bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Post‐PKS Tailoring Steps in Natural Product‐Producing Actinomycetes from the Perspective of Combinatorial Biosynthesis
Authors: Olano Carlos , Mendez Carmen , Salas Jose A.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Electrochemical Applications. How Click Chemistry Brought Biomimetic Models to the Next Level: Electrocatalysis under Controlled Rate of Electron Transfer
Authors: Decreau Richard A. , Collman James P. , Hosseini Ali
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Pathophysiological Roles of Transient Receptor Potential Channels in Glial Cells
Authors: Shirakawa Hisashi , Nakagawa Takayuki , Kaneko Shuji
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Engineering of Nanometer‐Sized Cross‐Linked Hydrogels for Biomedical Applications
Authors: Oh Jung Kwon
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Positional Selectivity in Electrophilic Substitution in π‐Excessive Heteroaromatics
Authors: Belen'kii L. I.
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: In silico Approaches for Fragment‐Based Drug Design
Authors: Takahashi Osamu , Masuda Yoshiaki , Muroya Ayumu , Furuya Toshio
Published: June 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Human papillomavirus status in head and neck cancer
Authors: Shuman Andrew G. , Wolf Gregory T.
Published: June 2010

Human papillomavirus (HPV) is an emerging causative factor for squamous carcinoma of the oropharynx and perhaps other head and neck cancers. There is a great deal of uncertainty regarding the clinical significance and implications of HPV status in this patient population. As a result, there is no established protocol for informing patients of the potential link between viral infection and their cancer. This paper discusses some of the ethical issues involved with informing head and neck cancer patients of their HPV status, recognizing the dilemma posed by unresolved clinical questions and the need to respect the autonomy of patients by disclosing relevant information. Cancer 2010; 116:4221–6. © 2010 American Cancer Society.
Methylene Blue Adsorption on a DMPA Lipid Langmuir Monolayer
Authors: Giner Casares Juan José , Camacho Luis , Martín‐Romero Maria Teresa , López Cascales José Javier
Published: June 2010

Adsorption of methylene blue (MB) onto a dimyristoylphosphatidic acid (DMPA) Langmuir air/water monolayer is studied by molecular dynamics (MD) simulations, UV reflection spectroscopy and surface potential measurements. The free‐energy profile associated with MB transfer from water to the lipid monolayer shows two minima of −66 and −60 kJ mol−1 for its solid and gas phase, respectively, corresponding to a spontaneous thermodynamic process. From the position of the free‐energy minima, it is possible to predict the precise location of MB in the interior of the DMPA monolayer. Thus, MB is accommodated in the phosphoryl or carbonyl region of the DMPA Langmuir air/water interface, depending on the isomorphic state (solid or gas phase, respectively). Reorientation of MB, measured from the bulk solution to the interior of the lipid monolayer, passes from a random orientation in bulk solution to an orientation parallel to the surface of the lipid monolayer when MB is absorbed.
Systematic Variation of Length Ratio and the Formation of Smectic A and Smectic C Phases
Authors: Kapernaum Nadia , Hartley C. Scott , Roberts Jeffrey C. , Schoerg Florian , Krueerke Daniel , Lemieux Robert P. , Giesselmann Frank
Published: June 2010

The phase diagrams of four binary mixtures of chemically similar smectogenic mesogens differing only in molecular length are investigated. In these bidisperse systems the length ratio varies systematically. The phase diagrams show the stabilization of the smectic A and the destabilization of the smectic C phase with increasing length ratio as a general trend. Detailed small‐angle X‐ray diffraction and electro‐optic measurements revealed a decrease in smectic translational order and a continuous reduction of the tilt angle with increasing length difference. These surprising results are of general interest for the understanding of the structure and dynamics of smectic phases. The remarkably strong impact of the length difference on the smectic layer structure and the phase behavior is discussed from a mechanistic point of view taking into account sterical interactions. For the observed structural changes in these bidisperse smectics we propose pronounced out‐of‐layer fluctuations with increasing length difference as driving force, causing neighboring molecules within nearest layer into a smectic A‐like packing.
TEM, chemical etching and FTIR characterization of ZnTe grown by physical vapor transport
Authors: Trigubó A. B. , Di Stefano M. C. , Gilabert U. , Martínez A. M. , D'Elía R. , Cánepa H. , Heredia E. , Aguirre M. H.
Published: June 2010

ZnTe ingots were obtained by the physical transport method, using an in‐house designed and built tubular furnace. The growth of ZnTe subsequently to the growth of a seed of this material allowed obtaining an ingot formed by only one large and single crystalline grain. TEM was used for the characterization of the as‐grown ZnTe single crystal ingots and commercial single‐crystalline wafers of the same material but grown by a higher temperature and more expensive technique, the Bridgman method. Both materials show very good crystalline microstructure, although some stacking faults were found in the commercial one. The infrared transmittance spectra of both materials were measured by FTIR and some differences, most likely due to differences in raw materials and growth methods, were found. The effectiveness and convenience of several chemical etchants to obtain the dislocation density and the minimal misorientation between adjacent subgrains in the as‐grown ZnTe wafers were checked. It has been found as the most advantageous the chemical solution that does not produce over‐etching. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electrical conductivity of sulfamic acid single crystals
Authors: Santhosh Kumar A. , Varughese G. , Iype L. , Rajesh R. , Joseph G. , Louis G.
Published: June 2010

Single crystals of sulfamic acid have been grown by the method of slow evaporation at constant temperature. DC electrical conductivity was measured in the temperature range 300 ‐ 440 K along a, b and c‐axes. Conductivity measurements show slope change near 330 K and 410 K. The slope change observed around 330 K may be attributed as due to a phase transition which has been well supported by the DSC and DTA measurements. Slope change observed around 410 K is attributed as the onset of the thermal decomcoposition as evidenced by TGA curve. TGA studies show the crystal is very stable up to 440 K. Activation energies for the conduction process are calculated for all measured crystallographic directions. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spin‐Hamiltonian parameters for Dy3+ion at the trigonal 12‐fold coordinated La3+site of La2Mg3(NO3)12·24H2O
Authors: Yang Wei‐Qing , Zheng Wen‐Chen , Liu Hong‐Gang
Published: June 2010

The spin‐Hamiltonian parameters (gfactorsg‖,g⊥and hyperfine structure constants161A‖,161A⊥,163A‖,163A⊥) for161Dy3+and161Dy3+isotopes in the trigonal 12‐fold coordinated La3+site of La2Mg3(NO3)12·24H2O crystal are calculated from a diagonalization (of energy matrix) method. In the method, the Zeeman and hyperfine interaction terms are added to the conventional Hamiltonian used in the studies of crystal‐field energy levels, and a 66×66 energy matrix concerning the ground multiplet6H15/2and the first to fifth excited multiplets6H13/2,6H11/2,6H9/2,6H7/2and6H5/2are applied. The calculated results are discussed. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ring oscillator structures with explicitly separated nonlinearity
Authors: Elwakil A. S.
Published: June 2010

In this letter, we propose RC and LC nonlinear sinusoidal ring oscillator structures which can also generate subsidiary quadrature outputs. A tanh(x) nonlinearity is employed and is explicitly separated from the oscillators' linear building block (a first‐order all‐pass filter). Numerical and spice simulation results are given. Copyright © 2010 John Wiley & Sons, Ltd.
Seismic vulnerability of historical masonry buildings for different earthquake characteristics: Case study of the mosque of Takiyya al‐Sulaymaniyya
Authors: Jäger Wolfram , Bakeer Tammam
Published: June 2010

Different factors influence the collapse behaviour of masonry structures, and one of the major factors is the characteristics of the earthquake itself. This effect is going to be more complicated for historical constructions, which involve different structure members of different geometries.

The present study focuses on the effect of earthquake characteristics on the collapse behaviour of historical masonry structures. The effect of earthquake direction and the frequency content of the earthquake are mainly considered. A brief background of the selected case study and modelling process are presented. The geometry of the whole structure is created using micro modelling strategy. The collapse analysis of the structure is performed under artificial model based on the earthquake characteristics. Unidirectional earthquake are applied to the structure from different angels in order to investigate the weakest situation. Finally, different earthquake models are generated with different frequency contents according the soil profiles and applied consequently on the structure to explore the worst situation.

Seismische Gefährdung von historischen Mauerwerksbauten infolge Erdbebeneinwirkung — Fallstudie: Die Moschee von Takiyya al‐Sulaymaniyya. Verschiedene Faktoren beeinflussen das Versagen von Mauerwerksstrukturen. Ein wesentlicher ist die Erdbebeneinwirkung selbst. Deren Charakteristik und Auswirkung ist für historische Konstruktionen, welche aufgrund der verschiedenen verwendeten und zusammenwirkenden Tragelemente und der großen Bandbreite geometrischer Formen eine komplexe Versagensabhängigkeit aufweisen, noch schwieriger einzuschätzen.

Die in diesem Beitrag beschriebene Fallstudie befasst sich mit dem Verhalten historischer Mauerwerkskonstruktionen beim Versagen infolge einer Erdbebenbelastung. Die Auswirkungen von Richtung und Frequenz eines Erdbebens sind die Hauptschwerpunkte der Studie. Ein kurz gefasster Hintergrund der gewählten Fallstudie und der Modellierungsprozess werden vorgestellt. Die Geometrie der gesamten Konstruktion wurde mittels Mikromodellierung erstellt. Die Versagensanalyse der Konstruktion ist mittels eines künstlich generierten Erdbebens durchgeführt worden. Das einachsige Erdbeben wurde mit variierenden Richtungswinkeln auf das Modell angesetzt, um die schwächste Achse zu ermitteln. Den Abschluss bildete die Erzeugung von verschiedenen Erdbebenverläufen in Abhängigkeit der Bodenprofile und Anwendung auf die Konstruktion, um wiederum den ungünstigsten Fall zu ermitteln.
Peoniflorin prevents the adhesion between inflammatory endothelial cells and leukocytes through inhibiting the activation of MAPKs and NF‐κB
Authors: Xu Huan , Gao Xinghua , Song Jie , Wang Fengyun , Xu Zhao , Lu Dan , Xu Xianxiang , Xia Yufeng , Dai Yue
Published: June 2010

The vascular endothelium can be activated by multiple factors, including lipopolysaccharide (LPS) functioning as a key component of the inflammatory response. Activated endothelium promotes the recruitment of leukocytes mainly by releasing various adhesion molecules and amplifies inflammation via a feedback loop. Peoniflorin, the main active constituent of the roots of Paeonia lactiora Pall., possesses anti‐inammatory, anti‐infective, and anti‐platelet aggregative properties. To elucidate the anti‐inammatory mechanism of peoniflorin, the present study was conducted to address its effects on the adhesion of inflammatory endothelial cells to leukocytes. Peoniflorin substantially reduced adhesion of either human acute monocytic leukemia cells (THP‐1) or human acute promyelocytic leukemia cells (HL‐60) to LPS‐stimulated human umbilical vein endothelial cells (HUVECs). It also markedly down‐regulated the expression of E‐selectin at both the gene and protein levels. However, peoniflorin only slightly reduced expression of intercellular adhesion molecule‐1 (ICAM‐1). Signal pathway analysis indicated that peoniflorin reduced phosphorylation of c‐Jun NH2‐terminal kinase (JNK) and p38 kinase, as well as the phosphorylation and degradation of IκB‐α in HUVECs. These findings suggest that prevention of the adhesion between inflammatory endothelial cells and leukocytes contributes, at least partially, to the anti‐inflammation action of peoniflorin. The anti‐adhesion mechanisms of peoniflorin were involved in the down‐regulation of the activation of mitogen‐activated protein kinases (MAPKs) and nuclear factor‐kappa B (NF‐κB), and a reduction of adhesion molecule expressions in endothelial cells. Drug Dev Res 2010.© 2010 Wiley‐Liss, Inc.
Competition between SLP76 and LAT for PLCγ1 binding in resting T cells
Authors: Jung Seung Hee , Jeong Ji Hye , Seul Hee Jung , Lee Jong Ran
Published: June 2010

The constitutive interaction between the P1 domain (a 67‐amino‐acid functional domain within the proline‐rich region) of SLP76 and the SH3 domain of phospholipase Cγ1 (PLCγ1) has been shown. To determine the significance of the interaction between SLP76 and PLCγ1 in resting T cells, we examined molecules associated with PLCγ1 in the absence of both SLP76 and, more specifically, the P1 domain of SLP76. Using a mutant Jurkat T‐cell line, we showed that PLCγ1 associated with LAT when the constitutive association with SLP76 was blocked. We also found that the PLCγ1 association with LAT occurred in the membranes of resting T cells. Further experiments demonstrated that LAT competed with SLP76 for PLCγ1 binding and that the LAT interaction with PLCγ1 was mediated by the SH3 domain of PLCγ1. Collectively, these results suggest that the constitutive association of SLP76 with PLCγ1 is required to prevent the association with LAT as well as the premature recruitment of PLCγ1 to the cell membrane.
Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation
Authors: Baru Abdul Mannan , Hartl Andrea , Lahl Katharina , Krishnaswamy Jayendra Kumar , Fehrenbach Heinz , Yildirim Ali Ö. , Garn Holger , Renz Harald , Behrens Georg M. N. , Sparwasser Tim
Published: June 2010

Recent studies highlight the role of Treg in preventing unnecessary responses to allergens and maintaining functional immune tolerance in the lung. We investigated the role of Treg during the sensitization phase in a murine model of experimental allergic airway inflammation by selectively depleting the Treg population in vivo. DEpletion of REGulatory T cells (DEREG) mice were depleted of Treg by diphtheria toxin injection. Allergic airway inflammation was induced using OVA as a model allergen. Pathology was assessed by scoring for differential cellular infiltration in bronchoalveolar lavage, IgE and IgG1 levels in serum, cytokine secretion analysis of lymphocytes from lung draining lymph nodes and lung histology. Use of DEREG mice allowed us for the first time to track and specifically deplete both CD25+ and CD25− Foxp3+ Treg, and to analyze their significance in limiting pathology in allergic airway inflammation. We observed that depletion of Treg during the priming phase of an active immune response led to a dramatic exacerbation of allergic airway inflammation in mice, suggesting an essential role played by Treg in regulating immune responses against allergens as early as the sensitization phase via maintenance of functional tolerance.
Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system
Authors: Prevot Nicolas , Briet Claire , Lassmann Hans , Tardivel Isabelle , Roy Edwige , Morin Joëlle , Mak Tak W. , Tafuri Anna , Boitard Christian
Published: June 2010

NOD mice spontaneously develop insulin‐dependent diabetes around 10–40 wk of age. Numerous immune gene variants contribute to the autoimmune process. However, genes that direct the autoimmune response toward β cells remain ill defined. In this study, we provide evidence that the Icos and Icosl genes contribute to the diabetes process. Protection from diabetes in ICOS−/− and ICOSL−/− NOD mice was unexpectedly associated with the development of an autoimmune disorder of the neuro‐muscular system, characterized by myositis, sensory ganglionitis and, to a reduced extent, inflammatory infiltrates in the CNS. This syndrome was reproduced upon adoptive transfer of CD4+ and CD8+ T cells from diseased donors to naïve NOD.scid recipients. Our data further show that protection from diabetes results from defective activation of autoimmune diabetogenic effector T cells in ICOS−/− NOD mice, whereas acceleration of diabetes in BDC2.5 ICOS−/− NOD mice is induced by a dominant defect in Treg. Taken together, our findings indicate that costimulation signals play a key role in regulating immune tolerance in peripheral tissues and that the ICOS/ICOSL costimulatory pathway influences the balance between Treg and diabetogenic effector T cells.
Molybdenum and Tungsten Nitrosyl Complexes in Hydrogen Activation
Authors: Dybov Alexander , Blacque Olivier , Berke Heinz
Published: June 2010

Two transition‐metal hydride complexes of the type [M(dippe)2(NO)(H)] [M = W (2a), Mo (2b); dippe = 1,2‐bis(diisopropylphosphanyl)ethane] have been prepared by the reaction of [M(dippe)2(NO)(Cl)] [M = W (1a), Mo (1b)] with LiBH4. The nitrosyl groups of the tungsten complexes 1a and 2a are capable to coordinate a LiBH4 molecule to form the stable adducts W(dippe)2(Cl)(NO···LiBH4) (1c) and W(dippe)2(H)(NO···LiBH4) (2c). Addition of ethylenediamine to a toluene solution of 2c led to rupture of the 2c adduct and afforded 2a in good yield. After the interaction of 2a with [H(Et2O)][BF4], the stable seven‐coordinated cationic dihydride [W(dippe)(H)2(dippe)(NO)][BF4] (6a) was isolated. The reaction between 2b and [H(Et2O)][BF4] led to the formation of [Mo(dippe)2(NO)(FBF3)] (6b) in which BF4– was found to be coordinated to the metal centre. The [H(Et2O)2][BArF4] [ArF = 3,5‐(CF3)2C6H3] acid interacted with 2a to yield the seven‐coordinated complex [W(dippe)(H)2(dippe)(NO)][BArF4] (5a) similar to 6a. In the reaction between 2b and [H(Et2O)2][BArF4], the 16e– five‐coordinated complex [Mo(dippe)2(NO)][BArF4] (4b) was formed. X‐ray diffraction revealed that 4a has a weak agostic interaction trans to the NO ligand. Complex 4b was found to react rapidly with hydrogen gas under ambient conditions to form the dihydride complex [Mo(dippe)(H)2(dippe)(NO)][BArF4] (5b), which is unstable in the absence of a hydrogen atmosphere. The equilibrium constant for the reversible reaction of 4b with hydrogen was found to be K = 2.6 bar–1 at 25 °C. Complex 4b was tested as a catalyst for acetone hydrogenation; a maximum TON of 7 was found.
A Joint Experimental and Theoretical Investigation on Nonlinear Optical (NLO) Properties of a New Class of Push–Pull Spirobifluorene Compounds
Authors: Rizzo Fabio , Cavazzini Marco , Righetto Stefania , De Angelis Filippo , Fantacci Simona , Quici Silvio
Published: June 2010

A new class of push–pull spirobifluorene compounds 1–5 has been synthesized. The nonlinear optical (NLO) properties (first and second hyperpolarizability β and γ, respectively)of spirobifluorene derivatives have been investigated forthe first time using electric field induced second harmonic(EFISH) and third harmonic generation (THG) methods. Moreover, a comparison with the corresponding push–pullfluorene monomers 1a–5a was carried out. Besides the experimental data, ab initio theoretical calculations on structural, electronic, and optical properties were carried out for all compounds. The analyses indicate that an increase in the β and γ values occur on passing from monomers to dimers without compromising the optical transparency.
A General Methodology for the Enantioselective Synthesis of 1‐Substituted Tetrahydroisoquinoline Alkaloids
Authors: Amat Mercedes , Elias Viviane , Llor Núria , Subrizi Fabiana , Molins Elies , Bosch Joan
Published: June 2010

Starting from tricyclic lactam 2, which is easily accessible by cyclocondensation of δ‐oxoester 1 with (R)‐phenylglycinol, a three‐step synthetic route to enantiopure 1‐substituted tetrahydroisoquinolines, including 1‐alkyl‐, 1‐aryl‐, and 1‐benzyltetrahydroisoquinoline alkaloids, as well as the tricyclic alkaloid (–)‐crispine A, has been developed. The key step is a stereoselective α‐amidoalkylation reaction using the appropriate Grignard reagent.
Rosai‐Dorfman disease presenting in the oropharynx
Authors: Silver Amanda L. , Farkash Evan A. , Pitman Martha B. , Rocco James W.
Published: June 2010

Background

We report a case of Rosai‐Dorfman disease (RDD) presenting as an oropharyngeal mass, and we provide a detailed discussion of this rare clinical entity.

Methods

An initial biopsy, described as being consistent with lymphoma, was reviewed at a second outside institution and was thought to be reactive lymphoid hyperplasia. The patient then presented to our institution for a second opinion. Direct laryngoscopy revealed a firm 1‐ to 2‐cm lesion involving the left soft palate and superior tonsillar pillar.

Results

The diagnosis of RDD was confirmed with immunohistochemical staining on both cytology and histology. The patient elected conservative management and has remained asymptomatic for over 15 months.

Conclusion

The diagnosis of RDD may be challenging in cases presenting initially with extranodal disease. Close follow‐up and repeat biopsies may be necessary. Identification of Rosai‐Dorfman cells with emperipolesis and confirmation with appropriate immunohistochemical staining on both cytology and histology is diagnostic of RDD. Conservative treatment is appropriate in select cases. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
A Multifaceted Imbalance of T Cells with Regulatory Function Characterizes Type 1 Autoimmune Hepatitis†,‡
Authors: Ferri Silvia , Longhi Maria Serena , De Molo Chiara , Lalanne Claudine , Muratori Paolo , Granito Alessandro , Hussain Munther J. , Ma Yun , Lenzi Marco , Mieli-Vergani Giorgina , Bianchi Francesco B. , Vergani Diego , Muratori Luigi
Published: June 2010

Immunotolerance is maintained by regulatory T cells (Tregs), including CD4+CD25hi, CD8+CD28−, γδ, and CD3+CD56+ [natural killer T (NKT)] cells. CD4+CD25hi cells are impaired in children with autoimmune hepatitis (AIH). Little is known about Tregs in adults with AIH. The aim of this study was to investigate the frequency and function of Treg subsets in adult patients with AIH during periods of active disease and remission. Forty-seven AIH patients (16 with active disease and 31 in remission) and 28 healthy controls were studied. Flow cytometry was used to evaluate surface markers and function-related intracellular molecules in γδ, CD8+CD28−, NKT, and CD4+CD25hi cells. CD4+CD25hi T cell function was determined by the ability to suppress proliferation and interferon gamma (IFN-γ) production by CD4+CD25− target cells. Liver forkhead box P3–positive (FOXP3+) cells were sought by immunohistochemistry. In AIH patients, particularly during active disease, CD4+CD25hi T cells were fewer, expressed lower levels of FOXP3, and were less effective at inhibiting target cell proliferation versus healthy controls. Moreover, although the numbers of CD8+CD28− T cells were similar in AIH patients and healthy controls, NKT cells were numerically reduced, especially during active disease, and produced lower quantities of the immunoregulatory cytokine interleukin-4 versus controls. In contrast, γδ T cells in AIH patients were more numerous versus healthy controls and had an inverted Vδ1/Vδ2 ratio and higher IFN-γ and granzyme B production; the latter was correlated to biochemical indices of liver damage. There were few FOXP3+ cells within the portal tract inflammatory infiltrate.

Conclusion:

Our data show that the defect in immunoregulation in adult AIH is complex, and γδ T cells are likely to be effectors of liver damage.
Bmi1 Promotes Hepatic Stem Cell Expansion and Tumorigenicity in Both Ink4a/Arf -Dependent and -Independent Manners in Mice†
Authors: Chiba Tetsuhiro , Seki Atsuyoshi , Aoki Ryutaro , Ichikawa Hitoshi , Negishi Masamitsu , Miyagi Satoru , Oguro Hideyuki , Saraya Atsunori , Kamiya Akihide , Nakauchi Hiromitsu , Yokosuka Osamu , Iwama Atsushi
Published: June 2010

We previously reported that forced expression of

Bmi1

(B lymphoma Moloney murine leukemia virus insertion region 1 homolog) in murine hepatic stem/progenitor cells purified from fetal liver enhances their self-renewal and drives cancer initiation. In the present study, we examined the contribution of the

Ink4a/Arf

tumor suppressor gene locus, one of the major targets of

Bmi1

, to stem cell expansion and cancer initiation.

Bmi1

−/− Delta-like protein (Dlk)+ hepatic stem/progenitor cells showed de-repression of the

Ink4a/Arf

locus and displayed impaired growth activity. In contrast,

Ink4a/Arf

−/− Dlk+ cells gave rise to considerably larger colonies containing a greater number of bipotent cells than wild-type Dlk+ cells. Although

Ink4a/Arf

−/− Dlk+ cells did not initiate tumors in recipient nonobese diabetic/severe combined immunodeficiency mice, enforced expression of

Bmi1

in

Ink4a/Arf

−/− Dlk+ cells further augmented their self-renewal capacity and resulted in tumor formation

in vivo

. Microarray analyses successfully identified five down-regulated genes as candidate downstream targets for Bmi1 in hepatic stem/progenitor cells. Of these genes, enforced expression of

sex determining region Y-box 17

(

Sox17

) in Dlk+ cells strongly suppressed colony propagation and tumor growth.

Conclusion:

These results indicate that repression of targets of Bmi1 other than the

Ink4a/Arf

locus plays a crucial role in the oncogenic transformation of hepatic stem/progenitor cells. Functional analyses of Bmi1 target genes would be of importance to elucidate the molecular machinery underlying hepatic stem cell system and explore therapeutic approaches for the eradication of liver cancer stem cells.
CX3CL1-CX3CR1 Interaction Prevents Carbon Tetrachloride-Induced Liver Inflammation and Fibrosis in Mice
Authors: Aoyama Tomonori , Inokuchi Sayaka , Brenner David A. , Seki Ekihiro
Published: June 2010

Chronic liver disease is associated with hepatocyte injury, inflammation, and fibrosis. Chemokines and chemokine receptors are key factors for the migration of inflammatory cells such as macrophages and noninflammatory cells such as hepatic stellate cells (HSCs). The expression of CX3CR1 and its ligand, CX3CL1, is up-regulated in chronic liver diseases such as chronic hepatitis C. However, the precise role of CX3CR1 in the liver is still unclear. Here we investigated the role of the CX3CL1-CX3CR1 interaction in a carbon tetrachloride (CCl4)–induced liver inflammation and fibrosis model. CX3CR1 was dominantly expressed in Kupffer cells in the liver. In contrast, the main source of CX3CL1 was HSCs. Mice deficient in CX3CR1 showed significant increases in inflammatory cell recruitment and cytokine production [including tumor necrosis factor α (TNF-α); monocyte chemoattractant protein 1; macrophage inflammatory protein 1β; and regulated upon activation, normal T cell expressed, and secreted (RANTES)] after CCl4 treatment versus wild-type (WT) mice. This suggested that CX3CR1 signaling prevented liver inflammation. Kupffer cells in CX3CR1-deficient mice after CCl4 treatment showed increased expression of TNF-α and transforming growth factor β and reduced expression of the anti-inflammatory markers interleukin-10 (IL-10) and arginase-1. Coculture experiments showed that HSCs experienced significantly greater activation by Kupffer cells from CCl4-treated CX3CR1-deficient mice versus WT mice. Indeed, augmented fibrosis was observed in CX3CR1-deficient mice versus WT mice after CCl4 treatment. Finally, CX3CL1 treatment induced the expression of IL-10 and arginase-1 in WT cultured Kupffer cells through CX3CR1, which in turn suppressed HSC activation.

Conclusion:

The CX3CL1-CX3CR1 interaction inhibits inflammatory properties in Kupffer cells/macrophages and results in decreased liver inflammation and fibrosis. (Hepatology 2010)
High-Fructose, Medium Chain Trans Fat Diet Induces Liver Fibrosis and Elevates Plasma Coenzyme Q9 in a Novel Murine Model of Obesity and Nonalcoholic Steatohepatitis†
Authors: Kohli Rohit , Kirby Michelle , Xanthakos Stavra A. , Softic Samir , Feldstein Ariel E. , Saxena Vijay , Tang Peter H. , Miles Lili , Miles Michael V. , Balistreri William F. , Woods Stephen C. , Seeley Randy J.
Published: June 2010

Diets high in saturated fat and fructose have been implicated in the development of obesity and nonalcoholic steatohepatitis (NASH) in humans. We hypothesized that mice exposed to a similar diet would develop NASH with fibrosis associated with increased hepatic oxidative stress that would be further reflected by increased plasma levels of the respiratory chain component, oxidized coenzyme Q9 (oxCoQ9). Adult male C57Bl/6 mice were randomly assigned to chow, high-fat (HF), or high-fat high-carbohydrate (HFHC) diets for 16 weeks. The chow and HF mice had free access to pure water, whereas the HFHC group received water with 55% fructose and 45% sucrose (wt/vol). The HFHC and HF groups had increased body weight, body fat mass, fasting glucose, and were insulin-resistant compared with chow mice. HF and HFHC consumed similar calories. Hepatic triglyceride content, plasma alanine aminotransferase, and liver weight were significantly increased in HF and HFHC mice compared with chow mice. Plasma cholesterol (

P

< 0.001), histological hepatic fibrosis, liver hydroxyproline content (

P

= 0.006), collagen 1 messenger RNA (

P

= 0.003), CD11b-F4/80+Gr1+ monocytes (

P

< 0.0001), transforming growth factor β1 mRNA (

P

= 0.04), and α-smooth muscle actin messenger RNA (

P

= 0.001) levels were significantly increased in HFHC mice. Hepatic oxidative stress, as indicated by liver superoxide expression (

P

= 0.002), 4-hydroxynonenal, and plasma oxCoQ9 (

P

< 0.001) levels, was highest in HFHC mice.

Conclusion:

These findings demonstrate that nongenetically modified mice maintained on an HFHC diet in addition to developing obesity have increased hepatic ROS and a NASH-like phenotype with significant fibrosis. Plasma oxCoQ9 correlated with fibrosis progression. The mechanism of fibrosis may involve fructose inducing increased ROS associated with CD11b+F4/80+Gr1+ hepatic macrophage aggregation, resulting in transforming growth factor β1–signaled collagen deposition and histologically visible hepatic fibrosis.
Role and Cellular Source of Nicotinamide Adenine Dinucleotide Phosphate Oxidase in Hepatic Fibrosis
Authors: De Minicis Samuele , Seki Ekihiro , Paik Yong-Han , Österreicher Christoph H. , Kodama Yuzo , Kluwe Johannes , Torozzi Luciano , Miyai Katsumi , Benedetti Antonio , Schwabe Robert F. , Brenner David A.
Published: June 2010

Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) is required for liver fibrosis. This study investigates the role of NOX in ROS production and the differential contribution of NOX from bone marrow (BM)-derived and non–BM-derived liver cells. Hepatic fibrosis was induced by bile duct ligation (BDL) for 21 days or by methionine-choline-deficient (MCD) diet for 10 weeks in wild-type (WT) mice and mice deficient in p47phox (p47phox knockout [KO]), a component of NOX. The p47phox KO chimeric mice were generated by the combination of liposomal clodronate injection, irradiation, and BM transplantation of p47phox KO BM into WT recipients and vice versa. Upon BDL, chimeric mice with p47phox KO BM-derived cells, including Kupffer cells, and WT endogenous liver cells showed a ˜25% reduction of fibrosis, whereas chimeric mice with WT BM-derived cells and p47phox KO endogenous liver cells, including hepatic stellate cells, showed a ˜60% reduction of fibrosis. In addition, p47phox KO compared to WT mice treated with an MCD diet showed no significant changes in steatosis and hepatocellular injury, but a ˜50% reduction in fibrosis. Cultured WT and p47phox KO hepatocytes treated with free fatty acids had a similar increase in lipid accumulation. Free fatty acids promoted a 1.5-fold increase in ROS production both in p47phox KO and in WT hepatocytes.

Conclusion:

NOX in both BM-derived and non–BM-derived cells contributes to liver fibrosis. NOX does not play a role in experimental steatosis and the generation of ROS in hepatocytes, but exerts a key role in fibrosis. (Hepatology 2010;)
Primary health‐care network monitoring: a hierarchical resource allocation modeling approach
Authors: Pur Aleksander , Bohanec Marko , Lavrač Nada , Cestnik Bojan
Published: June 2010

Management of a primary health‐care network (PHCN) is a difficult task in every country. A suitable monitoring system can provide useful information for PHCN management, especially given a large quantity of health‐care data that is produced daily in the network. This paper proposes a methodology for structured development of monitoring systems and a PHCN resource allocation monitoring model based on this methodology. The purpose of the monitoring model is to improve the allocation of health‐care resources. The proposed methodology is based on modules that are organized into a hierarchy, where each module monitors a particular aspect of the system. This methodology was used to design a PHCN monitoring model for Slovenia. Specific aspects of the Slovenian PHCN were taken into account such as varying needs of patients from different municipalities, existence of small municipalities having less than 1000 residents, the fact that many patients visit physicians in other municipalities, and that physicians may work at more than one location or organization. The main modules in the model are focused on the overall assessment of the PHCN, monitoring of patients visits to health‐care providers (HCPs), physical accessibility of health services, segment of patients in municipalities who have not selected a personal physician, assessment of the availability of HCPs for patients, physicians working on more than one location, and available human resources in the PHCN. Most of the model's components are general and can be adapted for other national health‐care systems. Copyright © 2010 John Wiley & Sons, Ltd.
Field observations of shallow freeze and thaw processes using high‐frequency ground‐penetrating radar
Authors: Steelman Colby M. , Endres Anthony L. , van der Kruk Jan
Published: June 2010

We have used reflection profiles and common‐midpoint (CMP) soundings with 900 MHz ground‐penetrating radar (GPR) to monitor freezing and thawing processes during winter seasonal periods at two separate sites located in Ontario, Canada. GPR responds to the large contrast in dielectric permittivity between liquid water and ice. The profiles reveal the long‐term development of a very shallow (<0·5 m) soil frost zone overlying unfrozen wet substratum. During the course of the winter season, long‐term travel time analysis yielded physical properties of the frozen and unfrozen layers as well as the spatial distribution of the base of the soil frost zone. Short‐term shallow thawing events overlying frozen substratum formed a dispersive waveguide for both the CMP and reflection profile surveys. Inversion of the dispersive wavefields for the CMP data yielded physical property estimates for the thawed and frozen soils and thawed layer thickness. We have shown that GPR can be used to monitor very shallow freezing and thawing events by responding to changes in the relative dielectric permittivity of the soil water phase (e.g. liquid water vs ice). The non‐invasive collection of such data permits interpretation of dynamic temporal and spatial freeze–thaw events, which are important for characterizing a range of hydrological processes. Copyright © 2010 John Wiley & Sons, Ltd.
Examining the large‐scale spatial coherence of European drought using regional indicators of precipitation and streamflow deficit
Authors: Hannaford J. , Lloyd‐Hughes B. , Keef C. , Parry S. , Prudhomme C.
Published: June 2010

Droughts tend to evolve slowly and affect large areas simultaneously, which suggests that improved understanding of spatial coherence of drought would enable better mitigation of drought impacts through enhanced monitoring and forecasting strategies. This study employs an up‐to‐date dataset of over 500 river flow time series from 11 European countries, along with a gridded precipitation dataset, to examine the spatial coherence of drought in Europe using regional indicators of precipitation and streamflow deficit. The drought indicators were generated for 24 homogeneous regions and, for selected regions, historical drought characteristics were corroborated with previous work. The spatial coherence of drought characteristics was then examined at a European scale. Historical droughts generally have distinctive signatures in their spatio‐temporal development, so there was limited scope for using the evolution of historical events to inform forecasting. Rather, relationships were explored in time series of drought indicators between regions. Correlations were generally low, but multivariate analyses revealed broad continental‐scale patterns, which appear to be related to large‐scale atmospheric circulation indices (in particular, the North Atlantic Oscillation and the East Atlantic–West Russia pattern). A novel methodology for forecasting was developed (and demonstrated with reference to the United Kingdom), which predicts ‘drought from drought’—i.e. uses spatial coherence of drought to facilitate early warning of drought in a target region, from drought which is developing elsewhere in Europe. Whilst the skill of the methodology is relatively modest at present, this approach presents a potential new avenue for forecasting, which offers significant advantages in that it allows prediction for all seasons, and also shows some potential for forecasting the termination of drought conditions. Copyright © 2010 John Wiley & Sons, Ltd.
Regionalization approaches for the periodic parameters of monthly flows: a case study of Ceyhan and Seyhan River basins
Authors: Özçelik Ceyhun , Benzeden Ertuǧrul
Published: June 2010

Five alternative regionalization approaches in two broad categories, named function‐free and functional approaches, have been proposed to predict periodic behaviours in the basic parameters of monthly stream flows throughout homogeneous regions defined. Function‐free and functional approaches rely on the standardized (or normalized) forms of raw and fitted values of the monthly periodic parameters considered. Homogeneous regions are identified based on these standardized/normalized parameters by means of the hierarchical clustering analysis. The proposed models are tested for two major river basins in south Turkey. It is concluded that the proposed regional models are very effective to estimate periodic behaviour of monthly flows. The functional approaches are quite plausible, and the function‐free approach needs much more parameters. Both types of regionalization approaches can be reliably used to get regional monthly flow estimates for the flow sections where monthly records are not available or too short. Copyright © 2010 John Wiley & Sons, Ltd.
Using stable isotopes to determine the water sources in alpine ecosystems on the east Qinghai‐Tibet plateau, China
Authors: Zhang Wenguang , Cheng Bin , Hu Zhibin , An Shuqing , Xu Zhen , Zhao Yongjun , Cui Jun , Xu Qing
Published: June 2010

To investigate the water circulation of eastern Qinghai‐Tibet plateau during rainy season, water samples of precipitation, throughfall, fog, soil, litter and xylem were collected for stable isotope analysis. The results showed that precipitation mainly originated as a result of the East Asian Monsoon, and the secondarily evaporated water from subalpine ecosystem was an important part in local atmospheric water cycle. The deuterium excess of rainfall in the alpine meadow was evidently higher than the precipitation in the Dengsheng stations. This suggests that a large part of precipitation in alpine meadow was derived from secondarily evaporated water and the mean contribution was 39·57%, about 3·65 mm produced shortly after rain events. Through the contrast of delta (d)‐excess value in different water samples, it could be concluded that the water in subalpine shrubland and transpiration of subalpine dark coniferous forest were the main source of secondarily evaporated water that transferred to alpine meadow. Hence, the precipitation on the east Qinghai‐Tibet plateau was doubly controlled by monsoon and local water circulation in alpine ecosystems. Copyright © 2010 John Wiley & Sons, Ltd.
Groundwater level responses in temperate mountainous terrain: regime classification, and linkages to climate and streamflow
Authors: Allen D. M. , Whitfield P. H. , Werner A.
Published: June 2010

Groundwater responses in temperate mountainous terrain are assessed using groundwater, hydrometric and climatic data from southern British Columbia, Canada. Well and stream hydrographs are analysed using a series of diagnostic tools including time series plots, hysteresis plots, and cross‐correlation plots. Characterizing the seasonal timing of the response requires consideration of the hydroclimatology of the region: rainfall‐dominated (pluvial), snowmelt‐dominated (nival) or hybrid (mixture of rain and snow). The magnitude and timing of the recharge and discharge response of the groundwater system was shown to depend on the storage and permeability characteristics of the aquifer and whether the system is stream‐driven or recharge‐driven. These two dominant stream‐aquifer system types were defined based on classifying different aquifer types found in the southwest portion of the province. The classification scheme and diagnostic tools have the potential to provide a framework for evaluating the responses of wells in other mountainous regions. Using this framework, the potential consequences of future climate change may then be better understood based on the interactions between the hydrogeological and hydroclimatic settings of these aquifers. Copyright © 2010 Her Majesty the Queen in right of Canada. Published by John Wiley & Sons. Ltd
Direct observation of complex Tóthian groundwater flow systems in the laboratory
Authors: Liang Xing , Liu Yu , Jin Menggui , Lu Xingchen , Zhang Renquan
Published: June 2010

Based on the theory of gravity‐driven groundwater flow systems, we have developed a complex Flow System Sand‐Box Model (FSM). It enables the visual observations of the development and characteristics and temporal evolution of complex Tóthian flow systems in the laboratory. The configuration of the regional, intermediate and local flow systems can be controlled and observed; hydraulic head, flow direction and travel time can be measured; and the scale and shape of the sub‐flow systems as well as the path lines and flow lines can be observed directly. The experiments demonstrate the Tóthian flow systems in a small basin with multiple sources and sinks. Greater local topographic (water table) undulation will lead to larger local flow systems. Greater regional and less local topographic undulation will enhance the development of intermediate and regional flow systems. In homogeneous media, increasing fluid‐potential differences between source and sink increase the spatial scale of the generated flow systems. The FSM is a useful teaching aid and experimental device to study and develop an intuitive insight into gravity‐driven groundwater flow systems. It helps to visualize and understand the hydraulic properties and controlling factors of Tóthian flow systems and may be used to study problems related to the chemical and temperature characteristics of the flow systems as well. Copyright © 2010 John Wiley & Sons, Ltd.
Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. I. Preparation and in vitro degradation
Authors: Fu Qiang , Rahaman Mohamed N. , Fu Hailuo , Liu Xin
Published: June 2010

Bioactive glass scaffolds with a microstructure similar to that of dry human trabecular bone but with three different compositions were evaluated for potential applications in bone repair. The preparation of the scaffolds and the effect of the glass composition on the degradation and conversion of the scaffolds to a hydroxyapatite (HA)‐type material in a simulated body fluid (SBF) are reported here (Part I). The in vitro response of osteogenic cells to the scaffolds and the in vivo evaluation of the scaffolds in a rat subcutaneous implantation model are described in Part II. Scaffolds (porosity = 78–82%; pore size = 100–500 μm) were prepared using a polymer foam replication technique. The glasses consisted of a silicate (13‐93) composition, a borosilicate composition (designated 13‐93B1), and a borate composition (13‐93B3), in which one‐third or all of the SiO2 content of 13‐93 was replaced by B2O3, respectively. The conversion rate of the scaffolds to HA in the SBF increased markedly with the B2O3 content of the glass. Concurrently, the pH of the SBF also increased with the B2O3 content of the scaffolds. The compressive strengths of the as‐prepared scaffolds (5–11 MPa) were in the upper range of values reported for trabecular bone, but they decreased markedly with immersion time in the SBF and with increasing B2O3 content of the glass. The results show that scaffolds with a wide range of bioactivity and degradation rate can be achieved by replacing varying amounts of SiO2 in silicate bioactive glass with B2O3. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.