bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of muscle acetylcholine receptor turnover by β subunit tyrosine phosphorylation
Authors: Rudell John B. , Ferns Michael J. 
Published: January 2013

ABSTRACTAt the neuromuscular junction (NMJ), the postsynaptic localization of muscle acetylcholine receptor (AChR) is regulated by neural signals and occurs via several processes including metabolic stabilization of the receptor. However, the molecular mechanisms that influence receptor stability remain poorly defined. Here, we show that neural agrin and the tyrosine phosphatase inhibitor, pervanadate slow the degradation of surface receptor in cultured muscle cells. Their action is mediated by tyrosine phosphorylation of the AChR β subunit, as agrin and pervandate had no effect on receptor half‐life in AChR‐β3F/3F muscle cells, which have targeted mutations of the β subunit cytoplasmic tyrosines. Moreover, in wild type AChR‐β3Y muscle cells, we found a linear relationship between average receptor half‐life and the percentage of AChR with phosphorylated β subunit, with half‐lives of 12.7 and 23 h for nonphosphorylated and phosphorylated receptor, respectively. Surprisingly, pervanadate increased receptor half‐life in AChR‐β3Y myotubes in the absence of clustering, and agrin failed to increase receptor half‐life in AChR‐β3F/3F myotubes even in the presence of clustering. The metabolic stabilization of the AChR was mediated specifically by phosphorylation of βY390 as mutation of this residue abolished β subunit phosphorylation but did not affect δ subunit phosphorylation. Receptor stabilization also led to higher receptor levels, as agrin increased surface AChR by 30% in AChR‐β3Y but not AChR‐β3F/3F myotubes. Together, these findings identify an unexpected role for agrin‐induced phosphorylation of βY390 in downregulating AChR turnover. This likely stabilizes AChR at developing synapses, and contributes to the extended half‐life of AChR at adult NMJs. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 399–410, 2013
Relevance of minor components stability in commercial olive oil quality during the market period
Authors: Fregapane Giuseppe , Gómez‐Rico Aurora , Inarejos Antonio M. , Salvador M. Desamparados 
Published: January 2013

AbstractThe aim of this research was to study the relevance of the stability of minor components in commercial Spanish extra virgin and olive oil (OO) categories, particularly with respect to the individual phenolic compounds, tocopherols (vitamin E) and volatile compounds, during the market period (12 months). The study was carried out classifying several commercial olive oils (n = 39) according to their content in phenolic compounds into three different groups: extra virgin olive oils with high (>290 mg/kg; HP‐VOO) and low (<210 mg/kg; LP‐VOO) phenolic level and OO, due to the impact of biophenols on oxidative stability, sensory properties and nutritional aspects. After a market period of 1 year, the α‐tocopherol content fell significantly (25–30% of its initial content) in the commercial oils. While the decrease in total phenolics and o‐diphenols was not statistically significant, a relevant increase (33% on average) in simple phenolics (hytroxytyrosol and tyrosol) was observed in all the studied samples, suggesting its use as freshness or ageing marker. Throughout the market period, a low oxidation rate and therefore a high stability of the products was observed. Moreover, the results found in the study suggest that a higher market price OO is apparently related to better quality and process control, giving a superior final product in terms of its content of minor components related to organoleptic properties.Practical applications: The quality of virgin olive oil – mainly its sensory characteristics and nutritional value – is directly related to its content in minor components, in particular phenolics and volatile compounds, and therefore to their stability during the market period. Nevertheless, this information is not available to consumers. As a consequence, it is very important for both producers and consumers to clarify and establish the real relevance of the stability of minor components in commercial olive oil categories during their shelf‐life: how long they will keep their stability, organoleptic and nutritional characteristics. This information would highlight the individual quality properties of a specific oil product, beyond the sometimes misleading commercial category.
Deposition Strategies for Osmium/Enzyme Films on Gold Electrode Based Sensing Arrays
Authors: McKenzie Jennifer R. , Zhang Chengxiao , Li Chen‐Zhong 
Published: January 2013

AbstractMulti‐analyte real‐time interrogation of cellular activity allows for the potential discovery of novel insights into disease. In this report, the addition of electrochemical biosensors to a previously developed platform utilizing Au microfabricated electrodes was explored. Glucose oxidase was immobilized at the electrode surface with an osmium redox polymer, using hand‐casting and electrodeposition techniques, allowing for the first comparison of deposition techniques at a Au microfabricated array. This preliminary work is the first step toward the goal of creating a multi‐analyte array for cellular analysis.
An aspect ratio agglomeration multigrid for unstructured grids
Authors: Li Zongzhe , Wang Zhenghua , Cao Wei , Yao Lu 
Published: January 2013

SUMMARYA robust aspect ratio‐based agglomeration algorithm to generate high quality of coarse grids for unstructured and hybrid grids is proposed in this paper. The algorithm focuses on multigrid techniques for the numerical solution of Euler and Navier–Stokes equations, which conform to cell‐centered finite volume special discretization scheme, combines vertex‐based isotropic agglomeration and cell‐based directional agglomeration to yield large increases in convergence rates. Aspect ratio is used as fusing weight to capture the degree of cell convexity and give an indication of cell stretching. Agglomeration front queue is established to propagate inward from the boundaries, which stores isotropic vertex and also high‐stretched cell marked with different flag according to aspect ratio. We conduct the present method to solve Euler and Navier–Stokes equations on unstructured and hybrid grids and compare the results with single grid as well as MGridGen, which shows that the present method is efficient in reducing computational time for large‐scale system equations. Copyright © 2013 John Wiley & Sons, Ltd.
Ingenol mebutate: a novel topical agent for actinic keratosis
Authors: Morton Colin A 
Published: January 2013

AbstractIngenol mebutate is a once‐daily topical treatment for actinic keratosis (AK) that is applied for only two or three days depending on body site. It has recently been approved by the FDA for the treatment of AK on the face, scalp, trunk and extremities and recommended for approval by the CHMP in September 2012. In this drug profile, the author reviews its mode of action, efficacy and tolerability and comments on the drug's likely place in practice. Copyright © 2013 John Wiley & Sons, Ltd.
Detailed Dynamic Modeling of a Molten Carbonate Fuel Cell Stack with Indirect Internal Reformers
Authors: Kim H. , Cho J. H. , Lee K. S. 
Published: January 2013

AbstractA detailed dynamic model of a molten carbonate fuel cell (MCFC) stack that can predict the distribution of process variables over the cell surface and along the stacking direction is presented. The model describes a repeating unit of the stack, which is composed of eight cells and one indirect internal reformer (IIR). The set of partial differential equations for the MCFC model is reduced to a set of ordinary differential equations through discretization using the cubic spline collocation method and the finite difference method. The steady‐state and dynamic behaviors of the eight‐cell stack model are compared with those of the one‐cell model, which has been commonly used in previous studies on MCFC dynamics, and three‐cell aggregate model. The distribution of the process variables along the stacking direction cannot be disregarded, and thus more detailed model should be used for the accurate reproduction of MCFC dynamics.
Proton Mobility in Sulfonated PolyEtherEtherKetone (SPEEK): Influence of Thermal Crosslinking and Annealing
Authors: Knauth P. , Pasquini L. , Maranesi B. , Pelzer K. , Polini R. , Di Vona M. L. 
Published: January 2013

AbstractSulfonated PolyEtherEtherKetone (SPEEK) was thermally treated at 180 and 140 °C to study the effects of polymer cross‐linking and annealing on the water uptake and proton conductivity. The kinetics of the cross‐linking reaction can be quantitatively described with an activation energy of (100 ± 2) kJ mol–1. The proton mobility u(H+) depends on the proton concentration c(H+) in excellent agreement with the power law u(H+) ∝ c(H+)–3 observed above the percolation threshold of hydrated nanometric channels. The proton mobility can be described by porosity and tortuosity as phenomenological parameters. Polymer annealing reduces the free volume and porosity of membranes. The proton conductivity can be modulated by changing the hydration number.
Electrocatalytic Activity and Preparation of Pt29Ru51P15/CNTs Catalyst Using the Assistance of Thioglycolic Acid Functionalization
Authors: Xie J. , Xia D.‐G. 
Published: January 2013

AbstractPt29Ru51P15 particles with a uniform size distribution of 2 nm supported on multi‐walled carbon nanotubes (CNTs) have been prepared with the assistance of thioglycolic acid functionalization using NaH2PO2 · H2O as a reducing agent. The Pt29Ru51P15/CNTs has been characterized by transmission electron microscopy (TEM), X‐ray diffraction (XRD), and X‐ray photoelectron spectroscopy (XPS). Its electrochemical properties have been examined by cyclic voltammetry (CV) and chronoamperometry (CA). The results show that Pt29Ru51P15/CNTs has a much narrower particle size distribution with no formation of aggregates, a greater electrochemically active surface area, and higher electrocatalytic activity for the electro‐oxidation of methanol
Dopamine D3 receptor activation promotes neural stem/progenitor cell proliferation through AKT and ERK1/2 pathways and expands type‐B and ‐C cells in adult subventricular zone
Authors: Lao Chu Lan , Lu Chin‐Song , Chen Jin‐Chung 
Published: January 2013

AbstractThe neurotransmitter dopamine acts on the subventricular zone (SVZ) to regulate both prenatal and postnatal neurogenesis, in particular through D3 receptor (D3R) subtype. In this study, we explored the cellular mechanism(s) underlying D3R‐mediated cell proliferation and tested if systemic delivery of a D3R agonist would induce SVZ multipotent neural stem/precursor cell (NSC/NPC) proliferation in vivo. We found that treatment with the D3R agonist, 7‐OH‐DPAT, enhances cell proliferation in a dose‐dependent manner in cultured SVZ neurospheres from wild‐type, but not D3R knock‐out mice. Furthermore, D3R activation also stimulates S‐phase and enhances mRNA and protein levels of cyclin D1 in wild‐type neurospheres, a process which requires cellular Akt and ERK1/2 signaling. Moreover, chronic treatment with low dose 7‐OH‐DAPT in vivo increases BrdU+ cell numbers in the adult SVZ, but this effect was not seen in D3R KO mice. Additionally, we probed the cell type specificity of D3R agonist‐mediated cell proliferation. We found that in adult SVZ, GFAP+ astrocytes, type‐B GFAP+/nestin+ and type‐C EGF receptor (EGFR+)/nestin+ cells express D3R mRNA, but type‐A Doublecortin (Dcx)+ neuroblasts do not. Using flow cytometry and immunofluorescence, we demonstrated that D3R activation increases GFAP+ type‐B and EGFR+ type‐C cell numbers, and the newly divided Dcx+ type‐A cells. However, BrdU+/Dcx+ cell numbers were decreased in D3R KO mice compared to wildtype, suggesting that D3R maintains constitutive NSC/NPCs population in the adult SVZ. Overall, we demonstrate that D3R activation induces NSC/NPC proliferation through Akt and ERK1/2 signaling and increases the numbers of type‐B and ‐C NSC/NPCs in the adult SVZ. © 2013 Wiley Periodicals, Inc.
Induction of atypical EAE mediated by transgenic production of IL‐6 in astrocytes in the absence of systemic IL‐6
Authors: Giralt Mercedes , Ramos Raquel , Quintana Albert , Ferrer Beatriz , Erta Maria , Castro‐Freire Marco , Comes Gemma , Sanz Elisenda , Unzeta Mercedes , Pifarré Paula , García Agustina , Campbell Iain L. , Hidalgo Juan 
Published: January 2013

AbstractInterleukin (IL)‐6 is crucial for the induction of many murine models of autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. While IL‐6‐deficient mice (IL‐6 KO) are resistant to EAE, we showed previously that in transgenic mice with astrocyte‐targeted production of IL‐6‐restricted to the cerebellum (GFAP‐IL6), EAE induced with MOG35–55 was redirected away from the spinal cord to the cerebellum. To further establish the importance of IL‐6 produced in the central nervous system, we have generated mice producing IL‐6 essentially only in the brain by crossing the GFAP‐IL6 mice with IL‐6 KO mice. Interestingly, GFAP‐IL6‐IL‐6 KO mice showed a milder but almost identical phenotype as the GFAP‐IL6 mice, which correlated with a lower load of inflammatory cells and decreased microglial reactivity. These results indicate that not only is cerebellar IL‐6 production and eventual leakage into the peripheral compartment the dominating factor controlling this type of EAE but that it can also facilitate induction of autoimmunity in the absence of normal systemic IL‐6 production. © 2013 Wiley Periodicals, Inc.
Microglial activation and expression of immune‐related genes in a rat ex vivo nervous system model after infection with Listeria monocytogenes
Authors: Remuzgo‐MartÍnez Sara , Pilares‐Ortega Lilian , Icardo Jose M. , ValdizÁn Elsa Maria , Vargas VerÓnica InÉs , Pazos Ángel , Ramos‐Vivas Jose 
Published: January 2013

AbstractA wide variety of microorganisms has previously been identified as causes of brain infection. Among them, Listeria monocytogenes has a particular tropism for the central nervous system. To gain knowledge about the immune response elicited by L. monocytogenes in the brain, we used a rat ex vivo organotypic nervous system culture as a model for Listeria infection. Scanning electron microscopy (SEM) revealed that activated microglial cells showing a typical amoeboid morphology are quickly recruited to the surface of the explants after the infection. After bacterial engulfment, these cells appear to act as Trojan horses, releasing the engulfed bacteria inside the brain tissue. We describe cycles of microglial phagocytosis, necrotic cell death and the subsequent removal of cell debris for the first time. Furthermore, we used this ex vivo model to assess the expression profiles of immune relevant genes up to 24 h postinfection by means of q‐PCR‐arrays, finding that a number of inflammation‐promoting genes are upregulated. Shortly after infection by L. monocytogenes, upregulated genes were those that encoded molecules involved in Th1 responses, being the Ccl2 chemokine and members of the interleukin1‐β family the most abundant immunomodulatory signals expressed. After 5 h of infection, L. monocytogenes caused a substantial increase in the expression of TLR1 and TLR2 genes, as well as in several downstream genes of the TLR signaling pathways. © 2013 Wiley Periodicals, Inc.
Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells
Authors: Choi Su Mi , Kim Yonghak , Shim Joong Sup , Park Joon Tae , Wang Rui-Hong , Leach Steven D. , Liu Jun O. , Deng Chuxia , Ye Zhaohui , Jang Yoon-Young 
Published: January 2013

Abstract

Patient-specific induced pluripotent stem cells (iPSCs) represent a potential source for developing novel drug and cell therapies. Although increasing numbers of disease-specific iPSCs have been generated, there has been limited progress in iPSC-based drug screening/discovery for liver diseases, and the low gene-targeting efficiency in human iPSCs warrants further improvement. Using iPSC lines from patients with alpha-1 antitrypsin (AAT) deficiency, for which there is currently no drug or gene therapy available, we established a platform to discover new drug candidates and correct disease-causing mutation with a high efficiency. A high-throughput format screening assay, based on our hepatic differentiation protocol, was implemented to facilitate automated quantification of cellular AAT accumulation using a 96-well immunofluorescence reader. To expedite the eventual application of lead compounds to patients, we conducted drug screening utilizing our established library of clinical compounds (the Johns Hopkins Drug Library) with extensive safety profiles. Through a blind large-scale drug screening, five clinical drugs were identified to reduce AAT accumulation in diverse patient iPSC-derived hepatocyte-like cells. In addition, using the recently developed transcription activator-like effector nuclease technology, we achieved high gene-targeting efficiency in AAT-deficiency patient iPSCs with 25%-33% of the clones demonstrating simultaneous targeting at both diseased alleles. The hepatocyte-like cells derived from the gene-corrected iPSCs were functional without the mutant AAT accumulation. This highly efficient and cost-effective targeting technology will broadly benefit both basic and translational applications.

Conclusions

: Our results demonstrated the feasibility of effective large-scale drug screening using an iPSC-based disease model and highly robust gene targeting in human iPSCs, both of which are critical for translating the iPSC technology into novel therapies for untreatable diseases.
Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection
Authors: Grebely Jason , Feld Jordan J. , Applegate Tanya , Matthews Gail V. , Hellard Margaret , Sherker Alana , Petoumenos Kathy , Zang Geng , Shaw Ineke , Yeung Barbara , George Jacob , Teutsch Suzy , Kaldor John M. , Cherepanov Vera , Bruneau Julie , Shoukry Naglaa H. , Lloyd Andrew R. , Dore Gregory J. 
Published: January 2013

Abstract

Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic hepatitis C virus (HCV). In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 299 individuals, 245 (181 male, 47 human immunodeficiency virus-positive [HIV+]) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ≥150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV coinfection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n = 137) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n = 77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248 ± 32 versus 142 ± 22 pg/mL,

P

= 0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22,

P

= 0.048) and 16% (27 of 165) and in those with and without plasma IP-10 levels ≥380 pg/mL. In adjusted analyses, favorable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance.

Conclusion

: High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance.
Soluble receptor for advanced glycation end products and risk of liver cancer
Authors: Moy Kristin A. , Jiao Li , Freedman Neal D. , Weinstein Stephanie J. , Sinha Rashmi , Virtamo Jarmo , Albanes Demetrius , Stolzenberg-Solomon Rachael Z. 
Published: January 2013

Abstract

Binding of advanced glycation end products (AGEs) to their receptor (RAGE) increases oxidative stress and inflammation and may be involved in liver injury and subsequent carcinogenesis. Soluble RAGE (sRAGE) may neutralize the effects mediated by the AGE/RAGE complex. Epidemiologic studies examining sRAGE or AGEs in association with liver cancer are lacking. We examined the associations between prediagnostic serum concentrations of sRAGE or Nε-(carboxymethyl)-lysine (CML)-AGE and hepatocellular carcinoma in a case-cohort study within a cohort of 29,133 Finnish male smokers who completed questionnaires and provided a fasting blood sample between 1985 and 1988. During follow-up beginning 5 years after enrollment through April 2006, 145 liver cancers occurred. Serum concentrations of sRAGE, CML-AGE, glucose, and insulin were measured in case subjects and 485 randomly sampled cohort participants. Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) were available in most cases and in a subset of the study population. Weighted Cox proportional hazards regression was used to calculate relative risks (RR) and 95% confidence intervals (CI) adjusted for age, years of smoking, and body mass index. sRAGE and CML-AGE concentrations were inversely associated with liver cancer. Further adjustment for glucose and insulin or exclusion of case subjects with chronic HBV or HCV did not change the associations.

Conclusion

: Our results support the hypothesis that sRAGE is inversely associated with liver cancer. The findings need confirmation, particularly in populations that include women and nonsmokers.
Application of L‐moments and Bayesian inference for low‐flow regionalization in Sefidroud basin, Iran
Authors: Dodangeh Esmaeel , Soltani Saeed , Sarhadi Ali , Shiau Jenq‐Tzong 
Published: January 2013

AbstractReliable estimation of low flows at ungauged catchments is one of the major challenges in water‐resources planning and management. This study aims at providing at‐site and ungauged sites low‐flow frequency analysis using regionalization approach. A two‐stage delineating homogeneous region is proposed in this study. Clustering sites with similar low‐flow L‐moment ratios is initially conducted, and L‐moment‐based discordancy and heterogeneity measures are then used to detect unusual sites. Based on the goodness‐of‐fit test statistic, the best‐fit regional model is identified in each hydrologically homogeneous region. The relationship between mean annual 7‐day minimum flow and hydro‐geomorphic characteristics is also constructed in each homogeneous region associated with the derived regional model for estimating various low‐flow quantiles at ungauged sites. Uncertainty analysis of model parameters and low‐flow estimations is carried out using the Bayesian inference. Applied in Sefidroud basin located in northwestern Iran, two hydrologically homogeneous regions are identified, i.e. the east and west regions. The best‐fit regional model for the east and west regions are generalized logistic and Pearson type III distributions, respectively. The results show that the proposed approach provides reasonably good accuracy for at‐site as well as ungauged‐site frequency analysis. Besides, interval estimations for model parameters and low flows provide uncertainty information, and the results indicate that Bayesian confidence intervals are significantly reduced when comparing with the outcomes of conventionalt‐distribution method. Copyright © 2013 John Wiley & Sons, Ltd.