species highly known for its host-cleaning symbiosis.

Pb


Input: In this study, the nominal PbNO (3) concentration of 1. 6 mg/L was capable of reducing feeding and resting bouts as early as 24 h of exposure while hyperactive swimming episodes were also detected.

PbNO (3)


Input: Such abnormal behaviors were tightly correlated to up-regulated orexin receptor (ORXR) mRNA expression levels in some brain areas such as the lateral thalamic nucleus (+ 213%) and the optic tectum (+ 90%) with respect to controls.


Input: Interestingly, these transcriptional effects seemed to be attenuated when Pb-exposed fish received either 100 ng/g of ORX-A (-70%) or 0. 1 mu g/g of gamma-aminobutyric acid (A) receptor (GABA (A) R) agonist muscimol (MUS;-97%) compared to fish exposed to Pb alone.

Pb

gamma-aminobutyric acid

GABA

muscimol

MUS

Pb


Input: Moreover, a net neurodegenerative process of the different brain areas was reported after Pb exposure as displayed by their marked amino cupric silver stained cells while these cells were devoid of any staining reaction after treatment with MUS only.

Pb

amino cupric silver

MUS


Input: Conversely, addition of the GABA (A) R antagonist bicuculline (BIC; 1 mu g/g) moderately (p < 0. 05) enhanced Pb-dependent behavioral and neurodegenerative actions.

GABA

bicuculline

BIC

Pb


Input: Overall, these first indications strongly point to altered ORXR/GABA (A) R interactions during neurotoxic events of a metal that by evoking harmful neurobiological dysfunctions may endanger the survival of commercially valuable fish with eventual repercussions on human health.

GABA


Input: A p21-activated kinase (PAK1) signaling cascade coordinately regulates F-actin remodeling and insulin granule exocytosis in pancreatic beta cells.


Input: Human islet studies implicate an important signaling role for the Cdc42 effector protein p21-activated kinase (PAK1) in the sustained/second-phase of insulin secretion.


Input: Because human islets from type 2 diabetic donors lack ~ 80% of normal PAK1 protein levels, the mechanistic requirement for PAK1 signaling in islet function was interrogated.


Input: Similar to MIN6 beta cells, human islets elicited glucose-stimulated PAK1 activation that was sensitive to the PAK1 inhibitor, IPA3.

glucose


Input: Given that sustained insulin secretion has been correlated with glucose-induced filamentous actin (F-actin) remodeling, we tested the hypothesis that a Cdc42-activated PAK1 signaling cascade is required to elicit F-actin remodeling to mobilize granules to the cell surface.

glucose


Input: Live-cell imaging captured the glucose-induced cortical F-actin remodeling in MIN6 beta cells; IPA3-mediated inhibition of PAK1 abolished this remodeling.

glucose


Input: IPA3 also ablated glucose-stimulated insulin granule accumulation at the plasma membrane, consistent with its role in sustained/second-phase insulin release.

glucose


Input: Both IPA3 and a selective inhibitor of the Cdc42 GTPase, ML-141, blunted the glucose-stimulated activation of Raf-1, suggesting Raf-1 to be downstream of Cdc42 --> PAK1.

glucose


Input: IPA3 also inhibited MEK1/2 activation, implicating the MEK1/2 --> ERK1/2 cascade to occur downstream of PAK1.


Input: Importantly, PD0325901, a new selective inhibitor of MEK1/2 --> ERK1/2 activation, impaired F-actin remodeling and the sustained/amplification pathway of insulin release.


Input: Taken together, these data suggest that glucose-mediated activation of Cdc42 leads to activation of PAK1 and prompts activation of its downstream targets Raf-1, MEK1/2 and ERK1/2 to elicit F-actin remodeling and recruitment of insulin granules to the plasma membrane to support the sustained phase of insulin release.

glucose


Input: Beta-glucogallin reduces the expression of lipopolysaccharide-induced inflammatory markers by inhibition of aldose reductase in murine macrophages and ocular tissues.

Beta-glucogallin

aldose


Input: Aldose reductase (AR) catalyzes the reduction of toxic lipid aldehydes to their alcohol products and mediates inflammatory signals triggered by lipopolysaccharide (LPS).

Aldose

aldehydes

alcohol


Input: Beta-glucogallin (BGG), a recently described AR inhibitor, was purified from extracts of the Indian gooseberry (Emblica officinalis).

Beta-glucogallin

BGG


Input: In this study, we found that BGG showed low cytotoxicity in Raw264. 7 murine macrophages and effectively inhibited AR activity as measured by a decrease in sorbitol accumulation.

BGG

sorbitol


Input: In addition, BGG-mediated inhibition of AR prevented LPS-induced activation of JNK and p38 and lowered ROS levels, which could inhibit LPS-induced apoptosis.

BGG


Input: Uveitis is a disease of the eye associated with chronic inflammation.


Input: In this study, we also demonstrated that treatment with BGG decreased the number of inflammatory cells that infiltrate the ocular media of mice with experimental uveitis.

BGG


Input: Accordingly, these results suggest BGG is a potential therapy for inflammatory diseases.

BGG


Input: Regulation of human carbonyl reductase 1 (CBR1, SDR21C1) gene by transcription factor Nrf2.

carbonyl


Input: Monomeric carbonyl reductase 1 (CBR1, SDR21C1) is a member of the short-chain dehydrogenase/reductase superfamily and is involved in the metabolism of anthracycline anti-cancer drugs, prostaglandins, and isatin, which is an endogenous inhibitor of monoamine oxidases.

carbonyl

anthracycline

prostaglandins

isatin

monoamine


Input: Additionally, cancer progression may be partly regulated by CBR1.


Input: In the present study, we screened more than 10 drugs for the induction of the human CBR1 gene to investigate its regulation.


Input: Of the drugs, butylated hydroxyanisole (BHA) was found to be an inducer.

butylated hydroxyanisole

BHA


Input: BHA induced the mRNA and protein expression of CBR1 in hepatoma HepG2 cells.

BHA


Input: In a luciferase reporter gene assay, the promoter region between-2062 bp and the transcription start site of CBR1 was also activated by BHA.


Input: The transcription factor Nrf2 is known to be activated by BHA.

BHA


Input: There are 2 anti-oxidant responsive elements (ARE) that are bound by Nrf2 in this region.


Input: Mutation analyses revealed that one of the AREs participates in the gene regulation of CBR1 by Nrf2.


Input: Electrophoretic mobility shift assay revealed that Nrf2 binds the site.


Input: Moreover, to determine whether the functional ARE of CBR1 is conserved with the promoter region of homologues in other species, the nucleotide sequences of the functional AREs of the Chcr1 and Chcr2 genes, which are the Chinese hamster homologues of CBR1, were determined.

nucleotide


Input: The region has 2 AREs, and these genes were also induced by the forced expression of Nrf2 (cotransfection of pNrf2) in the luciferase reporter gene assay.


Input: In conclusion, Nrf2 is a novel transcriptional regulator of CBR1 genes in humans and the Chinese hamster.


Input: Because the regulation of CBR1 appears to be important for diseases, the induction of CBR1 by Nrf2 may be a therapeutic target.


Input: Engineering polypeptide coatings to augment gene transduction and in vivo stability of adenoviruses.


Input: We sought to modify adenoviral (Ad) particles by incorporating the advantageous characteristics of non-viral gene delivery vehicles to complement the viral vectors.


Input: alpha-Amino acid-N-carboxyanhydride chemistry was used to synthesize homopolypeptides and diblock copolypeptides that possess well-defined secondary structures.

alpha-Amino acid-N-carboxyanhydride


Input: Using cryo-electron and fluorescence microscopy, we showed that these polypeptides can coat the surfaces of Ad particles in a non-covalent manner to modify their transduction properties.


Input: The coated Ad particles were found to bind to and be internalized by cells.


Input: In contrast to reports using covalently PEGylated Ad particles, we found that our physically coated Ad hybrid complexes facilitate gene transfer both in vitro and in vivo.


Input: We showed that our polypeptide coating was able to shield the Ad particles from the neutralizing effect of antibodies and mitigate the binding of blood coagulation factor (Factor X) in vitro.


Input: The coating also reduced the antigenicity of Ad in immunocompetent mice.


Input: The biodistribution of the systemically administered hybrid complexes mirrored the behavior of both viral and non-viral vectors, exhibiting liver tropism as well as enhanced lung transduction.


Input: These data demonstrated that our non-covalent modification was able to alter Ad' s interactions with cells and organs with retention of transduction efficiency.


Input: Advantages such as facile coating of the Ad vector, design flexibility and ease of attaching ligands to the polypeptides make this system potentially useful as a platform for adding functionalities to Ad to target cancer metastasis.


Input: Chirality recognition of the protonated serine dimer and octamer by infrared multiphoton dissociation spectroscopy.

serine


Input: Infrared multiphoton dissociation (IRMPD) spectroscopy has been used to record IR signatures of chirality recognition in the protonated serine dimer and octamer in the 3200-3800 cm (-1) region.

serine


Input: This is the first IRMPD study to investigate the heterochiral biomolecular system by utilizing the isotope-labelled species.


Input: Noticeable differences in the homo-versus heterochiral IRMPD spectra have been obtained experimentally for both the dimer and octamer.


Input: Different dissociation patterns have been noted not only between the homo-and heterochiral octamers, but also between the two-OH stretching vibrational bands of the same chirality species.

OH


Input: Systematic theoretical searches have been carried out to identify the most stable conformers of both the homo-and heterochiral protonated serine dimer and octamer.

serine


Input: The final geometry optimization and harmonic vibrational calculations have been performed at the MP2/6-311 + + G (d, p) level for the homo-and heterochiral protonated serine dimer and at the B3LYP/6-31G (d) level for the homo-and heterochiral protonated serine octamer.

serine


Input: For the homo-and heterochiral dimer, good agreement between the experimental and theoretical spectra has been achieved and the major conformers have been identified.


Input: For the homo-and heterochiral octamer, the main IR features observed have been satisfactorily reproduced theoretically and the dominant conformers identified.


Input: More than one main conformer has been identified for the homochiral octamer.


Input: This conclusion has been further supported by the analysis of the wavelength specific dissociation products.


Input: Sophorolipids-functionalized iron oxide nanoparticles.

iron oxide


Input: Functional iron oxide nanoparticles (NP) have been synthesized in a one and a two-step method using a natural functional glycolipid belonging to the family of sophorolipids (SL).

iron oxide


Input: These compounds, whose open acidic form is highly suitable for nanoparticle stabilization, are readily obtained by a fermentation process of the yeast Candida bombicola (polymorph Starmerella bombicola) in large amounts.


Input: The final carbohydrate coated iron oxide nanoparticles represent interesting potentially biocompatible materials for biomedical applications.

carbohydrate

iron oxide


Input: According to the synthesis strategy, magnetic properties can eventually be tuned, thus putting in evidence the direct effect of the glycolipid on the final material' s structure (maghemite and ferrihydrite have been obtained here).

maghemite

ferrihydrite


Input: A combination of FT-IR, Dynamic Light Scattering (DLS) and UV-Vis experiments shows that SL complex the nanoparticle surface via their accessible COOH group thus forming stable colloids, whose hydrodynamic diameter mostly varies between 10 nm and 30 nm, both in water and in KCl-containing (0. 01 M and 2 M) solutions.

COOH

KCl


Input: The materials can stand multiple filtration steps (up to 10) at different extents, where the largest recorded average aggregate size is 100 nm.


Input: In general, materials synthesized at T = 80 degrees C display better stability and smaller size distribution than those obtained at room temperature.


Input: Nicotinic receptors in addiction pathways.


Input: Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that consist of pentameric combinations of alpha and beta subunits.

acetylcholine


Input: These receptors are widely distributed throughout the brain and are highly expressed in addiction circuitry.


Input: The role of nAChRs in regulating neuronal activity and motivated behavior is complex and varies both in and among brain regions.


Input: The rich diversity of central nAChRs has hampered the characterization of their structure and function with use of classic pharmacological techniques.


Input: However, recent molecular approaches using null mutant mice with specific regional lentiviral re-expression, in combination with neuroanatomical and electrophysiological techniques, have allowed the elucidation of the influence of different nAChR types on neuronal circuit activity and behavior.


Input: This review will address the influence of nAChRs on limbic dopamine circuitry and the medial habenula-interpeduncular nucleus complex, which are critical mediators of reinforced behavior.

dopamine


Input: Characterization of the mechanisms underlying regulation of addiction pathways by endogenous cholinergic transmission and by nicotine may lead to the identification of new therapeutic targets for treating tobacco dependence and other addictions.

nicotine


Input: TGF beta receptor signaling is essential for inflammation-induced but not beta-cell workload-induced beta-cell proliferation.


Input: Protection and restoration of a functional beta-cell mass are fundamental strategies for prevention and treatment of diabetes.


Input: Consequently, knowledge of signals that determine the functional beta-cell mass is of immense clinical relevance.


Input: Transforming growth factor beta (TGF beta) superfamily signaling pathways play a critical role in development and tissue specification.


Input: Nevertheless, the role of these pathways in adult beta-cell homeostasis is not well defined.


Input: Here, we ablated TGF beta receptor I and II genes in mice undergoing two surgical beta-cell replication models (partial pancreatectomy or partial duct ligation), representing two triggers for beta-cell proliferation, increased beta-cell workload and local inflammation, respectively.


Input: Our data suggest that TGF beta receptor signaling is necessary for baseline beta-cell proliferation.


Input: By either provision of excess glucose or treatment with exogenous insulin, we further demonstrated that inflammation and increased beta-cell workload are both stimulants for beta-cell proliferation but are TGF beta receptor signaling dependent and independent, respectively.

glucose


Input: Collectively, by using a pancreas-specific TGF beta receptor-deleted mouse model, we have identified two distinct pathways that regulate adult beta-cell proliferation.


Input: Our study thus provides important information for understanding beta-cell proliferation during normal growth and in pancreatic diseases.


Input: Impact of restricted maternal weight gain on fetal growth and perinatal morbidity in obese women with type 2 diabetes.


Input: OBJECTIVE Since January 2008, obese women with type 2 diabetes were advised to gain 0-5 kg during pregnancy.


Input: The aim with this study was to evaluate fetal growth and perinatal morbidity in relation to gestational weight gain in these women.


Input: RESEARCH DESIGN AND METHODS A retrospective cohort comprised the records of 58 singleton pregnancies in obese women (BMI >= 30 kg/m (2)) with type 2 diabetes giving birth between 2008 and 2011.


Input: Birth weight was evaluated by SD z score to adjust for gestational age and sex.


Input: RESULTS Seventeen women (29%) gained <= 5 kg, and the remaining 41 gained > 5 kg.


Input: The median (range) gestational weight gains were 3. 7 kg (-4. 7 to 5 kg) and 12. 1 kg (5. 5-25. 5 kg), respectively.


Input: Prepregnancy BMI was 33. 5 kg/m (2) (30-53 kg/m (2)) vs. 36. 8 kg/m (2) (30-48 kg/m (2)), P = 0. 037, and median HbA1c was 6. 7% at first visit in both groups and decreased to 5. 7 and 6. 0%, P = 0. 620, in late pregnancy, respectively.


Input: Gestational weight gain <= 5 kg was associated with lower birth weight z score (P = 0. 008), lower rates of large-for-gestational-age (LGA) infants (12 vs. 39%, P = 0. 041), delivery closer to term (268 vs. 262 days, P = 0. 039), and less perinatal morbidity (35 vs. 71%, P = 0. 024) compared with pregnancies with maternal weight gain > 5 kg.


Input: CONCLUSIONS In this pilot study in obese women with type 2 diabetes, maternal gestational weight gain <= 5 kg was associated with a more proportionate birth weight and less perinatal morbidity.


Input: Statins and Risk of Diabetes: An analysis of electronic medical records to evaluate possible bias due to differential survival.

Statins


Input: OBJECTIVE Two meta-analyses of randomized trials of statins found increased risk of type 2 diabetes.

statins


Input: One possible explanation is bias due to differential survival when patients who are at higher risk of diabetes survive longer under statin treatment.

statin


Input: RESEARCH DESIGN AND METHODS We used electronic medical records from 500 general practices in the U. K. and included data from 285, 864 men and women aged 50-84 years from January 2000 to December 2010.


Input: We emulated the design and analysis of a hypothetical randomized trial of statins, estimated the observational analog of the intention-to-treat effect, and adjusted for differential survival bias using inverse-probability weighting.

statins


Input: RESULTS During 1. 2 million person-years of follow-up, there were 13, 455 cases of type 2 diabetes and 8, 932 deaths.


Input: Statin initiation was associated with increased risk of type 2 diabetes.

Statin


Input: The hazard ratio (95% CI) of diabetes was 1. 45 (1. 39-1. 50) before adjusting for potential confounders and 1. 14 (1. 10-1. 19) after adjustment.


Input: Adjusting for differential survival did not change the estimates.


Input: Initiating atorvastatin and simvastatin was associated with increased risk of type 2 diabetes.

atorvastatin

simvastatin


Input: CONCLUSIONS In this sample of the general population, statin therapy was associated with 14% increased risk of type 2 diabetes.

statin


Input: Differential survival did not explain this increased risk.


Input: Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione.

glutathione


Input: Increasing antibiotic resistance makes the identification of new antibacterial principles an urgent task.


Input: The thioredoxin system including thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH plays critical roles in cellular DNA synthesis and defense against oxidative stress.

NADPH


Input: Notably, TrxR is very different in structure and mechanism in mammals and bacteria.


Input: Ebselen [2-phenyl-1, 2 benzisoselenazol-3 (2H)-one], a well-known antioxidant and a substrate for mammalian TrxR and Trx, is rapidly bacteriocidal for methicillin-resistant Staphylococcus aureus by an unknown mechanism.

Ebselen

2-phenyl-1, 2 benzisoselenazol-3 (2H)-one

methicillin


Input: We have discovered that ebselen is a competitive inhibitor of Escherichia coli TrxR with a Ki of 0. 52 +/- 0. 13 mu M, through reaction with the active site dithiol of the enzyme.

ebselen

dithiol


Input: Bacteria lacking glutathione (GSH) and glutaredoxin, in which TrxR and Trx are essential for DNA synthesis, were particularly sensitive to ebselen.

glutathione

GSH


Input: In growth-inhibited E. coli strains, Trx1 and Trx2 were oxidized, demonstrating that electron transfer via thioredoxin was blocked.


Input: Ebselen and its sulfur analog ebsulfur were bactericidal for GSH-negative pathogens.

Ebselen

sulfur

ebsulfur

GSH


Input: Ebsulfur inhibited a clinically isolated Helicobacter pylori strain with a minimum inhibitory concentration value as low as 0. 39 mu g/ml.

Ebsulfur


Input: These results demonstrate that bacterial Trx and TrxR are viable antibacterial drug targets using benzisoselenazol and benzisothiazol derivates.-Lu, J., Vlamis-Gardikas, A., Kandasamy, K., Zhao, R., Gustafsson, T.

benzisoselenazol

benzisothiazol


Input: N., Engstrand, L., Hoffner, S., Engman, L., Holmgren, A.


Input: Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione.


Input: Progress of pharmacological studies on alkaloids from Apocynaceae.


Input: Alkaloid was a kind of biological active ingredient.


Input: There were various types of alkaloids in Apocynaceae.


Input: This paper reviewed the progress on alkaloids from Apocynaceae, which contained origin, structure, and pharmacological activity.


Input: Multifaceted ultrafast intramolecular charge transfer dynamics of 4-(dimethylamino) benzonitrile (DMABN).

4-(dimethylamino) benzonitrile

DMABN


Input: Intramolecular charge transfer (ICT) of DMABN has been the subject of extensive investigations.

DMABN


Input: Through the measurements of highly time-resolved fluorescence spectra (TRFS) over the whole emission region, we have examined the ICT dynamics of DMABN in acetonitrile free from the solvation dynamics and vibronic relaxation.

DMABN

acetonitrile


Input: The ICT dynamics was found to be characterized by a broad range of time scales; nearly instantaneous (< 30 fs), 160 fs, and 3. 3 ps.


Input: TRFS revealed that an ICT state with partially twisted geometry, ICT (P), is formed within a few hundred femtoseconds either directly from the initial photoexcited state or via the locally excited (LE) state.


Input: The ICT (P) state undergoes further relaxation along the intramolecular nuclear coordinate to reach the twisted ICT (TICT) state with the time constant of 4. 8 ps.


Input: A conformational diversity along the rotation of the dimethylamino group was speculated to account for the observed diffusive dynamics.

dimethylamino


Input: Light-harvesting and ultrafast energy migration in porphyrin-based metal-organic frameworks.

porphyrin


Input: Given that energy (exciton) migration in natural photosynthesis primarily occurs in highly ordered porphyrin-like pigments (chlorophylls), equally highly ordered porphyrin-based metal-organic frameworks (MOFs) might be expected to exhibit similar behavior, thereby facilitating antenna-like light-harvesting and positioning such materials for use in solar energy conversion schemes.

porphyrin

chlorophylls

porphyrin


Input: Herein, we report the first example of directional, long-distance energy migration within a MOF.


Input: Two MOFs, namely F-MOF and DA-MOF that are composed of two Zn (II) porphyrin struts [5, 15-dipyridyl-10, 20-bis (pentafluorophenyl) porphinato] zinc (II) and [5, 15-bis [4-(pyridyl) ethynyl]-10, 20-diphenylporphinato] zinc (II), respectively, were investigated.

Zn (II) porphyrin

[5, 15-dipyridyl-10, 20-bis (pentafluorophenyl) porphinato] zinc (II)

[5, 15-bis [4-(pyridyl) ethynyl]-10, 20-diphenylporphinato] zinc (II)


Input: From fluorescence quenching experiments and theoretical calculations, we find that the photogenerated exciton migrates over a net distance of up to ~ 45 porphyrin struts within its lifetime in DA-MOF (but only ~ 3 in F-MOF), with a high anisotropy along a specific direction.

porphyrin


Input: The remarkably efficient exciton migration in DA-MOF is attributed to enhanced pi-conjugation through the addition of two acetylene moieties in the porphyrin molecule, which leads to greater Q-band absorption intensity and much faster exciton-hopping (energy transfer between adjacent porphyrin struts).

acetylene

porphyrin

porphyrin


Input: The long distance and directional energy migration in DA-MOF suggests promising applications of this compound or related compounds in solar energy conversion schemes as an efficient light-harvesting and energy-transport component.


Input: Interaction of OH radicals with Arizona Test Dust: uptake and products.

OH


Input: Kinetics and products of the interaction of OH radicals with solid films of Arizona Test Dust (ATD) were studied using a low pressure flow reactor (0. 5-3 Torr) combined with a modulated molecular beam mass spectrometer for monitoring of the gaseous species involved.

OH


Input: The reactive uptake coefficient of OH was measured from the kinetics of OH consumption on Pyrex rods coated with ATD as a function of OH concentration ((0. 4-5. 2) x 10 (12) molecules cm (-3)), relative humidity (RH = 0. 03-25. 9%), temperature (T = 275-320 K), and UV irradiance intensity (J (NO (2)) = 0-0. 012 s (-1)).

OH

OH

OH

NO (2)


Input: Deactivation of ATD surface upon exposure to OH was observed.

OH


Input: The initial uptake coefficient was found to be independent of temperature and irradiation conditions and to decrease with relative humidity: gamma (0) = 0. 2/(1 + RH (0. 36)) (calculated using geometric surface area, with 30% estimated conservative uncertainty).


Input: H (2) O (2) and H (2) O were observed in the gas phase as products of the OH reaction with ATD surface with yields of (10 +/- 3) and (98 +/- 25)%, respectively.

H (2) O (2)

H (2) O

OH


Input: Quinpirole and 8-OH-DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit.

Quinpirole


Input: This study investigated whether the serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) can induce compulsive checking in a large open field, as does the dopamine D2/D3 receptor agonist quinpirole.

serotonin

8-hydroxy-2-(di-n-propylamino) tetralin

dopamine

quinpirole


Input: To induce compulsive checking, male rats were exposed to eight injections of either 8-OH-DPAT (1 mg/kg), quinpirole (0. 2 mg/kg), or saline.

quinpirole


Input: Subsequently, to assess cross-sensitization, rats received an acute challenge of 8-OH-DPAT or quinpirole.

quinpirole


Input: The results showed that treatment with 8-OH-DPAT induces compulsive checking and may have a stronger effect on this behavior compared with quinpirole.

quinpirole


Input: However, there was no cross-sensitization between 8-OH-DPAT and quinpirole on measures of compulsive checking and locomotion.

quinpirole


Input: Moreover, the spatial distribution of locomotor paths in 8-OH-DPAT animals was more confined and invariant than in quinpirole rats; their rate of locomotor sensitization was also faster than that in quinpirole animals.

quinpirole

quinpirole


Input: Thus, although 8-OH-DPAT and quinpirole can induce compulsive checking in a large open field, the results suggest that they do so differently.

quinpirole


Input: It is suggested that 8-OH-DPAT and quinpirole probably produce compulsive behavior by acting on different parts of a security motivation circuit underlying obsessive-compulsive disorder.

quinpirole


Input: Quinpirole may induce compulsive checking behavior by directly driving dopaminergic activity mediating the motivational drive to check.

Quinpirole


Input: Conversely, 8-OH-DPAT may perpetuate the activated motivational state by inhibiting the serotonergic-negative feedback signals that normally deactivate the obsessive-compulsive disorder circuit.


Input: Antibiotics that bind to the A site of the large ribosomal subunit can induce mRNA translocation.


Input: In the absence of elongation factor EF-G, ribosomes undergo spontaneous, thermally driven fluctuation between the pre-translocation (classical) and intermediate (hybrid) states of translocation.


Input: These fluctuations do not result in productive mRNA translocation.


Input: Extending previous findings that the antibiotic sparsomycin induces translocation, we identify additional peptidyl transferase inhibitors that trigger productive mRNA translocation.

sparsomycin


Input: We find that antibiotics that bind the peptidyl transferase A site induce mRNA translocation, whereas those that do not occupy the A site fail to induce translocation.


Input: Using single-molecule FRET, we show that translocation-inducing antibiotics do not accelerate intersubunit rotation, but act solely by converting the intrinsic, thermally driven dynamics of the ribosome into translocation.


Input: Our results support the idea that the ribosome is a Brownian ratchet machine, whose intrinsic dynamics can be rectified into unidirectional translocation by ligand binding.


Input: Circular RNAs are abundant, conserved, and associated with ALU repeats.


Input: Circular RNAs composed of exonic sequence have been described in a small number of genes.


Input: Thought to result from splicing errors, circular RNA species possess no known function.


Input: To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R.


Input: We identified > 25, 000 distinct RNA species in human fibroblasts that contained non-colinear exons (a " backsplice ") and were reproducibly enriched by exonuclease degradation of linear RNA.


Input: These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo.


Input: In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by > 10-fold.


Input: By conservative estimate, we identified ecircRNAs from 14. 4% of actively transcribed genes in human fibroblasts.


Input: Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs.


Input: Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice.


Input: Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes.


Input: Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs.


Input: Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats.


Input: These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.


Input: The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes.

bile acid

glucose


Input: We designed an experiment to examine the effect of bile acid sequestration with Colesevelam on fasting and postprandial glucose metabolism in type 2 diabetes.

bile acid

Colesevelam

glucose


Input: To do so, we tested the hypothesis that Colesevelam increases the disposition index (DI), and this increase is associated with increased glucagon-like peptide-1 (GLP-1) concentrations.

Colesevelam


Input: Thirty-eight subjects on metformin monotherapy were studied using a double-blind, placebo-controlled, parallel-group design.

metformin


Input: Subjects were studied before and after 12 weeks of Colesevelam or placebo using a labeled triple-tracer mixed meal to measure the rate of meal appearance (Meal Ra), endogenous glucose production (EGP), and glucose disappearance (Rd).

Colesevelam

glucose

glucose


Input: Insulin sensitivity and beta-cell responsivity indices were estimated using the oral minimal model and then used to calculate DI.


Input: Therapy with Colesevelam was associated with a decrease in fasting (7. 0 +/- 0. 2 vs. 6. 6 +/- 0. 2 mmol/L; P = 0. 004) and postprandial glucose concentrations (3, 145 +/- 138 vs. 2, 896 +/- 127 mmol/6 h; P = 0. 01) in the absence of a change in insulin concentrations.

Colesevelam

glucose


Input: Minimal model-derived indices of insulin secretion and action were unchanged.


Input: Postprandial GLP-1 concentrations were not altered by Colesevelam.

Colesevelam


Input: Although EGP and Rd were unchanged, integrated Meal Ra was decreased by Colesevelam (5, 191 +/- 204 vs. 5, 817 +/- 204 mu mol/kg/6 h; P = 0. 04), suggesting increased splanchnic sequestration of meal-derived glucose.

Colesevelam

glucose


Input: Comparison of tissue metal concentrations in Zucker lean, Zucker obese, and Zucker diabetic fatty rats and the effects of chromium supplementation on tissue metal concentrations.

fatty rats

chromium


Input: Diabetes results in several metabolic changes, including alterations in the transport, distribution, excretion, and accumulation of metals.


Input: While changes have been examined in several rat models of insulin resistance and diabetes, the metal ion concentrations in the tissues of Zucker lean, Zucker obese (an insulin resistance and early stage diabetes model), and Zucker diabetic fatty (ZDF, a type 2 diabetes model) have not previously been examined in detail.


Input: The concentration of Cu, Zn, Fe, Mg, and Ca were examined in the liver, kidney, heart and spleen, and Cr concentration in the liver and kidney of these rats were examined.

Cu

Zn

Fe

Mg

Ca

Cr


Input: Zucker obese rats have a reduction in the concentration of Cu, Zn, Fe, Mg in the liver compared to ZDF and/or lean Zucker rats, presumably as a result of the increased fat content of the liver of the obese rats.

Cu

Zn

Fe

Mg


Input: ZDF rats have increased concentrations of kidney Cu compared to the lean rats, while kidney Ca concentrations are increased in the Zucker obese rats.

Cu

Ca


Input: Spleen Fe concentrations are decreased in Zucker obese rats compared to the lean rats.

Fe


Input: No effects on metal concentrations in the heart were observed between the lean, obese, and ZDF rats, and no effects on Cr concentrations were identified.

Cr


Input: Cr (III) complexes have previously been shown to have beneficial effects on the signs of insulin resistance in Zucker obese and ZDF rats.

Cr (III)


Input: The effects of daily gavage administration of chromium picolinate ([Cr (pic) (3)]) (1 mg Cr/kg body mass), CrCl (3) (1 mg Cr/kg body mass), and Cr3 ([Cr (3) O (propionate) (6) (H (2) O) (3)] (+)) (33 mu g and 1 mg Cr/kg body mass) on metal concentrations in these tissues were examined.

chromium picolinate

[Cr (pic) (3)]

Cr

CrCl (3)

Cr

Cr3 ([Cr (3) O (propionate) (6) (H (2) O) (3)] (+))

Cr


Input: Treatment with CrCl (3) and Cr3, but not [Cr (pic) (3)], at 1 mg Cr/kg resulted in a statistically significant accumulation of Cr in the kidney of lean and obese but not ZDF rats but resulted in lowering the elevated levels of kidney Cu in ZDF rats, suggesting a beneficial effect on this symptom of type 2 diabetes.

CrCl (3)

[Cr (pic) (3)]

Cr

Cr

Cu


Input: Curcumin improves TNBS-induced colitis in rats by inhibiting IL-27 expression via the TLR4/NF-kappa B signaling pathway.

Curcumin


Input: Curcumin is a widely used spice with anti-inflammatory and anticancer properties.

Curcumin


Input: It has been reported to have beneficial effects in experimental colitis.


Input: This study explored whether curcumin improves colonic inflammation in a rat colitis model through inhibition of the TLR4/NF-kappa B signaling pathway and IL-27 expression.

curcumin


Input: After induction of colitis with 2, 4, 6-trinitrobenzene sulfonic acid, rats were intragastrically administered with curcumin or sulfasalazine daily for one week.

2, 4, 6-trinitrobenzene sulfonic acid

curcumin

sulfasalazine


Input: Rat intestinal mucosa was collected for evaluation of the disease activity index, colonic mucosa damage index, and histological score.


Input: Myeloperoxidase activity was detected by immunohistochemistry, and mRNA and protein expression levels of TLR4, NF-kappa B, and IL-27 in colonic mucosa were detected by RT-PCR and Western blot.


Input: Compared with the untreated colitis group, the curcumin-treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF-kappa B mRNA, IL-27 mRNA, TLR4 protein, NF-kappa B p65 protein, and IL-27 p28 protein (p < 0. 05).

curcumin


Input: TLR4 mRNA expression did not differ between groups.


Input: Disease activity index decreased more rapidly in the curcumin-treated group than in the sulfasalazine-treated group (p < 0. 05).

curcumin

sulfasalazine


Input: There was no significant difference in TLR4, NF-kappa B, and IL-27 mRNA and proteins between curcumin-treated and sulfasalazine-treated groups.

curcumin

sulfasalazine


Input: Curcumin shows significant therapeutic effects on 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis that are comparable to sulfasalazine.

Curcumin

2, 4, 6-trinitrobenzene sulfonic acid

sulfasalazine


Input: The anti-inflammatory actions of curcumin on colitis may involve inhibition of the TLR4/NF-kappa B signaling pathway and of IL-27 expression.

curcumin


Input: Lightweight and strong cellulose materials made from aqueous foams stabilized by nanofibrillated cellulose.


Input: A lightweight and strong porous cellulose material has been prepared by drying aqueous foams stabilized with surface-modified nanofibrillated cellulose (NFC).


Input: This material differs from other dry, particle stabilized foams in that renewable cellulose is used as stabilizing particles.


Input: Confocal microscopy and high speed video imaging show that the octylamine-coated, rod-shaped NFC nanoparticles residing at the air-liquid interface prevent the air bubbles from collapsing or coalescing.

octylamine


Input: Stable wet foams can be achieved at solids content around 1% by weight.


Input: Careful removal of the water results in a cellulose-based material with a porosity of 98% and a density of 30 mg cm (-3).


Input: These porous cellulose materials have a higher Young' s modulus than porous cellulose materials made from freeze-drying, at comparable densities, and have a compressive energy absorption of 56 kJ m (-3) at 80% strain.


Input: Measurement with the aid of an autoporosimeter revealed that most pores are in the range of 300 to 500 mu m.


Input: Total synthesis and evaluation of vinblastine analogues containing systematic deep-seated modifications in the vindoline subunit ring system: core redesign.

vinblastine

vindoline


Input: The total synthesis of a systematic series of vinblastine analogues that contain deep-seated structural modifications to the core ring system of the lower vindoline subunit is described.

vinblastine

vindoline


Input: Complementary to the vindoline 6, 5 DE ring system, compounds with 5, 5, 6, 6, and the reversed 5, 6 membered DE ring systems were prepared.

vindoline


Input: Both the natural cis and unnatural trans 6, 6-membered ring systems proved accessible, with the latter representing a surprisingly effective class for analogue design.


Input: Following Fe (III)-promoted coupling with catharanthine and in situ oxidation to provide the corresponding vinblastine analogues, their evaluation provided unanticipated insights into how the structure of the vindoline subunit contributes to activity.

Fe (III)

catharanthine

vinblastine

vindoline


Input: Two potent analogues (81 and 44) possessing two different unprecedented modifications to the vindoline subunit core architecture were discovered that matched the potency of the comparison natural products and both lack the 6, 7-double bond whose removal in vinblastine leads to a 100-fold drop in activity.

vindoline

vinblastine


Input: Analysis of 4-Hydroxy-1-(3-pyridyl)-1-butanone (HPB)-Releasing DNA Adducts in Human Exfoliated Oral Mucosa Cells by Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry.

HPB


Input: Quantitation of DNA adducts could provide critical information on the relationship between exposure to tobacco smoke and cancer risk in smokers.


Input: In this study, we developed a robust and sensitive liquid chromatography-tandem mass spectrometry method for the analysis of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts in human oral cells, a noninvasive source of DNA for biomarker studies.

HPB


Input: Isolated DNA undergoes acid hydrolysis, after which samples are purified by solid-phase extraction and analyzed by LC-ESI-MS/MS.


Input: The developed method was applied to the analysis of samples obtained via collection with a commercial mouthwash from 30 smokers and 15 nonsmokers.


Input: In smokers, the levels of HPB-releasing DNA adducts averaged 12. 0 pmol HPB/mg DNA (detected in 20 out of 28 samples with quantifiable DNA yield), and in nonsmokers, the levels of adducts averaged 0. 23 pmol/mg DNA (detected in 3 out of 15 samples).

HPB

HPB


Input: For the 30 smoking subjects, matching buccal brushings were also analyzed, and HPB-releasing DNA adducts were detected in 24 out of 27 samples with quantifiable DNA yield, averaging 44. 7 pmol HPB/mg DNA.

HPB

HPB


Input: The levels of adducts in buccal brushings correlated with those in mouthwash samples of smokers (R = 0. 73, p < 0. 0001).


Input: Potentially, the method can be applied in studies of individual susceptibility to tobacco-induced cancers in humans.


Input: Pyrenyl-linker-glucono gelators.

Pyrenyl

glucono


Input: Correlations of gel properties with gelator structures and characterization of solvent effects.


Input: A series of glucono-appended 1-pyrenesulfonyl derivatives containing alpha, omega-diaminoalkane spacers (Pn, where n, the number of methylene units separating the amino groups, is 2, 3, 4, 6, 7, and 8) have been prepared.

glucono

alpha, omega-diaminoalkane

methylene

amino


Input: Careful analyses of correlations between the structures of these molecules and their gels have provided important insights into the factors responsible for one-dimensional aggregation of small molecules containing both lipophilic and hydrophilic parts.


Input: The gelation behavior has been examined in 30 liquids of diverse structure and polarity, and the properties of their gels and the gelation mechanisms have been investigated using a variety of techniques.


Input: Possible reasons are discussed regarding why the Pn are better gelators than the corresponding naphthyl analogues (Nn) which had been investigated previously.

naphthyl


Input: P2 and P3 are ambidextrous gelators (i. e., they gelate both water and some organic liquids), and P4-P8 gelate some organic liquids which are protic and aprotic, but not water.


Input: In at least one of the liquids examined, P3, P4, P6, P7, and P8 form gels at less than 1 w/v% concentrations, and some of the gels in 1-decanol are thixotropic.


Input: Analyses of the gelation abilities using Hansen solubility parameters yield both qualitative and quantitative insights into the role of liquid-gelator interactions.


Input: For example, the critical gelation concentrations increase generally with increasing polar and hydrogen bonding interactions between the gelators and their liquid components.

hydrogen


Input: As revealed by FT-IR, (1) H NMR, UV-vis, and fluorescence spectra, hydrogen-bonding between glucono units and pi-pi stacking between pyrenyl groups are important in the formation and maintenance of the gel networks.

(1) H

hydrogen

glucono

pyrenyl


Input: The results from this study, especially those relating the aggregation modes and liquid properties, offer insights for the design of new surfactant-containing low-molecular-mass gelators with predefined gelating abilities.


Input: Antiproliferative withanolides from Datura wrightii.

withanolides


Input: A new withanolide, named withawrightolide (1), and four known withanolides (2-5) were isolated from the aerial parts of Datura wrightii.

withanolide

withawrightolide

withanolides


Input: The structure of compound 1 was elucidated through 2D NMR and other spectroscopic techniques.


Input: In addition, the structure of withametelin L (2) was confirmed by X-ray crystallographic analysis.

withametelin L


Input: Using MTS viability assays, withanolides 1-5 showed antiproliferative activities against human glioblastoma (U251 and U87), head and neck squamous cell carcinoma (MDA-1986), and normal fetal lung fibroblast (MRC-5) cells with IC50 values in the range between 0. 56 and 5. 6 mu M.

MTS

withanolides 1-5


Input: Putative impact of RNA editing on drug discovery.


Input: Virtually all organisms use RNA editing as a powerful post-transcriptional mechanism to recode genomic information and to increase functional protein diversity.


Input: The enzymatic editing of pre-mRNA by ADARs and CDARs is known to change the functional properties of neuronal receptors and ion channels regulating cellular excitability.


Input: However, RNA editing is also an important mechanism for genes expressed outside the brain.


Input: The fact that RNA editing breaks the' one gene encodes one protein' hypothesis is daunting for scientists and a probable drawback for drug development, as scientists might search for drugs targeting the' wrong' protein.


Input: This possible difficulty for drug discovery and development became more evident from recent publications, describing that RNA editing events have profound impact on the pharmacology of some common drug targets.


Input: These recent studies highlight that RNA editing can cause massive discrepancies between the in vitro and in vivo pharmacology.


Input: Here, we review the putative impact of RNA editing on drug discovery, as RNA editing has to be considered before using high-throughput screens, rational drug design or choosing the right model organism for target validation.


Input: The discovery of fused oxadiazepines as gamma secretase modulators for treatment of Alzheimer' s disease.

oxadiazepines


Input: In an attempt to further improve overall profiles of the oxadiazine series of GSMs, in particular the hERG activity, conformational modifications of the core structure resulted in the identification of fused oxadiazepines such as 7i which had an improved hERG inhibition profile and was a highly efficacious GSM in vitro and in vivo in rats.

oxadiazine

oxadiazepines


Input: These SAR explorations offer opportunities to identify potential drugs to treat Alzheimer' s disease.


Input: Distinct functions of human RECQ helicases WRN and BLM in replication fork recovery and progression after hydroxyurea-induced stalling.

hydroxyurea


Input: Human WRN and BLM genes are members of the conserved RECQ helicase family.


Input: Mutations in these genes are associated with Werner and Bloom syndromes.


Input: WRN and BLM proteins are implicated in DNA replication, recombination, repair, telomere maintenance, and transcription.


Input: Using microfluidics-assisted display of DNA for replication track analysis (ma-RTA), we show that WRN and BLM contribute additively to normal replication fork progression, and non-additively, in a RAD51-dependent pathway, to resumption of replication after arrest by hydroxyurea (HU), a replication-stalling drug.

hydroxyurea


Input: WRN but not BLM is required to support fork progression after HU.


Input: Resumption of replication by forks may be necessary but is not sufficient for timely completion of the cell cycle after HU arrest, as depletion of WRN or BLM compromises fork recovery to a similar degree, but only BLM depletion leads to extensive delay of cell division after HU, as well as more pronounced chromatin bridging.


Input: Finally, we show that recovery from HU includes apparent removal of some of the DNA that was synthesized immediately after release from HU, a novel phenomenon that we refer to as nascent strand processing, NSP.


Input: Phytoestrogen genistein protects against endothelial barrier dysfunction in vascular endothelial cells through PKA-mediated suppression of RhoA signaling.

genistein


Input: The soy-derived phytoestrogen genistein has received attention for its potential to improve vascular function, but its mechanism remains unclear.

genistein


Input: Here, we report that genistein at physiologically relevant concentrations (0. 1-10 mu M) significantly inhibited thrombin-induced increase in endothelial monolayer permeability.

genistein


Input: Genistein also reduced the formation of stress fibers by thrombin and suppressed thrombin-induced phosphorylation of myosin light chain (MLC) on Ser (19)/Thr (18) in endothelial cells (ECs).

Genistein

Ser

Thr


Input: Genistein had no effect on resting intracellular [Ca (2 +)] or thrombin-induced increase in Ca (2 +) mobilization.

Genistein

Ca (2 +)

Ca (2 +)


Input: Addition of the inhibitors of endothelial nitric oxide synthase or estrogen receptor did not alter the protective effect of genistein.

nitric oxide

estrogen

genistein


Input: RhoA is a small GTPase that plays an important role in actin-myosin contraction and endothelial barrier dysfunction.


Input: RhoA inhibitor blocked the protective effect of genistein on endothelial permeability and also ablated thrombin-induced MLC-phosphorylation in ECs.

genistein


Input: Inhibition of PKA significantly attenuated the effect of genistein on thrombin-induced EC permeability, MLC phosphorylation, and RhoA membrane translocation in ECs.

genistein


Input: Furthermore, thrombin diminished cAMP production in ECs, which were prevented by treatment with genistein.

cAMP

genistein


Input: These findings demonstrated that genistein improves thrombin-induced endothelial barrier dysfunction in ECs through PKA-mediated suppression of RhoA signaling.

genistein


Input: Intrinsically green iron oxide nanoparticles?

iron oxide


Input: From synthesis via (eco-) toxicology to scenario modelling.


Input: Iron oxide nanoparticles (IONP) are currently being studied as green magnet resonance imaging (MRI) contrast agents.

Iron oxide


Input: They are also used in huge quantities for environmental remediation and water treatment purposes, although very little is known on the consequences of such applications for organisms and ecosystems.


Input: In order to address these questions, we synthesised polyvinylpyrrolidone-coated IONP, characterised the particle dispersion in various media and investigated the consequences of an IONP exposure using an array of biochemical and biological assays.

polyvinylpyrrolidone


Input: Several theoretical approaches complemented the measurements.


Input: In aqueous dispersion IONP had an average hydrodynamic diameter of 25 nm and were stable over six days in most test media, which could also be predicted by stability modelling.


Input: The particles were tested in concentrations of up to 100 mg Fe per L.

Fe


Input: The activity of the enzymes glutathione reductase and acetylcholine esterase was not affected, nor were proliferation, morphology or vitality of mammalian OLN-93 cells although exposure of the cells to 100 mg Fe per L increased the cellular iron content substantially.

glutathione

acetylcholine

Fe

iron


Input: Only at this concentration, acute toxicity tests with the freshwater flea Daphnia magna revealed slightly, yet insignificantly increased mortality.


Input: Two fundamentally different bacterial assays, anaerobic activated sludge bacteria inhibition and a modified sediment contact test with Arthrobacter globiformis, both rendered results contrary to the other assays: at the lowest test concentration (1 mg Fe per L), IONP caused a pronounced inhibition whereas higher concentrations were not effective or even stimulating.


Input: Preliminary and prospective risk assessment was exemplified by comparing the application of IONP with gadolinium-based nanoparticles as MRI contrast agents.

gadolinium


Input: Predicted environmental concentrations were modelled in two different scenarios, showing that IONP could reduce the environmental exposure of toxic Gd-based particles by more than 50%.

Gd


Input: Application of the Swiss " Precautionary Matrix for Synthetic Nanomaterials " rendered a low precautionary need for using our IONP as MRI agents and a higher one when using them for remediation or water treatment.


Input: Since IONP and (considerably more reactive) zerovalent iron nanoparticles are being used in huge quantities for environmental remediation purposes, it has to be ascertained that these particles pose no risk to either human health or to the environment.

iron


Input: Low percentage of KRAS mutations revealed by locked nucleic acid polymerase chain reaction: implications for treatment of metastatic colorectal cancer.


Input: Metastatic colorectal cancer (mCRC) is frequently characterized by the presence of mutations of the KRAS oncogene, which are generally associated with a poor response to treatment with anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies.


Input: With the methods currently used, a case is classified as KRAS-mutated when approximately 20% of the cells bear an activating KRAS mutation.


Input: These considerations raise the question of whether cells with a mutated KRAS can be found in mCRC cases classified as KRAS wild-type when more sensitive methods are used.


Input: In addition, the issue arises of whether these mCRC cases with low proportion of KRAS-mutated cells could account at least in part for the therapeutic failure of anti-EGFR therapies that occur in 40-60% of cases classified as KRAS wild type.


Input: In this study, we compared the classical assays with a very sensitive test, a locked nucleic acid (LNA) polymerase chain reaction (PCR), capable of detecting KRAS-mutated alleles at extremely low frequency (detection sensitivity limit 0. 25% mutated DNA/wild-type DNA).


Input: By analyzing a cohort of 213 mCRC patients for KRAS mutations, we found a 20. 6% discordance between the sequencing/TheraScreen methods and the LNA-PCR.


Input: Indeed, 44 mCRC patients initially considered KRAS wild type were reclassified as KRAS mutated by using the LNA-PCR test.


Input: These patients were more numerous among individuals displaying a clinical failure to anti-EGFR therapies.


Input: Failure to respond to these biological treatments occurred even in the absence of mutations in other EGFR pathway components such as BRAF.


Input: Formation of RNA phosphodiester bond by histidine-containing dipeptides.

phosphodiester

histidine

dipeptides


Input: A new scenario for prebiotic formation of nucleic acid oligomers is presented.


Input: Peptide catalysis is applied to achieve condensation of activated RNA monomers into short RNA chains.


Input: As catalysts, L-dipeptides containing a histidine residue, primarily Ser-His, were used.

L-dipeptides

histidine

Ser-His


Input: Reactions were carried out in self-organised environment, a water-ice eutectic phase, with low concentrations of reactants.


Input: Incubation periods up to 30 days resulted in the formation of short oligomers of RNA.


Input: During the oligomerisation, an active intermediate (dipeptide-mononucleotide) is produced, which is the reactive species.

dipeptide-mononucleotide


Input: Details of the mechanism and kinetics, which were elucidated with a set of control experiments, further establish that the imidazole side chain of a histidine at the carboxyl end of the dipeptide plays a crucial role in the catalysis.

imidazole

histidine

carboxyl

dipeptide


Input: These results suggest that this oligomerisation catalysis occurs by a transamination mechanism.


Input: Because peptides are much more likely products of spontaneous condensation than nucleotide chains, their potential as catalysts for the formation of RNA is interesting from the origin-of-life perspective.

nucleotide


Input: Finally, the formation of the dipeptide-mononucleotide intermediate and its significance for catalysis might also be viewed as the tell-tale signs of a new example of organocatalysis.

dipeptide-mononucleotide


Input: Structural and stereochemical studies of hydroxyanthraquinone derivatives from the endophytic fungus Coniothyrium sp.

hydroxyanthraquinone


Input: Four known hydroxyanthraquinones (1-4) together with four new derivatives having a tetralone moiety, namely coniothyrinones A-D (5-8), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands.

hydroxyanthraquinones

tetralone

coniothyrinones A-D


Input: The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data.


Input: The absolute configurations of coniothyrinones A (5), B (6), and D (8) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C (7) as well.

coniothyrinones A (5), B (6), and D

coniothyrinone C


Input: Coniothyrinones A (5), B (6), and D (8) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives.

Coniothyrinones A (5), B (6), and D

tetralone


Input: This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp.

anthraquinones


Input: These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium.


Input: Tungsten carbide nanoparticles as efficient cocatalysts for photocatalytic overall water splitting.

Tungsten carbide


Input: Tungsten carbide exhibits platinum-like behavior, which makes it an interesting potential substitute for noble metals in catalytic applications.

Tungsten carbide

platinum


Input: Tungsten carbide nanocrystals (=~ 5 nm) are directly synthesized through the reaction of tungsten precursors with mesoporous graphitic C (3) N (4) (mpg-C (3) N (4)) as the reactive template in a flow of inert gas at high temperatures.

Tungsten carbide

tungsten

C (3) N (4)

C (3) N (4)


Input: Systematic experiments that vary the precursor compositions and temperatures used in the synthesis selectively generate different compositions and structures for the final nanocarbide (W (2) C or WC) products.

W (2) C

WC


Input: Electrochemical measurements demonstrate that the WC phase with a high surface area exhibits both high activity and stability in hydrogen evolution over a wide pH range.

WC

hydrogen


Input: The WC sample also shows excellent hydrogen oxidation activity, whereas its activity in oxygen reduction is poor.

WC

hydrogen

oxygen


Input: These tungsten carbides are successful cocatalysts for overall water splitting and give H (2) and O (2) in a stoichiometric ratio from H (2) O decomposition when supported on a Na-doped SrTiO (3) photocatalyst.

tungsten carbides

H (2)

O (2)

H (2) O

SrTiO (3)


Input: Herein, we present tungsten carbide (on a small scale) as a promising and durable catalyst substitute for platinum and other scarce noble-metal catalysts in catalytic reaction systems used for renewable energy generation.

tungsten carbide

platinum


Input: Dandelion leaf extract protects against liver injury induced by methionine-and choline-deficient diet in mice.

methionine

choline


Input: We investigated the hepatoprotective effects of the extract of dandelion leaves (EDL) on a murine model of methionine-and choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH).

methionine

choline


Input: C57BL/6 mice were fed for 4 weeks with one of the following diets: control diet (Cont), MCD diet (MCD), MCD diet supplemented with EDL at 200 mg/kg body weight. daily (MCD + D200), and MCD diet supplemented with EDL at 500 mg/kg body weight. daily (MCD + D500).


Input: Hepatic function was assessed by evaluating the following parameters: liver histology; plasma levels of alanine aminotransferase (ALT), triglyceride (TG), malondialdehyde (MDA), and reduced glutathione (GSH); expression levels of TNF-alpha and IL-6; and levels of caspase-3 and pJNK/JNK protein.

alanine

triglyceride

malondialdehyde

MDA

reduced glutathione

GSH


Input: Histopathological evaluations revealed that addition of EDL to the MCD diet dampens the severity of the clinical signs of NASH.


Input: Moreover, EDL led to a significant decrease in the serum levels of ALT, hepatic TG, and MDA, and in the expression levels of TNF-alpha, and IL-6; on the contrary, the levels of reduced GSH increased.

MDA

reduced GSH


Input: At the post-transcriptional level, EDL significantly decreased the activation of procaspase-3 to active caspase-3, and the phosphorylation of JNK.


Input: These results suggest that the beneficial effects of EDL on NASH are mainly due to its antioxidant and anti-inflammatory activities.


Input: Trigonelline ameliorates oxidative stress in type 2 diabetic Goto-Kakizaki rats.

Trigonelline


Input: Previously, we showed that trigonelline (TRG) exerts antidiabetic effects in type 2 diabetic Goto-Kakizaki (GK) rats and also lowers blood and liver thiobarbituric acid reactive substances and urinary 8-hydroxydeoxyguanosine when compared with those levels in GK control rats without TRG.

trigonelline

TRG

thiobarbituric acid


Input: These results suggested that TRG also mitigates oxidative stress, which accelerates diabetes.

TRG


Input: In this study, the mechanisms of TRG prevention of oxidative stress were determined by measuring erythrocyte and liver antioxidant enzyme activities, and expressions of genes associated with reactive oxygen species production, and carbohydrate and lipid metabolisms by DNA microarray.

TRG

oxygen

carbohydrate


Input: Erythrocyte and liver glutathione peroxidase, and liver catalase activities in the GK rats fed with TRG were significantly lower than those of the GK control rats.

glutathione

TRG


Input: TRG downregulated the gene expressions involved with NADPH oxidase and mitochondrial electron transfer system when compared with those of the GK control group.

TRG

NADPH


Input: These results suggested that mitigation of diabetes by TRG is mediated by its ameliorating effects on oxidative stress.

TRG


Input: Metabolic effects of honey in type 1 diabetes mellitus: a randomized crossover pilot study.


Input: The aim of this study was to evaluate the metabolic effects of 12-week honey consumption on patients suffering from type 1 diabetes mellitus (DM).


Input: This was a randomized crossover clinical trial done in the National Institute for Diabetes and Endocrinology, Cairo, Egypt.


Input: Twenty patients of both sexes aged 4-18 years with type 1 DM and HbA1C < 10% participated in the study.


Input: They were randomized into two equal groups (intervention to control and control to intervention).


Input: The dietary intervention was 12-week honey consumption in a dose of 0. 5 mL/kg body weight per day.


Input: The main outcome measures were serum glucose, lipids, and C-peptide, and anthropometric measurements.

glucose


Input: None of participants were lost in follow-up.


Input: The intervention resulted in significant decreases in subscapular skin fold thickness (SSFT; P =. 002), fasting serum glucose (FSG; P =. 001), total cholesterol (P =. 0001), serum triglycerides (TG; P =. 0001), and low-density lipoprotein (P =. 0009), and significant increases in fasting C-peptide (FCP; P =. 0004) and 2-h postprandial C-peptide (PCP; P =. 002).

glucose

cholesterol

triglycerides


Input: As possible long-term effects of honey after its withdrawal, statistically significant reductions in midarm circumference (P =. 000), triceps skin fold thickness (P =. 006), SSFT (P =. 003), FSG (P =. 005), 2-h postprandial serum glucose (P =. 000), TG (P =. 003), and HbA1C (P =. 043), and significant increases in FCP (P =. 002) and PCP (P =. 003) were observed.

glucose


Input: This small clinical trial suggests that long-term consumption of honey might have positive effects on the metabolic derangements of type 1 DM.


Input: Fit-for-purpose bioanalytical cross-validation for LC-MS/MS assays in clinical studies.


Input: The paradigm shift of globalized research and conducting clinical studies at different geographic locations worldwide to access broader patient populations has resulted in increased need of correlating bioanalytical results generated in multiple laboratories, often across national borders.


Input: Cross-validations of bioanalytical methods are often implemented to assure the equivalency of the bioanalytical results is demonstrated.


Input: Regulatory agencies, such as the US FDA and European Medicines Agency, have included the requirement of cross-validations in their respective bioanalytical validation guidance and guidelines.


Input: While those documents provide high-level expectations, the detailed implementation is at the discretion of each individual organization.


Input: At Bristol-Myers Squibb, we practice a fit-for-purpose approach for conducting cross-validations for small-molecule bioanalytical methods using LC-MS/MS.


Input: A step-by-step proposal on the overall strategy, procedures and technical details for conducting a successful cross-validation is presented herein.


Input: A case study utilizing the proposed cross-validation approach to rule out method variability as the potential cause for high variance observed in PK studies is also presented.


Input: Ballistic InAs nanowire transistors.


Input: Ballistic transport of electrons at room temperature in top-gated InAs nanowire (NW) transistors is experimentally observed and theoretically examined.


Input: From length dependent studies, the low-field mean free path is directly extracted as ~ 150 nm.


Input: The mean free path is found to be independent of temperature due to the dominant role of surface roughness scattering.


Input: The mean free path was also theoretically assessed by a method that combines Fermi' s golden rule and a numerical Schr o dinger-Poisson simulation to determine the surface scattering potential with the theoretical calculations being consistent with experiments.


Input: Near ballistic transport (~ 80% of the ballistic limit) is demonstrated experimentally for transistors with a channel length of ~ 60 nm, owing to the long mean free path of electrons in InAs NWs.


Input: Morphology-dependent trap formation in bulk heterojunction photodiodes.


Input: We show that local structural variation affects the rate of aging in nanostructured polymer solar cells by comparing time-resolved electrostatic force microscopy (trEFM) and conventional device measurements on model polymer blends.


Input: Specifically, we study photovoltaic devices made from 1: 1 blends of the polyfluorene copolymers poly (9, 9'-dioctylfluorene-co-bis-N, N'-(4-butylphenyl)-bis-N, N'-phenyl-1, 4-phenylene-diamine) (PFB) and poly (9, 9'-dioctylfluorene-co-benzothiadiazole) (F8BT).

polyfluorene

poly (9, 9'-dioctylfluorene-co-bis-N, N'-(4-butylphenyl)-bis-N, N'-phenyl-1, 4-phenylene-diamine

PFB

poly (9, 9'-dioctylfluorene-co-benzothiadiazole


Input: We photooxidize these films in situ using 365, 405, and 455 nm illumination under ambient conditions, with the wavelengths chosen to preferentially excite the different components.


Input: During photooxidation, we observe a faster loss of photocurrent generation from F8BT-rich domains, leaving the PFB-rich phases to show higher photoresponse even at wavelengths absorbed predominantly by F8BT.

PFB


Input: We propose that this effect is due to the more rapid degradation of PFB hole-transport pathways in the F8BT-rich regions, resulting in a loss of percolation pathways for hole transport in the F8BT-rich phase.

PFB


Input: First-principles prediction of the effects of temperature and solvent selection on the dimerization of benzoic acid.

benzoic acid


Input: We introduce a procedure of quantum chemical calculations (B3P86/6-31G * *) to study carboxylic acid dimerization and its correlation with temperature and properties of the solvent.

carboxylic acid


Input: Benzoic acid is chosen as a model system for studying dimerization via hydrogen bonding.

Benzoic acid

hydrogen


Input: Organic solvents are simulated using the self-consistent reaction field (SCRF) method with the polarized continuum model (PCM).


Input: The cyclic dimer is the most stable structure both in gas phase and solution.


Input: Dimer mono-and dihydrates could be found in the gas phase if acid molecules are in contact with water vapor.

mono-and dihydrates


Input: However, the formation of these hydrated conformers is very limited and cyclic dimer is the principal conformer to coexist with monomer acid in solution.


Input: Solvation of the cyclic dimer is more favorable compared to other complexes, partially due to the diminishing of hydrogen bonding capability and annihilation of dipole moments.

hydrogen


Input: Solvents have a strong effect on inducing dimer dissociation and this dependence is more pronounced at low dielectric constants.


Input: By accounting for selected terms in the total free energy of solvation, the solvation entropy could be incorporated to predict the dimer behavior at elevated temperatures.


Input: The temperature dependence of benzoic acid dimerization obtained by this technique is in good agreement with available experimental measurements, in which a tendency of dimer to dissociate is observed with increased temperatures.

benzoic acid


Input: In addition, dimer breakup is more sensitive to temperature in low dielectric environments rather than in solvents with a higher dielectric constant.


Input: Universal concept for the implementation of a single cleavable unit at tunable position in functional poly (ethylene glycol) s.

poly (ethylene glycol) s


Input: Poly (ethylene glycol) (PEG) with acid-sensitive moieties gained attention particularly for various biomedical applications, such as the covalent attachment of PEG (PEGylation) to protein therapeutics, the synthesis of stealth liposomes, and polymeric carriers for low-molecular-weight drugs.

Poly (ethylene glycol)

PEG

PEG


Input: Cleavable PEGs are favored over their inert analogues because of superior pharmacodynamic and/or pharmacokinetic properties of their formulations.

PEGs


Input: However, synthetic routes to acetal-containing PEGs published up to date either require enormous efforts or result in ill-defined materials with a lack of control over the molecular weight.

acetal

PEGs


Input: Herein, we describe a novel methodology to implement a single acetaldehyde acetal in well-defined (hetero) functional poly (ethylene glycol) s with total control over its position.

acetaldehyde acetal

(hetero) functional poly (ethylene glycol) s


Input: To underline its general applicability, a diverse set of initiators for the anionic polymerization of ethylene oxide (cholesterol, dibenzylamino ethanol, and poly (ethylene glycol) monomethyl ether (mPEG)) was modified and used to synthesize the analogous labile PEGs.

ethylene oxide

cholesterol

dibenzylamino ethanol

poly (ethylene glycol) monomethyl ether

mPEG

PEGs


Input: The polyether bearing the cleavable lipid had a degree of polymerization of 46, was amphiphilic and exhibited a critical micelle concentration of 4. 20 mg. L (-1).

polyether


Input: From dibenzylamino ethanol, three heterofunctional PEGs with different molecular weights and labile amino termini were generated.

dibenzylamino ethanol

PEGs

amino


Input: The transformation of the amino functionality into the corresponding squaric acid ester amide demonstrated the accessibility of the cleavable functional group and activated the PEG for protein PEGylation, which was exemplarily shown by the attachment to bovine serum albumin (BSA).

amino

squaric acid ester amide

PEG


Input: Furthermore, turning mPEG into a macroinitiator with a cleavable hydroxyl group granted access to a well-defined poly (ethylene glycol) derivative bearing a single cleavable moiety within its backbone.

mPEG

hydroxyl

poly (ethylene glycol)


Input: All the acetal-containing PEGs and PEG/protein conjugates were proven to degrade upon acidic treatment.

acetal

PEGs

PEG


Input: Enhancing biocompatibility of D-oligopeptide hydrogels by negative charges.


Input: Oligopeptide hydrogels are emerging as useful matrices for cell culture with commercial products on the market, but L-oligopeptides are labile to proteases.


Input: An obvious solution is to create D-oligopeptide hydrogels, which lack enzymatic recognition.


Input: However, D-oligopeptide matrices do not support cell growth as well as L-oligopeptide matrices.


Input: In addition to chiral interactions, many cellular activities are strongly governed by charge-charge interactions.


Input: In this work, the effects of chirality and charge on human mesenchymal stem cell (hMSC) behavior were studied using hydrogels assembled from oppositely charged oligopeptides.


Input: It was found that negative charges significantly improved hMSC viability and proliferation in D-oligopeptide gels but had little effect on their interactions with L-oligopeptide gels.


Input: This result points to the possibility of using charge and other factors to engineer biomaterials whose chirality is distinct from that of natural biomaterials, but whose performance is close to that of natural biomaterials.


Input: Magnetostructural correlation for rational design of Mn (II) hybrid-spin complexes.

Mn (II)


Input: The magnetic properties of a series of manganese (II) diacetylacetonate and dihexafluoroacetylacetonate hybrid-spin complexes with neutral pyridine-based organic radicals were characterized theoretically by DFT calculations.

manganese (II) diacetylacetonate and dihexafluoroacetylacetonate

pyridine


Input: Three stable radicals, in which a radical group is bound in either para or meta position with respect to the pyridine nitrogen atom, were considered.

pyridine nitrogen


Input: The correct stable structures and multiplets of the complexes were obtained by full geometry optimization starting from an ideal structure.


Input: A total of three important geometry descriptors of the complexes were monitored and related to their magnetic characteristics.


Input: These structural parameters are (i) the torsion angle governing the conjugation of the organic radical m-PyNO (anti versus gauche), (ii) the coordination geometry of the acetyl acetonate ligands around the metal ion (square versus rhombic), and (iii) the relative orientation of the organic radical with respect to the acetyl acetonate plane (parallel versus perpendicular).

m-PyNO

acetyl acetonate

acetyl acetonate


Input: It was found that the magnetic properties are not sensitive to the orientation of the radicals with respect to the equatorial plane but do depend on the conformation of the organic radicals.


Input: Even a spin switch between the ferromagnetic (S = (7)/(2)) and antiferromagnetic (S = (3)/(2)) ground state was found to be feasible for one of the complexes upon variation of the organic radical geometry, namely, the dihedral angle between the organic radical moiety and the pyridine ring.

pyridine


Input: The pattern of molecular orbital overlap was determined to be the key factor governing the exchange coupling in the modeled systems.


Input: Bonding pi-type overlap provides antiferromagnetic coupling in all complexes of the para radicals.


Input: In the meta analogues, the spins are coupled through the sigma orbitals.


Input: A low-spin ground state occurs whenever a continuous sigma-overlap pathway is present in the complex.


Input: Ferromagnetic interaction requires sigma-pi orthogonality of the pyridine atomic orbitals and/or pi-antibonding Mn-pyridine natural orbital overlap.

pyridine

Mn

pyridine


Input: Using an estimate of the donor-acceptor energy stabilization, the affinity of a given Mn (II) d-orbital to mix with the sp (2) orbital from pyridine can be predicted.

Mn (II)

pyridine


Input: Antioxidants and mucolytics in COPD management: when (if ever) and in whom?


Input: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide.


Input: Oxidative stress is an important mechanism in the pathogenesis of this disease.


Input: The oxidant/antioxidant imbalance occurring in smokers and patients with COPD is well established.


Input: Thus, therapeutic strategies targeting oxidative stress with pharmacological antioxidant agents or boosting the endogenous levels of antioxidants is likely to be beneficial as an adjunctive tool in the treatment of COPD patients.


Input: Thiol compounts such as N-acetyl-L-cysteine (NAC), carbocysteine, erdosteine, and fudosteine have been extensively studied.

Thiol

N-acetyl-L-cysteine

NAC

carbocysteine

erdosteine

fudosteine


Input: Although some results remain controversial, NAC and carbocysteine seem to have beneficial effect in patients not receiving inhaled corticosteroids who suffer from frequent exacerbations.

NAC

carbocysteine

corticosteroids


Input: In addition, other antioxidants like superoxide dismutase (SOD) mimetics and nuclear factor-erythroid 2 related factor 2 (Nrf2) are shown to decrease markers of oxidative stress in patients with emphysema, while others like glutathione peroxidase (GPx) mimetics and NO synthase (iNOS) can prevent both inflammation and oxidative stress in clinical trials in vivo (or in mouse models).

superoxide

glutathione

NO


Input: In this article we review the effectiveness of various antioxidant factors in COPD and their potential beneficial effect in the treatment of the disease.


Input: Effect of rehabilitative exercise training on peripheral muscle remodelling in patients with COPD: targeting beyond the lungs.


Input: Locomotor muscle dysfunction and weakness are frequently observed in patients with Chronic Obstructive Pulmonary Disease (COPD).


Input: In addition to intolerable sensations of dyspnoea which importantly contribute to exercise limitation, intrinsic muscle abnormalities have also been implicated in inducing leg muscle fatigue/discomfort during exercise in these patients.


Input: It is, however, uncertain whether these intrinsic muscle abnormalities are linked to a specific' myopathy' or they constitute a consequence of the disease.


Input: Besides muscle disuse, other factors which may contribute to peripheral muscle dysfunction include systemic inflammation, oxidative and nitrosative stress, chronic hypoxia, corticosteroid use and malnutrition.


Input: There is clear evidence that rehabilitative exercise training induces significant skeletal muscle fibre remodelling and improvements in functionality in the absence of changes in lung function.


Input: The ultimate purpose of this review is to identify and summarize the results of studies implementing diverse types of exercise training on peripheral muscle fibre phenotypic and genotypic modifications in patients with COPD.


Input: Clonazepam for the treatment of panic disorder.

Clonazepam


Input: Clonazepam was initially licensed as an anti-epileptic agent, but its use in a wide variety of psychiatric conditions, including panic disorder (PD) has now been well established.

Clonazepam


Input: This overview evaluates the current role of clonazepam alone or in combination with antidepressants and/or behavioral therapy in the treatment of PD.

clonazepam


Input: We review the data establishing the use of clonazepam in the treatment of PD as well as new information, particularly confirmation of longterm efficacy and safety.

clonazepam


Input: We also discuss a regimen for safely tapered withdrawal of clonazepam, the characteristics of the respiratory subtype of PD, and CO2-induced panic attacks as a diagnostic measure and predictor for therapeutic success.

clonazepam


Input: It has been shown that panic attacks can more readily be induced by CO2 in PD patients with the respiratory subtype than those with the non-respiratory subtype.


Input: More than 25 years after the first report of efficacy in PD in 1984, clonazepam, alone or combined with selective serotonin reuptake inhibitors (SSRIs) and/or behavioral therapy, remains an important therapeutic modality for the management of PD.

clonazepam

serotonin


Input: Effects of formation conditions on the physicochemical properties, aggregation, and phase transformation of iron oxide nanoparticles.

iron oxide


Input: In this work, hematite transformation from a precursor 6-line ferrihydrite phase was investigated by systematically altering the forced hydrolysis hematite synthesis.

hematite

ferrihydrite

hematite


Input: Specifically, we used a combination of in situ and ex situ characterization techniques to examine the effects of varying the Fe (III) injection rates and cooling methods on the hematite and 6-line ferrihydrite nanoparticle size, isoelectric point, mineral phase, and aggregation.

Fe (III)

hematite

ferrihydrite


Input: Finally, As (V) adsorption experiments were performed to determine how the two iron oxide phases existed in the reaction system.

As (V)

iron oxide


Input: Nanoparticle synthesis thermodynamics and kinetics were found to control the extent of distinct 6-line ferrihydrite phases in the iron oxide nanoparticle solutions, as well as the particle size and isoelectric point.

ferrihydrite

iron oxide


Input: Conversion of 6-line ferrihydrite to hematite was greatly influenced by the degree of aggregation (determined by synthesis conditions) during drying.

ferrihydrite

hematite


Input: As (V) adsorption experiments revealed that 6-line ferrihydrite and hematite exist as a linear combination of two separate phases.

As (V)

ferrihydrite

hematite


Input: These results provide unique information regarding how in situ iron oxide nanoparticle properties can direct their ex situ behavior.

iron oxide


Input: The evolution of S100B inhibitors for the treatment of malignant melanoma.


Input: Malignant melanoma continues to be an extremely fatal cancer due to a lack of viable treatment options for patients.


Input: The calcium-binding protein S100B has long been used as a clinical biomarker, aiding in malignant melanoma staging and patient prognosis.

calcium


Input: However, the discovery of p53 as a S100B target and the consequent impact on cell apoptosis redirected research efforts towards the development of inhibitors of this S100B-p53 interaction.


Input: Several approaches, including computer-aided drug design, fluorescence polarization competition assays, NMR, x-ray crystallography and cell-based screens have been performed to identify compounds that block the S100B-p53 association, reactivate p53 transcriptional activities and induce cancer cell death.


Input: Eight promising compounds, including pentamidine, are presented in this review and the potential for future modifications is discussed.

pentamidine


Input: Synthesis of compound derivatives will likely exhibit increased S100B affinity and mimic important S100B-target dynamic properties that will result in high specificity.


Input: HR-MAS NMR Spectroscopy of Reconstructed Human Epidermis: Potential for the in Situ Investigation of the Chemical Interactions between Skin Allergens and Nucleophilic Amino Acids.

Amino Acids


Input: High-resolution magic angle spinning (HR-MAS) is a nuclear magnetic resonance (NMR) technique that enables the characterization of metabolic phenotypes/metabolite profiles of cells, tissues, and organs, under both normal and pathological conditions, without resorting to time-consuming extraction techniques.


Input: In this article, we explore a new domain of application of HR-MAS, namely, reconstructed human epidermis (RHE) and the in situ observation of chemical interactions between skin sensitizers and nucleophilic amino acids.

amino acids


Input: First, the preparation, storage, and analysis of RHE were optimized, and this work demonstrated that HR-MAS NMR was well adapted for investigating RHE with spectra of good quality allowing qualitative as well as quantitative studies of metabolites.


Input: Second, in order to study the response of RHE to chemical sensitizers, the ((13) C) methyldodecanesulfonate was chosen as an NMR probe, and we compared adducts formed on human serum albumin (HSA) in solution and adducts formed in RHE.

((13) C) methyldodecanesulfonate


Input: Thus, while the modification of proteins or peptides in solution takes several days to lead to a significant amount of modification, in RHE the modifications of nucleophilic amino acids were observable already at 24 h.

amino acids


Input: The chemioselectivity also appeared to be different with major modifications taking place on histidine, methionine, and cysteine residues in RHE, while on HSA, significant modifications were observed on lysine residues with the formation of methylated and dimethylated amino groups.

histidine

methionine

cysteine

lysine

amino


Input: We thus demonstrated that RHE could be used to investigate in situ chemical interactions taking place between skin sensitizers and nucleophilic amino acids.

amino acids


Input: This opens perspectives for the molecular understanding of the skin immune system activation by sensitizing chemicals.


Input: The RNA polymerase of marine cyanophage Syn5.


Input: A single subunit DNA-dependent RNA polymerase was identified and purified to apparent homogeneity from cyanophage Syn5 that infects the marine cyanobacteria Synechococcus.


Input: Syn5 is homologous to bacteriophage T7 that infects Escherichia coli.


Input: Using the purified enzyme its promoter has been identified by examining transcription of segments of Syn5 DNA and sequencing the 5'-termini of the transcripts.


Input: Only two Syn5 RNAP promoters, having the sequence 5'-ATTGGGCACCCGTAA-3', are found within the Syn5 genome.


Input: One promoter is located within the Syn5 RNA polymerase gene and the other is located close to the right genetic end of the genome.


Input: The purified enzyme and its promoter have enabled a determination of the requirements for transcription.


Input: Unlike the salt-sensitive bacteriophage T7 RNA polymerase, this marine RNA polymerase requires 160 mm potassium for maximal activity.

potassium


Input: The optimal temperature for Syn5 RNA polymerase is 24 degrees C, much lower than that for T7 RNA polymerase.


Input: Magnesium is required as a cofactor although some activity is observed with ferrous ions.

Magnesium

ferrous


Input: Syn5 RNA polymerase is more efficient in utilizing low concentrations of ribonucleotides than T7 RNA polymerase.

ribonucleotides


Input: Super-stable ultrafine beta-tungsten nanocrystals with metastable phase and related magnetism.

beta-tungsten


Input: Ultrafine tungsten nanocrystals (average size of 3 nm) with a metastable phase (beta-tungsten with A15 structure, beta-W) have been prepared by laser ablation of tungsten in liquid nitrogen.

tungsten

beta-tungsten

W

tungsten

nitrogen


Input: The as-prepared metastable nanocrystals exhibited super-stablity, and can keep the same metastable structure over a period of 6 months at room temperature.


Input: This super-stability is attributed to the nanosized confinement effect of ultrafine nanocrystals.


Input: The magnetism measurements showed that the beta-W nanocrystals have weak ferromagnetic properties at 2 K, which may arise from surface defects and unpaired electrons on the surface of the ultrafine nanocrystals.

W


Input: These findings provided useful information for the application of ultrafine beta-W nanocrystals in microelectronics and spintronics.

W


Input: The comprehensive epigenome map of piRNA clusters.


Input: PIWI-interacting RNA (piRNA) clusters act as anti-transposon/retrovirus centers.


Input: Integration of selfish jumping elements into piRNA clusters generates de novo piRNAs, which in turn exert trans-silencing activity against these elements in animal gonads.


Input: To date, neither genome-wide chromatin modification states of piRNA clusters nor a mode for piRNA precursor transcription have been well understood.


Input: Here, to understand the chromatin landscape of piRNA clusters and how piRNA precursors are generated, we analyzed the transcriptome, transcription start sites (TSSs) and the chromatin landscape of the BmN4 cell line, which harbors the germ-line piRNA pathway.


Input: Notably, our epigenomic map demonstrated the highly euchromatic nature of unique piRNA clusters.


Input: RNA polymerase II was enriched for TSSs that transcribe piRNA precursors.


Input: piRNA precursors possessed 5'-cap structures as well as 3'-poly A-tails.


Input: Collectively, we envision that the euchromatic, opened nature of unique piRNA clusters or piRNA cluster-associated TSSs allows piRNA clusters to capture new insertions efficiently.


Input: A three-generational study of In ovo exposure to PBDE-99 in the zebra finch.


Input: Based on a literature review of avian data for polybrominated diphenyl ethers (PBDEs), ecologically relevant doses, low (10 ng/egg), medium (100 ng/egg), and high (1, 000 ng/egg) of the 2, 2', 4, 4', 5-pentabromodiphenyl ether (BDE-99) congener along with dimethylsulfoxide (DMSO) control were injected into the yolk sac of un-incubated eggs of zebra finch, Taeniopygia guttata.

polybrominated diphenyl ethers

PBDEs

2, 2', 4, 4', 5-pentabromodiphenyl ether

dimethylsulfoxide

DMSO


Input: Offspring development and adult phenotype were followed over three generations.


Input: No effects of in ovo PBDE exposure on hatching success, chick growth, thyroid hormone levels, or hematological traits were measured at sexual maturity (90 d posthatching).

PBDE


Input: However, the authors did detect significant effects of BDE-99 treatment on adult phenotype of in ovo-exposed birds by breeding observations, in which clutch size was significantly smaller in all PBDE-dosed birds (low, medium, and high) compared with controls.

PBDE


Input: A trend was also seen for longer laying intervals in PBDE-dosed birds (13-14 d) compared with control birds (8 d).

PBDE


Input: In addition, a significant effect of PBDE was found on growth of the second-generation offspring of in ovo-treated females; body mass was significantly lower in the high-PBDE dosed birds compared with controls from hatch through to fledging (day 30).

PBDE

PBDE


Input: The authors found no evidence of effects over the longer term and in successive generations, whether in adult, reproductive phenotype of the second-generation offspring of in ovo-treated birds, or in the growth of their (third-generation) offspring.


Input: Their results suggest that egg levels as low as 10 ng/g BDE-99 may affect reproduction in small passerines by reducing clutch size.


Input: Assessing ongoing sources of dissolved-phase polychlorinated biphenyls in a contaminated stream.

polychlorinated biphenyls


Input: Few studies assess the potential of ongoing sources of " fresh " polychlorinated biphenyls (PCBs) to aquatic systems when direct discharge to the environment has been eliminated.

polychlorinated biphenyls

PCBs


Input: In the present study, the authors used single-layered, low-density polyethylene samplers (PEs) to measure total PCB concentrations, congener profiles, and enantiomeric fractions (EFs) in a contaminated stream and to provide multiple lines of evidence for assessing ongoing inputs of PCB.

polyethylene

PCB

PCB