bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of 4‐Benzylamino‐Substituted α‐Carbolines as a Novel Class of Receptor Tyrosine Kinase Inhibitors
Authors: Krug Martin , Wichapong Kanin , Erlenkamp German , Sippl Wolfgang , Schächtele Christoph , Totzke Frank , Hilgeroth Andreas
Published: December 2010

Within the last decade, interest in the development of new anticancer drugs increased mainly from emerging resistance against established drugs, which were found to be limited by the multidrug resistance (MDR) phenomenon. Several anticancer targets have been investigated for the development of structurally new drugs which were thought to be unaffected by the MDR phenomenon. Receptor tyrosine kinases (RTKs) make up one interesting group of anticancer targets. The overexpression and mutation of RTKs lead to an ongoing stimulus of cell growth and cancer progression. Early approaches to selective inhibition of single RTKs were generally disappointing in clinical studies, due in part to occurring resistance. Therefore, a new strategy involves the identification of multi‐kinase inhibitors to slow the development of potential resistance. Moreover, the expected side effects of the first nonselective inhibitors were less dramatic than had been expected. We have discovered novel 4‐benzylamino‐α‐carbolines as a new class of RTK inhibitors. Docking studies suggest a binding mode to the addressed target structures of the epidermal growth factor receptor (EGFR) and to the vascular endothelial growth factor receptor 2 (VEGFR2). Selectivity profiling against a panel of kinases and antiproliferative studies have highlighted one inhibitor, active in the nanomolar range, as a highly interesting candidate for further clinical studies.
Magnetic resonance imaging of printed text
Authors: Hornak Joseph P.
Published: December 2010

Many electrophotographic print engines use toner with ferromagnetic particles that become fused with the paper. When text printed with this toner is placed in a uniform magnetic field, the text distorts the field. Placing this text adjacent to a material with a spatially uniform magnetic resonance signal causes a distortion in the signal, thus making the text visible in a magnetic resonance image of the material. An example of this process is presented using electrophotographically printed text and an aqueous solution. Applications might include analysis of paintings. © 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part A 36A: 347–348, 2010.
Systems biology of symmetry breaking during neuronal polarity formation
Authors: Inagaki Naoyuki , Toriyama Michinori , Sakumura Yuichi
Published: December 2010

Polarization, in which a single axon and multiple dendrites are formed, is crucial for neuronal functions, and symmetry breaking is the initial step of this process. Accumulating studies have revealed a number of molecules that act asymmetrically in neurons, and thereby regulate neuronal polarity. Thus, one of the major goals of current research is to understand how asymmetric signals are generated during the symmetry‐breaking step. Current models of neuronal symmetry breaking generally involve “local activation” for induction of axon outgrowth and “global inhibition” to suppress formation of multiple axons and can be categorized into “one‐takes‐all” and “activator–inhibitor” models. Both types of model incorporate a positive feedback loop to execute local activation, but differ in the manner of global inhibition. Quantitative experimentation combined with computational modeling is a powerful strategy in systems biology, and analyses in this direction have begun to yield a more profound understanding of how neurons break their symmetry during polarity formation. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 584–593, 2011
The vertebrate retina: A model for neuronal polarization in vivo
Authors: Randlett Owen , Norden Caren , Harris William A.
Published: December 2010

The vertebrate retina develops rapidly from a proliferative neuroepithelium into a highly ordered laminated structure, with five distinct neuronal cell types. Like all neurons, these cells need to polarize in appropriate orientations order integrate their neuritic connections efficiently into functional networks. Its relative simplicity, amenability to in vivo imaging and experimental manipulation, as well as the opportunity to study varied cell types within a single tissue, make the retina a powerful model to uncover how neurons polarize in vivo. Here we review the progress that has been made thus far in understanding how the different retinal neurons transform from neuroepithelial cells into mature neurons, and how the orientation of polarization may be specified by a combination of pre‐established intrinsic cellular polarity set up within neuroepithelial cells, and extrinsic cues acting upon these differentiating neurons. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 567–583, 2011
Neuronal polarity in C. elegans
Authors: Ou Chan‐Yen , Shen Kang
Published: December 2010

Neuronal polarity sets the foundation for information processing and signal transmission within neural networks. However, fundamental question of how a neuron develops and maintains structurally and functionally distinct processes, axons and dendrites, is still an unclear. The simplicity and availability of practical genetic tools makes C. elegans as an ideal model to study neuronal polarity in vivo. In recent years, new studies have identified critical polarity molecules that function at different stages of neuronal polarization in C. elegans. This review focuses on how neurons guided by extrinsic cues, break symmetry, and subsequently recruit intracellular molecules to establish and maintain axon‐dendrite polarity in vivo. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 554–566, 2011
Compartmentalization within neurites: Its mechanisms and implications
Authors: Katsuki Takeo , Joshi Rajshri , Ailani Deepak , Hiromi Yasushi
Published: December 2010

Neurons are morphologically characterized by long processes extending from a cell body. These processes, the dendrites and axon, are major sub‐cellular compartments defined by morphological, molecular, and functional differences. However, evidence from vertebrates and invertebrates suggests that, based on molecular distribution, individual axons and dendrites are further divided into distinct compartments; many membrane molecules involved in axon guidance and synapse formation are localized to specific segments of axons or dendrites that share a boundary of localization. In this review, we describe recent progress in understanding the mechanisms of intra‐neurite patterning, and discuss its potential roles in the development and function of the nervous system. Each protein employs different ways to achieve compartment‐specific localization; some membrane molecules localize via cell‐autonomous ability of neurons, while others require extrinsic signals for localization. The underlying regulatory mechanisms include transcriptional regulation, local translation, diffusion barrier, endocytosis, and selective membrane targeting. We propose that intra‐neurite compartmentalization could provide platforms for structural and functional diversification of individual neurons. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71:458–473, 2011
Regulated expression of transgenes in embryonic stem cell‐derived neural cells
Authors: Lorberbaum David S. , Gottlieb David
Published: December 2010

Discovery and characterization of gene promoters, enhancers and repressor binding elements is an important research area in neuroscience. Here, the suitability of embryonic stem cells and their neural derivatives as a model system for this research is investigated. Three neural transgenic constructs (from the Mnx1, Fabp7, and tuba1a genes) that have been validated in transgenic mice were inserted into embryonic stem cells as stable transgenes. These transgenic embryonic stem cells were differentiated into neural cultures and the pattern of transgene expression across a series of inducing conditions determined. The pattern of expression matched that predicted from transgenic mouse experiments for each of the three transgenes. The results show that embryonic stem cells and their neural derivatives comprise a promising model for investigating the mechanisms that control cell‐ and temporal‐specific neural gene transcription. genesis 49:66–74, 2011. © 2010 Wiley‐Liss, Inc.
Reconstructing embryonic development
Authors: Khairy Khaled , Keller Philipp J.
Published: December 2010

Novel approaches to bio‐imaging and automated computational image processing allow the design of truly quantitative studies in developmental biology. Cell behavior, cell fate decisions, cell interactions during tissue morphogenesis, and gene expression dynamics can be analyzed in vivo for entire complex organisms and throughout embryonic development. We review state‐of‐the‐art technology for live imaging, focusing on fluorescence light microscopy techniques for system‐level investigations of animal development, and discuss computational approaches to image segmentation, cell tracking, automated data annotation, and biophysical modeling. We argue that the substantial increase in data complexity and size requires sophisticated new strategies to data analysis to exploit the enormous potential of these new resources. genesis 49:488–513, 2011. © 2010 Wiley‐Liss, Inc.
Reactivity of Quinones with Phosphagermaallene Tip(tBu)Ge=C=PMes* Leading to Four‐ and Six‐Membered Heterocycles with an Exocyclic P=C Double Bond
Authors: Ghereg Dumitru , Gornitzka Heinz , Escudié Jean
Published: December 2010

Phosphagermaallene Tip(tBu)Ge=C=PMes* (1) (Tip = 2,4,6‐triisopropylphenyl, Mes* = 2,4,6‐tri‐tert‐butylphenyl) reacts with one equivalent of p‐quinone (1,4‐benzoquinone, 2,3,5,6‐tetramethyl‐1,4‐benzoquinone, 1,4‐naphthoquinone, and 9,10‐anthraquinone) to form spiro 1‐oxa‐2‐germacyclobutane compounds 2–5 with an exocyclic P=C double bond by [2 + 2] cycloaddition between the Ge=C and one of the C=O double bonds. With two equivalents of 1 a double [2 + 2] cycloaddition occurs involving both unsaturated C=O bonds of 1,4‐benzoquinone to give the dispiro compound 6. [2 + 4] Cycloadditions are observed between the Ge=C double bond of 1 and the O=C–C=O unit of an α‐diketone (benzil) and an o‐quinone (9,10‐phenanthrenequinone) to give the corresponding 1,4‐dioxa‐2‐germa‐5‐cyclohexenes 7 and 8.
In Situ Synthesis of Chlorinated Fullerenes by the High‐Frequency Furnace Method
Authors: Mueller Andreas , Ziegler Karolin , Amsharov Konstantin Yu. , Jansen Martin
Published: December 2010

Exohedrally chlorinated fullerenes have been synthesized by in situ chlorination using the high‐frequency furnace method in the presence of carbon tetrachloride as reagent. In addition to the previously reported chlorinated non‐IPR (isolated pentagon rule) fullerene cages of C2nCl2m (n = 25, 27, 28, 30, 32 and 33, m = 2–6), a C68 and various new higher fullerenes including C2nCl2m with n = 36, 37 and 39 were present in the soot extracts in significant quantities, as shown by HPLC/off‐line mass spectrometric analyses. A more detailed analysis showed the presence of several species with the same carbon content that could arise from either the formation of different isomers or different degrees of chlorination.
Land‐use change emissions: How green are the bioplastics?
Authors: Piemonte Vincenzo , Gironi Fausto
Published: December 2010

Recently, a discussion has emerged around greenhouse gas emissions due to direct and indirect land use change (LUC) of expanding agricultural areas dedicated to bio‐products production. Converting rainforests, peatlands, savannas, or grasslands to produce food crop‐based bio‐products creates a “carbon debt” by releasing 9 to 170 times more CO2 than the annual greenhouse gas (GHG) reductions that these bio‐products (such as the bioplastics) would provide by displacing petroleum‐based products (conventional plastics).

 In this work, we demonstrate the importance of accounting for the LUC emissions in the LCA studies devoted to the analysis of the environmental impact of bio‐based products and in particular of the bioplastics. To this end, an original case study has been carried out on the comparison between the LCAs of shoppers made from Mater‐Bi (corn‐based bioplastic) and polyethylene, including the LUC emissions. The obtained results highlight the strong influence of the LUC emissions on the GHGs saving achievable by displacing petroleum‐based plastics with bioplastics and point out the importance of using waste biomass or biomass grown on degraded and abandoned agricultural lands to produce bioplastics that, in this manner, can offer immediate and sustained GHG advantages. © 2010 American Institute of Chemical Engineers Environ Prog, 2010
Can sediment total organic carbon and grain size be used to diagnose organic enrichment in estuaries?
Authors: Pelletier Marguerite C , Campbell Daniel E , Ho Kay T , Burgess Robert M , Audette Charles T , Detenbeck Naomi E
Published: December 2010

Eutrophication (i.e., nutrient enrichment, organic enrichment, and oxygen depletion) is one of the most common sources of impairment in Clean Water Act 303(d)-listed waters in the United States. Although eutrophication can eventually cause adverse effects to the benthos, it may be difficult to diagnose. Sediment organic carbon (OC) content has been used as an indicator of enrichment in sediments, but the amount of surface area available for carbon adsorption must be considered. We investigated the utility of the relationship between OC and sediment grain size as an indicator of eutrophication. Data from the U.S. Environmental Protection Agency's Environmental Monitoring and Assessment Program was used to test this relationship. However, anthropogenic contaminants are also capable of causing adverse effects to the benthos and often co-occur with elevated levels of OC. Contaminant analysis and toxicity tests were not consistently related to enrichment status as defined by relationship between total OC and grain size. Although variability in response occurred, reflecting the variance in the water column factors (dissolved oxygen, chlorophyll a, and nutrients) and limited sample sizes, the data supported the hypothesis that sites designated as enriched were eutrophied. Dissolved oxygen levels were reduced at enriched sites, whereas chlorophyll a and nutrients were higher at enriched sites. This suggests that the relationship of OC to grain size can be used as a screening tool to diagnose eutrophication. Environ. Toxicol. Chem. 2011; 30:538–547. © 2010 SETAC
Sublethal genotoxicity and cell alterations by organophosphorus pesticides in MCF-7 cells: Implications for environmentally relevant concentrations
Authors: Ukpebor Justina , Llabjani Valon , Martin Francis L , Halsall Crispin J
Published: December 2010

Organophosphorus pesticide (OPP) toxicity is believed to be mediated through inhibition of acetylcholinesterase (AChE). Given their widespread distribution in aquatic systems and their ability to undergo chemical transformation, their environmental impacts at sublethal concentrations in nontarget organisms have become an important question. We conducted a number of mammalian-cell genotoxic and gene expression assays and examined cellular biochemical changes that followed low-dose exposure of MCF-7 cells to fenitrothion, diazinon, and the aqueous degradate of diazinon, 2-isopropyl-6-methyl-4-pyrimidinol (IMP). After exposure to the OPPs at low concentrations (10−12 M to 10−8 M), greater than twofold elevations in micronucleus formation were noted in MCF-7 cell cultures that went on to exhibit greater than 75% clonogenic survival; these levels of chromosomal damage were comparable to those induced by 10−6 M benzo[a]pyrene, a known genotoxic agent. At this low concentration range, a fenitrothion-induced twofold elevation in B-cell leukemia/lymphoma-2 (BCL-2) and cytochrome P450 isoenzyme (CYP1A1) gene expressions was observed. Principal component analysis-linear discriminant analysis (PCA-LDA) of derived infrared (IR) spectra of vehicle control (nonexposed) and OPP-exposed cells highlighted that both fenitrothion and diazinon induced marked biochemical alterations in the lipid, protein, and DNA/RNA absorbance regions. Our findings demonstrate that the two OPP parent chemicals and IMP degradate can mediate a number of toxic effects or cellular alterations at very low concentrations. These are independent of just selective inhibition of AChE, with potential consequences for nontarget organisms exposed at environmentally relevant concentrations. Further assays on relevant aquatic organism cell lines are now recommended to understand the mechanistic low-dose toxicity of these chemicals present in aquatic systems. Environ. Toxicol. Chem. 2011; 30:632–639. © 2011 SETAC
A mixture toxicity approach for environmental risk assessment of multiple insect resistance genes
Authors: Wolt Jeffrey D
Published: December 2010

Multiple substance considerations applied to chemical mixtures in ecological risk assessments can be logically extended to nontarget organism (NTO) risk assessment for pyramided trait crops expressing multiple insect resistance genes. A case instance is developed that considers a two-protein pyramid of Cry1F and Cry1Ac synthetic proteins expressed in cotton (Gossypium hirsutum L.). A mixture toxicity approach was used to arrive at the aggregated multisubstance potentially affected fraction (msPAF) of NTOs that may be at risk from exposure to Cry1F + Cry1Ac cotton in representative-use environments. Development of the msPAF for putative susceptible NTOs considered laboratory toxicity data for Lepidoptera expressed in terms of additive mixture toxicity as well as data on in planta expression of the Cry1F and Cry1Ac proteins and their translation into environmental loads and exposure concentrations. The msPAF based on tier 1 estimated environmental concentrations (EECs) and toxicity to Lepidoptera species—used as surrogate data for adverse effects to a putative susceptible species—provided a highly conservative estimate of effects on beneficial species and therefore is a ready means to conduct screening-level NTO risk assessments for pyramided crops. Environ. Toxicol. Chem. 2011; 30:763–772. © 2011 SETAC
AC pollution flashover circuit model for composite insulator based on multiple arcs series
Authors: Shu Lichun , Yuan Qianfei , Zhang Zhijing , Jiang Xingliang , Hu Qin , Sun Caixin
Published: December 2010

With the increasing application of composite insulator in the power system, pollution flashover often occurs. However, no model can exactly predict pollution flashover voltage of composite insulator at present. Based on high‐speed photography of AC pollution flashover process, a model, which is in view of pollution severity, air pressure, shed configuration, and hydrophobicity level and which is suitable for composite insulator with any shed configuration, is proposed. Influences of pollution severity and hydrophobicity on flashover voltage and pressure characteristic exponent are analyzed, from which derives a calculative formula of flashover voltage. Calculated results from the model, validated by experiments, demonstrate that there is a power function relationship between flashover voltage and hydrophobicity levelβ, and characteristic exponent of hydrophobicity levelβis the same as that of pollution severity. Meanwhile, the exponent characterizing the influence of air pressure increases with the fall of pollution severity and the rise of hydrophobicity. Copyright © 2010 John Wiley & Sons, Ltd.
Reliability analysis of voltage instability risk indicator based on a novel real‐time identification algorithm
Authors: Corsi Sandro , Taranto Glauco N.
Published: December 2010

This paper focuses the performance and robustness of an algorithm recently proposed in the literature for real‐time voltage instability risk indication. Based on local phasor measurements, the real‐time identification of the proximity of the equivalent Thevenin impedance seen from an EHV bus and its load impedance is the key to recognize the voltage instability risk at the time it is approaching. The paper highlights the impact of the dynamics of on‐load tap changing transformers and generators over‐excitation limiters on the Thevenin equivalent identification (and consequently on the timely voltage instability indication). The paper also shows the high reliability of the algorithm with respect to load characteristics and to critical load profiles corresponding to very large perturbations. The paper presents simulation results obtained from a detailed dynamic model of an equivalent single‐generator system, as well as from the actual Italian EHV network. Copyright © 2010 John Wiley & Sons, Ltd.
Depression in Alzheimer's disease: specificity of depressive symptoms using three different clinical criteria
Authors: Engedal Knut , Barca Maria Lage , Laks Jerson , Selbaek Geir
Published: December 2010

Background

Previous studies report contradictory results on whether the symptoms of depression in Alzheimer's disease patients are the same as in cognitively normal persons. Thus, provisional criteria for depression in Alzheimer's disease (PDC‐dAD) have been developed.

Aim

To examine which symptoms in AD patients are significant in diagnosing depression according to PDC‐dAD compared to those for the DSM‐IV‐TR and ICD‐10 criteria.

Methods

We included 112 patients with Alzheimer's disease. They were interviewed by a psychiatrist who diagnosed depression according to PDC‐dAD, DSM‐IV‐TR and ICD‐10. Without knowledge of that diagnosis, trained nurses interviewed the caregivers of the patients using the Cornell scale for depression in dementia (CSDD).

Results

Mean age of the patients was 83.0 (s.d. 7.9), 77 (69.6%) were female. The proportion with depression according to each set of criteria was: PDC‐dAD 53.5%, ICD‐10, 47.3% and DSM‐IV‐TR, 34.8%. Sadness, loss of interest and agitation/retardation were the most prevalent symptoms in depressed subjects as evaluated by the psychiatrists. According to CSDD sadness, anxiety, suicidal thoughts, poor self‐esteem, multiple physical complaints and pessimism best distinguished the depressed patients from the non‐depressed. In multiple logistic regression analyses poor self‐esteem, delusion and multiple physical complaints best predicted depression using PDC‐dAD criteria, whereas sadness, suicidal thoughts and poor self‐esteem best predicted depression using ICD‐10 and DSM‐IV‐TR.

Conclusion

The most significant symptoms for a depressive disorder in AD are pretty much the same as for patients without dementia using the DSM‐IV‐TR and ICD‐10 criteria, whereas they differ using the PDC‐dAD criteria. Copyright © 2010 John Wiley & Sons, Ltd.
Enrichment of Nur77 Mediated by Retinoic Acid Receptor β Leads to Apoptosis of Human Hepatocellular Carcinoma Cells Induced by Fenretinide and Histone Deacetylase Inhibitors §Δ
Authors: Yang Hui , Zhan Qi , Wan Yu-Jui Yvonne
Published: December 2010

The synthetic retinoid fenretinide is one of the most promising clinically tested retinoids. Previously, we have shown that fenretinide induces apoptosis of Huh7 cells, but HepG2 cells are relatively resistant to fenretinide-induced apoptosis. This study examines the interactive role of fenretinide and histone deacetylase inhibitors (HDACi) in inducing apoptosis of human hepatocellular carcinoma (HCC) cells and the underlying mechanism. Trichostatin A and scriptaid can either enhance fenretinide-induced apoptosis in the fenretinide sensitive HCC cells (Huh7 and Hep3B) or sensitize the fenretinide resistant cells (HepG2) to become sensitive to the apoptotic effect of fenretinide in a cancer cell–specific manner. The sensitivity of cells to fenretinide-induced apoptosis was not associated with reactive oxygen species production nor with antioxidant gene expression. However, the level of retinoic acid receptor β (RARβ) and Nur77 (NR4A1) was important for inducing apoptosis. Upon fenretinide and HDACi treatment, the expression of RARβ and Nur77 were induced and colocalized in the cytosol. The induction of Nur77 protein level, but not the messenger RNA level, was RARβ-dependent. In addition, RARβ interacted with Nur77. Nur77 was essential for fenretinide-induced and HDACi-induced apoptosis of Huh7 cells. Induction of the expression, the interaction, and the nuclear export of RARβ and Nur77 mediate fenretinide-induced and HDACi-induced apoptosis.

Conclusion:

Our findings suggest that targeting Nur77 and RARβ simultaneously provides an effective way to induce HCC cell death. (Hepatology 2011)
Bile Proteomic Profiles Differentiate Cholangiocarcinoma From Primary Sclerosing Cholangitis and Choledocholithiasis §Δ
Authors: Lankisch Tim O. , Metzger Jochen , Negm Ahmed A. , Voβkuhl Katja , Schiffer Eric , Siwy Justyna , Weismüller Tobias J. , Schneider Andrea S. , Thedieck Kathrin , Baumeister Ralf , Zürbig Petra , Weissinger Eva M. , Manns Michael P. , Mischak Harald , Wedemeyer Jochen
Published: December 2010

Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes CC from nonmalignant lesions. We used capillary electrophoresis mass spectrometry (CE-MS) to identify disease-specific peptide patterns in patients with choledocholithiasis (n = 16), PSC (n = 18), and CC (n = 16) in a training set. A model for differentiation of choledocholithiasis from PSC and CC (PSC/CC model) and another model distinguishing CC from PSC (CC model) were subsequently validated in independent cohorts (choledocholithiasis [n = 14], PSC [n = 18] and CC [n = 25]). Peptides were characterized by sequencing. Application of the PSC/CC model in the independent test cohort resulted in correct exclusion of 12/14 bile samples from patients with choledocholithiasis and identification of 40/43 patients with PSC or CC (86% specificity, 93% sensitivity). The corresponding receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.82-0.98,

P

= 0.0001). The CC model succeeded in an accurate detection of 14/18 bile samples from patients with PSC and 21/25 samples with CC (78% specificity, 84% sensitivity) in the independent cohort, resulting in an AUC value of 0.87 (95% CI: 0.73-0.95,

P

= 0.0001) in ROC analysis. Eight out of 10 samples of patients with CC complicating PSC were identified.

Conclusion:

Bile proteomic analysis discriminates benign conditions from CC accurately. This method may become a diagnostic tool in future as it offers a new possibility to diagnose malignant bile duct disease and thus enables efficient therapy particularly in patients with PSC. (Hepatology 2010;)
Concerted Action of Sulfiredoxin and Peroxiredoxin I Protects Against Alcohol-Induced Oxidative Injury in Mouse Liver σ
Authors: Bae Soo Han , Sung Su Haeng , Cho Eun Jung , Lee Se Kyoung , Lee Hye Eun , Woo Hyun Ae , Yu Dae-Yeul , Kil In Sup , Rhee Sue Goo
Published: December 2010

Peroxiredoxins (Prxs) are peroxidases that catalyze the reduction of reactive oxygen species (ROS). The active site cysteine residue of members of the 2-Cys Prx subgroup (Prx I to IV) of Prxs is hyperoxidized to cysteine sulfinic acid (Cys-SO2) during catalysis with concomitant loss of peroxidase activity. Reactivation of the hyperoxidized Prx is catalyzed by sulfiredoxin (Srx). Ethanol consumption induces the accumulation of cytochrome P450 2E1 (CYP2E1), a major contributor to ethanol-induced ROS production in the liver. We now show that chronic ethanol feeding markedly increased the expression of Srx in the liver of mice in a largely Nrf2-dependent manner. Among Prx I to IV, only Prx I was found to be hyperoxidized in the liver of ethanol-fed wildtype mice, and the level of Prx I-SO2 increased to ≈30% to 50% of total Prx I in the liver of ethanol-fed Srx−/− mice. This result suggests that Prx I is the most active 2-Cys Prx in elimination of ROS from the liver of ethanol-fed mice and that, despite the up-regulation of Srx expression by ethanol, the capacity of Srx is not sufficient to counteract the hyperoxidation of Prx I that occurs during ROS reduction. A protease protection assay revealed that a large fraction of Prx I is located together with CYP2E1 at the cytosolic side of the endoplasmic reticulum membrane. The selective role of Prx I in ROS removal is thus likely attributable to the proximity of Prx I and CYP2E1.

Conclusion:

The pivotal functions of Srx and Prx I in protection of the liver in ethanol-fed mice was evident from the severe oxidative damage observed in mice lacking either Srx or Prx I. (Hepatology 2011)
GC‐binding factor 2 interacts with dishevelled and regulates Wnt signaling pathways in human carcinoma cell lines
Authors: Ohtsuka Hideo , Oikawa Masaya , Ariake Kyohei , Rikiyama Toshiki , Motoi Fuyuhiko , Katayose Yu , Unno Michiaki , Johnson Alfred C.
Published: December 2010

GC‐binding factor 2 (GCF2), a transcriptional repressor that decreases the activity of several genes is capable of binding directly to the GC‐rich sequence of the EGFR promoter and repressing the transcriptional activity of EGFR. In addition to its function as a transcriptional repressor, GCF2 can directly interact with other proteins such as flightless‐1 (Fli‐1). Many previous findings pertaining to the function of Fli‐1 have suggested a role for fli‐1 in providing a direct link between molecules involved in signal transduction pathways and the actin cytoskeleton. We hypothesized that GCF2, together with Fli‐1, plays a role in regulating cytoskeleton function, cell migration, and/or morphology. In our study, we observed that GCF2 is crucial for the activation of RhoA, a small GTPase that plays a key role in the regulation of the actin cytoskeleton. RhoA was markedly inactivated as a result of the decreased expression of GCF2. Co‐immunoprecipitations were subsequently performed to further investigate the mechanism for the repressive function. We identified dishevelled (Dvl), which is the key mediator for the Wnt pathway, as a binding partner with GCF2. These results strongly suggest that GCF2 plays a role in the Wnt‐noncanonical planar cell polarity (PCP) signaling pathway. Consequently, GCF2 may regulate the cytoskeleton or migration via Dvls and RhoA.
Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases
Authors: Tian Liyuan , Wang Yu , Xu Dabin , Gui Junhao , Jia Xingwang , Tong Hongli , Wen Xinyu , Dong Zhennan , Tian Yaping
Published: December 2010

We have investigated the changing rule of serum form of GP73 (sGP73) in different hepato‐pathologic processes and identified the sGP73 role in inflammation, fibrosis and carcinogenesis since sGP73 has been regarded as a candidate tumor marker. Quantitative enzyme‐linked immunosorbent assay detected sGP73 in 535 subjects with hepatocellular carcinoma (HCC), liver cirrhosis (LC), hepatitis, focal nodular hyperplasia (FNH), angioma, intra‐hepatic cholangio‐carcinoma (ICC) and metastatic cancer from adenocarcinomas (MC). Median sGP73 in LC was higher than in HCC and hepatitis (p = 0.001), and sGP73 in all three groups were higher than those in healthy individuals (p < 0.001); sGP73 in LC patients with Child‐Pugh class A was lower than in class B and C (p = 0.001), no significant difference was found between early and advanced HCC groups (110.4 μg/L vs. 102.8 μg/L). AFP/GP73 had a sensitivity of 75.8% and specificity of 79.7% with an area under the receiver operating curve (AUROC) of 0.844 vs. 0.812 for AFP (p = 0.055) with a sensitivity of 95.2% and specificity of 47.1%; in detecting early HCC, AUROC of AFP/GP73 was 0. 804 vs. 0.766 for AFP (p = 0.086). sGP73 correlated with AST, AST/ALT, ALB, A/G and ALP in LC. The positive rate of sGP73 in angioma, FNH, ICC, and MC was 0, 50, 63.3, 53.3%, respectively; AFP/GP73 was 0.796 with the sensitivity of 81.4% and specificity of 70.0% when differentiating MC from AFP‐negative HCC. Increased sGP73 is related to hepatic impairment and chronic fibrosis, and when combined with AFP could improve the differential diagnosis of hepatic diseases.
PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
Authors: Rhee Yumie , Allen Matthew R , Condon Keith , Lezcano Virginia , Ronda Ana C , Galli Carlo , Olivos Naomi , Passeri Giovanni , O'Brien Charles A , Bivi Nicoletta , Plotkin Lilian I , Bellido Teresita
Published: December 2010

The periosteal and endocortical surfaces of cortical bone dictate the geometry and overall mechanical properties of bone. Yet the cellular and molecular mechanisms that regulate activity on these surfaces are far from being understood. Parathyroid hormone (PTH) has profound effects in cortical bone, stimulating periosteal expansion and at the same time accelerating intracortical bone remodeling. We report herein that transgenic mice expressing a constitutive active PTH receptor in osteocytes (DMP1-caPTHR1 mice) exhibit increased cortical bone area and an elevated rate of periosteal and endocortical bone formation. In addition, DMP1-caPTHR1 mice display a marked increase in intracortical remodeling and cortical porosity. Crossing DMP1-caPTHR1 mice with mice lacking the Wnt coreceptor, LDL-related receptor 5 (LRP5), or with mice overexpressing the Wnt antagonist Sost in osteocytes (DMP1-Sost mice) reduced or abolished, respectively, the increased cortical bone area, periosteal bone formation rate, and expression of osteoblast markers and Wnt target genes exhibited by the DMP1-caPTHR1 mice. In addition, DMP1-caPTHR1 lacking LRP5 or double transgenic DMP1-caPTHR1;DMP1-Sost mice exhibit exacerbated intracortical remodeling and increased osteoclast numbers, and markedly decreased expression of the RANK decoy receptor osteoprotegerin. Thus, whereas Sost downregulation and the consequent Wnt activation is required for the stimulatory effect of PTH receptor signaling on periosteal bone formation, the Wnt-independent increase in osteoclastogenesis induced by PTH receptor activation in osteocytes overrides the effect on Sost. These findings demonstrate that PTH receptor signaling influences cortical bone through actions on osteocytes and defines the role of Wnt signaling in PTH receptor action. © 2011 American Society for Bone and Mineral Research.
An atypical subtrochanteric femoral fracture from pycnodysostosis: A lesson from nature
Authors: Yates Christopher J , Bartlett Miriam J , Ebeling Peter R
Published: December 2010

This case describes a man with an unusual cause of an atypical subtrochanteric fracture, pycnodysostosis. This condition results from mutations involving the cathepsin K gene. New antiresorptive treatments for osteoporosis inhibit the cathepsin K enzyme in osteoclasts. Therefore, there should be vigilant monitoring for the development of long-term complications noted to occur in diseases of reduced osteoclast function, including pycnodysostosis, in patients receiving these novel antiresorptive agents. © 2011 American Society for Bone and Mineral Research.
Ganoderma atrum polysaccharide induces anti‐tumor activity via the mitochondrial apoptotic pathway related to activation of host immune response
Authors: Li Wen‐Juan , Chen Yi , Nie Shao‐Ping , Xie Ming‐Yong , He Ming , Zhang Shen‐Shen , Zhu Ke‐Xue
Published: December 2010

Ganoderma atrum polysaccharide (PSG‐1), the major active ingredient isolated from Ganoderma atrum, has been suggested as a candidate for cancer therapy. The aim of this study was to investigate the anti‐tumor effect of PSG‐1 using sarcoma 180 (S‐180) transplanted mice and further to examine the molecular mechanisms of PSG‐1‐induced anti‐tumor effect. Results showed that PSG‐1 significantly inhibited tumor growth in S‐180‐bearing mice. PSG‐1‐induced tumor apoptosis was associated with the alteration of Bcl‐2 family proteins, increase of reactive oxygen species generation, loss of mitochondrial membrane potential (Δψm), release of cytochrome c from the mitochondria into cytosol, and activation of caspase‐3 and ‐9. Elevation of immune function was also shown during PSG‐1‐induced tumor apoptosis, as evidenced by increase of spleen and thymus indexes, lymphocyte proliferation, concentrations of tumor necrosis factor (TNF)‐α, and interleukin‐2 in serum. Furthermore, the combined treatment of PSG‐1 and cyclophosphamide (CTX) results in an enhancement of the anti‐tumor effect of CTX alone via increased host immune response. These results suggested that PSG‐1 had a potent anti‐tumor activity by induction of tumor apoptosis through mitochondrial pathways, and immunoenhancement effect of PSG‐1 was related to its anti‐tumor effect. In addition, PSG‐1 enhanced CTX‐induced anti‐tumor activity in S‐180‐bearing mice. J. Cell. Biochem. 112: 860–871, 2011. © 2010 Wiley‐Liss, Inc.
Polyamines, androgens, and skeletal muscle hypertrophy
Authors: Lee Nicole K. L. , MacLean Helen E.
Published: December 2010

The naturally occurring polyamines, spermidine, spermine, and their precursor putrescine, play indispensible roles in both prokaryotic and eukaryotic cells, from basic DNA synthesis to regulation of cell proliferation and differentiation. The rate‐limiting polyamine biosynthetic enzymes, ornithine decarboxylase (ODC) and S‐adenosylmethionine decarboxylase, are essential for mammalian development, with knockout of the genes encoding these enzymes, Odc1 and Amd1, causing early embryonic lethality in mice. In muscle, the involvement of polyamines in muscle hypertrophy is suggested by the concomitant increase in cardiac and skeletal muscle mass and polyamine levels in response to anabolic agents including β‐agonists. In addition to β‐agonists, androgens, which increase skeletal mass and strength, have also been shown to stimulate polyamine accumulation in a number of tissues. In muscle, androgens act via the androgen receptor to regulate expression of polyamine biosynthetic enzyme genes, including Odc1 and Amd1, which may be one mechanism via which androgens promote muscle growth. This review outlines the role of polyamines in proliferation and hypertrophy, and explores their possible actions in mediating the anabolic actions of androgens in muscle. J. Cell. Physiol. 226: 1453–1460, 2011. © 2010 Wiley‐Liss, Inc.
Polymethylmethacrylate and titanium alloy particles activate peripheral monocytes during periprosthetic inflammation and osteolysis
Authors: Yang Shang‐You , Zhang Kai , Bai Ling , Song Zheng , Yu Haiying , McQueen David A. , Wooley Paul H.
Published: December 2010

We investigated the interactions of particulate PMMA or titanium alloy, patient blood monocytes, and periprosthetic tissues using a SCID‐hu model of aseptic loosening. Periprosthetic tissues and bone chips obtained at revision surgery for loosening were transplanted into muscles of SCID mice. Peripheral blood monocytes (PBMCs) isolated from the same donors were fluorescently labeled and co‐cultured with PMMA or Ti‐6Al‐4V particles before intraperitoneal injection. Control mice with periprosthetic tissue or non‐inflammatory ligament xenografts received naive PBMCs transfusion. Mice were euthanized 2 weeks after PBMC transfusion. The human tissues were well accepted in SCID mice. Transfused fluorescent‐labeled PBMCs were markedly accumulated in transplanted periprosthetic tissues. Multinucleated osteoclast‐like cells were commonly seen within retrieved xenograft tissue, and focal bone erosions were ubiquitous. Total cell densities and CD68+ cells within the xenograft were significantly increased in mice transfused with PMMA and Ti‐provoked PBMCs compared to the naïve PBMC animals (p < 0.05). Immunohistochemical staining identified much stronger positive IL‐1 and TNF stains in xenografts from either PMMA or Ti‐stimulated monocytes transfusion groups (p < 0.05). TRAP+ cells were found around bone chips in both activated‐PBMCs groups, although markedly more aggregated TRAP+ cells in the PMMA‐challenged group than in the titanium group (p < 0.05). MicroCT assessment confirmed the significant decrease of bone mineral density in chips interacted with activated‐monocytes/osteoclasts. In conclusion, PMMA or titanium particles readily activate peripheral monocytes and promote the cell trafficking to the debris‐containing prosthetic tissues. Particles‐provoked PBMCs participated in and promoted the local inflammatory process, osteoclastogenesis, and bone resorption. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:781–786, 2011
Soil base saturation affects root growth of European beech seedlings§
Authors: Richter Anika K. , Hirano Yasuhiro , Luster Jörg , Frossard Emmanuel , Brunner Ivano
Published: December 2010

To assess the potential effects of Al toxicity on the roots of young European beech (Fagus sylvatica L.), seeds were sown in soil monoliths taken from the Ah and B horizons of forest soils with very low base saturation (BS) and placed in the greenhouse. The Ah horizons offered a larger supply of exchangeable cation nutrients than the B horizons. After 8 weeks of growth under optimal moisture conditions, the seedlings were further grown for 14 d under drought conditions. Root‐growth dynamics were observed in rhizoboxes containing soils from the Ah and B horizons. The concentrations of Al3+, base cations, and nitrate in the soil solution and element concentrations in the root tissue were compared with above‐ and belowground growth parameters and root physiological parameters. There was no strong evidence that seedling roots suffered from high soil‐solution Al3+ concentrations. Within the tested range of BS (1.2%–6.5%) our results indicated that root physiological parameters such as O2 consumption decreased and callose concentration increased in soils with a BS < 3%. In contrast to the B horizons, seedlings in the Ah horizons had higher relative shoot‐growth rates, specific root lengths, and lengths and branching increments, but a lower root‐to‐shoot ratio and root‐branching frequency. In conclusion, these differences in growth patterns were most likely due to differences in nutrient availability and to the drought application and not attributable to differences in Al3+ concentrations in the soil solution.
Raman spectroscopic investigation of lanthana‐doped neodymium‐yttria transparent ceramics
Authors: Zhang Haojia , Yang Qiuhong , Zhang Bin , Lu Shenzhou
Published: December 2010

Transparent ceramics of the formula (Nd0.01LaxY0.99−x)2O3 (x = 0, 0.05, 0.10) were made with nanopowders and sintered in H2 atmosphere. The Raman spectra of Ln2O3 (Ln = Y, La, Nd) powders and (Nd0.01LaxY0.99−x)2O3 ceramics were investigated. The results show that both La2O3 and Nd2O3 powders are of hexagonal structure, and all (Nd0.01LaxY0.99−x)2O3 ceramics exhibit the same cubic Y2O3 crystal structure. Their lattice parameters were refined by the Rietveld method. The full‐widths at half‐maximum of Raman peaks increase with the increase in La2O3 content in transparent (Nd0.01Y0.99)2O3 ceramics, while their intensities decrease. At the same time, All Raman peaks shift to lower wavenumbers, and the phonon energy is slightly reduced. Copyright © 2010 John Wiley & Sons, Ltd.
The CD40‐CD154 interaction would correlate with proliferation and immune escape in pancreatic ductal adenocarcinoma
Authors: Shoji Yasuhito , Miyamoto Masaki , Ishikawa Keidai , Yoshioka Tatsuya , Mishra Roshan , Ichinokawa Kazuomi , Matsumura Yoshiyuki , Itoh Tomoo , Shinohara Toshiya , Hirano Satoshi , Kondo Satoshi
Published: December 2010

Background

CD40 and CD154 are associated with lymphocyte signaling pathways and they are also expressed in some malignant neoplasms, but the significance in pancreatic cancer is unknown.

Methods

Eighty pancreatic cancer specimens were stained immunohistochemically, and the results were correlated with the patients' clinicopathologic features. Subsequently, in vitro analysis of CD40‐CD154 signaling was performed.

Result

Immunohistochemical analysis of tumor cells showed that 29 patients (36.3%) were positive for CD40, and 17 patients (21.3%) had very high CD154 expression. The survival of patients who had very high CD154 expression was significantly better than that of others (P = 0.0198). Univariate and multivariate analysis revealed that very high CD154 expression in cancer cells was not an independent, favorable prognostic factor (risk ratio, 0.493; P = 0.0224). On in vitro proliferation assay, the growth of PK‐45P and KP‐4 cells was blocked by CD40 and CD154 blocking antibodies. Moreover, on in vitro cytokine assay, Th‐2 cytokines from PK‐45P and SUIT‐2 were blocked by CD40 or CD154 blocking antibody.

Conclusion

These results suggest that the CD40–CD154 interaction would correlate with cell proliferation and secretion of cytokines in PDAC cells, and CD154 overexpression could be a favorable prognostic factor in PDAC patients. J. Surg. Oncol. 2011; 103:230–238. © 2010 Wiley‐Liss, Inc.
Multiwalled carbon nanotubes as efficient adsorbent for solid‐phase extraction of chemical warfare agents and related chemicals from water
Authors: Kanaujia Pankaj K. , Purohit Ajay , Pardasani Deepak , Tak Vijay , Dubey D. K.
Published: December 2010

Optimization of extraction and enrichment parameters of chemical warfare agents and their related chemicals from water are presented using multiwalled carbon nanotubes (MWCNTs) as solid‐phase extractant. Selected analytes were O,O'‐dialkyl alkylphosphonates, nerve agent and mustards. Extraction parameters, including sample volume, nature and volume of washing and eluting solvent, were optimized. Recoveries of analytes were determined by GC–MS and ranged from 81 to 104%. A comparison with C18, hydrophilic–lipophilic balance and active carbon sorbents demonstrated the superiority of MWCNTs for non‐toxic analogues of nerve agents. Optimized conditions involve 40 mg MWCNTs as the sorbent, 5.0 mL water as the washing solvent, 3 mL ethyl acetate as the eluent and sample loading of 10 mL water spiked at 0.1 μg/mL. The limits of detection (LOD) were achieved down to 1 and 0.05 ng/mL in full scan and selected ion‐monitoring modes, respectively.
Dispersive liquid–liquid microextraction coupled with high‐performance liquid chromatography‐diode array detection for the determination of N‐methyl carbamate pesticides in vegetables
Authors: Lin Xiangyun , Chen Xiaohui , Huo Xin , Yu Zhiguo , Bi Kaishun , Li Qing
Published: December 2010

This paper described a simple, rapid and efficient method for the determination of N‐methyl carbamate pesticides in tomato, cucumber, carrot and lettuce samples by dispersive liquid–liquid microextraction coupled with HPLC‐diode array detection. Some experimental parameters that influenced the extraction efficiency, such as types and volumes of extraction and disperser solvents, extraction time and salt effect were examined and optimized. Under optimum conditions, the LOD of the method were 0.5–3.0μg/kg depending on the compounds and the kind of vegetables. The linearities of the method were obtained in the range of 10.0–300 μg/kg for aldicarb, MTMC, carbofuran and carbaryl, and 20.0–600 μg/kg for isoprocarb, with the correlation coefficients ranging from 0.9921 to 0.9993. The RSD varied from 2.9 to 7.5% (n=5). The recoveries of the method for the five carbamates from vegetable samples at two different spiking levels were ranged from 77.8 to 98.2%. Results showed that the method we proposed can meet the requirements for the determination of N‐methyl carbamate in vegetable samples and was finally applied to the analysis of target pesticides in vegetable samples taken from local markets.