Input: For the met-enkephalin pentapeptide at a water-graphite interface, we were able to obtain accurate predictions for the location of the adsorbed peptide and its free energy of adsorption from around 50 and 80 SMD simulations, respectively.

met-enkephalin pentapeptide

graphite


Input: It was also shown that adsorption in this system is both energetically and entropically driven.


Input: The free energy of adsorption was also decomposed into that associated with formation of the cavity in the water near the graphite surface sufficient to accommodate the adsorbed peptide and that associated with insertion of the peptide into this cavity.

graphite


Input: This decomposition reveals that the former is modestly energetically and entropically unfavorable, whereas the latter is the opposite in both regards to a much greater extent.


Input: Gate-modulated thermoelectric power factor of hole gas in Ge-Si core-shell nanowires.

Ge

Si


Input: We experimentally studied the thermoelectric power factor of hole gas in individual Ge-Si core-shell nanowires with Ge core diameters ranging from 11 to 25 nm.

Ge

Si

Ge


Input: The Ge cores are dopant-free, but the Fermi level in the cores is pinned by surface and defect states in the epitaxial Si shell thereby doping the cores into the degenerate regime.

Ge

Si


Input: This doping mechanism avoids the high concentration of dopants usually encountered in bulk thermoelectric materials and provides a unique opportunity to enhance the carrier mobility with suppressed ionized impurity scattering.


Input: Moreover, the carrier concentration in small diameter nanowires has also been effectively modulated by field effect, allowing one to probe the electrical conductivity and thermopower within a wide range of carrier concentrations, which is crucial to understand the thermoelectric transport behavior.


Input: We found that the thermopower of nanowires with Ge core diameters down to 11 nm still follows the behavior of bulk Ge.

Ge

Ge


Input: As a result, the power factor is found to be closely correlated with the carrier mobility, which is higher than that of bulk Ge in one of the core-shell nanowires studied here.

Ge


Input: Interfacing quantum dots and graphitic surfaces with chlorine atomic ligands.

chlorine


Input: The performance of devices based on semiconductor nanocrystals (NCs) improves both with stronger interface interactions among NCs and between NCs and solid electrode surfaces.


Input: The combination of X-ray photoelectron spectroscopy (XPS) and solid (31) P CP/MAS NMR (cross-polarization/magic angle spinning nuclear magnetic resonance) shows that the selective substitution of long organic chains by chlorine atomic ligands during the colloidal synthesis by the hot injection method promotes the adsorption of CdSe NCs to carbon sp (2) surfaces, leading to the formation of well-ordered NC monolayers on graphitic materials.

(31) P

chlorine

CdSe

carbon


Input: Sustained PU. 1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells.


Input: To provide a lifelong supply of blood cells, hematopoietic stem cells (HSCs) need to carefully balance both self-renewing cell divisions and quiescence.


Input: Although several regulators that control this mechanism have been identified, we demonstrate that the transcription factor PU. 1 acts upstream of these regulators.


Input: So far, attempts to uncover PU. 1' s role in HSC biology have failed because of the technical limitations of complete loss-of-function models.


Input: With the use of hypomorphic mice with decreased PU. 1 levels specifically in phenotypic HSCs, we found reduced HSC long-term repopulation potential that could be rescued completely by restoring PU. 1 levels.


Input: PU. 1 prevented excessive HSC division and exhaustion by controlling the transcription of multiple cell-cycle regulators.


Input: Levels of PU. 1 were sustained through autoregulatory PU. 1 binding to an upstream enhancer that formed an active looped chromosome architecture in HSCs.


Input: These results establish that PU. 1 mediates chromosome looping and functions as a master regulator of HSC proliferation.


Input: The Hunger Games: p53 regulates metabolism upon serine starvation.

serine


Input: Cancer cells reprogram their metabolism to support a high proliferative rate.


Input: A new study shows that, upon serine starvation, the tumor suppressor p53 activates p21 to shift metabolic flux from purine biosynthesis to glutathione production, which enhances cellular proliferation and viability by combating ROS (Maddocks et al., 2013).

serine

purine

glutathione


Input: Structural analogs of huperzine A improve survival in guinea pigs exposed to soman.

huperzine A


Input: Chemical warfare nerve agents such as soman exert their toxic effects through an irreversible inhibition of acetylcholinesterase (AChE) and subsequently glutamatergic function, leading to uncontrolled seizures.


Input: The natural alkaloid (-)-huperzine A is a potent inhibitor of AChE and has been demonstrated to exert neuroprotection at an appropriate dose.

(-)-huperzine A


Input: It is hypothesized that analogs of both (+)-and (-)-huperzine A with an improved ability to interact with NMDA receptors together with reduced AChE inhibition will exhibit more effective neuroprotection against nerve agents.

(+)-and (-)-huperzine A

NMDA


Input: In this manuscript, the tested huperzine A analogs 2 and 3 were demonstrated to improve survival of guinea pigs exposed to soman at either 1. 2 or 2 x LD (50).

huperzine A


Input: Synthesis and biological evaluation of new cytotoxic indazolo [4, 3-gh] isoquinolinone derivatives.

indazolo [4, 3-gh] isoquinolinone


Input: A series of indazolo [4, 3-gh] isoquinolinones derivatives have been synthesized to decrease cardiotoxic side effects in comparison to Mitoxantrone.

indazolo [4, 3-gh] isoquinolinones

Mitoxantrone


Input: The antiproliferative effects of different side chains were investigated and tested on at least four different cell lines of cervix, ovarian, CNS, NSCLC (non-small-cell lung cancer) and colon carcinoma.


Input: In addition to antiproliferative activities, influence on cell cycle and intercalation behavior have been tested.


Input: Lactose substituted zinc phthalocyanine: a near infrared fluorescence imaging probe for liver cancer targeting.

Lactose

zinc phthalocyanine


Input: A near infrared fluorescence probe, lactose substituted zinc phthalocyanine, [2, 9 (10), 16 (17), 23 (24)-tetrakis ((1-(beta-d-lactose-2-yl)-1H-1, 2, 3-triazol-4-yl) methoxyl) phthalocyaninato] zinc (II), was synthesized via click reaction.

lactose

zinc phthalocyanine

[2, 9 (10), 16 (17), 23 (24)-tetrakis ((1-(beta-d-lactose-2-yl)-1H-1, 2, 3-triazol-4-yl) methoxyl) phthalocyaninato] zinc (II)


Input: Structural characterization and optical experiment demonstrated its excellent biocompatibility and fluorescence imaging ability.


Input: Near infrared fluorescence imaging in vivo for liver cancer, lung cancer and melanoma cancer with tumor bearing nude mice as models demonstrated that lactose substituted zinc phthalocyanine has specifically targeting ability to liver cancer while no targeting to lung cancer or melanoma, which implied its potential in liver cancer diagnosis as a near infrared optical probe.

lactose

zinc phthalocyanine


Input: Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line.

dispirooxindole-pyrrolidine


Input: Novel dispirooxindole-pyrrolidine derivatives have been synthesized through 1, 3-dipolar cycloaddition of an azomethine ylide generated from isatin and sarcosine with the dipolarophile 3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3-ylidene) propanenitrile, and also spiro compound of acenaphthenequinone obtained by the same optimized reaction condition.

dispirooxindole-pyrrolidine

azomethine

isatin

sarcosine

3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3-ylidene) propanenitrile

acenaphthenequinone


Input: Synthesized compounds were evaluated for their antimicrobial activity and all the compounds shown significant activity.


Input: Anticancer activity was evaluated against A549 human lung adenocarcinoma cancer cell lines.


Input: Compounds 7b, 7g, 7i and 7r exhibit very good anticancer activity 62. 96%, 62. 03%, 67. 67% and 60. 22%, respectively, at the dose of 200 mu g/mL and compound 7i shows IC50 value in 50 mu g/mL.


Input: Manganese-loaded lipid-micellar theranostics for simultaneous drug and gene delivery to lungs.

Manganese


Input: Gadolinium (Gd) contrast agents are predominantly used for T (1) MR imaging.

Gadolinium

Gd


Input: However, the high toxicity of Gd (3 +) and potential side effects including nephrogenic systemic fibrosis have led to the search for alternative T (1) contrast agents.

Gd (3 +)


Input: Since manganese (Mn) has paramagnetic properties with five unpaired electrons that permit high spin number, long electronic relaxation times, and labile water exchange, we evaluated Mn as a T (1) magnetic resonance imaging (MRI) contrast agent for lung imaging.

manganese

Mn

Mn


Input: Here we report on the design and synthesis of multifunctional lipid-micellar nanoparticles (LMNs) containing Mn oxide (M-LMNs) for MRI that can also be used for DNA and drug delivery.

Mn oxide


Input: Oleic acid-coated MnO nanoparticles were encapsulated in micelles composed of polyethylene glycol (PEG-2000), phosphatidylethanolamine (PE), DC-cholesterol, and dioleoyl-phosphatidylethanolamine (DOPE).

Oleic acid

MnO

polyethylene glycol

phosphatidylethanolamine

cholesterol

dioleoyl-phosphatidylethanolamine

DOPE


Input: The particles are taken up in vitro by human embryonic kidney (HEK293), Lewis lung carcinoma (LLC1), and A549 cells and are devoid of cytotoxicity.


Input: When administered to mice intranasally, they preferentially accumulate in the lungs.


Input: In vitro phantom and ex vivo lung MRI results confirmed that M-LMNs are able to enhance T (1) MRI contrast.


Input: M-LMNs loaded with plasmid DNA and/or doxorubicin are efficiently taken up by HEK293 cells in vitro and by target cells in vivo.

doxorubicin


Input: Taken together, these results demonstrate that M-LMNs are capable of simultaneously providing MRI contrast and DNA and/or drug delivery to target cells in the lung and therefore may prove useful as a lung theranostic, especially for lung cancers.


Input: Xestospongin C induces monocytic differentiation of HL60 cells through activation of the ERK pathway.

Xestospongin C


Input: Xestospongin C (XC), which is a group of macrocyclic bis-1-oxaquinolizidines, is a potent inhibitor of sarcoendoplasmic reticulum calcium transport ATPase and IP3 receptor.

Xestospongin C


Input: Nevertheless, very less information is available regarding whether XC induces AML differentiation.


Input: We investigated the potential role of XC in the differentiation of human leukemia HL60 cells and mechanisms underlying XC actin.


Input: XC treatment inhibited proliferation by inducing G1-phase cell cycle arrest in the HL60 cells.


Input: In addition, XC induced differentiation of HL60 cells into the CD14 (+) monocytic lineage, which was indicated by morphological changes, nitroblue tetrazolium reduction assay, and expressions of CD11b and CD14 surface antigens.

nitroblue tetrazolium


Input: Our results also showed that XC promotes phagocytic activity and granularity in HL60 cells, suggesting that the cells are functionally activated.


Input: Furthermore, XC enhanced tumor necrosis factor (TNF)-alpha-mediated cytotoxic effect by increasing the numbers of TNF receptors.


Input: Moreover, we showed that XC activates extracellular signal-regulated kinase (ERK) pathway in the differentiation stages.


Input: Inhibition of ERK activation using PD98059 significantly decreased NBT + HL60 cells induced by XC treatment.


Input: Taken together, the results show that XC promotes monocytic differentiation of HL60 cells via ERK pathway activation, suggesting that XC could be a candidate for use as a differentiation-inducing agent for AML treatment.


Input: Identification of polyphenols and their metabolites in human urine after cranberry-syrup consumption.

polyphenols


Input: As the beneficial effects of American cranberry (Vaccinium macrocarpon) can be partly attributed to its phenolic composition, the evaluation of the physiological behaviour of this fraction is crucial.

phenolic


Input: A rapid and sensitive method by ultra-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) has been used to identify phenolic metabolites in human urine after a single dose of cranberry syrup.

phenolic


Input: Prior to the analysis, metabolites were extracted using an optimised solid-phase extraction procedure.


Input: All possible metabolites were investigated based on retention time, accurate mass data and isotope and fragmentation patterns.


Input: Free coumaroyl hexose (isomer 1 and 2), dihydroxybenzoic acid, caffeoyl glucose, dihydroferulic acid 4-O-beta-d-glucuronide, methoxyquercetin 3-O-galactoside, scopoletin, myricetin and quercetin, together with other 23 phase-I and phase-II metabolites, including various isomers, could be tentatively identified in the urine.

coumaroyl hexose

dihydroxybenzoic acid

caffeoyl glucose

dihydroferulic acid 4-O-beta-d-glucuronide

methoxyquercetin 3-O-galactoside

scopoletin

myricetin

quercetin


Input: Afterwards, the metabolites were simultaneously screened in the urine of different subjects at 0, 2, 4, and 6h after the ingestion of cranberry syrup by Target Analysis (TM) software.


Input: gamma-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes.

gamma-Oryzanol

cadmium


Input: Cadmium is a non-essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke.

Cadmium


Input: The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of gamma-oryzanol (ORY).

cadmium

gamma-oryzanol

ORY


Input: Mice were administrated with a single dose of 2. 5mg/kg of CdCl2, and then treated with ORY (50mM in canola oil, 5mL/kg).

ORY


Input: Testes were removed after 24h and tested for lipid peroxidation (TBARS), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non-proteic thiols contents, and for the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and delta-aminolevulic acid dehydratase (delta-ALA-D).

ascorbic acid

cadmium

thiols

superoxide

glutathione

glutathione S

delta-aminolevulic acid

delta-ALA


Input: Cadmium presented a significant alteration in all parameters, except GPx and CAT activities.

Cadmium


Input: Therapy reduced in a slight degree cadmium concentration in testes (around 23%).

cadmium


Input: ORY restored SOD and GST activities as well as TBARS production to the control levels.

ORY


Input: Furthermore, ORY partially recovered delta-ALA-D activity inhibited by cadmium.

ORY

delta-ALA

cadmium


Input: This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium-induced testicular toxicity.

ORY

cadmium


Input: Support vector machine: Classifying and predicting mutagenicity of complex mixtures based on pollution profiles.


Input: Powerful, robust in silico approaches offer great promise for classifying and predicting biological effects of complex mixtures and for identifying the constituents of greatest concern.


Input: Support vector machine (SVM) methods can deal with high dimensional data and small sample size and examine multiple interrelationships among samples.


Input: In this work, we applied SVM methods to examine pollution profiles and mutagenicity of 60 water samples obtained from 6 cities in China during 2006-2011.


Input: Pollutant profiles were characterized in water extracts by gas chromatography-mass spectrometry (GC/MS) and mutagenicity examined by Ames assays.


Input: We encoded feature vectors of GS-MS peaks in the mixtures and used 48 samples as the training set, reserving 12 samples as the test set.


Input: The SVM model and regression were constructed from whole pollution profiles that ranked compounds in relation to their correlation to the mutagenicity.


Input: Both classification and prediction performance were evaluated.


Input: The SVM model based on whole pollution profiles showed lower performance (sensitivity, specificity, accuracy and correlation coefficient were 69. 5-70. 7%, 70. 6-73. 2%, 69. 9-72. 1%, and 0. 55-0. 59%, respectively) than one based on compounds with highest association with mutagenicity.


Input: A SVM model with the top 10 compounds had the highest performance (sensitivity, specificity, accuracy, and correlation coefficient were 89. 8-90. 3%, 90. 1-92. 1%, 90. 1-91. 3%, and 0. 80-0. 82%, respectively), with negligible decreases in performance between the test and training set.


Input: SVM can be a powerful, robust classifier of the relationship of pollutants and mutagenicity in complex real-world mixtures.


Input: The top 14 compounds have the greatest contribution to mutagenicity and deserve further studies to identify these constituents.


Input: Site dependent intestinal absorption of darunavir and its interaction with ketoconazole.

darunavir

ketoconazole


Input: The expression of P-gp increases from proximal to distal parts of the small intestine, whereas for P450 enzymes the expression is reported to be highest in duodenum and jejunum, decreasing to more distal sites.


Input: To evaluate to what extent the regional differences in expression of P-gp and P450 enzymes affect the absorption of a dual substrate, we investigated the transport of darunavir across different small intestinal segments (duodenum, proximal jejunum and ileum).

darunavir


Input: Moreover, the effect of ketoconazole on the intestinal absorption of darunavir was explored, since these drugs are commonly co-administered.

ketoconazole

darunavir


Input: Performing the rat in situ intestinal perfusion technique with mesenteric blood sampling, we found no significant differences in the transport of darunavir at the different intestinal segments.

darunavir


Input: The involvement of P-gp in the absorption of darunavir was clearly shown by coperfusion of darunavir with the P-gp inhibitor zosuquidar.

darunavir

darunavir

zosuquidar


Input: In presence of zosuquidar, a 2. 2-, 4. 2-and 5. 7-fold increase in Papp values were measured for duodenum, proximal jejunum and ileum, respectively.

zosuquidar


Input: Involvement of P450 mediated metabolism in the absorption of darunavir could not be demonstrated in this rat model.

darunavir


Input: Upon studying the drug-drug interaction of darunavir with ketoconazole, data were indicative for an inhibitory effect of ketoconazole on P-gp as the main mechanism for the increased transport of darunavir across the small intestine.

darunavir

ketoconazole

ketoconazole

darunavir


Input: Cellular Mechanisms of Nociceptin/Orphanin FQ (N/OFQ) Peptide (NOP) Receptor Regulation and Heterologous Regulation by N/OFQ.


Input: The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is the fourth and most recently discovered member of the opioid receptor superfamily that also includes mu, delta, and kappa opioid receptor subtypes (MOR, DOR, and KOR, respectively).


Input: The widespread anatomic distribution of the NOP receptor enables the modulation of several physiologic processes by its endogenous agonist, N/OFQ.


Input: Accordingly, the NOP receptor has gained a lot of attention as a potential target for the development of ligands with therapeutic use in several pathophysiological states.


Input: NOP receptor activation frequently results in effects opposing classic opioid receptor action; therefore, regulation of the NOP receptor and conditions affecting its modulatory tone are important to understand.


Input: Mounting evidence reveals a heterologous interaction of the NOP receptor with other G protein-coupled receptors, including MOR, DOR, and KOR, which may subsequently influence their function.


Input: Our focus in this review is to summarize and discuss the findings that delineate the cellular mechanisms of NOP receptor signaling and regulation and the regulation of other receptors by N/OFQ and the NOP receptor.


Input: Dissolved azaspiracids are absorbed and metabolized by blue mussels (Mytilus edulis).

azaspiracids


Input: The relationship between azaspiracid shellfish poisoning and a small dinoflagellate, Azadinium spinosum, has been shown recently.

azaspiracid


Input: The organism produces AZA1 and-2, while AZA3 and other analogues are metabolic products formed in shellfish.

AZA1 and-2


Input: We evaluated whether mussels were capable of accumulating dissolved AZA1 and-2, and compared the toxin profiles of these mussels at 24 h with profiles of those exposed to live or lysed A. spinosum.

AZA1 and-2


Input: We also assessed the possibility of preparative production of AZA metabolites by exposing mussels to semi-purified AZA1.

AZA


Input: We exposed mussels to similar concentration of AZAs: dissolved AZA1 + 2 (crude extract) at 7. 5 and 0. 75 mu g L (-1), dissolved AZA1 + 2 (7. 5 mu g L (-1)) in combination with Isochrysis affinis galbana, and lysed and live A. spinosum cells at 1 x 10 (5) and 1 x 10 (4) cell mL (-1) (containing equivalent amounts of AZA1 + 2).

AZAs

AZA1 + 2

AZA1 + 2

AZA1 + 2


Input: Subsequently, we dissected and analysed digestive glands, gills and remaining flesh.


Input: Mussels (whole flesh) accumulated AZAs to levels above the regulatory limit, except at the lower levels of dissolved AZAs.

AZAs

AZAs


Input: The toxin profile of the mussels varied significantly with treatment.


Input: The gills contained 42-46% and the digestive glands 23-24% of the total toxin load using dissolved AZAs, compared to 3-12% and 75-90%, respectively, in mussels exposed to live A. spinosum.

AZAs


Input: Exposure of mussels to semi-purified AZA1 produced the metabolites AZA17 (16. 5%) and AZA3 (1. 7%) after 4 days of exposure, but the conversion efficiency was too low to justify using this procedure for preparative isolation.


Input: Polycationic nanoparticles synthesized using ARGET ATRP for drug delivery.


Input: This work provides a systemic comparison for ARGET ATRP and UV-initiated polycationic nanoparticles for drug delivery and a guide to deciding which type of polycationic nanoparticles have the best properties for specific applications.


Input: Polycationic nanoparticles were synthesized using a previously developed UV-initiated photoemulsion polymerization or a newly developed ARGET ATRP synthesis technique.


Input: The effect of the ratio of hydrophobic monomer in the feed was evaluated.


Input: Increasing the feed ratio of hydrophobic monomer was necessary to maintain biocompatibility and pH-responsive membrane disruptive characteristics when switching from the UV-initiated polymerization to ARGET ATRP.


Input: The resulting polycationic nanoparticles have utility as drug delivery carriers for hydrophobic drugs and/or nucleic acids.


Input: Change in the transfer profile of orally administered tetrodotoxin to non-toxic cultured pufferfish Takifugu rubripes depending of its development stage.

tetrodotoxin


Input: To investigate the effects of growth (organ development) on tetrodotoxin (TTX) dynamics in the pufferfish body, TTX-containing feed homogenate was administered to 6-and 15-month old non-toxic cultured specimens of the pufferfish Takifugu rubripes at a dose of 40 mouse units (MU) (8. 8 mu g)/20 g body weight by oral gavage.

tetrodotoxin

TTX

TTX


Input: After 24 h, the specimens were killed and the skin tissues (dorsal and ventral), muscle, liver, digestive tract, and gonads were separated.


Input: TTX content (mu g/g) in each tissue, determined by liquid chromatography/mass spectrometry, revealed that the TTX distribution profile, particularly the TTX content of the liver, greatly differed between the two ages; the TTX score of 15-month old fish (3. 3 mu g/g) was nearly 5-fold that of 6-month old fish (0. 68 mu g/g).

TTX

TTX

TTX

TTX


Input: The total remaining TTX amount per individual (relative amount to the given dose) was 31% in 6-month old fish, of which 71% was in the skin, and 84% in 15-month old fish, of which 83% was in the liver.

TTX


Input: The gonadosomatic index (GSI) and hepatosomatic index (HSI) scores, and histologic observations of the gonads and liver suggest that although there is little difference in maturation stage between these two ages, there are clear distinctions in the developmental stage of the liver.


Input: The results suggest that the TTX dynamics in T. rubripes are linked to the development of the liver, i. e., the TTX taken up into the pufferfish body via food organisms is eliminated or transferred mainly to the skin in young fish with an undeveloped liver, but as the fish grow and the liver continues to develop, most of the TTX is transferred to and accumulated in the liver.

TTX

TTX

TTX


Input: Protein carbonylation in human endothelial cells exposed to cigarette smoke extract.


Input: Cigarette smoke is a significant independent risk factor for vascular diseases and is a leading cause of structural and functional alterations of the vascular endothelium.


Input: In this study, we show protein carbonylation in the human umbilical vein endothelial cell line (ECV-304) exposed to whole-phase cigarette smoke extract.


Input: The main carbonylated proteins, including cytoskeletal proteins, glycolytic enzymes, xenobiotic metabolizing and antioxidant enzymes, and endoplasmic reticulum proteins, were identified by means of two-dimensional electrophoresis and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometry (redox proteomics).


Input: Morphological analyses by fluorescence microscopy evidenced alterations in the microtubule cytoskeleton, especially at longer exposure time to cigarette smoke extract.


Input: Morphological analyses by transmission electron microscopy showed vacuolisation of the cytoplasm, alteration of mitochondria ultrastructure, and some enlargement of the perinuclear space.


Input: The possible role played by protein carbonylation caused by reactive species contained in cigarette smoke in the cigarette smoke-induced endothelial injury is discussed.


Input: Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes.


Input: Death domain-associated protein (Daxx) cooperates with X-linked alpha-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3. 3 deposition and transcriptional repression of cellular promoters.

sucrose

ATP


Input: Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression.


Input: Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein-protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX.


Input: To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase.


Input: Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5.


Input: We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling.


Input: Structural and mechanical properties of individual human telomeric G-quadruplexes in molecularly crowded solutions.


Input: Recent experiments provided controversial observations that either parallel or non-parallel G-quadruplex exists in molecularly crowded buffers that mimic cellular environment.


Input: Here, we used laser tweezers to mechanically unfold structures in a human telomeric DNA fragment, 5'-(TTAGGG) 4TTA, along three different trajectories.


Input: After the end-to-end distance of each unfolding geometry was measured, it was compared with PDB structures to identify the best-matching G-quadruplex conformation.


Input: This method is well-suited to identify biomolecular structures in complex settings not amenable to conventional approaches, such as in a solution with mixed species or at physiologically significant concentrations.


Input: With this approach, we found that parallel G-quadruplex coexists with non-parallel species (1: 1 ratio) in crowded buffers with dehydrating cosolutes [40% w/v dimethyl sulfoxide (DMSO) or acetonitrile (ACN)].

dimethyl sulfoxide

DMSO

acetonitrile

ACN


Input: In crowded solutions with steric cosolutes [40% w/v bovine serum albumin (BSA)], the parallel G-quadruplex constitutes only 10% of the population.


Input: This difference unequivocally supports the notion that dehydration promotes the formation of parallel G-quadruplexes.


Input: Compared with DNA hairpins that have decreased unfolding forces in crowded (9 pN) versus diluted (15 pN) buffers, those of G-quadruplexes remain the same (20 pN).


Input: Such a result implies that in a cellular environment, DNA G-quadruplexes, instead of hairpins, can stop DNA/RNA polymerases with stall forces often < 20 pN.


Input: Parathyroid hormone (1-34) counteracts the suppression of interleukin-11 expression by glucocorticoid in murine osteoblasts: a possible mechanism for stimulating osteoblast differentiation against glucocorticoid excess.


Input: Glucocorticoid (GC) excess causes a rapid loss of bone with a reduction in bone formation.


Input: Intermittent PTH (1-34) administration stimulates bone formation and counteracts the inhibition of bone formation by GC excess.


Input: We have previously demonstrated that mechanical strain enhances interleukin (IL)-11 gene transcription by a rapid induction of Delta FosB expression and protein kinase C (PKC)-delta-mediated phosphorylation of phosphorylated mothers against decapentaplegic (Smad)-1.


Input: Because IL-11 suppresses the expression of dickkopf-1 and-2 and stimulates Wnt signaling, IL-11 appears to mediate at least a part of the effect of mechanical strain on osteoblast differentiation and bone formation.


Input: The present study was undertaken to examine the effect of PTH (1-34) and GCs on IL-11 expression in murine primary osteoblasts (mPOBs).


Input: PTH (1-34) treatment of mPOBs enhanced IL-11 expression in a time-and dose-dependent manner.


Input: PTH (1-34) also stimulated Delta FosB expression and Smad1 phosphorylation, which cooperatively stimulated IL-11 gene transcription.


Input: PTH (1-34)-induced Smad1 phosphorylation was mediated via PKC delta and was abrogated in mPOBs from PKC delta knockout mice.


Input: Dexamethasone suppressed IL-11 gene transcription enhanced by PTH (1-34) without affecting Delta FosB expression or Smad1 phosphorylation, and dexamethasone-GC receptor complex was bound to JunD, which forms heterodimers with Delta FosB.

Dexamethasone

dexamethasone


Input: High doses of PTH (1-34) counteracted the effect of dexamethasone on apoptosis of mPOBs, which was blunted by neutralizing anti-IL-11 antibody or IL-11 small interfering RNA.

dexamethasone


Input: These results demonstrate that PTH (1-34) and GCs interact to regulate IL-11 expression in parallel with osteoblast differentiation and apoptosis and suggest that PTH (1-34) and dexamethasone may regulate osteoblast differentiation and apoptosis via their effect on IL-11 expression.

dexamethasone


Input: A prospective open-label trial of paliperidone monotherapy for the treatment of bipolar spectrum disorders in children and adolescents.

paliperidone


Input: RATIONALE: Treatment studies for the management of pediatric bipolar disorder are limited.


Input: OBJECTIVES: This study evaluates the safety and efficacy of paliperidone monotherapy as an acute treatment of mania and related symptoms in youth with bipolar spectrum disorders.

paliperidone


Input: METHODS: An 8-week, prospective, open-label paliperidone monotherapy trial to assess effectiveness and tolerability in treating pediatric bipolar spectrum and related disorders (depression, psychosis, attention-deficit/hyperactivity disorder [ADHD]).

paliperidone


Input: Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impression scale (CGI), Children' s Depression Rating Scale-Revised (CDRS-R), and Brief Psychiatric Rating Scale (BPRS).


Input: Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis.


Input: RESULTS: Fifteen youth with bipolar spectrum disorders (YMRS at entry: 32. 8 +/- 6. 1) were enrolled in the study and 11 (73%) completed the 8-week trial.


Input: The total daily dose of paliperidone at study endpoint was 3 mg in 12 subjects and 6 mg in three subjects.

paliperidone


Input: Treatment with paliperidone was associated with statistically significant levels of improvement in mean YMRS scores (-18. 7 +/- 13. 9, p < 0. 001) at endpoint.

paliperidone


Input: Paliperidone treatment also resulted in significant improvement in the severity of ADHD and psychotic symptoms.

Paliperidone


Input: Although treatment with paliperidone was generally well tolerated and was not associated with clinically significant change in cardiovascular or metabolic parameters, increases in body weight (4. 1 +/- 5. 5 lb) were substantial.

paliperidone


Input: CONCLUSIONS: Open-label paliperidone treatment appears to be beneficial in the treatment of bipolar spectrum disorders and associated conditions in youth.

paliperidone


Input: Future placebo-controlled studies are warranted to confirm these findings.


Input: White light from a single-emitter light-emitting electrochemical cell.


Input: We report a novel and generic approach for attaining white light from a single-emitter light-emitting electrochemical cell (LEC).


Input: With an active-layer comprising a multifluorophoric conjugated copolymer (MCP) and an electrolyte designed to inhibit MCP energy-transfer interactions during LEC operation, we are able to demonstrate LECs that emit broad-band white light with a color rendering index of 82, a correlated-color temperature of 4000 K, and a current conversion efficacy of 3. 8 cd/A.


Input: It is notable that this single-emitter LEC configuration eliminates color-drift problems stemming from phase separation, which are commonly observed in conventional blended multiemitter devices.


Input: Moreover, the key role of the electrolyte in limiting undesired energy-transfer reactions is highlighted by the observation that an electrolyte-free organic light-emitting diode comprising the same MCP emits red light.


Input: Retinoids and glucocorticoids target common genes in hippocampal HT22 cells.

Retinoids


Input: Vitamin A metabolite retinoic acid (RA) plays a major role in the aging adult brain plasticity.

Vitamin A

retinoic acid


Input: Conversely, chronic excess of glucocorticoids (GC) elicits some deleterious effects in the hippocampus.


Input: We questioned here the involvement of RA and GC in the expression of target proteins in hippocampal neurons.


Input: We investigated proteins involved either in the signaling pathways [RA receptor beta (RAR beta) and glucocorticoid receptor (GR)] or in neuron differentiation and plasticity [tissue transglutaminase 2 (tTG) and brain-derived neurotrophic factor (BDNF)] in a hippocampal cell line, HT22.


Input: We applied RA and/or dexamethasone (Dex) as activators of the pathways and investigated mRNA and protein expression of their receptors and of tTG and BDNF as well as tTG activity and BDNF secretion.

dexamethasone

Dex


Input: Our results confirm the involvement of RA-and GC-dependent pathways and their interaction in our neuronal cell model.


Input: First, both pathways regulate the transcription and expression of own and reciprocal receptors: RA and Dex increased RAR beta and decreased GR expressions.


Input: Second, Dex reduces the expression of tTG when associated with RA despite stimulating its expression when used alone.

Dex


Input: Importantly, when they are combined, RA counteracts the deleterious effect of glucocorticoids on BDNF regulation and thus may improve neuronal plasticity under stress conditions.


Input: In conclusion, GC and RA both interact through regulations of the two receptors, RAR beta and GR.


Input: Furthermore, they both act, synergistically or oppositely, on other target proteins critical for neuronal plasticity, tTG and BDNF.


Input: Inhibition of ghrelin O-acyltransferase attenuates food deprivation-induced increases in ingestive behavior.

O


Input: Ghrelin is an orexigenic hormone produced by the stomach in direct proportion to the time since the last meal and has therefore been called a' hunger signal'.


Input: The octanoylation of ghrelin is critical for its orexigenic functions and is dependent upon ghrelin O-acyltransferase (GOAT) catalyzation.

O


Input: The GOAT inhibitor, GO-CoA-Tat, decreases the circulating concentrations of octanoylated ghrelin and attenuates weight gain on a high fat diet in mice.


Input: Unlike rats and mice, Siberian hamsters and humans do not increase food intake after food deprivation, but increase food hoarding after food deprivation.


Input: In Siberian hamsters, exogenous ghrelin increases ingestive behaviors similarly to 48-56h food deprivation.


Input: Therefore, we tested the necessity of increased ghrelin in food-deprived Siberian hamsters to stimulate ingestive behaviors.


Input: To do so we used our simulated natural housing system that allows hamsters to forage for and hoard food.


Input: Animals were given an injection of GO-CoA-Tat (i. p., 11 mu mol/kg) every 6h because that is the duration of its effective inhibition of octanoylated ghrelin concentrations during a 48h food deprivation.


Input: We found that GO-CoA-Tat attenuated food foraging (0-1h), food intake (0-1 and 2-4h), and food hoarding (0-1h and 2 and 3days) post-refeeding compared with saline treated animals.


Input: This suggests that increased octanoylated ghrelin concentrations play a role in the food deprivation-induced increases in ingestive behavior.


Input: Therefore, ghrelin is a critical aspect of the multi-faceted mechanisms that stimulate ingestive behaviors, and might be a critical point for a successful clinical intervention scheme in humans.


Input: Chemically diverse microtubule stabilizing agents initiate distinct mitotic defects and dysregulated expression of key mitotic kinases.


Input: Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined.


Input: The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied.

taccalonolide AJ

laulimalide

fijianolide B

paclitaxel


Input: These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling.


Input: Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins.


Input: Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent than paclitaxel or laulimalide, which is consistent with the distinct defects in expression and activation of Plk1 and Eg5 caused by each stabilizer.

Taccalonolide AJ

paclitaxel

laulimalide


Input: Localization studies revealed that TPX2 and Aurora A are associated with each spindle aster formed by each stabilizer.


Input: This suggests a common mechanism of aster formation.


Input: However, taccalonolide AJ also causes pericentrin accumulation on every spindle aster.

taccalonolide AJ


Input: The presence of pericentrin at every spindle aster initiated by taccalonolide AJ might facilitate the maintenance and stability of the highly focused asters formed by this stabilizer.

taccalonolide AJ


Input: Laulimalide and paclitaxel cause completely different patterns of expression and activation of these proteins, as well as phenotypically different spindle phenotypes.

Laulimalide

paclitaxel


Input: Delineating how diverse microtubule stabilizers affect mitotic signaling pathways could identify key proteins involved in modulating sensitivity and resistance to the antimitotic actions of these compounds.


Input: Creation and screening of a multi-family bacterial oxidoreductase library to discover novel nitroreductases that efficiently activate the bioreductive prodrugs CB1954 and PR-104A.


Input: Two potentially complementary approaches to improve the anti-cancer strategy gene-directed enzyme prodrug therapy (GDEPT) are discovery of more efficient prodrug-activating enzymes, and development of more effective prodrugs.


Input: Here we demonstrate the utility of a flexible screening system based on the Escherichia coli SOS response to evaluate novel nitroreductase enzymes and prodrugs in concert.


Input: To achieve this, a library of 47 candidate genes representing 11 different oxidoreductase families was created and screened to identify the most efficient activators of two different nitroaromatic prodrugs, CB1954 and PR-104A.


Input: The most catalytically efficient nitroreductases were found in the NfsA and NfsB enzyme families, with NfsA homologues generally more active than NfsB.


Input: Some members of the AzoR, NemA and MdaB families also exhibited low-level activity with one or both prodrugs.


Input: The results of SOS screening in our optimised E. coli reporter strain SOS-R2 were generally predictive of the ability of nitroreductase candidates to sensitise E. coli to CB1954, and of the kcat/Km for each prodrug substrate at a purified protein level.


Input: However, we also found that not all nitroreductases express stably in human (HCT-116 colon carcinoma) cells, and that activity at a purified protein level did not necessarily predict activity in stably transfected HCT-116.


Input: These results highlight a need for all enzyme-prodrug partners for GDEPT to be assessed in the specific context of the vector and cell line that they are intended to target.


Input: Nonetheless, our oxidoreductase library and optimised screens provide valuable tools to identify preferred nitroreductase-prodrug combinations to advance to preclinical evaluation.


Input: The fundamental chemical equation of aromaticity.


Input: In the search for the chemical measure of molecular aromaticity, namely the energetic gain of a cyclic delocalized structure for just being cyclic, the numerous definitions of generic aromatic stabilisation energies proposed hitherto stand as approximates of the conceptual limit devised within the framework of spectral graph theory, i. e. the topological resonance energy (TRE).


Input: After a 36 year challenge, the TRE acyclic reference of any pi-cyclic molecule, originally merely defined by an abstract matching polynomial, is now given a real chemical structure: the M o bius-twisted head-to-tail metathesis cyclo-dimer of the parent ring.


Input: The original treatment at the H u ckel molecular orbital level of theory can now be extended to DFT or ab initio levels.


Input: The corresponding ring opening-closing-twisting chemical transformation provides the observable basis for the measure of aromaticity under either vertical or adiabatic conditions.


Input: The importance of the TiO2/quantum dots interface in the recombination processes of quantum dot sensitized solar cells.


Input: Quantum dot sensitized solar cells (QDSSCs) present a promising technology for next generation photovoltaic cells, having exhibited a considerable leap in performance over the last few years.


Input: However, recombination processes occurring in parallel at the TiO (2)-QDs-electrolyte triple junction constitute one of the major limitations for further improvement of QDSSCs.

TiO (2)


Input: Reaching higher conversion efficiencies necessitates gaining a better understanding of the mechanisms of charge recombination in these kinds of cells; this will essentially lead to the development of new solutions for inhibiting the described losses.


Input: In this study we have systematically examined the contribution of each interface formed at the triple junction to the recombination of the solar cell.


Input: We show that the recombination of electrons at the TiO (2)/QDs interface is as important as the recombination from TiO (2) and QDs to the electrolyte.

TiO (2)

TiO (2)


Input: By applying conformal MgO coating both above and below the QD surface, recombination rates were significantly reduced, and an improvement of more than 20% in cell efficiency was recorded.

MgO


Input: Self-templating synthesis of hollow mesoporous silica and their applications in catalysis and drug delivery.

silica


Input: Hollow mesoporous silica materials have been intensively pursued because of their unique properties for various applications.

silica


Input: Yolk/shell structured hollow mesoporous silica with functional cores inside their hollow interior can further broaden the applications of hollow mesoporous silica.

silica

silica


Input: The self-templating strategy has been developed as one of the most important strategies to effectively fabricate hollow mesoporous silicas and their yolk/shell counterparts.


Input: In this feature article, we provide an overview of advances in the self-templating synthesis of hollow mesoporous silica based on the following three strategies: surface-protected etching, structural difference-based selective etching, and cationic surfactant assisted self-templating.

silica


Input: We then discuss some important applications of these self-templating strategy-derived hollow mesoporous silicas, such as nanoreactors for confined catalysis and multifunctional platforms for combined therapy.

silicas


Input: Finally, some perspectives for the future development of this active research field are provided.


Input: An algorithm to detect adverse drug reactions in the neonatal intensive care unit.


Input: Critically ill newborns in neonatal intensive care units (NICUs) are at greater risk of developing adverse drug reactions (ADRs).


Input: Differentiation of ADRs from reactions associated with organ dysfunction/immaturity is difficult.


Input: Current ADR algorithm scoring was established arbitrarily without validation in infants.


Input: The study objective was to develop a valid and reliable algorithm to identify ADRs in the NICU.


Input: Algorithm development began with a 24-item questionnaire for data collection on 100 previously suspected ADRs.


Input: Five pediatric pharmacologists independently rated cases as definite, probable, possible, and unlikely ADRs.


Input: Consensus " gold standard " was reached via teleconference.


Input: Logistic regression and iterative C programs were used to derive the scoring system.


Input: For validation, 50 prospectively collected ADR cases were assessed by 3 clinicians using the new algorithm and the Naranjo algorithm.


Input: Weighted kappa and intraclass correlation coefficient (ICC) were used to compare validity and reliability of algorithms.


Input: The new algorithm consists of 13 items.


Input: Kappa and ICC of the new algorithm were 0. 76 and 0. 62 versus 0. 31 and 0. 43 for the Naranjo algorithm.


Input: The new algorithm developed using actual patient data is more valid and reliable than the Naranjo algorithm for identifying ADRs in the NICU population.


Input: Because of the relatively small and nonrandom samples, further refinement and additional testing are needed.


Input: F1-ATPase of Escherichia coli: the epsilon-inhibited state forms after ATP hydrolysis, is distinct from the ADP-inhibited state, and responds dynamically to catalytic site ligands.

ATPase

ADP


Input: F1-ATPase is the catalytic complex of rotary nanomotor ATP synthases.

ATPase


Input: Bacterial ATP synthases can be autoinhibited by the C-terminal domain of subunit epsilon, which partially inserts into the enzyme' s central rotor cavity to block functional subunit rotation.

ATP

C


Input: Using a kinetic, optical assay of F1. epsilon binding and dissociation, we show that formation of the extended, inhibitory conformation of epsilon (epsilon X) initiates after ATP hydrolysis at the catalytic dwell step.

ATP


Input: Prehydrolysis conditions prevent formation of the epsilon X state, and post-hydrolysis conditions stabilize it.


Input: We also show that epsilon inhibition and ADP inhibition are distinct, competing processes that can follow the catalytic dwell.

ADP


Input: We show that the N-terminal domain of epsilon is responsible for initial binding to F1 and provides most of the binding energy.

N


Input: Without the C-terminal domain, partial inhibition by the epsilon N-terminal domain is due to enhanced ADP inhibition.

C

N

ADP


Input: The rapid effects of catalytic site ligands on conformational changes of F1-bound epsilon suggest dynamic conformational and rotational mobility in F1 that is paused near the catalytic dwell position.


Input: Imposex effects on the veined rapa whelk (Rapana venosa) in Bohai Bay, China.


Input: Environmentally relevant concentrations of organotin compounds (OTs) may trigger sex changes in marine invertebrates and pose a threat to the marine ecosystem.

organotin


Input: In this study, we investigated organotin levels and the biological responses of wild veined rapa whelk (Rapana venosa) from L u juhe district (LJH), Dashentang district (DST), and Nanpaihe district (NPH) in Bohai Bay, China.

organotin


Input: We found that 11. 11 and 22. 95% of the veined rapa whelks from DST and NPH exhibited imposex characteristics with a relative penis size index (RPSI) of 12. 50 and 12. 31, respectively.


Input: The RNA/DNA ratio was significantly lower in females from DST than those from LJH (p < 0. 05), and a slight increase in DNA damage was observed in females and imposex individuals compared to males.


Input: Moreover, less genetic distance occurred between LJH and NPH (0. 016) than between LJH and DST (0. 028), although they belonged to the same regional population.


Input: OTs analysis showed that triphenyltin chloride concentrations (41. 45 ng/g dried weight) were significantly higher than tributyltin concentrations (9. 51 ng/g dried weight) in tissues (p < 0. 05), but no significant differences were observed in sediments (p > 0. 05).

triphenyltin chloride

tributyltin


Input: In conclusion, the occurrence of imposex individuals and biological responses of the wild veined rapa whelk from Bohai Bay suggest that the marine ecosystem might be at risk.


Input: The accumulation of metal (Co, Cr, Cu, Mn and Zn) in freshwater Ulva (Chlorophyta) and its habitat.

Co

Cr

Cu

Mn

Zn


Input: The possibility of using freshwater Ulva (Chlorophyta) as a bioaccumulator of metals (Co, Cr, Cu, Mn and Zn) in lake and river water was examined weekly in the summer of 2010 in three types of samples: the water, the sediment and the thalli of Ulva.

Co

Cr

Cu

Mn

Zn


Input: Samples of freshwater Ulva were collected from two aqueous ecosystems lie 250 km away from the basin of the Baltic Sea and 53 km from each other.


Input: A flow lake located in the centre of the big city was the first water reservoir (ten sites) and second, the suburban river (six sites).


Input: The mean metal concentrations in the Ulva tissue from the river and the lake decreased in the following order: Mn > Zn > Cr > Cu > Co and Mn > Cr > Zn > Cu > Co, respectively.

Mn

Zn

Cr

Cu

Co

Mn

Cr

Zn

Cu

Co


Input: Moreover, a negative and statistically significant correlation between Mn concentrations in the Ulva thalli and the river water was observed.

Mn


Input: Additionally, numerous correlations were noted between the different concentrations of metals within the Ulva thalli, in the water and in the sediment.


Input: The great concentrations of Mn and Zn and the smallest of Co were found in thalli of Ulva, irrespective of the type of the ecosystem from which samples of algal thalli originated.

Mn

Zn

Co


Input: Freshwater Ulva populations examined in this study were clearly characterized a dozen or so times by the higher Mn and Cr accumulation than taxa from that genera coming from sea ecosystems.

Mn

Cr


Input: The calculated bioconcentration factor confirm the high potential for freshwater Ulva to be a bioaccumulator of trace metals in freshwater ecosystems.


Input: Abo-, inco-, ona-, and rima-botulinum toxins in clinical therapy: a primer.


Input: Botulinum neurotoxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular-blocking agent used for the treatment of a variety of medical and cosmetic indications.

acetylcholine


Input: Currently, in the United States, there are four BoNT formulations licensed for use: abobotulinumtoxinA, incobotulinumtoxinA, onabotulinumtoxinA, and rimabotulinumtoxinB.


Input: These revised name designations were established to reinforce the understanding that each BoNT product has an individual potency and is not interchangeable with any other BoNT product.


Input: The therapeutic use of BoNTs is expanding and new formulations are on the horizon.


Input: This article is a primer that describes distinctions among currently available, licensed BoNT formulations.


Input: Toxin pharmacology, product characteristics, storage, handling, preparation, and dosages will be reviewed.


Input: In addition, issues related to dose equivalency ratios, immunogenicity, potency, and toxin spread will be discussed.


Input: Therapeutic indications and safety are discussed briefly.


Input: Knowledge of the available and licensed BoNT formulations and the ability to make distinctions in toxin pharmacology, product characteristics, and indications are vital for product selection, preparation, drug information, avoidance of drug errors, quality assurance, and patient safety.


Input: Bioaccumulation and biomagnification of mercury and selenium in the sarasota bay ecosystem.

mercury

selenium


Input: The bioaccumulation and biomagnification of Hg and Se were investigated in Sarasota Bay, Florida, USA, to characterize the Hg exposure risks to wild bottlenose dolphins in the bay.

Hg

Se

Hg


Input: Concentrations of total mercury (THg), monomethylmercury (MMHg), and total selenium (TSe) were monitored in the bay, the latter of which might reduce Hg toxicity.

mercury

monomethylmercury

MMHg

selenium

Hg


Input: The food web structure and dolphins' trophic level-specific consumption rates were evaluated using stable isotope ratios of carbon (delta (13) C) and nitrogen (delta (15) N).

carbon

(13) C

nitrogen

(15) N


Input: Regressions developed for Hg biomagnification in the food chain were log10 CTHg (nanograms per gram) = 0. 27 x delta (15) N (/1000)-0. 42, R (2) = 0. 87, for THg and log10 CMMHg = 0. 33 x delta (15) N (/1000)-1. 0, R (2) = 0. 93, for MMHg.

Hg

(15) N

(15) N

MMHg


Input: Unlike Hg, nearly constant TSe concentrations were observed at 248 +/- 179 ng g (-1) in the food web, and the TSe-to-THg molar ratio was predicted by log10 (CTSe/CTHg) =-0. 10 x delta (15) N (/1000) + 2. 8, R (2) = 0. 60.

Hg

(15) N


Input: The THg-uptake rates of Sarasota bottlenose dolphins are estimated to vary between 2. 1 and 4. 9 micro g kg (-1) d (-1); however, the estimated TSe-uptake rates (15. 1 micro g kg (-1) d (-1)) were higher than those for THg, and the Hg-exposure risks of the Sarasota Bay resident bottlenose dolphins are considered to be low.


Input: Approaches employed in the present study can be extended to other environments to characterize Hg contamination in aquatic systems and Hg exposure risks in top predators.

Hg

Hg


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1143-1152.


Input: (c) 2013 SETAC.


Input: Neurogenetic disorders and treatment of associated seizures.


Input: Seizures are a frequent complication associated with several neurogenetic disorders.


Input: Antiepileptic medications remain the mainstay of treatment in these patients.


Input: We summarized the available data associated with various antiepileptic therapies used to treat patients with neurogenetic disorders who experienced recurrent seizures.


Input: A MEDLINE search was conducted to identify articles and abstracts describing the use of antiepileptic therapy for the treatment of various neurogenetic syndromes.


Input: Of all the neurogenetic syndromes, only autism spectrum disorders, Angelman syndrome, Rett syndrome, Dravet syndrome, and tuberous sclerosis complex were identified as having sufficient published information to evaluate therapy.


Input: Some efficacy trends were identified, including frequent successes with valproic acid with clonazepam for epilepsy with Angelman syndrome; valproic acid, stiripentol, and clobazam (triple combination therapy) for epilepsy with Dravet syndrome; and vigabatrin for infantile spasms associated with tuberous sclerosis complex.

valproic acid

clonazepam

valproic acid

stiripentol

clobazam

vigabatrin


Input: Due to a paucity of information regarding the mechanisms by which seizures are generated in the various disorders, approach to seizure control is primarily based on clinical experience and a limited amount of study data exploring patient outcomes.


Input: Although exposure of the developing brain to antiepileptic medications is of some concern, the control of epileptic activity is an important undertaking in these individuals, as the severity of eventual developmental delay often appears to correlate with the severity of seizures.


Input: As such, early aggressive therapy is warranted.


Input: Guidelines for Resident Teaching Experiences.


Input: Postgraduate year one (PGY1) and postgraduate year two (PGY2) residencies serve to develop pharmacists into skillful clinicians who provide advanced patient-centered care in various general and specialized areas of pharmacy practice.


Input: Pharmacy residencies are a minimum requirement for many clinical pharmacy positions, as well as for positions in academia.


Input: The role of clinical pharmacists typically includes teaching, regardless of whether they pursue an academic appointment.


Input: Common teaching duties of pharmacist-clinicians include giving continuing education or other invited presentations, providing education to colleagues regarding clinical initiatives, precepting pharmacy students (early and advanced experiences) and residents, and educating other health care professionals.


Input: Although ASHP provides accreditation standards for PGY1 and PGY2 residencies, the standards pertaining to teaching or education training are vague.


Input: Through the years, teaching certificate programs that develop residents' teaching skills and better prepare residents for a diverse pharmacy job market have increased in popularity; moreover, teaching certificate programs serve as an attractive recruitment tool.


Input: However, the consistency of requirements for teaching certificate programs is lacking, and standardization is needed.


Input: The Task Force on Residencies developed two sets of guidelines to define teaching experiences within residencies.


Input: The first guideline defines the minimum standards for teaching experiences in any residency-training program.


Input: The second guideline is for programs offering a teaching certificate program to provide standardization, ensuring similar outcomes and quality on program completion.


Input: One of the main differences between the guidelines is the recommendation that residency programs offering a teaching certificate program be affiliated with an academic institution to provide the pedagogy and variety of teaching experiences for the resident.


Input: Residency program directors should consider adopting these guidelines to offer consistent teaching experiences.


Input: In addition, residents should inquire about the elements of teaching in a program as an aid to selecting the training best suited to their needs.


Input: Genetic loci that control the loss and regain of trabecular bone during unloading and reambulation.


Input: Changes in trabecular morphology during un-and re-loading are marked by large variations between individuals, implicating a strong genetic influence on the magnitude of the response.


Input: Here, we subjected more than 350 second-generation (BALBxC3H) 4mo old adult female mice to 3wk of hindlimb unloading followed by 3wk of reambulation to identify the quantitative trait loci (QTLs) that define an individual' s propensity to either lose trabecular bone when weightbearing is removed or to gain trabecular bone when weightbearing is reintroduced.


Input: Longitudinal in vivo micro CT scans demonstrated that individual mice lost between 15% and 71% in trabecular BV/TV in the distal femur during unloading (average:-43%).


Input: Changes in trabecular BV/TV during the 3wk reambulation period ranged from a continuation of bone loss (-18%) to large additions (56%) of tissue (average: + 10%).


Input: During unloading, six QTLs accounted for 21% of the total variability in changes in BV/TV while one QTL accounted for 6% of the variability in changes in BV/TV during reambulation.


Input: QTLs were also identified for changes in trabecular architecture.


Input: Most of the QTLs defining morphologic changes during unloading or reambulation did not overlap with those QTLs identified at baseline, suggesting that these QTLs harbor genes that are specific for sensing changes in the levels of weightbearing.


Input: The lack of overlap in QTLs between unloading and reambulation also emphasizes that the genes modulating the trabecular response to unloading are distinct from those regulating tissue recovery during reloading.


Input: The identified QTLs contain the regulatory genes underlying the strong genetic regulation of trabecular bone' s sensitivity to weightbearing and may help to identify individuals that are most susceptible to unloading induced bone loss and/or the least capable of recovering.


Input: (c) 2013 American Society for Bone and Mineral Research.


Input: Desired professional development pathways for clinical pharmacists.


Input: The 2012 American College of Clinical Pharmacy (ACCP) Certification Affairs Committee was charged with developing guidelines for the desired professional development pathways for clinical pharmacists.


Input: This document summarizes recommendations for postgraduate education and training for graduates of U. S. schools and colleges of pharmacy and describes the preferred pathways for achieving, demonstrating, and maintaining competence as clinical pharmacists.


Input: After initial licensure within the state or jurisdiction in which the pharmacist intends to practice, completion of an accredited PGY1 pharmacy residency is recommended to further develop the knowledge and skills needed to optimize medication therapy outcomes.


Input: An accredited PGY2 pharmacy residency should be completed if a pharmacist wishes to seek employment in a specific therapeutic area or practice setting, if such a residency exists.


Input: Clinical pharmacists intending to conduct advanced research that is competitive for federal funding are encouraged to complete a fellowship or graduate education.


Input: Initial certification by the Board of Pharmacy Specialties (BPS) or other appropriate sponsoring organizations should be completed in the desired primary therapeutic area or practice setting within 2 years after accepting a position within the desired specific therapeutic area or practice setting.


Input: Clinical pharmacists subsequently will need to meet the requirements to maintain pharmacist licensure and board certification.


Input: Traineeships, practice-based activities, and certificate programs can be used to obtain additional knowledge and skills that support professional growth.


Input: Pharmacists are strongly encouraged to adopt a lifelong, systematic process for professional development and work with ACCP and other professional organizations to facilitate the development and implementation of innovative strategies to assess core practice competencies.


Input: Modeling environmental and human health risks of veterinary medicinal products applied in pond aquaculture.


Input: A model called ERA-AQUA was developed to assess the risks posed by the use of veterinary medicinal products (VMPs) applied in aquaculture ponds for the targeted produce, surrounding aquatic ecosystems, consumers, and trade of the aquaculture produce.


Input: The model calculates risks by following a risk quotient approach, calculating predicted exposure concentrations (exposure assessment) and predicted no-effect concentrations (effect assessment) for the endpoint under study.


Input: The exposure assessment is performed by combining information on the environmental characteristics of the aquaculture pond, characteristics of the cultured species, aquaculture management practices, and physicochemical properties of the compound under study.


Input: The model predicts concentrations of VMPs in the pond water, pond sediment, cultured species, and watercourse receiving pond effluent discharges by mass balance equations.


Input: The effect assessment is performed by combining (eco) toxicological information and food safety threshold concentrations for the studied compound.


Input: In the present study, the scientific background, strengths, and limitations of the ERA-AQUA model are presented together with a sensitivity analysis and an example showing its potential applications.


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1196-1207.


Input: (c) 2013 SETAC.


Input: Toxicity and toxicokinetics of binary combinations of petroleum hydrocarbon distillates with the earthworm Eisenia andrei.

petroleum hydrocarbon


Input: Petroleum hydrocarbons (PHCs) act via narcosis and are expected to have additive toxicity.

Petroleum hydrocarbons

PHCs


Input: However, previous work has demonstrated less-than-additive toxicity with PHC distillates and earthworms.

PHC


Input: A study was initiated to investigate this through toxicity and toxicokinetic studies with the earthworm Eisenia andrei.


Input: Three petroleum distillate fractions, F2 (> C10-C16), F3a (> C16-C23), and F3b (> C23-C34), were used in two binary combinations, F2F3a and F3aF3b.


Input: In the toxicity study, clean soil was spiked with equitoxic combinations of the two distillates ranging from 0. 5 to 2. 5 toxic units.


Input: In the toxicokinetic study, a binary combination consisting of one concentration of each distillate was used.


Input: On a soil concentration basis, the toxicity of the binary combinations of distillates was less than additive.


Input: Accumulation of the individual distillates, however, was generally reduced when a second distillate was present, resulting in lower body burden.


Input: This is thought to be due to the presence of a nonaqueous-phase liquid at the soil concentrations used.


Input: On a tissue concentration basis, toxicity was closer to additive.


Input: The results demonstrate that tissue concentrations are the preferred metric for toxicity for earthworms.


Input: They also demonstrate that the Canada-wide soil standards based on individual distillates are likely protective.


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1016-1026.


Input: (c) 2013 SETAC.


Input: Inter-and intraspecific variation in mercury bioaccumulation by snakes inhabiting a contaminated river floodplain.

mercury


Input: Although mercury (Hg) is a well-studied contaminant, knowledge about Hg accumulation in snakes is limited.

mercury

Hg

Hg


Input: The authors evaluated Hg bioaccumulation within and among four snake species (northern watersnakes, Nerodia sipedon; queen snakes, Regina septemvittata; common garter snakes, Thamnophis sirtalis; and rat snakes, Elaphe obsoleta [Pantherophis alleghaniensis]) from a contaminated site on the South River (Waynesboro, VA, USA) and two nearby reference sites.

Hg


Input: Total Hg (THg) concentrations in northern watersnake tail tissue at the contaminated site ranged from 2. 25 to 13. 84 mg/kg dry weight (mean: 4. 85 +/- 0. 29), or 11 to 19 times higher than reference sites.

Hg


Input: Blood THg concentrations (0. 03-7. 04 mg/kg wet wt; mean: 2. 24 +/- 0. 42) were strongly correlated with tail concentrations and were the highest yet reported in a snake species.


Input: Within watersnakes, nitrogen stable isotope values indicated ontogenetic trophic shifts that correlated with THg bioaccumulation, suggesting that diet plays a substantial role in Hg exposure.

nitrogen


Input: Female watersnakes had higher mean THg concentrations (5. 67 +/- 0. 46 mg/kg) than males (4. 93 +/- 0. 49 mg/kg), but no significant differences between sexes were observed after correcting for body size.


Input: Interspecific comparisons identified differences in THg concentrations among snake species, with more aquatic species (watersnakes and queen snakes) accumulating higher mean concentrations (5. 60 +/- 0. 40 and 4. 59 +/- 0. 38 mg/kg in tail tissue, respectively) than the more terrestrial species, garter snakes and rat snakes (1. 28 +/- 0. 32 and 0. 26 +/- 0. 09 mg/kg, respectively).


Input: The results of the present study warrant further investigation of potential adverse effects and will aid in prioritizing conservation efforts.


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1178-1186.


Input: (c) 2013 SETAC.


Input: Mild oxidation of thiofunctional polymers to cytocompatible and stimuli-sensitive hydrogels and nanogels.


Input: Nanogels consist of three dimensionally cross-linked hydrophilic polymer chains and can thus be easily modified through functionalization of the polymeric building blocks, for example to yield stimuli-sensitive materials.


Input: For drug transport and intracellular release, redox-sensitive systems are especially of interest, as the intracellular space is reductive.


Input: In this study, parameters that allow preparation of nanogels with tunable size between 150 and 350 nm are systematically evaluated and identified.


Input: Most importantly, a new and mild oxidation catalyst, alloxan, is introduced for the preparation of the nanogels.

alloxan


Input: This broadens the range of possible payloads to more-sensitive molecules.


Input: Particle stability, degradation in cytosolic conditions, and cytocompatibility in concentrations up to 10 mg. mL (-1) are demonstrated.


Input: EFFECT OF C60 FULLERENES ON THE ACCUMULATION OF WEATHERED p, p'-DDE BY PLANT AND EARTHWORM SPECIES UNDER SINGLE AND MULTISPECIES CONDITIONS.

C60 FULLERENES

p, p'-DDE


Input: The use of engineered nanomaterials has increased dramatically in recent years, but an understanding of nanomaterial fate and effects in the environment is lacking.


Input: In particular, the interaction of nanomaterials with coexisting organic contaminants and the subsequent implications for sensitive biota is almost completely unknown.


Input: Here, the effect of C60 fullerenes on the accumulation of weathered dichlorodiphenyldichloroethylene (p, p'-DDE; DDT metabolite) by Cucurbita pepo (pumpkin) and Eisenia fetida (earthworm) was determined under single and multispecies conditions.

C60 fullerenes

dichlorodiphenyldichloroethylene

p, p'-DDE

DDT


Input: The plants, in the presence or absence of earthworms, were grown in soil containing weathered DDE (200 ng/g) and 0 or 1, 670 mg/kg C60 fullerenes.

DDE

C60 fullerenes


Input: Plants and earthworms were added either simultaneously or sequentially (earthworms after plants).


Input: Neither DDE nor C60 had an impact on survival or biomass of plants and earthworms, although fullerenes significantly decreased (29. 6-39. 0%) the relative root mass.

DDE

fullerenes


Input: Under single or multispecies conditions, C60 had little impact on DDE bioaccumulation by either species.

DDE


Input: The DDE concentrations in non-fullerene-exposed shoots, roots, and earthworms were 181, 7, 400, and 8, 230 ng/g, respectively.

DDE

fullerene


Input: On fullerene exposure, the DDE content was nonsignificantly lower at 163, 7280, and 7540 ng/g, respectively.

fullerene

DDE


Input: In the presence of the earthworms, C60 significantly decreased the shoot DDE content (28. 6%), but no impact on root concentrations was observed.

DDE


Input: Root DDE content was unaffected by the presence of fullerenes and decreased by 21. 6 to 37. 5% during coexposure with earthworms.

DDE

fullerenes


Input: Earthworm DDE content was decreased by plant presence.

DDE


Input: Earthworms added to soils after plant harvest accumulated more DDE but were unaffected by the C60 exposure.

DDE


Input: Additional work is necessary, but these findings suggest that fullerenes may have minimal impact on the bioaccumulation of weathered cocontaminants in soil.


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1117-1123.


Input: (c) 2013 SETAC.


Input: Effects of Lepidium sativum, Nigella sativa and Trigonella foenum-graceum on Phenytoin Pharmacokinetics in Beagle Dogs.

Phenytoin


Input: The present work was designed to evaluate the effect of some commonly used herbs viz. garden cress (Lepidium sativum), black seed (Nigella sativa) and fenugreek (Trigonella foenum-graceum) on the disposition of phenytoin after oral administration in a dog model.

phenytoin


Input: Phenytoin was given orally at a dose of 50 mg, and blood samples were obtained for the determination of drug' s pharmacokinetic parameters.

Phenytoin


Input: After a suitable washout period, animals were commenced on a specific herb treatment for one week.


Input: Garden cress treatment caused a modest increase in maximum observed concentration (C (max)) and terminal half-life (T (1/2 lambda)) of phenytoin with a reduction in clearance by 33%.

phenytoin


Input: The effect of black seed therapy was more drastic on drug elimination and to a lesser extent on its volume of distribution at steady state (V (ss)) with a consequent reduction in systemic exposure measured by area under the curve (AUC (0-infinity)) by about 87%.


Input: The effect of fenugreek therapy resembled, albeit to a lesser extent, that of black seed with a significant reduction in AUC (0-infinity) by ~ 72%.


Input: In addition, there was a 73% increase in V (ss).


Input: Our findings suggest that the phenytoin disposition can be significantly altered by the concurrent consumption of tested herbal products.

phenytoin


Input: Copyright (c) 2013 John Wiley & Sons, Ltd.


Input: Soluble metal pool as affected by soil addition with organic inputs.


Input: The potential impact of diverse inputs of organic matter (hay, maize straw, and peat) on the mobility and bioavailability of Cd, Cu, Pb, and Zn was examined at laboratory scale for three soils with contrasting properties and for two moisture regimes: field capacity and saturated conditions.

Cd

Cu

Pb

Zn


Input: Soil solution was characterized for total soluble metals, dissolved soil organic carbon, and ultraviolet absorbance at 254 nm.

carbon


Input: Speciation analyses were performed with WHAM VI.


Input: For field capacity conditions, metal mobility increased (Pb > Cu > Zn > Cd) for all soils and treatments compared with controls and was significantly correlated (p < 0. 05) with dissolved organic matter (r = 0. 540).

Pb

Cu

Zn

Cd


Input: Solubilization of organic matter was mostly driven by Al mobilization (r = 0. 580, p < 0. 05) and variations in solution pH.

Al


Input: The bioavailable pool of metals, estimated as free ion activities, decreased with the increasing occurrence of metal-organic matter complexes, which was accompanied by an increase in solution of highly aromatic organic matter.


Input: Soil saturation generally decreased metal mobility and the ratio of metal-organo matter complexes in solution.


Input: Consistently, such effects were accompanied by a decrease in the solubilization of organic matter and lower mobilization of Al, Fe, and Mn.

Al

Fe

Mn


Input: Environ Toxicol Chem 2013; 32: 1027-1032.


Input: (c) 2013 SETAC.


Input: Novel Schiff-base-derived FabH inhibitors with dioxygenated rings as antibiotic agents.

Schiff-base


Input: Fatty acid biosynthesis plays a vital role in bacterial survival and several key enzymes involved in this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents.

Fatty acid


Input: Of these promising targets, beta-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) is the most attractive target that could trigger the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and-negative bacteria.

beta-ketoacyl

acyl

fatty acid


Input: Designing small molecules with FabH inhibitory activity displays great significance for developing antibiotic agents, which should be highly selective, nontoxic and broad-spectrum.


Input: In this manuscript, a series of novel Schiff base compounds were designed and synthesized, and their biological activities were evaluated as potential inhibitors.

Schiff base


Input: Among these 21 new compounds, (E)-N-((3, 4-dihydro-2H-benzo [b] [1, 4] dioxepin-7-yl) methylene) hexadecan-1-amine (10) showed the most potent antibacterial activity with a MIC value of 3. 89-7. 81 mu M (-1) against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with an IC (50) value of 1. 6 mu M.

(E)-N-((3, 4-dihydro-2H-benzo [b] [1, 4] dioxepin-7-yl) methylene) hexadecan-1-amine


Input: Docking simulation was performed to position compound 10 into the E. coli FabH active site to determine the probable binding conformation.


Input: Comparing sorption behavior of pyrethroids between formulated and natural sediments.

pyrethroids


Input: Formulated sediments are recommended for use in toxicity tests to achieve standardized evaluations.


Input: However, the organic matter used in formulated sediments may differ qualitatively from that in natural sediments, which may lead to different chemical partition patterns and, hence, different toxicity effects.


Input: By deriving partition coefficients for organic carbon and dissolved organic carbon (KOC and KDOC, respectively) for eight pyrethroid insecticides from three formulated and five natural sediments, the authors characterized the differences between formulated and natural sediments in pesticide sorption.

carbon

carbon

pyrethroid


Input: For all pyrethroids, the mean values of KOC and KDOC of formulated sediments were two to three, and three to 10 times smaller than those of natural sediments, respectively.

pyrethroids


Input: The two formulated sediments containing alpha-cellulose or Manitoba peat showed significantly (p < 0. 0001) smaller KOC and KDOC values than natural sediments based on statistical analyses, while the difference was not significant for the formulated sediment containing New Brunswick peat.


Input: The KOC values were closely correlated (p < 0. 001) with soot carbon content, while the amount of carboxylic or phenolic functional groups may have affected KDOC.

carbon

carboxylic

phenolic


Input: Therefore, the source and quality of organic matter are likely the most important factors in formulated sediments and must be standardized to provide consistency in sediment toxicity tests.


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 1033-1039.


Input: (c) 2013 SETAC.


Input: Bifunctional Star-Burst Amorphous Molecular Materials for OLEDs: Achieving Highly Efficient Solid-State Luminescence and Carrier Transport Induced by Spontaneous Molecular Orientation.


Input: Bifunctional star-burst amorphous molecular materials displaying both efficient solid-state luminescence and high hole-transport properties are developed in this study.


Input: A high external electroluminescence quantum efficiency up to 5. 9% is attained in OLEDs employing the developed amorphous materials.


Input: It is revealed that the spontaneous horizontal orientation of these light-emitting molecules in their molecular-condensed states leads to a remarkable enhancement of the electroluminescence efficiencies and carrier-transport properties.


Input: Hemifluorinated maltose-neopentyl glycol (HF-MNG) amphiphiles for membrane protein stabilisation.

maltose-neopentyl glycol

MNG


Input: SOAP OPERA: Fluorinated amphiphile F4-MNG confers greater stability on Rhodobacter capsulatus superassembly relative to conventional detergents and nonfluorinated MNGs.

MNGs


Input: Such amphiphiles are attractive as tools for membrane science because of their ease of preparation and structure variation.


Input: Plant consumption by grizzly bears reduces biomagnification of salmon-derived polychlorinated biphenyls, polybrominated diphenyl ethers, and organochlorine pesticides.

polychlorinated biphenyls

polybrominated diphenyl ethers

organochlorine


Input: The present study characterizes the uptake and loss of persistent organic pollutants (POPs) in grizzly bears (Ursus arctos horribilis) by sampling and analyzing their terrestrial and marine foods and fecal material from a remote coastal watershed in British Columbia, Canada.


Input: The authors estimate that grizzly bears consume 341 to 1, 120 micro g of polychlorinated biphenyls (PCBs) and 3. 9 to 33 micro g of polybrominated diphenyl ethers daily in the fall when they have access to an abundant supply of returning salmon.

polychlorinated biphenyls

PCBs

polybrominated diphenyl ethers


Input: The authors also estimate that POP elimination by grizzly bears through defecation is very low following salmon consumption (typically < 2% of intake) but surprisingly high following plant consumption (> 100% for PCBs and organochlorine pesticides).

PCBs

organochlorine


Input: Excretion of individual POPs is largely driven by a combination of fugacity (differences between bear and food concentrations) and the digestibility of the food.


Input: The results of the present study are substantiated by a principal components analysis, which also demonstrates a strong role for log KOW in governing the excretion of different POPs in grizzly bears.


Input: Collectively, the present study' s results reveal that grizzly bears experience a vegetation-associated drawdown of POPs previously acquired through the consumption of salmon, to such an extent that net biomagnification is reduced.


Input: Environ.


Input: Toxicol.


Input: Chem.


Input: 2013; 32: 995-1005.


Input: (c) 2013 SETAC.


Input: Formation of nanostructured MnO/Co/solid-electrolyte interphase ternary composites as a durable anode material for lithium-ion batteries.

MnO

Co

lithium


Input: Nanoporous MnO frameworks with highly dispersed Co nanoparticles were produced from MnCO3 precursors prepared in a gel matrix.

MnO

Co


Input: The MnO frameworks that contain 20 mol% Co exhibited excellent cycle performance as an anode material for Li-ion batteries.

MnO

Co

Li


Input: The solid-electrolyte interphase (SEI) formed in the frameworks through the electrochemical reaction mediates the active materials, such as MnO, Mn, and Li2O, during the conversion reaction in the charge-discharge cycle.

MnO

Mn


Input: The Co nanoparticles and SEI provide the electron and Li-ion conductive networks, respectively.

Co

Li


Input: The ternary nanocomposites of the MnO framework, metallic Co nanoparticles, and embedded SEI are categorized as durable anode materials for Li-ion batteries.

MnO

Co

Li


Input: From spots to beads-PTM-peptide bead arrays for the characterization of anti-histone antibodies.


Input: Antibodies that recognize PTMs of histones play a central role in epigenetic proteomic research.


Input: Modification-specific antibodies are employed in chromatin immunoprecipitation, for Western blotting and during the immunoprecipitation steps for MS-based global proteomic analyses.


Input: Knowledge about the antibodies' off-target binding is essential for the interpretation of experimental data.


Input: To address this challenge we developed a fast and cost efficient system for generating peptide bead arrays.


Input: We employed this method to establish a bead-based peptide array containing 384 peptides displaying phosphorylated, acetylated, methylated, and citrullinated N-terminal regions of histones H2A, H2B, H3 and H4 and controls.

N


Input: We profiled the binding of 40 PTM-specific antibodies important for epigenetic proteomic research.


Input: Epigenetic Regulation Is a Crucial Factor in the Repression of UGT1A1 Expression in the Human Kidney.


Input: Human UDP-glucuronosyltransferase (UGT) 1A1 catalyzes the metabolism of numerous clinically and pharmacologically important compounds such as bilirubin and SN-38.

UDP

bilirubin


Input: UGT1A1 is predominantly expressed in the liver and intestine, but not in the kidney.


Input: The purpose of this study was to uncover the mechanism of the tissue-specific expression of UGT1A1, focusing on its epigenetic regulation.


Input: Bisulfite sequence analysis revealed that the CpG-rich region near the UGT1A1 promoter (-85 to + 40) was hypermethylated (83%) in the kidney, whereas it was hypomethylated (37%) in the liver.

Bisulfite

CpG


Input: A chromatin immunoprecipitation assay demonstrated that histone H3 near the promoter was hypoacetylated in the kidney but was hyperacetylated in the liver; this hyperacetylation was accompanied by the recruitment of HNF1 alpha to the promoter.


Input: The UGT1A1 promoter in human kidney-derived HK-2 cells that do not express UGT1A1 was fully methylated, but was relatively unmethylated in human liver-derived HuH-7 cells that express UGT1A1.


Input: Treatment with 5-aza-2'-deoxycytidine (5-Aza-dC), an inhibitor of DNA methylation, resulted in an increase of UGT1A1 mRNA expression in both cell types, but the increase was much larger in HK-2 cells than in HuH-7 cells.


Input: The transfection of an HNF1 alpha expression plasmid into the HK-2 cells resulted in an increase of UGT1A1 mRNA only in the presence of 5-Aza-dC.


Input: In summary, we found that DNA hypermethylation along with histone hypoacetylation interferes with the binding of HNF1 alpha, resulting in the defective expression of UGT1A1 in the human kidney.


Input: Thus, epigenetic regulation is a crucial determinant of tissue-specific expression of UGT1A1.


Input: Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice.

linoleic acid


Input: The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat.

linoleic acid


Input: Young male mice were fed three combinations of fatty acids at three doses (0. 06%, 0. 2%, and 0. 6%, w/w) incorporated into AIN76 diets for 7 weeks.

fatty acids


Input: The types of fatty acids were linoleic acid (control), an equal mixture of trans-10, cis-12 (10, 12) CLA plus linoleic acid, and an equal isomer mixture of 10, 12 plus cis-9, trans-11 (9, 11) CLA.

fatty acids

linoleic acid

linoleic acid


Input: Mice receiving the 0. 2% and 0. 6% dose of 10, 12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver.

linoleic acid


Input: Notably, in mice receiving 0. 2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT.


Input: CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation.


Input: Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment.


Input: These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade inflammation due to consumption of 10, 12 CLA.


Input: Measuring in situ primary and competitive DNA hybridization activity on microspheres.


Input: Microspheres serve as convenient substrates for studying DNA activity on surfaces.


Input: Here, in addition to employing conventional sample preparation involving multiple wash and resuspension steps prior to flow cytometry measurements, we also directly sampled the reaction volume to acquire in situ measurements of primary and competitive hybridization events.


Input: Even in the absence of post hybridization wash steps, nonspecific binding events were negligible and thus allowed for direct, quantitative assessment of hybridization events as they occurred on colloidal surfaces.


Input: The in situ results indicate that primary duplex formation between immobilized probes and soluble targets on microsphere surfaces is less favorable than predicted by solution models.


Input: The kinetics of competitive displacement of primary hybridization partners by secondary targets measured in situ or post washing also deviate from expectations based on theoretical solution thermodynamics, but are consistent with predicted kinetic trends stemming from differences in either the toehold base length or branch migration.


Input: Binding between proteins and cationic spherical polyelectrolyte brushes: effect of pH, ionic strength, and stoichiometry.


Input: Cationic spherical polyelectrolyte brushes (SPBs) were synthesized by photoemulsion polymerization, consisting of a polystyrene core with a diameter around 80 nm and a poly (2-aminoethylmethacrylate hydrochloride) (PAEMH) shell with a thickness from 10 to 50 nm densely grafted on the core surface.

polystyrene

poly (2-aminoethylmethacrylate hydrochloride)

PAEMH


Input: The binding of various proteins onto SPBs was observed by turbidimetric titration, dynamic light scattering (DLS), zeta potential, and isothermal titration calorimetry (ITC).


Input: The binding, aggregation, and releasing of proteins by SPB can be tuned by modulating pH.


Input: The pH regions of binding for bovine serum albumin (BSA), beta-lactoglobulin (BLG), and papain onto SPBs are markedly different and tunable by ionic strength and stoichiometry between protein and SPB.


Input: Binding energetics, affinity, and amount of various proteins onto cationic SPBs were determined by ITC.


Input: These findings lay the foundation for SPB applications in the protein purification and selective immobilization of different proteins, enzymes, and antibodies.


Input: Characterization of the acyl-adenylate linked metabolite of mefenamic Acid.

acyl

adenylate

mefenamic Acid


Input: Mefenamic acid, (MFA), a carboxylic acid-containing nonsteroidal anti-inflammatory drug (NSAID), is metabolized into the chemically reactive conjugates MFA-1-O-acyl-glucuronide (MFA-1-O-G) and MFA-S-acyl-CoA (MFA-CoA), which are both implicated in the formation of MFA-S-acyl-glutathione (MFA-GSH) conjugates, protein-adduct formation, and thus the potential toxicity of the drug.

Mefenamic acid

MFA

carboxylic acid

MFA-S-acyl-CoA

MFA-CoA

MFA-S-acyl-glutathione

MFA-GSH


Input: However, current studies suggest that an additional acyl-linked metabolite may be implicated in the formation of MFA-GSH.

acyl

MFA-GSH


Input: In the present study, we investigated the ability of MFA to become bioactivated into the acyl-linked metabolite, mefenamyl-adenylate (MFA-AMP).

MFA

acyl

mefenamyl

adenylate

MFA-AMP


Input: In vitro incubations in rat hepatocytes with MFA (100 mu M), followed by LC-MS/MS analyses of extracts, led to the detection of MFA-AMP.

MFA

MFA-AMP


Input: In these incubations, the initial rate of MFA-AMP formation was rapid, leveling off at a maximum concentration of 90. 1 nM (20 s), while MFA-GSH formation increased linearly, reaching a concentration of 1. 7 mu M after 60 min of incubation.

MFA-AMP

MFA-GSH


Input: In comparison, MFA-CoA was undetectable in incubation extracts until the 4 min time point, achieving a concentration of 45. 6 nM at the 60 min time point, and MFA-1-O-G formation was linear, attaining a concentration of 42. 2 mu M after 60 min of incubation.

MFA-CoA


Input: In vitro incubation in buffer with the model nucleophile glutathione (GSH) under physiological conditions showed MFA-AMP to be reactive toward GSH, but 11-fold less reactive than MFA-CoA, while MFA-1-O-G exhibited little reactivity.

glutathione

GSH

MFA-AMP

GSH

MFA-CoA


Input: However, in the presence of glutathione-S-transferase (GST), MFA-AMP mediated formation of MFA-GSH increased 6-fold, while MFA-CoA mediated formation of MFA-GSH only increased 1. 4-fold.

glutathione

S

MFA-AMP

MFA-GSH

MFA-CoA

MFA-GSH


Input: Collectively, in addition to the MFA-1-O-G, these results demonstrate that mefenamic acid does become bioactivated by acyl-CoA synthetase enzyme (s) in vitro in rat hepatocytes into the reactive transacylating derivatives MFA-AMP and MFA-CoA, both of which contribute to the transacylation of GSH and may be involved in the formation of protein adducts and potentially elicit an idiosyncratic toxicity.

mefenamic acid

acyl-CoA

MFA-AMP

MFA-CoA

GSH


Input: Role of nitric oxide in the chemistry and anticancer activity of etoposide (VP-16, 213).

nitric oxide

etoposide

VP-16, 213


Input: Originally identified as an innate cytotoxin, nitric oxide ((.) NO) formation in tumors can influence chemotherapy and exacerbate cancer progression.

nitric oxide

(.) NO


Input: Here, we examined the hypothesis that (.) NO generation contributes to cancer cell drug resistance toward the widely used anticancer drug Etoposide (VP-16).

(.) NO

Etoposide


Input: The UV-vis spectrum of VP-16 was not changed by exposure of VP-16 to (.) NO in aqueous buffer.

(.) NO


Input: In contrast, reddish-orange compound (s) characteristic of o-quinone-and nitroso-VP-16 were readily generated in a hydrophobic medium (chloroform) in an oxygen-dependent manner.

o-quinone-and nitroso-VP-16

chloroform

oxygen


Input: Similar products were also formed when the VP-16 radical, generated from VP-16 and horseradish peroxidase/H2O2, was exposed directly to (.) NO in chloroform in the presence of oxygen.

(.) NO

chloroform

oxygen


Input: Separation and spectral analysis of VP-16 reaction extracts by electron spin resonance and UV-vis indicated the generation of the phenoxy radical and the o-quinone of VP-16, as well as putative nitroxide, iminoxyl, and other nitrogen oxide intermediates.

phenoxy

o-quinone

nitroxide

iminoxyl

nitrogen oxide


Input: Nitric oxide products of VP-16 displayed significantly diminished topoisomerase II-dependent cleavage of DNA and cytotoxicity to human HL-60 leukemia cells.

Nitric oxide


Input: LPS-mediated induction of nitric oxide synthase in murine macrophages resulted in VP-16 resistance compared to Raw cells.

nitric oxide


Input: Furthermore, (.) NO products derived from iNOS rapidly reacted with VP-16 leading to decreased DNA damage and cytotoxicity.

(.) NO


Input: Together, these observations suggest that the formation of (.) NO in tumors (associated macrophages) can contribute to VP-16 resistance via the detoxification of VP-16.

(.) NO


Input: Conducting the temperature-dependent conformational change of macrocyclic compounds to the lattice dilation of quantum dots for achieving an ultrasensitive nanothermometer.


Input: We report a ligand decoration strategy to enlarge the lattice dilation of quantum dots (QDs), which greatly enhances the characteristic sensitivity of a QD-based thermometer.


Input: Upon a multiple covalent linkage of macrocyclic compounds with QDs, for example, thiolated cyclodextrin (CD) and CdTe, the conformation-related torsional force of CD is conducted to the inner lattice of CdTe under altered temperature.

CdTe

CdTe


Input: The combination of the lattice expansion/contraction of CdTe and the stress from CD conformation change greatly enhances the shifts of both UV-vis absorption and photoluminescence (PL) spectra, thus improving the temperature sensitivity.

CdTe


Input: As an example, beta-CD-decorated CdTe QDs exhibit the 0. 28 nm shift of the spectra per degree centigrade (0. 28 nm/degrees C), 2. 4-fold higher than those of monothiol-ligand-decorated QDs.

CdTe

monothiol


Input: Polymerase chain reaction-free variable-number tandem repeat typing using gold nanoparticle-DNA monoconjugates.


Input: In this work, we report a novel polymerase chain reaction (PCR)-free variable-number tandem repeat (VNTR) typing method using a T-shaped gold nanoparticle-DNA monoconjugate, called the " watching-gene assay ".


Input: The T-shaped DNA probe was synthesized by " click " chemistry and linked with the gold nanoparticle to form the gold nanoparticle-DNA monoconjugate (a VNTR probe).


Input: Through a simple annealing and ligation reaction of the VNTR probe on a synthetic DNA template mimicking the human D1S80 VNTR locus, the number of tandem repeat units could be deciphered by counting the self-assembled gold nanoparticles.


Input: The number of tandem repeat units could be identified with more than 50% yield if the repeat number was less than four.


Input: In the case of the real human genomic DNA, the 18 repeat unit number could be successfully revealed by observing the 18-gold-nanoparticle cluster, which exactly corresponded to the number of tandem repeats of the real sample.


Input: Our " watching-gene assay " is rapid, simple, and direct for data interpretation, thereby providing an advanced PCR-free genetic polymorphism analysis platform.


Input: Health benefits of blue-green algae: prevention of cardiovascular disease and nonalcoholic fatty liver disease.


Input: Blue-green algae (BGA) are among the most primitive life forms on earth and have been consumed as food or medicine by humans for centuries.


Input: BGA contain various bioactive components, such as phycocyanin, carotenoids, gamma-linolenic acid, fibers, and plant sterols, which can promote optimal health in humans.

gamma-linolenic acid

sterols