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Eribulin is a new anticancer agent currently in Phase III clinical trials for the treatment of metastatic breast cancer. In the current studies, we have investigated the effects of P-glycoprotein (P-gp) on the in vivo disposition of eribulin using CF-1 abcb1a-deficient mice, and the influence of eribulin on P-gp-mediated efflux of digoxin in Caco-2 cells. Eribulin was administered intravenously and orally in both CF-1 wild-type and CF-1 abcb1a-deficient mice. P-gp-mediated efflux of digoxin in Caco-2 cell monolayers was measured in the presence of eribulin. The plasma exposure to eribulin was higher in CF-1 abcb1a-deficient mice than that in CF-1 wild-type mice after intravenous (IV) and oral (PO) administrations. The oral bioavailability of eribulin was 62.3% in CF-1 abcb1a-deficient mice...

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BackgroundAurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently...Full Text Available

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Purpose of reviewPhysicians, researchers and policy makers must understand the myriad consequences of multidrug and extensively drug-resistant tuberculosis (TB) within...Full Text Available

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BACKGROUNDNew diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid,...Full Text Available

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For rapid and low-cost detection of multidrug-resistant (MDR) Mycobacterium tuberculosis, we applied the nitrate reductase assay (NRA) using a liquid medium directly to sputum samples....Full Text Available

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ColV plasmids of extraintestinal pathogenic Escherichia coli (ExPEC) encode a variety of fitness and virulence factors and have long been associated with septicemia and avian colibacillosis....Full Text Available

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Multidrug-resistant tuberculosis is an increasing public health concern in many parts of the world, especially in low-income countries, where most cases occur. Traditional drug susceptibility testing...Full Text Available

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Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for Klebsiella...Full Text Available

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Background The scale-up of treatment for HIV and multidrug-resistant tuberculosis (MDR-TB) in developing countries requires a long-term relationship with the...Full Text Available

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The Gram-negative bacterium Francisella tularensis is the causative agent of tularemia. Interest in this zoonotic pathogen has increased due to its classification as a category A agent...Full Text Available

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This article proposes Bayesian analysis of mediation effects. Compared to conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers...Full Text Available

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Resistance (R) protein mediated recognition of pathogen avirulence effectors triggers signaling that induces a very robust form of species-specific immunity in plants. The soybean Rpg1-b protein mediates...Full Text Available

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Udgivelsesdato: 2007/7

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Somite boundary formation is crucial for segmentation of vertebrate somites and vertebrae and skeletal muscle morphogenesis. Previously, we developed a Tol2 transposon-mediated...Full Text Available

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The purpose of this study was to determine whether resistance exercise training-induced reductions in inflammation are mediated via melanocortin 3 receptor expression in obese (BMI 32.7 ± 3.7)...Full Text Available

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3-Deazaadenosine (deazaAdo) inhibits lymphocyte-mediated cytolysis in vitro at micromolar concentrations and is potentiated markedly in this activity by L-homocysteine thiolactone....Full Text Available

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Dectin-1, the major β-glucan receptor in leukocytes, triggers an effective immune response upon fungal recognition. Here we use sortase-mediated transpeptidation, a technique that allows placement...Full Text Available

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Short-hairpin RNA (shRNA)–mediated gene knockdown is a powerful tool for targeted gene silencing and an emerging novel therapeutic strategy. Recent publications, however, reported unexpected...Full Text Available

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Objective: To investigate the mechanism of carbapenem resistance and the occurrence of plasmid-mediated quinolone resistance determinants qnr and aac(6′)-Ib-cr...Full Text Available

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The world of antibiotic drug discovery and development is driven by the necessity to overcome antibiotic resistance in common Gram-positive and Gram-negative pathogens. However, the lack of Gram-negative activity among both recently approved antibiotics and compounds in the developmental pipeline is a general trend despite the fact that the plethora of covered drug targets are well-conserved across the bacterial kingdom. Such intrinsic resistance in Gram-negative bacteria is largely attributed to the activity of multidrug resistance (MDR) efflux pumps. Moreover, these pumps also play a significant role in acquired clinical resistance. Together, these considerations make efflux pumps attractive targets for inhibition in that the resultant efflux pump inhibitor (EPI)/antibiotic combination d...

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Abstract NorUDCA (24 norursodeoxycholic acid), the C23 homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic Mdr2 (Abcb4) (multidrug resistance protein 2/ATP binding cassette b4) knockout mice with sclerosing/fibrosing cholangitis. In contrast to UDCA, norUDCA is inefficiently conjugated in human and rodent liver, and conjugation has been discussed as a key step for the anticholestatic action of UDCA in cholestasis. We compared the choleretic, anticholestatic, and antiapoptotic properties of unconjugated and taurine conjugated UDCA (C24) and norUDCA (C23) in isolated perfused rat liver (IPRL) and in natrium/taurocholate cotransporting polypeptide (Ntcp) transfected human hepatoma (HepG2) cells. Taurolithocholic acid (TLCA) was used to induce a predomi...

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In this paper, the effects of surface mediation on the adsorption isotherm and isosteric heat of adsorption on a graphite surface were investigated, as the surface mediation is known to affect the intermolecular interaction of adsorbed molecules close to the surface. Kim and Steele (Phys. Rev. B 45 (11) (1992) 6226-6233) and others have assumed that the surface mediation is confined only to the first layer. This will be tested in this paper with a combined experimental and Grand Canonical Monte Carlo (GCMC) simulation of adsorption of argon on graphitized thermal carbon black (GTCB) over a range of temperatures (77-95.25K). By matching the simulation results against the experimental data, we have found that the surface mediation is extended up to the fourth layer, rather than only the firs...

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BackgroundAlternative splicing is an important mechanism mediating the diversified functions of genes in multicellular organisms, and such event occurs in around 40-60% of human...Full Text Available

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... for mediating the effects of early adverse experiences since they are affected

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The effects of low concentrations (10 nm or less) of indoleacetic acid and abscisic acid on the phytochrome-mediated attachment of barley root (Hordeum vulgare L., var. Compana)...Full Text Available

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A modest reduction in body temperature prolongs longevity and possibly retards aging in both poikilotherm and homeotherm animals. Some of the possible mechanisms mediating these effects are...Full Text Available

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... M. Taylor, T. Kurt Kyser. (2009) Feather isotope analysis discriminates age-classes of Western, Least, and Semipalmated sandpipers when plumage ... ...

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Background:Alopecia areata (AA) is an immune-mediated form of hair loss that occurs in all ethnic groups, ages, and both sexes. Helicobacter pylori has...Full Text Available

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We report herein that trefoil factor 3 (TFF3) is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Forced expression of TFF3 in mammary carcinoma cells increased cell proliferation...Full Text Available

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SummaryThe transcriptional co-repressor SMRT utilizes two major receptor interacting domains (RID1 and RID2) to mediate nuclear receptor (NR) signaling through epigenetic modification....Full Text Available

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In diabetes complications, CCN-2 (known originally as CTGF) has been implicated in diabetic nephropathy both as a marker and a mediator of disease. This commentary addresses CCN-2 in diabetic nephropathy, in the context of the recent publication of the first human study to inhibit CCN-2 bioactivity in diabetic kidney disease.

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The ζ chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression...Full Text Available

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BACKGROUND: Although definitions vary, infected nonunion has been defined as a state of failure of union and persistence of infection at the fracture site for 6 to 8 months.>). Infected nonunions of the supracondylar region of the femur are uncommon and are mostly due to a severe open fracture with extensive comminution and segmental bone loss or after internal fixation of a comminuted closed fracture. Associated factors include exposed bone devoid of vascularized periosteal coverage for more than 6 weeks, purulent discharge, a positive bacteriological culture from the depth of the wound, and histologic evidence of necrotic bone containing empty lacunae. Soft-tissue loss with multiple sinuses, osteomyelitis, osteopenia, complex deformities with limb-length inequality, stiffness of the adjacent joint, polybacterial multidrug-resistant infection, and smoking all complicate treatment and recovery. Although uncommon in incidence, infected nonunions of the long bones ...

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Sleep symptoms are a prominent feature of mental health disorders like PTSD and depression. However, it is unknown whether sleep symptoms mediate the relationship between combat stress and these disorders. We examined the mediating role of sleep symptoms on the relationship between combat stress and PTSD; and the relationship between combat stress and depression using data from 576 Army veterans of the Iraq War surveyed in 2004. Correlational analyses revealed that when insomnia was included in the model, the correlation between combat stressors and other depression symptoms decreased by 65%; and when nightmares were included in the model, the correlation between combat stressors and other PTSD symptoms decreased by 69%. We replicated these analyses using individual items assessing PTSD an...

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The rice blast resistance (R) gene Pi-ta mediates gene-for-gene resistance against strains of the fungus Magnaporthe grisea that express avirulent...Full Text Available

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The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin...Full Text Available

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Sensory rhodopsins (SRs) belong to a subfamily of heptahelical transmembrane proteins containing a retinal chromophore. These photoreceptors mediate the cascade of vision in animal eyes and phototaxis...Full Text Available

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Mating signals are often directed at numerous senses and provide information about species identity, gender, receptiveness, individual identity and mate quality. Given the diversity of colourful body...Full Text Available

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In addition to the well documented role of cytokines in mediating tissue-level interactions, it is now clear that matrix macromolecules fulfil a complementary regulatory function. Data highlighted in...Full Text Available

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Devastating central nervous system injuries and diseases continue to occur in spite of the tremendous efforts of various prevention programs. The enormity of and annual escalation of healthcare...Full Text Available

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Krabbe disease (KD) is an inherited neurological disorder caused by the deficiency of galactocerebrosidase activity resulting in accumulation of psychosine, which leads to energy depletion,...Full Text Available

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Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen...Full Text Available

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BackgroundIn Arabidopsis, INDOLE-3-BUTYRIC ACID RESPONSE5 (IBR5), a putative dual-specificity protein phosphatase,...Full Text Available

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BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available

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Syndecan-2, a transmembrane heparan sulfate proteoglycan, is a critical mediator in the tumorigenesis of colon carcinoma cells. We explored the function of syndecan-2 in melanoma, one of the most invasive...Full Text Available

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4-Hydroxynonenal (HNE), a major electrophilic product of lipid peroxidation, is regarded as both a marker of oxidative stress and a mediator of oxidative damage. At subtoxic concentrations,...Full Text Available

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In utero electroporation is widely used to study neuronal development and function by introducing plasmid DNA into neural progenitors during embryogenesis. This is an effective and...Full Text Available

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The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M₃ subtype, with the M₂...Full Text Available

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The intracellular bioavailability of lead (Pb) at low dosage levels in major target organs such as the kidney and brain appears to be largely determined by complexation with a group of low molecular...Full Text Available

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Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal...Full Text Available

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PurposeEctopic expression of light-sensitive proteins, such as channelrhodopsin-2, represent a novel approach for restoring light-detection capabilities to degenerated retina. A...Full Text Available

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Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to evaluate if these effects of GH on...Full Text Available

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Activation of the innate immune system results in a rapid microbicidal response against microorganisms, which needs to be fine-tuned because uncontrolled immune responses can lead to infection and cancer,...Full Text Available

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BackgroundThe circadian rhythm in mammals is orchestrated by a central pacemaker in the brain, but most peripheral tissues contain their own intrinsic circadian oscillators. The...Full Text Available

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Effective small interfering RNA (siRNA)–mediated therapeutics require the siRNA to be delivered into the cellular RNA-induced silencing complex (RISC). Quantitative information of this essential...Full Text Available

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BackgroundThe lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding...Full Text Available

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BackgroundSurrogate immunologic markers for natural and vaccine-mediated protection against tuberculosis (TB) have not been identified.MethodsHIV-infected...Full Text Available

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Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and a cellular infiltrate dominated by eosinophils. Numerous epidemiological studies have related the exacerbation of allergic...Full Text Available

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Generations 5 and 6 (G5 and G6) poly(amidoamine) (PAMAM) dendrimers have been shown to be highly efficient nonviral carriers in in vitro gene delivery. However, their high toxicity...Full Text Available

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Background and purpose:The chicken anterior mesenteric artery contains an outer longitudinal smooth muscle layer, whose neural regulation remains to be elucidated. ATP evokes a depolarization...Full Text Available

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Experimental metastases in the brain of mice are infiltrated by microglia, and parabiosis experiments of green fluorescent protein (GFP⁺) and GFP^- mice revealed that these microglia...Full Text Available

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The CNS can exhibit features of inflammation in response to injury, infection or disease, whereby resident cells generate inflammatory mediators, including cytokines, prostaglandins, free radicals and...Full Text Available

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BackgroundWe have previously reported that low concentrations of cigarette smoke extract induce DNA damage without leading to apoptosis or necrosis in human bronchial epithelial...Full Text Available

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Calpains are Ca²⁺-dependent proteinases that mediate protein turnover in crustacean skeletal muscles. We used an antibody directed against lobster muscle-specific calpain (Ha-CalpM)...Full Text Available

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The Far UpStream Element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream...Full Text Available

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Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been implicated in Multiple Sclerosis demyelination through activation of complement and/or macrophage-effector processes. We presented...Full Text Available

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Glycoprotein 60 (gp60) is a normal plasma protein (mean concentration in normal serum 34 micrograms/ml) that is present in increased levels (mean concentration 97 micrograms/ml) in the sera of patients...Full Text Available

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Neuronal death is known to trigger reactive microgliosis. However, little is known regarding the manner by which microglia are activated by injured neurons and how microgliosis participates...Full Text Available

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Despite the demonstrated clinical efficacy of CD20 monoclonal antibody (mAb) for lymphoma therapy, the in vivo mechanisms of tumor depletion remain controversial and variable. To identify the molecular...Full Text Available

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In Syrian hamsters (Mesocricetus auratus), the expression of reproductive behavior requires the perception of social odors. The behavioral response to these odors is mediated...Full Text Available

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Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis....Full Text Available

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Study objectiveThe study aim was to improve our understanding of the relationships between contextual socioeconomic characteristics and coronary heart disease (CHD)...Full Text Available

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To investigate the fate of intrinsic factor and cobalamin during cobalamin absorption, we incubated enterocytes isolated from guinea pig ileum for periods of up to 30 min with ⁵⁷Co-labeled...Full Text Available

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The cytokine interleukin-7 (IL-7) has essential growth activities that maintain the homeostatic balance of the immune system. Little is known of the mechanism by which IL-7 signaling regulates metabolic...Full Text Available

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The inhibitory effects of indole-3-acetic acid (IAA) and 1-aminocyclopropane-1-carboxylic acid (ACC) on elongation growth of pea (Pisum sativum L.) seedling roots were investigated...Full Text Available

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Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) for which the molecular mediators remain unclear. We therefore conducted an expression analysis of human...Full Text Available

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Methylation of the arginine residues of histones by methyltransferases has important consequences for chromatin structure and gene regulation; however, the molecular mechanism(s) of methyltransferase...Full Text Available

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ABSTRACTObjectivesTo test the feasibility of human immune globulin (IG, Gamimune N, 10%) as a new treatment for endophthalmitis, the ocular tolerance, distribution,...Full Text Available

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BackgroundThe zinc-finger transcription factor GLI3 is an important mediator of Sonic hedgehog signaling and crucial for patterning of many aspects of the vertebrate body plan. In...Full Text Available

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Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit...Full Text Available

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Following the descovery of its transposition activity in mammalian culture systems, the Sleeping Beauty (SB) transposon has since been applied to achieve germline mutagenesis in mice....Full Text Available

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Candida albicans frequently causes superficial infections by invading and damaging epithelial cells, but may also cause systemic infections by...Full Text Available

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Female mammals are particularly sensitive to changes in food availability. The mechanisms that affect sexual behavior and food intake are closely related to one another; chief among the mechanisms...Full Text Available

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BackgroundLeukotrienes (LTs) belong to the large family of lipid mediators implicated in various inflammatory conditions such as asthma and rheumatoid arthritis. Four distinct types...Full Text Available

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BackgroundEscherichia coli strain EL350 contains chromosomally integrated phage lambda Red recombinase genes enabling this strain to be used for modifying the sequence...Full Text Available

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BackgroundNeuropathic pain (NP) is partially mediated by neuroinflammatory mechanisms, and also modulates local neurogenic inflammation. Dietary lipids, in particular the total amount...Full Text Available

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B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated...Full Text Available

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SpoIIIE is an FtsK-related protein that transports the forespore chromosome across the Bacillus subtilis sporulation septum. We use membrane photobleaching and protoplast assays to...Full Text Available

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the role of the AHR...Full Text Available

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Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular...Full Text Available

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We sought to determine whether the third component of complement (C3) is localized in ischemic baboon myocardium after coronary artery ligation. Furthermore, we assessed the effects of prior C3 depletion...Full Text Available

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The mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway plays a key role in mediating estrogen actions in the brain and neuronal sensitization during inflammation....Full Text Available

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Different tombusviruses were able to support the replication of either homologous or heterologous defective interfering (DI) RNAs, and those infected plants usually developed typical attenuated symptoms....Full Text Available

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Cytokinins are distributed through the vascular system and trigger responses of target cells via receptor-mediated signal transduction. Perception and transduction of the signal can occur at the plasma...Full Text Available

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The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter...Full Text Available

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Medulloblastoma and neuroblastoma belong to a group of neoplasms designated as primitive neuroectodermal tumors (PNETs). Secreted Protein, Acidic and Rich in Cysteine (SPARC) is a matrix-associated...Full Text Available

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Benzodiazepine withdrawal anxiety is associated with potentiation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) currents in hippocampal CA1 pyramidal...Full Text Available

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Motor function requires that motor axons extend from the spinal cord at regular intervals and that they are myelinated by Schwann cells. Little attention has been given to another cellular structure,...Full Text Available

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During blastocyst formation the segregation of the inner cell mass (ICM) and trophectoderm is governed by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2. Evidence indicates...Full Text Available

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Tooth enamel biomineralization is mediated by enamel proteins synthesized by ameloblast cells. Two classes of proteins have been described: enamelins and amelogenins. In lower vertebrates the absence...Full Text Available

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Atg9 is a transmembrane protein essential for autophagy which cycles between the Golgi network, late endosomes and LC3-positive autophagosomes in mammalian cells during starvation through a mechanism...Full Text Available

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Average human behavior in cue combination tasks is well predicted by Bayesian inference models. As this capability is acquired over developmental timescales, the question arises, how it is learned....Full Text Available

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Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and ...Full Text Available

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A sensitive and specific detection method was developed for Xanthomonas hyacinthi; this method was based on amplification of a subsequence of the type IV fimbrial-subunit gene fimA...Full Text Available

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The aggregation substance (AS) of Enterococcus faecalis, encoded on sex pheromone plasmids, is a surface-bound glycoprotein that mediates aggregation between bacteria thereby facilitating...Full Text Available

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BackgroundBacterial constituents, such as Gram-negative derived lipopolysaccharide (LPS), can initiate inflammatory bone loss through induction of host-derived inflammatory...Full Text Available

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Normal urinary bladder function requires contraction and relaxation of the detrusor smooth muscle (DSM). The DSM undergoes compensatory hypertrophy in response to partial bladder outlet obstruction...Full Text Available

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1. To explore mechanisms of urinary obstruction in benign prostatic hyperplasia (BPH), the features of contraction and relaxation in human hyperplastic and non-hyperplastic (control) prostatic tissues...Full Text Available

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Trapped ions are a near ideal system to study quantum information processing due to the high degree of control over the ion's external confinement and internal degrees of freedom. We demonstrate the key steps necessary for trapped ion quantum computing and focus on phonon-mediated entangling gates. We highlight several key algorithms implemented over the last decade with these gates and give a detailed description of Grover's quantum database search implemented with two trapped ion qubits.

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We present the draft genome sequence and its analysis for Fusobacterium nucleatum sub spp. vincentii (FNV), and compare that genome with F. nucleatum ATCC 25586 (FN). A total of 441 FNV open reading frames (ORFs) with no orthologs in FN have been identified. Of these, 118 ORFs have no known function and are unique to FNV, whereas 323 ORFs have functional orthologs in other organisms. In addition to the excretion of butyrate, H2S and ammonia-like FN, FNV has the additional capability to excrete lactate and aminobutyrate. Unlike FN, FNV is likely to incorporate galactopyranose, galacturonate, and sialic acid into its O-antigen. It appears to transport ferrous iron by an anaerobic ferrous transporter. Genes for eukaryotic type serine/threonine kinase and phosphatase, transpeptidase E-transglycosylase Pbp1A are found in FNV but not in FN. Unique ABC transporters, cryptic phages, and three types of restriction-modification systems have been identified in FNV. ORFs for ethanolamine ...

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Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome 11, are implicated in more than 95% of Ewing's sarcomas, ...

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In this paper we investigate the effects of surface mediation on the adsorption behavior of argon at different temperatures on homogeneous graphitized thermal carbon black and on heterogeneous nongraphitized carbon black surface. The grand canonical Monte Carlo (GCMC) simulation is used to study the adsorption, and its performance is tested against a number of experimental data on graphitized thermal carbon black (which is known to be highly homogeneous) that are available in the literature. The surface-mediation effect is shown to be essential in the correct description of the adsorption isotherm because without accounting for that effect the GCMC simulation results are always greater than the experimental data in the region where the monolayer is being completed. This is due to the overestimation of the fluid-fluid interaction between particles in the first layer close to the solid surface. It is the surface mediation ...

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Prejudice against overweight people is rife. However, there is a paucity of research on the underlying reasons for it. In two studies the relationship between body image, the tendency to make physical appearance-related comparisons (PACS), and both explicit and implicit anti-fat attitudes was examined. In Study 1 (n = 227) people with a high tendency to make physical appearance-related comparisons (high PACS scorers) reported lower self-appearance evaluation, but higher appearance orientation and explicit anti-fat attitudes. The PACS fully mediated the relationship between appearance orientation and explicit anti-fat attitudes. Study 2 (n = 134) found that the PACS also mediated the relationship between appearance orientation and implicit anti-fat attitudes. Thus, individual differences in factors such as body image and the tendency to make appearance-related comparisons, appear to play a central role in both explicit and implicit anti-fat ...

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The immune system modulates many key biological processes in humans. However, the exact role of the immune system in particle-associated periprosthetic osteolysis is controversial. Human tissue retrieval studies, in vivo and in vitro experiments suggest that the immune response to polymer particles is non-specific and macrophage-mediated. Lymphocytes may modulate this response. However direct lymphocyte activation by polymer particle-protein complexes seems unlikely. However, metallic byproducts may complex with serum proteins and lead to a Type IV, lymphocyte-mediated immune reaction. In predisposed individuals, this reaction may rarely lead to persistent painful joint effusions, necessitating debridement and excision of the bearing surfaces of the prosthesis. In these patients, retrieved...

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Testosterone influences various aspects of affective behavior, which is mediated by different brain regions within the emotion circuitry. Previous neuroimaging studies have demonstrated that testosterone increases neural activity in the amygdala. To investigate whether this could be due to altered regulation of amygdala functioning which is thought to be mediated by the prefrontal cortex, we studied the effects of exogenous testosterone on the interaction between the amygdala and other brain regions. Healthy middle-aged women received a single nasal testosterone dose in a randomized, placebo-controlled, crossover manner, and performed an emotional face matching task while their brain activity was measured with functional MRI. The results show that testosterone rapidly reduced functional co...

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Nucleotides released upon brain injury signal to astrocytes and microglia playing an important role in astrogliosis, but the participation of microglia in the purinergic modulation of astrogliosis is still unclear. Highly enriched astroglial cultures and co-cultures of astrocytes and microglia were used to investigate the influence of microglia in the modulation of astroglial proliferation mediated by nucleotides. In highly enriched astroglial cultures, adenosine-5?-triphosphate (ATP), adenosine 5?-O-(3-thio)-triphosphate (ATP?S), adenosine 5?-O-(3-thio)-diphosphate (ADP?S; 0.01?1?mM), and adenosine-5?-diphosphate (ADP; 0.1?1?mM) increased proliferation up to 382%, an effect abolished in co-cultures containing 8% of microglia. The loss of ATP proliferative effect in co-cultures is supporte...

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Objective To evaluate the inhibitory property of de-glycyrrhizinated extract of Glycyrrhiza glabra root and its phytoconstituents (glabridin, isoliquiritigenin and glycyrrhizin) on LPS-induced production of pro-inflammatory mediators. Materials and methods Inhibitory effect of G. glabra extract and its phytoconstituents were studied on lipopolysaccharide (LPS)-induced nitric oxide (NO), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels in J774A.1 murine macrophages. Results G. glabra and isoliquiritigenin significantly inhibited LPS stimulated NO, IL-1 beta and IL-6 production. Glabridin showed significant inhibition of NO and IL-1 beta release, but failed to attenuate IL-6 levels at the tested concentrations. In addition, glycyrrhizin did not exhibit inhibitory response towar...

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In this study, we investigated the kinetics of linoleic acid production via lipase-mediated hydrolysis of corn DDGS oil in a batch reactor with continuous mechanical agitation and developed a kinetic model that incorporated the product inhibition to study the complete hydrolysis. The model agreed very well with observed data; though situations with low enzyme dosage or low stirring rates were modeled successfully without product inhibition, actual product concentration in such situations was too low to exert any inhibitory effects. Increasing the enzyme concentration increased hydrolysis, and beyond certain enzyme concentrations, effects tended to fade away because of excessive enzyme desorption from the interface. An enzyme dosage within the range of 40-60KLU/L of oil dispersion could be ...

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Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drug target for obesity and obesity-mediated metabolic syndrome. Dysfunction of enlarged adipocytes in obesity is involved in obesity-mediated metabolic syndrome. Adipocytokines, such as adiponectin released from small adipocytes, are able to prevent these disorders. In this study, we found that honokiol, an ingredient of Magnolia officinalis used in traditional Chinese and Japanese medicines, enhanced adipocyte differentiation in 3T3-L1 preadipocytes. Oil Red O staining showed that treatment with honokiol in the presence of insulin dose-dependently increased lipid accumulation in 3T3-L1 preadipoyctes although its activity was weak compared with r...

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Abstract Background- Cyclosporine is used for treatment of transplanted patients and for immune-mediated diseases. Cyclosporine is known to cause a combination of metabolic side effects including hypertension, hyperkalemia, hypercalciuria and hypomagnesemia. These side effects except for hypomagnesemia are the cardinal features of familial hyperkalemia and hypertension (FHHt), also called pseudohypoaldosteronism type II (PHA II). FHHt is caused by mutations in the kinases WNK1 and WNK4 resulting in an increase in renal Na-Cl cotransporter (NCC) apical distribution and function. Therefore, we studied whether cyclosporine-s metabolic side effects are mediated by WNK4 and NCC. Design- Sprague-Dawley (SD) rats were treated by cyclosporine 25-mg-kg-1 subcutaneously for 14-days. Blood pressure, ...

Science.gov (United States)

We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro.

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Antisense- or RNAi-mediated suppression of the biosynthesis of nutritionally inferior storage proteins is a promising strategy for improving the amino acid profile of seeds. However, the potential pleiotropic effects of this on interconnected pathways and the agronomic quality traits need to be addressed. In the current study, a transcriptomic analysis of an antisense C-hordein line of barley was performed, using a grain-specific cDNA array. The C-hordein antisense line is characterized by marked changes in storage protein and amino acid profiles, while the seed weight is within the normal range and no external morphological irregularities were observed. The results of the transcriptome analysis showed excellent correlation with data on changes in the relative proportions of storage protei...

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Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosi...

International Nuclear Information System (INIS)

Contrary to the electronic excitation induced phenomena of desorption and sputtering, we observed incorporation of oxygen in a thin Fe film during its irradiation with swift heavy ions. It is observed that the adsorbed oxygen diffuses in to the Fe film. The incorporation of oxygen and its diffusion in the bulk of the film is a manifestation of extremely large electronic energy deposition by the incident ions. It is shown that the experimentally observed high diffusivity of oxygen in Fe during irradiation is due to the existence of transient melt phase of Fe.

UK PubMed Central (United Kingdom)

Food animals are a potential source of CTX-M resistance genes for humans. We evaluated the transfer of the bla_CTX-M-9 gene from an animal strain of Salmonella enterica...Full Text Available

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Self-grooming in response to the odors of conspecifics is a form of olfactory communication among meadow voles. The amount of time meadow voles spend self-grooming when they encounter the odors of conspecifics varies seasonally, with males targeting the odors of reproductively active females only during the breeding season. Other odor related behaviors in male voles such as odor preferences for conspecifics and the attractiveness of their odors to conspecifics vary seasonally as well. For male meadow voles, these behaviors are mediated by seasonal variations in testosterone (T) and prolactin (PRL) titers. The objective of this study was to determine whether seasonal differences in the amount of time male meadow voles self-groom in response to odors of conspecifics are mediated by seasonal rhythms in their circulating T and PRL titers. We tested the hypothesis that high titers of both T and PRL are necessary for reproductively active ...

Science.gov (United States)

Bacteriocins are an abundant class of antimicrobial molecules that appear to mediate population dynamics within species. The bacteriocins of Escherichia coli have served as a model for exploring the ecological role of these potent toxins. Studies suggest that colicins provide a competitive edge in nutrient-poor environments and that there might be a trade-off between the costs and benefits of colicin production. PMID:10203843

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Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation...Full Text Available

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We report that the fission yeast nucleoporin Nup124p is required for the nuclear import of both, retrotransposon Tf1-Gag as well as the retroviral HIV-1 Vpr. Failure to import Tf1-Gag into the nucleus...Full Text Available

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RNA interference (RNAi) is an effective tool for studying gene function in oocytes, but no studies have targeted somatic cells of primary cultured cumulus cell-oocyte complexes (COCs). This...Full Text Available

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Matrix metalloproteinase (MMP) plays a crucial role in periodontal disease and is up-regulated by oral Gram-negative, pathogen-derived LPS. In this study, we reported that simvastatin, a 3-hydroxyl-3-methylglutaryl-CoA...Full Text Available

UK PubMed Central (United Kingdom)

Inhibition of large conductance calcium-activated potassium (BK_Ca) channels mediates, in part, oxygen sensing by carotid body type I cells. However, BK_Ca channels remain active...Full Text Available

UK PubMed Central (United Kingdom)

The movement of cells and cell fragments in an electric field provided a means for determining the nature of cellular surface charges. We found that changes in ionic strength and particularly changes...Full Text Available

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BackgroundA_δ and C fibers are the major pain-conducting nerve fibers, activate only partly the same brain areas, and are differently involved in pain syndromes....Full Text Available

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The properties of a nonviable, aqueous ether-extracted Brucela abortus preparation, Bru-Pel, are described. In addition to inducing a "virus-type" interferon response and protecting mice against challenge with otherwise lethal doses of Semliki Forest virus, Bru-Pel is demonstrated to have potent antitumor properties in mice. These antitumor effects appear to be mediated by an increase in nonspecific resistance similar to that seen with other experimental antitumor agents. PMID:728911

UK PubMed Central (United Kingdom)

Hyperthermia (HT) is a strong adjuvant treatment with radiotherapy and chemotherapy because it causes tumor reoxygenation. However, the detailed molecular mechanisms of how HT enhances tumor oxygenation...Full Text Available

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Although matrix metalloproteinase-9 (MMP-9) is involved in cardiomyocytes contractility dysfunction, tissue inhibitor of metalloproteinase-4 (TIMP-4) mitigates the effect of MMP-9, and proteinase-activated...Full Text Available

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Despite intensive efforts, the intracellular signaling pathways that mediate apoptosis remain unclear. The human B lymphoma cell line, B104, possesses characteristics that make it an attractive model...Full Text Available

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Inhibition of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. Specifically, we show that at doses sufficient to down-regulate levels of phospho-S6 and the negative immune regulator B7-H1 in tumor cells, Honokiol does not ...

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BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available

UK PubMed Central (United Kingdom)

Differential host-pathogen interactions direct viral replication in infected cells. In HIV-1 infected cells, nuclear export of viral RNA transcripts into cellular cytoplasm is governed by interaction...Full Text Available

UK PubMed Central (United Kingdom)

Backgroundβ₂-Adrenergic receptors (β₂AR) play important regulatory roles in a variety of cells and organ systems and are important therapeutic...Full Text Available

UK PubMed Central (United Kingdom)

Human Fas/Apo-1 is a cell-surface protein that mediates apoptosis upon ligation with Fas ligand. The gene lies on the long arm of chromosome 10, consists of nine exons, and spans more than 26 kb of...Full Text Available

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Activities of glycogen synthase (GS) and GS phosphatase were determined on human muscle biopsies before and after isometric contraction at 2/3 maximal voluntary force. Total GS activity did not change...Full Text Available

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Bovine leukemia virus (BLV), a retrovirus related to human T-cell leukemia virus types 1 and 2, can induce persistent nonneoplastic expansion of the CD5⁺ B-cell population, termed...Full Text Available

UK PubMed Central (United Kingdom)

A collection of neurons in the upper lumbar spinal cord of male rats projects to the lower lumbar spinal cord, releasing gastrin-releasing peptide (GRP) onto somatic and autonomic centers known to regulate...Full Text Available

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In superior cervical ganglion (SCG) neurons calcium-induced calcium release (CICR), mediated by ryanodine receptors (RyRs), contributes to stimulation-evoked intracellular calcium ([Ca²⁺]_i)...Full Text Available

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This report investigates acute changes in the sensitivity of 5-HT_1A receptors in dorsal raphe (dr) neurons in response to elevated serotonin. DR neurons were isolated from adult rats...Full Text Available

UK PubMed Central (United Kingdom)

Arf GTPases control vesicle formation from different intracellular membranes and are regulated by Arf guanine nucleotide exchange factors (GEFs). Outside of their conserved catalytic domains, known...Full Text Available

International Nuclear Information System (INIS)

Purpose: We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86. Methods and Materials: From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk tumors (extremity tumors =# 100 cm"3). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and treatment time as for ...

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A set of equations describing a stress-mediated evolution of the nonequilibrium dopant-defect system has been derived and analyzed. Together with coupled diffusion of dopant atoms and point defects, we consider the drift of all mobile species in different charge states, namely vacancies, self-interstitials, and pairs 'dopant atom-point defect', in the field of stress. It has been shown that stresses may affect the diffusion of dopant atoms mainly in two ways: (1) directly, due to the drift of the pairs in the field of stress; (2) indirectly, by the formation of nonuniform defect distribution due to the drift of point defects. On this basis, various features of doping processes, such as phenomena of 'uphill' impurity diffusion near the surface (within the framework of the first or second mechanisms) and the peculiarities of high concentration phosphorus diffusion (due to the second mechanism), can be explained. Numerical ...

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The authors present a search for excited and exotic muon states {mu}*, conducted using an integrated luminosity of 371 pb{sup -1} of data collected in p{bar p} collisions at {radical}s = 1.96 TeV at the Tevatron with the CDF II detector. They search for associated production of {mu}{mu}* followed by the decay {mu}* {yields} {mu}{gamma}, resulting in the {mu}{mu}{gamma} final state. They compare the data to model predictions as a function of the mass of the excited muon M{sub {mu}*}, the compositeness energy scale {Lambda}, and the gauge coupling factor f. No signal above the standard model expectation is observed in the {mu}{gamma} mass spectrum. In the contact interaction model, they exclude 107 < M{sub {mu}*} < 853 GeV/c{sup 2} for {Lambda} = M{sub {mu}*}; in the gauge-mediated model, they exclude 100 < M{sub {mu}*} < 410 GeV/c{sup 2} for f/{Lambda} = 10{sup -2} GeV{sup -1}. These 95% confidence level exclusions extend previous limits ...

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The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ 3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activatin observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analyzed with the restriction enzymes Msp I and Hpa II, the c-myc locus of MCAQ 3-5 and MCAQ 1-4 was found hypomethylated as ...

CERN Document Server

We propose a new scenario that solves the slepton negative mass squared problem of the minimal supersymmetric standard model with anomaly mediated supersymmetry breaking. The solution is achieved by including three trilinear R-parity violating operators in the superpotential. The soft supersymmetry breaking terms satisfy renormalisation group invariant relations in terms of supersymmetric couplings and the overall supersymmetry breaking mass scale. Flavour changing neutral currents are naturally highly suppressed. The model predicts tan beta=4.2 +/- 1.0. Excluding sleptons, the supersymmetric particle spectrum depends upon two remaining free parameters. In the case of the R-parity violating couplings at their quasi-fixed points at a supersymmetric GUT scale, the whole sparticle spectrum approximately depends upon only one free parameter. Imposing experimental limits leads to a constrained and distinctive phenomenology. The lightest CP-even Higgs of mass m_h=118 GeV ...

CERN Document Server

we report an ultrafast synchrotron x-ray phase contrast imaging study of the primary breakup mechanism of a coaxial air-assisted water jet. We demonstrate that there exist great similarities in the phenomenology of primary breakup with that of the secondary breakup. Especially, a membrane-mediated breakup mechanism dominates the breakup process for a wide range of air speeds. This finding reveals the intrinsic connections of these two breakup regimes and has deep implications on the unified theoretical approach in treating the breakup mechanism of high speed liquid jet.

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The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.

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Carbalkoxylation of vinyl electrophiles was investigated using platinum complexes. This reaction occurs in two steps: (a) carbonyl insertion of {sigma}-vinyl Pt(II) halides and (b) alcoholysis of vinylic acyl Pt(II) complexes. Alcoholysis of vinylic acyl Pt(II) triflate complexes is investigated kinetically. Vinylic acyl Pt(II) complexes were isolated and characterized. 51 refs., 5 figs., 6 tabs.

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Central nervous system (CNS) development, homeostasis, stress responses, and plasticity are all mediated by epigenetic mechanisms that modulate gene expression and promote selective deployment of functional gene networks in response to complex profiles of interoceptive and environmental signals. Thus, not surprisingly, disruptions of these epigenetic processes are implicated in the pathogenesis of a spectrum of neurological and psychiatric diseases. Epigenetic mechanisms involve chromatin remodeling by relatively generic complexes that catalyze DNA methylation and various types of histone modifications. There is increasing evidence that these complexes are directed to their sites of action by long non-protein-coding RNAs (lncRNAs), of which there are tens if not hundreds of thousands speci...

CERN Document Server

multi-parton interactions and underlying event structure, $\\gamma$-mediated processes and luminosity determination, Monte Carlo tuning and even MSSM Higgs discovery in central exclusive production. In this article, the forward detector instrumentation around the CMS interaction point is described and the prospects for diffractive and forward physics using the CMS forward detectors are summarized. In addition, first observation of forward jets as well as early measurements of the forward energy flow in the pseudorapidity range $3.15

International Nuclear Information System (INIS)

Environmental computer science is a new partial discipline of applied computer science, which makes use of methods and techniques of information processing in environmental protection. Thanks to the inter-disciplinary nature of environmental problems, computer science acts as a mediator between numerous disciplines and institutions in this sector. The handbook reflects the broad spectrum of state-of-the art environmental computer science. The following important subjects are dealt with: Environmental databases and information systems, environmental monitoring, modelling and simulation, visualization of environmental data and knowledge-based systems in the environmental sector. (orig.).

International Nuclear Information System (INIS)

Higgs mediated flavor violating electromagnetic interactions, induced at the one-loop level by a nondiagonal Hf_if_j vertex, with f_i and f_j charged leptons or quarks, are studied within the context of a completely general effective Yukawa sector that comprises SU_L(2)xU_Y(1)-invariant operators of up to dimension-six. Exact formulae for the one-loop #gamma#f_if_j and #gamma##gamma#f_if_j couplings are presented and their related processes used to study the phenomena of Higgs mediated lepton flavor violation. The experimental limit on the #mu##->#e#gamma# decay is used to derive a bound on the branching ratio of the #mu##->#e#gamma##gamma# transition, which is 6 orders of magnitude stronger than the current experimental limit. Previous results on the #tau##->##mu##gamma# and #tau##->##mu##gamma##gamma# decays are reproduced. The possibility of detecting signals of lepton flavor violation at #gamma##gamma# colliders is explored ...

Science.gov (United States)

Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of ...

British Library Electronic Table of Contents (United Kingdom)

Amyloid precursor protein (APP), a key protein in pathogenesis of Alzheimer's disease (AD), is a type I transmembrane protein which can be cleaved by b- and g-secretase to release the amyloidogenic b-amyloid peptides (Ab) and the APP intracellular domain (AICD). While Ab has been widely believed to initiate pathogenic cascades culminating AD, the physiological functions and regulations of AICD remain elusive. In present study, endogenous AICD was demonstrated to be increased by canonical Wnt signal. Instead of due to g-secretase activity, enhanced AICD expression was found due to the increased protein stability by Wnt/b-catenin. b-Catenin was demonstrated to be an associating partner of AICD, capable of promoting AICD mediated transcriptional activity. Investigation by AICD mutants proved ...

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Short synthetic single-stranded oligodeoxyribonucleotides (ssODNs) can be used to introduce subtle modifications into the genome of mouse embryonic stem cells (ESCs). We have previously shown that effective application of ssODN-mediated gene targeting in ESC requires (transient) suppression of DNA mismatch repair (MMR). However, whereas transient down-regulation of the mismatch recognition protein MSH2 allowed substitution of 3 or 4 nucleotides, 1 or 2 nucleotide substitutions were still suppressed. We now demonstrate that single- or dinucleotide substitution can effectively be achieved by transient down-regulation of the downstream MMR protein MLH1. By exploiting highly specific real-time PCR, we demonstrate the feasibility of substituting a single basepair in a non-selectable gene. Howev...

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l-Carnitine is a critical metabolite indispensable for the metabolism of lipids as it facilitates fatty acid transport into the mitochondrion where b-oxidation occurs. Human astrocytes (CCF-STTG1 cells) and hepatocytes (HepG2 cells) exposed to aluminum (Al) and hydrogen peroxide (H2O2), were characterized with lower levels of l-carnitine, diminished b-oxidation, and increased lipid accumulation compared to the controls. g-Butyrobetainealdehyde dehydrogenase (BADH) and butyrobetaine dioxygenase (BBDOX), two key enzymes mediating the biogenesis of l-carnitine, were sharply reduced during Al and H2O2 challenge. Exposure of the Al and H2O2-treated cells to a-ketoglutarate (KG), led to the recovery of l-carnitine production with the concomitant reduction in ROS levels. It appears that the chann...

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Mood in humans is a complex phenomenon that integrates emotion (e.g. happiness and sadness), cognition, perception, ideation, and action in a coherent manner. In bipolar disorder extremes of mood (up or down) occur outside the normal range, in which all the above functions are coherently affected. Mood is controlled by a series of separate but interactive brain circuits that involve much of the brain, but particularly the limbic system. The question addressed in this paper is whether the coordination of all these separate systems into one coherent functional mood is mediated by non-linear dynamics acting between these systems as equal participants; or whether it is affected by a single master regulator controlling the others. The possible roles, as master regulators, of non-linear dynamica...

International Nuclear Information System (INIS)

Two no-carrier-added "1"2"5I-labelled photoaffinity rapamycin analogs were prepared: 7-demethoxy-7-(4-azido-3-"1"2"5I-benzyloxy) rapamycin and its C_2_8-C_2_9 seco analog. The key reactions of the synthesis were substitution of the C_7 methoxyl of rapamycin with 4-azido-3-tributylstannylbenzyloxy group, exchange of tributyltin with "1"2"5I using Na"1"2"5I and Chloramine-T, and a ZnCl_2 mediated retro-Aldol cleavage of the C_2_8-C_2_9 bond of rapamycin. (author).

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This study describes the chemical composition of the essential oil of Artemisia maritima (Am.Oil) and the pharmacological basis for its medicinal use in gut and airways disorders. Twenty five compounds, composing 93.7% of the oil, were identified; among these, chrysanthenyl propionate and elixene were identified for the first time from any Artemisia species. The Am.Oil (0.3?1.0 mg/mL) suppressed spontaneous and high K+ (80 mM)-induced contractions in isolated rabbit jejunum, suggestive of an antispasmodic effect mediated possibly through calcium channel blockade. The calcium channel blockade activity was confirmed when pre-treatment of the tissue with Am.Oil (0.01?0.03 mg/mL) shifted the Ca++ concentration-response curves to the right, similar to verapamil and papaverine. In isolated trach...

Energy Technology Data Exchange (ETDEWEB)

The Mediated Electrochemical Oxidation (MEO) system is an aqueous process which treats low-level mixed wastes by oxidizing the organic components of he waste into carbon dioxide and water. As MEO system continues to run, dissolved ash and radionuclides slowly accumulate in the anolyte and must be removed to maintain process efficiency. At such time, all of the anolyte is pumped into a still feed tank, and the silver ions need to be removed before sending the solution to a thin-film evaporator for further concentration. The efficiency of removing silver ions in the solution needs to be high enough such that the residual silver sent to Final Forms would be less than 1% wt. The purpose of this work is to develop an efficient process to remove silver ions during the MEO cleanout and to demonstrate the capability of centrifugation for separating small silver chloride particles from the solution. This development work includes lab scale experiments and bench scale tests. ...

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Background and purpose: The aims of this study were to investigate the anti-cancer activity of SZ-685C, an anthracycline analogue isolated from marine-derived mangrove endophytic fungi, and to explore the molecular mechanisms underlying such activity. Experimental approach: The effect of SZ-685C on the viability of cancer cell lines was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. SZ-685C-induced apoptosis was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay and analysis of caspase activation. The effect of SZ-685C on the Akt/FOXO pathway was studied using Western blotting analysis, and the in vivo anti-tumour efficacy was examined in ...

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Insect attraction to host plants may be partly mediated by visual stimuli. In the present study, the responses of adult Hycleus apicicornis (Gur.) (Coleoptera: Meloidae) to plant models of different colours, different combinations of two colours, or three hues of blue of different shapes are compared. Single-colour models comprised the colours sky blue, bright green, yellow, red, white and black. Sky blue (reflecting light in the 440-500 nm region) is the most attractive, followed by white, which reflects light over a broader range (400-700 nm). On landing on sky blue targets, beetles exhibit feeding behaviour immediately. When different hues of blue (of different shapes) are compared, sky blue is preferred over turquoise, followed by dark blue, indicating that H. apicicornis is more attra...

International Nuclear Information System (INIS)

The ability of the R46 R factor and its derivative pKM101 to modify sensitivity to "6"0Co #gamma# radiation was studied. In Escherichia coli K12 both plasmids enhanced bacterial survival after "6"0Co #gamma# irradiation. This effect was dependent on recA"+ genotype but not on recB"+, recB"+recC"+, and recF"+ genotypes. 5-Fluorouracil eliminated the R46 R factor from the parent and its rec"- mutant strains. These strains lost not only the antibiotic resistance coded for R46 R factor but their radioresistance as well.

British Library Electronic Table of Contents (United Kingdom)

This research proposes that the concept of emotional attachment, and specifically the independent constructs of psychological ownership and affective reaction, can help explain many of the endowment effect findings documented in the literature. We define these constructs and then test them across a set of nine studies in which we both replicate previous and generate new endowment effect findings, and then show that psychological ownership and affective reaction can mediate the effects. In doing so, we offer direct empirical support for the idea of emotional attachment as a driver of loss aversion while also providing practitioners and future endowment effect researchers with new insights about the psychological processes that underlie the endowment effect.

Science.gov (United States)

Pinealectomy completely prevented gonadal regression as well as reduction in body weight and white adipose tissue content of the gonadal and retroperitoneal fat deposits in male meadow voles transferred from long to short day lengths. Pineal influences on pelage characteristics depended on which parameter was assessed. For instance, the increase in guard hair length observed in short-day control voles was blocked by pinealectomy; however, a similar increase in underhair length was unaffected by removal of the pineal gland. Photoperiod-dependent changes in fat deposition, testicular activity, and guard hair length presumably rely on altered pineal secretory activity to transduce the effects of day length on the neuroendocrine axis; however, mechanisms independent of pineal activity may be capable of mediating photoperiodic control of underhair growth. PMID:2979644

CERN Document Server

The generation and control of quantum states of light constitute fundamental tasks in cavity quantum electrodynamics (QED). The superconducting realization of cavity QED, circuit QED, enables on-chip microwave photonics, where superconducting qubits control and measure individual photon states. A long-standing issue in cavity QED is the coherent transfer of photons between two or more resonators. Here, we use circuit QED to implement a three-resonator architecture on a single chip, where the resonators are interconnected by two superconducting phase qubits. We use this circuit to shuffle one- and two-photon Fock states between the three resonators, and demonstrate qubit-mediated vacuum Rabi swaps between two resonators. This illustrates the potential for using multi-resonator circuits as photon quantum registries and for creating multipartite entanglement between delocalized bosonic modes.

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Summary Background Current management of egg allergy relies on egg elimination from the diet. It does not protect patients from reactions after accidental ingestion of the food and it has a negative influence on quality of life. To solve these problems, some desensitization protocols have been described that are safe and effective, but only one study of a rush regimen for egg with a small patient sample has been published. Objective To evaluate the safety, efficacy and immunologic effects of an oral rush desensitization protocol for immediate egg allergy. Methods Subjects aged 5 years or older with symptomatic IgE-mediated allergy to hen's egg underwent a 5-day oral tolerance induction regimen and were subsequently maintained on a regular egg intake. The variables studied were the reaction...

Energy Technology Data Exchange (ETDEWEB)

The growth of thin Pd[sub 2]Si films on Si(111) surfaces is studied using [ital in] [ital situ] transmission electron microscope under ultrahigh vacuum conditions. No immediate reaction of deposited Pd with Si is observed at room temperature. At [similar to]200 [degree]C, uniform Pd[sub 2]Si films can be formed. The thin Pd[sub 2]Si films are found to grow into strained islands at elevated temperatures. Interfacial misfit dislocations associated with interfacial steps propagate across the strained islands, causing the islands to grow layer-by-layer at the interface. The strain fields associated with the misfit dislocations are believed to be responsible for this behavior.

CERN Document Server

In the paper we investigate a mathematical model describing the growth of tumor in the presence of immune response of a host organism. The dynamics of tumour and immune cells is based on the generic Michaelis-Menten kinetics describing interaction and competition between the tumour and the immune system. The appropriate phenomenological equation modeling cell-mediated immune surveillance against cancer is of the predator-prey form and within a given choice of parameters exhibits bistability. Under the influence of spontaneous weak fluctuations, the model may be analyzed in terms of a stochastic differential equation bearing the form of an overdamped Langevin-like dynamics in the external quasi-potential represented by a double well. We analyze properties of the system within the range of parameters for which the potential wells are of the same depth and when the additional perturbation describing a periodic treatment is insufficient to overcome the barrier height ...

British Library Electronic Table of Contents (United Kingdom)

Manganese toxicity can cause a neurodegenerative disorder affecting cortical and basal ganglia structures with a neurological presentation resembling features of Parkinson's disease. Children are more sensitive to Mn-induced neurological dysfunction than adults, and recent studies from our laboratory revealed a marked sensitivity of male juvenile mice to neuroinflammatory injury from Mn, relative to females. To determine the role of estrogen (E2) in mediating sex-dependent vulnerability to Mn-induced neurotoxicity, we exposed transgenic mice expressing an NF-kB-driven enhanced green fluorescent protein (EGFP) reporter construct (NF-kB-EGFP mice) to Mn, postulating that supplementing male mice with E2 during juvenile development would attenuate neuroinflammatory changes associated with glia...

British Library Electronic Table of Contents (United Kingdom)

Isolation of functional and intact mitochondria from solid tissue is crucial for studies that focus on the elucidation of normal mitochondrial physiology and/or mitochondrial dysfunction in conditions such as aging, diabetes, and cancer. There is growing recognition of the importance of mitochondria both as targets for drug development and as off-target mediators of drug side effects. Unfortunately, mitochondrial isolation from tissue is generally carried out using homogenizer-based methods that require extensive operator experience to obtain reproducible high-quality preparations. These methods limit dissemination, impede scale-up, and contribute to difficulties in reproducing experimental results over time and across laboratories. Here we describe semiautomated methods to disrupt tissue ...

British Library Electronic Table of Contents (United Kingdom)

Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunize...

CERN Document Server

In QCD the spontaneous breaking of chiral symmetry and the U(1) axial anomaly can be understood considering instantons as the gauge configurations mediating quark-quark interaction. The existence of an exact zero mode solution of the Dirac equation in the field of a single instanton is the fundamental ingredient of this analysis. Explicit expressions for psi_0 are available for T different from 0 and mu=0, and mu different from 0 and T=0. In this paper we derive the solution for the most general case T different from 0 and mu different from 0. This new result opens the possibility of investigating the QCD dynamics associated with instantons in the full phase diagram. As a first step in this direction we will study the dependence of the instanton density from the thermodynamic coordinates.

British Library Electronic Table of Contents (United Kingdom)

The herbicide atrazine is a known immunotoxicant and an inhibitor of human natural killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell-mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24-h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test t...

British Library Electronic Table of Contents (United Kingdom)

PP2B is a Ca2+/calmodulin-dependent protein phosphatase that is ubiquitously expressed in mammals. Among other actions, it is an effector mechanism in NMDA-mediated glutamate neurotransmission as well as a regulator of GSK3? and MAPK signaling cascades. Because all of these mechanisms have demonstrable roles in the control of circadian rhythyms, we hypothesized that PP2B would be a key regulator of rhythm generation and entrainment, and that through inhibition of its phosphatase activity, the circadian system would be affected by immunosuppressant drug therapy. We report here that immunosuppressant drugs (cyclosporin A, FK506) (1) block the circadian responses to light that underlie photic entrainment; (2) produce circadian phase shifts with a characteristic nonphotic profile; and (3) disr...

British Library Electronic Table of Contents (United Kingdom)

In this work, a highly-sensitive polymeric membrane ion selective electrode for determination of tetracycline was constructed by using molecularly imprinted polymer (MIP) particles as quasi-ionophore. The water-compatible MIP particles targeting tetracycline were synthesized with tetracycline as a template molecule, methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a cross-linker, 2,2?-azobisisobutyronitrile as an initiator and lanthanum ion as a mediator. Benefited from the distinctive performance of the quasi-ionophore and the optimized composition of the membrane and the inner filling solution, the lower detection limit of the electrode was decreased to about 1 ? 10?8 mol/l. It exhibited a good electrode slope 59.8 mV/decade near the theoretical Nernstian one, ...

Energy Technology Data Exchange (ETDEWEB)

The objective of this work was to combine asymmetric somatic hybridization (donor-recipient fusion or gamma fusion) to microprotoplast-mediated chromosome transfer, as a tool to be used for chromosome mapping in Citrus. Swinglea glutinosa micro protoplasts were irradiated either with 50, 70, 100 or 200 gamma rays and fused to cv. Ruby Red grapefruit or Murcott tangor protoplasts. Cell colonies were successfully formed and AFLP analyses confirmed presence of S. glutinosa in both 'Murcott' tangor and 'Ruby Red' grapefruit genomes. (author)

Science.gov (United States)

Three in vivo assays were used to measure the immunocompetence of chickens in two generations of a selection experiment. The obtained data were used to estimate the variance components for sire and dam for antibody production to Pasteurella multocida and Mycoplasma gallisepticum vaccines, for T-cell-mediated immunity evaluated by a phytohemagglutinin wing web assay, and for clearance of foreign particles from the circulatory system. Heritabilities of and genetic correlations among these immunological traits were calculated from the sire variance components. Heritability estimates of the immunological traits based on the sire component of variance ranged from .06 to .53, and genetic correlations among immunological traits were generally negative. PMID:1956847

British Library Electronic Table of Contents (United Kingdom)

One proposed solution to the problem of ballast-mediated aquatic invasions involves chemically treating ballast water to kill key target organisms. Here, we examine the efficacy of three commercially available ballast water biocides using vegetative microalgae, dinoflagellate resting cysts and bacteria as test organisms. Chemicals tested were the ballast water biocides SeaKleen and Peraclean Ocean, and the chlorine dioxide biocide Vibrex. Results demonstrate that the applicability of each of the three chemical biocides as a routine ballast water treatment is limited by factors such as cost, biological effectiveness and possible residual toxicity of the discharged ballast water (assessed on the basis of impact on motility of vegetative marine microalgae). Of the three biocides tested, Perac...

CERN Document Server

We investigate the effect of the intrinsic spin of a fundamental spinor field on the surrounding spacetime geometry. We show that despite the lack of a rotating stress-energy source (and despite claims to the contrary) the intrinsic spin of a spin-half fermion gives rise to a frame-dragging effect analogous to that of orbital angular momentum, even in Einstein-Hilbert gravity where torsion is constrained to be zero. This resolves a paradox regarding the counter-force needed to restore Newton's third law in the well known spin-orbit interaction. In addition, the frame-dragging effect gives rise to a {\\it long-range} gravitationally mediated spin-spin dipole interaction coupling the {\\it internal} spins of two sources. We argue that despite the weakness of the interaction, the spin-spin interaction will dominate over the ordinary inverse square Newtonian interaction in any process of sufficiently high-energy for quantum field theoretical effects to be ...

British Library Electronic Table of Contents (United Kingdom)

The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12?weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished ...

Energy Technology Data Exchange (ETDEWEB)

The adhesion of microorganisms onto materials surface mediated by extracellular polymeric substances (EPS) lead to an important modification of the metal-solution interface. The requirement of modern civilization with the heightened sense of environmental responsibilities and quality of life can be met by using some eco-friendly microbiocides with different spectra of activity. Some N{sub 2}O{sub 2} donor Schiff base compounds were synthesized and characterized by IR, NMR and ESR spectroscopy. These compounds were found effective in controlling the growth of biofilm of E. coli, Pseudomonas fluorescens and Thiobacillus thiooxidans on copper surface. The optimum concentration of these compounds are in the range of 1--10 ppm. Various electrochemical, microbiological and surface-analytical techniques were used to monitor the biofilm in the presence of microbiocides.

International Nuclear Information System (INIS)

The talk will focus on spin-dependent competition between oblate and prolate shape minima in the potential energy landscape of "1"8"0Hf (the most neutron-rich stable isotope), mediated via the alignment of valence nucleons. Results of a prompt spectroscopic study, using deep inelastic reactions with Gammasphere and CHICO, bombarding a thin "2"3"2Th target with a "1"8"0Hf beam #approx#25% above the Coulomb barrier, will be presented. Nucleon alignments in both prolate and oblate minima will be discussed, as well as the favoring of oblate collective rotation at high spins, observed through a mixing with gamma vibrations built on the prolate shape.

British Library Electronic Table of Contents (United Kingdom)

It is uncertain if downregulation of ?-adrenoceptor signaling pathway is promoted by an enhanced adrenergic tone at an early stage of cardiac disease, or it develops secondary to detrimental local myocardial changes in advanced heart failure. We examined the integrity of ?-adrenoceptor signaling pathway upon chronic infusion of isoproterenol, a ?-adrenoceptor agonist, at a dose producing no structural left ventricular (LV) remodeling and systolic dysfunction. Subcutaneous isoproterenol infusion (400??g?kg?1?h?1 over 16?days) to guinea pigs using osmotic minipumps produced no change in cardiac weights, LV internal dimensions, myocyte cross-sectional area, extent of interstitial fibrosis, and basal contractile function. Isolated, perfused heart preparations from isoproterenol-treated guinea ...

British Library Electronic Table of Contents (United Kingdom)

Potential of spent biomass of a cyanobacterium, Nostoc linckia HA 46, from a hydrogen bioreactor was studied for biosorption of a textile dye, reactive red 198. The waste biomass was immobilized in calcium alginate and used for biosorption of the dye from aqueous solution using response surface methodology (RSM). Kinetics of the dye in aqueous solution was studied in batch mode. Interactive effects of initial dye concentration (100-500mg/L), pH (2-6) and temperature (25-45^oC) on dye removal were examined using Box-Behnken design. Maximum adsorption capacity of the immobilized biomass was 93.5mg/g at pH 2.0, initial concentration of 100mg/L and 35^oC temperature, when 94% of the dye was removed. Fourier transform infrared (FT-IR) studies revealed that biosorption was mainly mediated by fun...

British Library Electronic Table of Contents (United Kingdom)

Gold nanoparticles were synthesized by using banana peel extract (BPE) as a simple, non-toxic, eco-friendly 'green material'. The boiled, crushed, acetone precipitated, air-dried peel powder was used to reduce chloroauric acid. A variety of nanoparticles were formed when the reaction conditions were altered with respect to pH, BPE content, chloroauric acid concentration and temperature of incubation. The reaction mixtures displayed vivid colors and UV-vis spectra characteristic of gold nanoparticles. Dynamic light scattering (DLS) studies revealed that the average size of the nanoparticles under standard synthetic conditions was around 300nm. Scanning electron microscopy and energy dispersive spectrometry (EDS) confirmed these results. A coffee ring phenomenon, led to the aggregation of th...

British Library Electronic Table of Contents (United Kingdom)

Bio-inspired palladium nanoparticles were synthesized by using banana peel extract (BPE), a non-toxic eco-friendly material. Boiled, crushed, acetone precipitated, air-dried peel powder was used to reduce palladium chloride. The palladium nanoparticles were characterized by using UV-Visible spectroscopy, scanning electron microscope-energy dispersive spectra (SEM-EDS) and X-ray diffraction (XRD) analysis. Dynamic light scattering (DLS) studies revealed the average size of nanoparticles to be 50nm. Fourier transform infra red spectroscopy (FTIR) implicated the role of carboxyl, amine and hydroxyl groups in the synthetic process. This paper thus describes a novel green method for the synthesis of palladium nanoparticles.

British Library Electronic Table of Contents (United Kingdom)

Coral populations have precipitously declined on Caribbean reefs while algal abundance has increased, leading to enhanced competitive damage to corals, which likely is mediated by the potent allelochemicals produced by both macroalgae and benthic cyanobacteria. Allelochemicals may affect the composition and abundance of coral-associated microorganisms that control host responses and adaptations to environmental change, including susceptibility to bacterial diseases. Here, we demonstrate that extracts of six Caribbean macroalgae and two benthic cyanobacteria have both inhibitory and stimulatory effects on bacterial taxa cultured from the surfaces of Caribbean corals, macroalgae, and corals exposed to macroalgal extracts. The growth of 54 bacterial isolates was monitored in the presence of l...