bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormonal and physical markers of puberty and their relationship to adolescent‐typical novelty‐directed behavior
Authors: Vetter‐O'Hagen Courtney S. , Spear Linda P.
Published: September 2011

The extent to which characteristic adolescent behaviors are associated with pubertal changes or driven by more general, puberty‐independent developmental alterations is largely unknown. Using physiological and hormonal markers of puberty, this experiment characterized pubertal timing across adolescence and examined the relationships among these variables and novelty‐directed behaviors. Males and females were tested for response to novelty at P28, P32, P36, P40, P44, P48, and P75, and examined for balano‐preputial skinfold separation and sperm presence (males) or vaginal opening (females), followed by blood collection for hormonal assessments. Despite earlier pubertal maturation in females, with maturation generally completed by P36 in females and P44 in males, novelty‐directed behavior peaked at P32 and P36 in both sexes, and was unrelated to pubertal measures. These data support the suggestion that the ontogenetic peak in this behavior during adolescence is not notably puberty dependent. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 523–535, 2012.
Application of multiwalled carbon nanotubes/ionic liquid modified electrode for amperometric determination of sulfadiazine
Authors: Hong Xiaoping , Zhu Yan , Ma Jingying
Published: September 2011

A highly sensitive amperometric sulfadiazine sensor based on coating multiwalled carbon nanotubes (MWCNTs) and N‐octyl‐pyridinium‐hexafluorophosphate (OPPF6) ionic liquid composite on a glassy carbon (GC) electrode is described. The MWCNTs/OPPF6 composite contributed new properties to electrochemical sensors by combining the advantages of both ionic liquids and MWCNTs. Compared with bare GC electrode, the electrocatalytic activity of MWCNTs/OPPF6 generated a greatly improved electrochemical detection of sulfadiazine including low oxidation potential, high current responses, and good anti‐fouling performance. The oxidation peak currents of sulfadiazine obtained on the MWCNTs/OPPF6 coated GC electrode were proportional to the concentration of sulfadiazine within the range of 3.3‐35.4 μM with a detection limit of 0.21 μM. Copyright © 2011 John Wiley & Sons, Ltd.
Hepatocyte growth factor–regulated tyrosine kinase substrate (Hgs) is involved in BMP signaling through phosphorylation of smads and TAK1 in early mouse embryo
Authors: Miura Shigeto , Mishina Yuji
Published: September 2011

Hepatocyte growth factor–regulated tyrosine kinase substrate that is encoded by Hgs promotes degradation of ubiquitinated signaling molecule in the early endosome. We previously reported that a targeted mutation in Hgs results in embryonic lethality soon after gastrulation in the mouse. Here, we report that downstream target genes for BMP signaling were highly down‐regulated in the Hgs mutant embryos. We also showed that Hgs is required for phosphorylation of SMAD1/5/8 and TAK1/p38 to transduce BMP signaling. Furthermore, we found that HGS functions to localize TAK1 in early endosome for its activation. These results suggest that HGS is critical to localize TAK1 to early endosome for transducing BMP signaling for proper development. Our data revealed a new mechanism to modify BMP signaling by Hgs during early mouse development. Developmental Dynamics 240:2474–2481, 2011. © 2011 Wiley‐Liss, Inc.
Toward an unbiased evolutionary platform for unraveling Xenopus developmental gene networks
Authors: Beer Ronny , Wagner Florian , Grishkevich Vladislav , Peshkin Leonid , Yanai Itai
Published: September 2011

The availability of both the Xenopus tropicalis genome and the soon to be released Xenopus laevis genome provides a solid foundation for Xenopus developmental biologists. The Xenopus community has presently amassed expression data for ∼2,300 genes in the form of published images collected in the Xenbase, the principal Xenopus research database. A few of these genes have been examined in both X. tropicalis and X. laevis and the cross‐species comparison has been proven invaluable for studying gene function. A recently published work has yielded developmental expression profiles for the majority of Xenopus genes across fourteen developmental stages spanning the blastula, gastrula, neurula, and the tail‐bud. While this data was originally queried for global evolutionary and developmental principles, here we demonstrate its general use for gene‐level analyses. In particular, we present the accessibility of this dataset through Xenbase and describe biases in the characterized genes in terms of sequence and expression conservation across the two species. We further indicate the advantage of examining coexpression for gene function discovery relating to developmental processes conserved across species. We suggest that the integration of additional large‐scale datasets—comprising diverse functional data—into Xenbase promises to provide a strong foundation for researchers in elucidating biological processes including the gene regulatory programs encoding development. genesis 50:186–191, 2012. © 2011 Wiley Periodicals, Inc.
Synthesis of facial image with expression based on muscular contraction parameters using linear muscle and sphincter muscle
Authors: Ahn Seonju , Ozawa Shinji
Published: September 2011

We aim to synthesize individual facial images with expression based on muscular contraction parameters. We have proposed a method of calculating the muscular contraction parameters from an arbitrary face image without using learning for each individual. As a result, we were able to generate not only individual facial expressions, but also the facial expressions of various persons. In this paper, we propose a muscle‐based facial model, in which the facial muscles defined are both linear muscles and sphincter muscles. Additionally, we propose a method of synthesizing individual facial images with expression based on muscular contraction parameters. First, an individual facial model with expression is generated by fitting using an arbitrary face image. Next, the muscular contraction parameters that correspond to the expression displacement of the input face image are calculated. Finally, the facial expression is synthesized by the vertex displacements of a neutral facial model based on the calculated muscular contraction parameters. Experimental results reveal that the newly included sphincter muscles make it possible to synthesize facial expressions of the facial image which correspond to the actual face image with arbitrary expressions of the mouth or eyes. © 2011 Wiley Periodicals, Inc. Electron Comm Jpn, 94(10): 17–25, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10362
Highly efficient liquid flow actuator operated by surface acoustic waves
Authors: Saiki Tsunemasa , Okada Katsuhide , Utsumi Yuichi
Published: September 2011

Surface acoustic wave (SAW) devices, because of their very simple structures, can be used as component parts for micro total analysis systems. We focused on a liquid flow actuator operated by SAWs and investigated highly efficient interdigital transducers (IDTs) to generate SAWs. The IDTs were fabricated by patterning Al/Cr on a LiNbO3 substrate. In an IDT with a stripline pitch of 200 μm, effective water droplet streaming was produced. We also fabricated a continuous liquid flow actuator consisting of both an IDT and a flow channel made of epoxy‐based negative resist SU‐8 on one chip. To diversify the liquids used, we created an actuator design in which the IDT and liquid do not directly touch one another at the partition wall. Using this chip, we succeeded in creating a continuous flow of liquid using the SAWs. When 160 mW of electric power was applied, the liquid flow rate of the actuator was approximately 7.8 μL/s. We experimentally found that the electric power applied to the IDT was proportional to flow velocity and that the IDT with 200 μm pitch produced effective continuous liquid flow as well as water droplet streaming. © 2011 Wiley Periodicals, Inc. Electron Comm Jpn, 94(10): 10–16, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10367
Tetrahydroisoquinoline‐Based N‐Oxides as Chiral Organocatalysts for the Asymmetric Allylation of Aldehydes
Authors: Naicker Tricia , Arvidsson Per I. , Kruger Hendrik G. , Maguire Glenn E. M. , Govender Thavendran
Published: September 2011

The short synthesis of a series of novel chiral N‐oxideorganocatalysts and their evaluation in the asymmetric allylation reaction of aromatic and α‐β‐unsaturated aldehydes with allyltrichlorosilane is reported. These readily modifiable organocatalysts are the first of their kind based on the tetrahydroisoquinoline framework. The chiral homoallyl products were obtained with good chemical efficiency (up to 93 % yield) and high enantioselectivity (up to 91 % ee) under mild reaction conditions (23 °C).
Highly Efficient Synthesis of 5‐Substituted 1H‐Tetrazoles Catalyzed by Cu–Zn Alloy Nanopowder, Conversion into 1,5‐ and 2,5‐Disubstituted Tetrazoles, and Synthesis and NMR Studies of New Tetrazolium Ionic Liquids
Authors: Aridoss Gopalakrishnan , Laali Kenneth K.
Published: September 2011

A series of 5‐substituted 1H‐tetrazoles were synthesized through [3+2] cycloaddition reactions between nitriles RCN and NaN3 in the presence of Cu–Zn alloy nanopowder as catalyst. The 1,5‐dibutyl, 1‐butyl‐5‐hexyl, 2,5‐dibutyl, and 2‐butyl‐5‐hexyl derivatives were then used as building blocks to synthesize several novel tetrazolium ionic liquids (ILs) with EtSO4–, OTf–, and NTf2– counterions. Whereas alkylation of the 2,5‐dialkyltetrazoles selectively gave the N‐4 alkylated onium salts, with the 1,5‐dialkyl derivatives approximately 1:1 mixtures of two tetrazolium salts were formed by alkylation at N‐3 and N‐4. The triflate and ethyl sulfate salts are room‐temperature ILs that are hydrophilic, whereas the NTf2 salts are low‐melting ILs and are hydrophobic. The resulting tetrazolium‐based ionic liquids were studied by various multinuclear and 2D NMR techniques including natural abundance 15N and 1H/15N correlations.
Enantioselective Syntheses of Tetrahydroquinolines Based on Iridium‐Catalyzed Allylic Substitutions: Total Syntheses of (+)‐Angustureine and (–)‐Cuspareine
Authors: Satyanarayana Gedu , Pflästerer Daniel , Helmchen Günter
Published: September 2011

A protecting‐group‐free two‐step approach for the preparation of tetrahydroquinolines has been developed. The procedure involves a highly regio‐ and enantioselective intermolecular iridium‐catalyzed allylic amination followed by one‐pot hydroboration and intramolecular Suzuki–Miyaura cross‐coupling. This method was applied in total syntheses of the alkaloids (+)‐angustureine and (–)‐cuspareine.
BF3·OEt2‐Mediated 1,3‐Hydride Shift Followed by 6π Electrocyclization: An Efficient Route for the Synthesis of Pyridopyrimidine, Pyranoquinoline, and Phenanthroline Derivatives
Authors: Majumdar Krishna C. , Ponra Sudipta , Nandi Raj Kumar
Published: September 2011

The synthesis of pyridopyrimidine, pyranoquinoline, and phenanthroline derivatives can be easily and efficiently accomplished by the direct reaction of a 1‐aminopenta‐1,4‐diene fragment, an aromatic aldehyde, and BF3·OEt2 in the absence of any metal catalyst. The notable features of this procedure are mild reaction conditions, good to high yields, and operational simplicity.
A Tandem “On‐Palladium” Heck–Jeffery Amination Route Toward the Synthesis of Functionalized Indole‐2‐carboxylates
Authors: McNulty James , Keskar Kunal
Published: September 2011

A direct synthesis of functionalized indole‐2‐carboxylates involving a PdII‐catalyzed annulation of ortho‐iodoanilines onto a vinyl ether is described. The reaction mechanism is shown to be distinct from a stepwise Heck, intramolecular amination pathway, likely involving a tandem “on‐palladium” Heck–Jeffery amination process incorporating a novel intramolecular amination step.
Concise Synthesis of Highly Substituted Benzo[a]quinolizines by a Multicomponent Reaction/Allylation/Heck Reaction Sequence
Authors: den Heeten René , van der Boon Léon J. P. , Broere Daniël L. J. , Janssen Elwin , de Kanter Frans J. J. , Ruijter Eelco , Orru Romano V. A.
Published: September 2011

The combination of the recently developed multicomponent construction of highly substituted 3,4‐dihydropyridones with subsequent allylation and intramolecular Heck‐type cyclization allows the straightforward construction of benzo[a]quinolizines, a class of polycyclic compounds that – despite their interesting pharmacological and photochemical properties – have little precedent in the literature. After optimization of the individual steps, we used this reliable three‐step sequence to generate a small library of diversely substituted benzo[a]quinolizines and various heterocyclic analogs.
Gas Sensing Mechanism of Gold Nanoparticles Decorated Single‐Walled Carbon Nanotubes
Authors: Mubeen Syed , Lim Jae‐Hong , Srirangarajan Aarti , Mulchandani Ashok , Deshusses Marc A. , Myung Nosang V.
Published: September 2011

Metal nanoparticles decorated single‐walled carbon nanotubes (SWNTs) can lead to considerable enhancement in sensing performance towards different gas analytes, however the sensing mechanism was not clearly elucidated. The detailed sensing mechanism of hybrid gold‐SWNT nanostructures toward hydrogen sulfide was investigated using field effect transistor (FET) transfer characteristics. At low H2S concentrations (≤100 ppbV), FET transfer characteristics show that the gold nanoparticles at the surface of SWNTs acted as nano‐Schottky barriers to predominately modulate transconductance upon exposure to unfunctionalized SWNTs on gold electrodes which showed little or no response upon exposure. Although the sensitivity of Au/SWNT toward H2S was strongly dependent upon the size and number of gold nanoparticles, the sensing mechanism was independent of it.
A simple model to include fuzziness in the seismic fragility curve and relevant effect compared with randomness
Authors: Colangelo Felice
Published: September 2011

Damage has to be quantified in civil structures to assess their seismic performance and risk and loss on a regional scale. Fragility curves have proved to be suitable for coping with randomness inherent in such an issue. Recently, the cognitive source of uncertainty has been stressed. Because the seismic limit states are defined descriptively more than analytically, fuzziness is inherent as well. In this study, a model to include fuzziness in the seismic fragility curve is implemented and appraised. First, several methods to compute seismic fragility are briefly reviewed. Consistent with the first‐order second‐moment reliability method, a simple extension is proposed and the explicit formulation of the probability measure is derived. Conclusions about the effect of fuzziness are drawn based on this analytical formulation. Above all, fragility increases at lower seismic intensity, whereas it decreases at higher intensity. Steepness of the fragility curve, that is, sensitivity to the ground motion, decreases with increase of fuzziness. This effect is shown to be similar to the effect of randomness. However, the greater the randomness, the smaller is the importance of fuzziness. Fuzziness aside, deterministic capacity may give excessive overestimation of fragility. A numerical example is presented. The fuzzy random fragility curves of a masonry infilled reinforced concrete frame are compared with the curves with fuzziness neglected and with different degrees of randomness. All results by the proposed model are reasonable. Copyright © 2011 John Wiley & Sons, Ltd.
Shake‐table tests of a three‐story reinforced concrete frame with masonry infill walls
Authors: Stavridis Andreas , Koutromanos I. , Shing P. B.
Published: September 2011

This paper presents the shake‐table tests of a 2/3‐scale, three‐story, two‐bay, reinforced concrete frame infilled with unreinforced masonry walls. The specimen is representative of the construction practice in California in the 1920s. The reinforced concrete frame had nonductile reinforcement details and it was infilled with solid masonry walls in one bay and infill walls with window openings in the other bay. The structure was subjected to a sequence of dynamic tests including white‐noise base excitations and 14 scaled historical earthquake ground motion records of increasing intensity. The performance of the structure was satisfactory considering the seismic loads it was subjected to. The paper summarizes the design of the specimen and the major findings from the shake‐table tests, including the dynamic response, the load resistance, the evolution of damage, and the final failure mechanism. Copyright © 2011 John Wiley & Sons, Ltd.
Bioconcentration of methylmercury in microzooplankton in a temperate river
Authors: Kim Hyunji , Noh Seam , Kim Eunhee , Poopal Rama Krishnan , Lee Hak Young , Han Seunghee
Published: September 2011

To understand the bioconcentration of methylmercury (MeHg) at the base of the riverine food chain, we determined levels of dissolved organic carbon, microseston, Hg, and MeHg in surface water in relation to the microzooplankton MeHg from Yeongsan River. The spatial distribution of unfiltered Hg (0.29–3.1 ng/L) and dissolved Hg (0.15–0.74 ng/L) closely followed the microseston distribution. The spatial distribution of unfiltered MeHg (0.0078–0.077 ng/L) and dissolved MeHg (0.0069–0.018 ng/L) increased with increasing distance from the river mouth and appeared to arise from the shallow wetlands surrounding the upper riverbanks and then to be transported downstream. The logarithm of the MeHg bioconcentration factor for microzooplankton ranged from 5.3 to 6.0 (5.7 ± 0.18), and for microseston ranged from 4.0 to 5.4 (4.9 ± 0.35). Linear correlation statistics comparing microzooplankton MeHg and river water characteristics revealed that microzooplankton MeHg concentration was most significantly correlated with unfiltered MeHg (r = 0.83) and particulate MeHg (r = 0.80) levels. This result suggests that MeHg in unfiltered river water, which is relatively easy to determine, can be used as a surrogate for MeHg in microzooplankton that may influence MeHg levels in higher-trophic-level organisms. Environ. Toxicol. Chem. 2011;30:2860–2867. © 2011 SETAC
A family of multi‐point flux approximation schemes for general element types in two and three dimensions with convergence performance
Authors: Pal Mayur , Edwards Michael G.
Published: September 2011

A family of flux‐continuous, locally conservative, control‐volume‐distributed multi‐point flux approximation (CVD‐MPFA) schemes has been developed for solving the general geometry‐permeability tensor pressure equation on structured and unstructured grids. These schemes are applicable to the full‐tensor pressure equation with generally discontinuous coefficients and remove the O(1) errors introduced by standard reservoir simulation schemes when applied to full‐tensor flow approximation. The family of flux‐continuous schemes is characterized by a quadrature parameterization. Improved numerical convergence for the family of CVD‐MPFA schemes using the quadrature parameterization has been observed for structured and unstructured grids in two dimensions.

The CVD‐MPFA family cell‐vertex formulation is extended to classical general element types in 3‐D including prisms, pyramids, hexahedra and tetrahedra. A numerical convergence study of the CVD‐MPFA schemes on general unstructured grids comprising of triangular elements in 2‐D and prismatic, pyramidal, hexahedral and tetrahedral shape elements in 3‐D is presented. Copyright © 2011 John Wiley & Sons, Ltd.
Barriers to and facilitators for the use of an evidence‐based occupational therapy guideline for older people with dementia and their carers
Authors: Van't Leven Netta , Graff Maud J.L. , Kaijen Marleen , de Swart Bert J.M. , Olde Rikkert Marcel G.M. , Vernooij‐Dassen Myrra J.M.
Published: September 2011

Objective

Implementing evidence‐based guidelines is not a simple task. This study aimed to define barriers to and facilitators for implementing the proven and effective Community Occupational Therapy in Dementia (COTiD) guideline for older people with dementia and their carers.

Methods

The qualitative method we used was the grounded theory. We collected data from focus group interviews with 17 occupational therapists (OTs) and telephone interviews with 10 physicians and 4 managers. We analysed the data with the constant comparative method by identifying codes, categories, and main themes.

Results

The main themes in barriers that OTs encountered were that they did not feel competent in treating older people with dementia at home according to the guideline; they had difficulties prioritising in this complex treatment, both for the client and themselves; and they were unsure about the minimal criteria for guideline adherence. The intensity of this programme was the main barrier. The barriers that confronted physicians and managers were lack of knowledge about occupational therapy and its reimbursement and lack of available trained OTs. For the OTs, the guideline's content and focus, evidence, and external support facilitated the use of the guideline. For physicians and managers, the guideline's evidence base and its benefits for clients and carers were the main facilitators.

Conclusions

This study generates knowledge for applying innovations in health care settings. Improvement of the OTs' knowledge and self‐confidence is needed for using the guideline. We expect that more competent OTs will motivate their physicians and managers to use this successful COTiD intervention. Copyright © 2011 John Wiley & Sons, Ltd.
Acute‐phase response reactants as objective biomarkers of radiation‐induced mucositis in head and neck cancer
Authors: Mohammed Fazilat F. , Poon Ian , Zhang Liying , Elliott Liz , Hodson Ian D. , Sagar Stephen M. , Wright James
Published: September 2011

Background

Current evaluation of radiation‐induced mucositis in head and neck cancer relies on subjective scoring with interrater variability. We evaluated serum erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) as objective markers of radiation‐induced mucositis.

Methods

Weekly serum CRP and ESR levels were measured in patients treated for head and neck cancer with radiation ± chemotherapy. Acute radiation toxicity was evaluated using National Cancer Institute of Canada‐Common Toxicity Criteria (NCIC‐CTC) version 2.0 and the Head and Neck Radiotherapy Questionnaire (HNRQ).

Results

ESR and CRP levels were significantly elevated by 3 weeks (p = .01) and 6 weeks (p = .0002), respectively, and independent of age or pretreatment surgery. ESR was significantly dependent on radiation dose (p = .0004) and significantly higher with chemoradiation (p = .03).

Conclusion

Serum ESR and CRP rise reliably in a radiation dose‐dependent manner. ESR correlated with clinical symptoms and distinguished patients receiving chemoradiation. ESR and CRP may be an objective and sensitive marker of radiation‐induced mucositis. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
miR-25 Targets TNF-Related Apoptosis Inducing Ligand (TRAIL) Death Receptor-4 and Promotes Apoptosis Resistance in Cholangiocarcinoma
Authors: Razumilava Nataliya , Bronk Steve F. , Smoot Rory L. , Fingas Christian D. , Werneburg Nathan W. , Roberts Lewis R. , Mott Justin L.
Published: September 2011

It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles. In this study, we identify elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as patient samples. In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates miR-25 production. Functionally, miR-25 was shown to protect cells against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly, antagonism of miR-25 in culture sensitized cells to apoptotic death. Computational analysis identified the TRAIL Death Receptor-4 (DR4) as a potential novel miR-25 target, and this prediction was confirmed by immunoblot, cell staining, and reporter assays.

Conclusion:

These data implicate elevated miR-25 levels in the control of tumor cell apoptosis in cholangiocarcinoma. The identification of the novel miR-25 target DR4 provides a mechanism by which miR-25 contributes to evasion of TRAIL-induced cholangiocarcinoma apoptosis. (Hepatology 2012)
Myeloid Suppressor Cells Induced by Hepatitis C Virus Suppress T-Cell Responses Through the Production of Reactive Oxygen Species
Authors: Tacke Robert S. , Lee Hai-Chon , Goh Celeste , Courtney Jeremy , Polyak Stephen J. , Rosen Hugo R. , Hahn Young S.
Published: September 2011

Impaired T-cell responses in chronic hepatitis C virus (HCV) patients have been reported to be associated with the establishment of HCV persistent infection. However, the mechanism for HCV-mediated T-cell dysfunction is yet to be defined. Myeloid-derived suppressor cells (MDSCs) play a pivotal role in suppressing T-cell responses. In this study we examined the accumulation of MDSCs in human peripheral blood mononuclear cells (PBMCs) following HCV infection. We found that CD33+ mononuclear cells cocultured with HCV-infected hepatocytes, or with HCV core protein, suppress autologous T-cell responses. HCV core-treated CD33+ cells exhibit a CD14+CD11b+/lowHLADR−/low phenotype with up-regulated expression of p47phox, a component of the NOX2 complex critical for reactive oxygen species (ROS) production. In contrast, immunosuppressive factors, arginase-1 and inducible nitric oxide synthase (iNOS), were not up-regulated. Importantly, treatment with an inactivator of ROS reversed the T-cell suppressive function of HCV-induced MDSCs. Lastly, PBMCs of chronic HCV patients mirror CD33+ cells following treatment with HCV core where CD33+ cells are CD14+CD11b+HLADR−/low, and up-regulate the expression of p47phox.

Conclusion:

These results suggest that HCV promotes the accumulation of CD33+ MDSC, resulting in ROS-mediated suppression of T-cell responsiveness. Thus, the accumulation of MDSCs during HCV infection may facilitate and maintain HCV persistent infection. (Hepatology 2012)
Osteopontin, an Oxidant Stress Sensitive Cytokine, Up-regulates Collagen-I via Integrin αVβ3 Engagement and PI3K/pAkt/NFκB Signaling
Authors: Urtasun Raquel , Lopategi Aritz , George Joseph , Leung Tung-Ming , Lu Yongke , Wang Xiaodong , Ge Xiaodong , Fiel Maria Isabel , Nieto Natalia
Published: September 2011

A key feature in the pathogenesis of liver fibrosis is fibrillar Collagen-I deposition; yet, mediators that could be key therapeutic targets remain elusive. We hypothesized that osteopontin (OPN), an extracellular matrix (ECM) cytokine expressed in hepatic stellate cells (HSCs), could drive fibrogenesis by modulating the HSC pro-fibrogenic phenotype and Collagen-I expression. Recombinant OPN (rOPN) up-regulated Collagen-I protein in primary HSCs in a transforming growth factor beta (TGFβ)–independent fashion, whereas it down-regulated matrix metalloprotease-13 (MMP13), thus favoring scarring. rOPN activated primary HSCs, confirmed by increased α-smooth muscle actin (αSMA) expression and enhanced their invasive and wound-healing potential. HSCs isolated from wild-type (WT) mice were more profibrogenic than those from OPN knockout (

Opn

−/−) mice and infection of primary HSCs with an Ad-OPN increased Collagen-I, indicating correlation between both proteins. OPN induction of Collagen-I occurred via integrin αvβ3 engagement and activation of the phosphoinositide 3-kinase/phosphorylated Akt/nuclear factor kappa B (PI3K/pAkt/NFκB)–signaling pathway, whereas cluster of differentiation 44 (CD44) binding and mammalian target of rapamycin/70-kDa ribosomal protein S6 kinase (mTOR/p70S6K) were not involved. Neutralization of integrin αvβ3 prevented the OPN-mediated activation of the PI3K/pAkt/NFκB–signaling cascade and Collagen-I up-regulation. Likewise, inhibition of PI3K and NFκB blocked the OPN-mediated Collagen-I increase. Hepatitis C Virus (HCV) cirrhotic patients showed coinduction of Collagen-I and cleaved OPN compared to healthy individuals. Acute and chronic liver injury by CCl4 injection or thioacetamide (TAA) treatment elevated OPN expression. Reactive oxygen species up-regulated OPN

in vitro

and

in vivo

and antioxidants prevented this effect. Transgenic mice overexpressing OPN in hepatocytes (

Opn

HEP Tg) mice developed spontaneous liver fibrosis compared to WT mice. Last, chronic CCl4 injection and TAA treatment caused more liver fibrosis to WT than to

Opn

−/− mice and the reverse occurred in

Opn

HEP Tg mice.

Conclusion :

OPN emerges as a key cytokine within the ECM protein network driving the increase in Collagen-I protein contributing to scarring and liver fibrosis. (Hepatology 2012)
The Human Gallbladder Secretes Fibroblast Growth Factor 19 Into Bile: Towards Defining the Role of Fibroblast Growth Factor 19 in the Enterobiliary Tract
Authors: Zweers Serge J.L.B. , Booij Klaske A.C. , Komuta Mina , Roskams Tania , Gouma Dirk J. , Jansen Peter L.M. , Schaap Frank G.
Published: September 2011

Fibroblast growth factor 19 (FGF19) plays a crucial role in the negative feedback regulation of bile salt synthesis. In the postprandial state, activation of ileal farnesoid X receptor (FXR) by bile salts results in transcriptional induction of FGF19 and elevation of circulating FGF19 levels. An intestinal-liver axis of FGF19 signaling results in down-regulation of bile salt synthesis. The aim of this study was to explore a broader signaling activity of FGF19 in organs engaged in the enterohepatic circulation of bile salts. For this aim, FGF19 expression and aspects of FGF19 signaling were studied in surgical specimens and in cell lines of hepatobiliary and intestinal origin. FGF19 messenger RNA was found to be abundantly expressed in the human gallbladder and in the common bile duct, with only minor expression observed in the ileum. Interestingly, human gallbladder bile contains high levels of FGF19 (21.9 ± 13.3 versus 0.22 ± 0.14 ng/mL in the systemic circulation). Gallbladder explants secrete 500 times more FGF19 than FXR agonist-stimulated ileal explants. Factors required for FGF19 signaling (i.e., FGFR4 and βKlotho) are expressed in mucosal epithelial cells of the gallbladder and small intestine. FGF19 was found to activate signaling pathways in cell lines of cholangiocytic, enteroendocrine, and enterocytic origin.

Conclusion :

The combined findings raise the intriguing possibility that biliary FGF19 has a signaling function in the biliary tract that differs from its established signaling function in the portal circulation. Delineation of the target cells in bile-exposed tissues and the affected cellular pathways, as well as a possible involvement in biliary tract disorders, require further studies. (Hepatology 2012)
A low‐dimensional hillslope‐based catchment model for layered groundwater flow
Authors: Broda S. , Larocque M. , Paniconi C. , Haitjema H.
Published: September 2011

Despite the strong interaction between surface and subsurface waters, groundwater flow representation is often oversimplified in hydrological models. For instance, the interplay between local or shallow aquifers and deeper regional‐scale aquifers is typically neglected. In this work, a novel hillslope‐based catchment model for the simulation of combined shallow and deep groundwater flow is presented. The model consists of the hillslope‐storage Boussinesq (hsB) model representing shallow groundwater flow and an analytic element (AE) model representing deep regional groundwater flow. The component models are iteratively coupled via a leakage term based on Darcy's law, representing delayed recharge to the regional aquifer through a low conductivity layer. Simulations on synthetic single hillslopes and on a two‐hillslope open‐book catchment are presented, and the results are compared against a benchmark three‐dimensional Richards equation model. The impact of hydraulic conductivity, hillslope plan geometry (uniform, convergent, divergent), and hillslope inclination (0.2%, 5%, and 30%) under drainage and recharge conditions are examined. On the single hillslopes, good matches for heads, hydrographs, and exchange fluxes are generally obtained, with the most significant differences in outflows and heads observed for the 30% slope and for hillslopes with convergent geometry. On the open‐book catchment, cumulative outflows are overestimated by 1–4%. Heads in the confined and unconfined aquifers are adequately reproduced throughout the catchment, whereas exchange fluxes are found to be very sensitive to the hillslope drainable porosity. The new model is highly efficient computationally compared to the benchmark model. The coupled hsB/AE model represents an alternative to commonly used groundwater flow representations in hydrological models, of particular appeal when surface–subsurface exchanges, local aquifer–regional aquifer interactions, and low flows play a key role in a watershed's dynamics. Copyright © 2011 John Wiley & Sons, Ltd.
Improving executive functions in 5‐ and 6‐year‐olds: Evaluation of a small group intervention in prekindergarten and kindergarten children
Authors: Röthlisberger Marianne , Neuenschwander Regula , Cimeli Patriza , Michel Eva , Roebers Claudia M.
Published: September 2011

Research suggests a central role of executive functions for children's cognitive and social development during preschool years, especially in promoting school readiness. Interventions aiming to improve executive functions are therefore being called for. The present study examined the effect of a small group intervention implemented in kindergarten settings focusing on basic components of executive functions, i.e., working memory, interference control and cognitive flexibility. A total of 135 children enrolled in Swiss prekindergarten (5‐year‐olds) and kindergarten (6‐year‐olds) were involved. Results revealed that the small group intervention promoted gains in all three included components of executive functions: prekindergarten children substantially improved their working memory and cognitive flexibility processes, whereas significant training effects were found for the kindergarten children in interference control. Implications of these findings for early intervention programs and for tailoring preschool curricula are discussed, particularly with respect to children's school readiness. Copyright © 2011 John Wiley & Sons, Ltd.
Comparison between two different methods of immobilizing NGF in poly(DL‐lactic acid‐co‐glycolic acid) conduit for peripheral nerve regeneration by EDC/NHS/MES and genipin
Authors: Hsieh Shu‐Chih , Tang Cheng‐Ming , Huang Wen‐Tao , Hsieh Ling‐Ling , Lu Chun‐Mei , Chang Chen‐Jung , Hsu Shan‐hui
Published: September 2011

For surface modification and nerve regeneration, chitosan, followed by nerve growth factor (NGF), was immobilized onto the interior surface of poly (lactic acit‐co‐glycolic) conduits, using EDC/NHS/MES system (EDCs) and genipin (GP). Four new conduits were, therefore, obtained and named by immobilizing order‐EDCs/EDCs, GP/EDCs, EDCs/GP, and GP/GP groups. The immobilized methods used were evaluated and compared, respectively. The researchers found that the EDCs‐ and GP‐cross‐linked chitosan displayed higher hydrophilic than pure poly (DL‐lactic acid‐co‐glycolic acid) (PLGA) in water contact angle experiment, which meant the cell compatibility was improved by the modification. Scanning electron microscopic observations revealed that the GP‐cross‐linking of chitosan greatly improved cell compatibility while cultured rat PC12 cells were flatter and more spindle‐shaped than EDCs‐cross‐linked chitosan. The results concerning the GP‐cross‐linked chitosan revealed significant proliferation of the seeded cells relative to pure PLGA films, as determined by counting cells and MTT assay. The NGF was released from the modified conduits in two separate periods—an initial burst in 5 days and then slow release from day 10 to day 40. The GP/EDCs group had the highest NGF value among all groups after the 5th day. Finally, the controlled‐release conduits were used to bridge a 10 mm rat sciatic nerve defect. Six weeks following implantation, morphological analysis revealed the highest numbers of myelinated axons in the midconduit and distal regenerated nerve in GP/EDCs group. Therefore, the results confirm that GP/EDCs groups with good cell compatibility and effective release of NGF can considerably improve peripheral nerve regeneration. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
A conductive nanostructured polymer electrodeposited on titanium as a controllable, local drug delivery platform
Authors: Sirivisoot Sirinrath , Pareta Rajesh A. , Webster Thomas J.
Published: September 2011

Infection and inflammation associated with orthopedic implants can be life threatening, time consuming, and expensive, thus, motivating the development of a local drug delivery platform that could prevent such deleterious events. For this purpose, nanostructured polypyrrole (PPy) incorporating antibiotics and anti‐inflammatory drugs (penicillin/streptomycin (P/S) or dexamethasone (Dex), respectively) were coated on commercially pure titanium through an easy to use electrochemical deposition method. As shown in our previous study, about 80% (compared with initial amount) of these incorporated drugs were released after electrical stimulation spanning five cycles (voltage was varied between −1 V and 1 V). In a further continuation of this work, nanostructured P/S incorporated PPy coatings on titanium were demonstrated to be bactericidal against Staphylococcus epidermis after 1 h, and when incorporated with Dex, inhibited macrophage (an inflammatory and immune response cell) growth after 8 and 13 h of in vitro culture. Moreover, nanostructured PPy‐drug films coated on titanium enhanced osteoblast (bone forming cells) proliferation, while at the same time, suppressed fibroblast (fibrous tissue forming cells) proliferation for up to 5 days. After electrical stimulation, antimicrobial and anti‐inflammatory‐coated devices yielded lower bacteria colonies and macrophage growth compared with unincorporated‐drug PPy films (controls). This study, thus, suggests that drug incorporated nanostructured PPy coatings on titanium are capable of effectively treating potential orthopedic implant infection and inflammation, and lays the foundation for the further development of local and controllable on‐demand drug delivery coatings to improve orthopedic implant efficacy. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Effect of thiol functionalization on the hemo‐compatibility of PLGA nanoparticles
Authors: Thasneem Y. M. , Sajeesh S. , Sharma Chandra P.
Published: September 2011

In this study, an attempt was made to reduce the interaction of poly(D,L‐lactic acid/glycolic acid) (PLGA) nanoparticles with the opsonins and phagocytic cells upon functionalization with thiol groups. Terminal carboxylic groups in PLGA were conjugated to the amino group of cysteine and nanoparticles were prepared by solvent evaporation technique. Detailed in vitro investigations were performed on PLGA and cysteine modified PLGA (Cys‐PLGA) nanoparticles to asses their blood compatibility. The effect of these nanoparticles on the release of proinflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) from human macrophage cells were evaluated. Thiolation was confirmed by fourier transform infrared spectroscopy and Ellman's assay; both PLGA and modified nanoparticles had average size in the range of 250 nm. Thiolation was an effective strategy in reducing the protein adsorption, complement activation, and platelet activation of PLGA nanoparticles. PLGA and modified PLGA nanoparticles were compatible with the blood cells and no hemolytic effect was detected. Particles were noncytotoxic on L929 cells and release of proinflammatory cytokines from macrophage cells was rather unaffected with the modification strategy. From these studies, it seems that thiolation of particulate delivery system is an interesting approach in manipulating the blood‐particle interactions and appears to be an effective candidate for injectable drug delivery applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Hydroxyapatite/polylactide biphasic combination scaffold loaded with dexamethasone for bone regeneration
Authors: Son Jun‐Sik , Kim Su‐Gwan , Oh Ji‐Su , Appleford Mark , Oh Sunho , Ong Joo L , Lee Kyu‐Bok
Published: September 2011

This study presents a novel design of a ceramic/polymer biphasic combination scaffold that mimics natural bone structures and is used as a bone graft substitute. To mimic the natural bone structures, the outside cortical‐like shells were composed of porous hydroxyapatite (HA) with a hollow interior using a polymeric template‐coating technique; the inner trabecular‐like core consisted of porous poly(D,L‐lactic acid) (PLA) that was loaded with dexamethasone (DEX) and was directly produced using a particle leaching/gas forming technique to create the inner diameter of the HA scaffold. It was observed that the HA and PLA parts of the fabricated HA/PLA biphasic scaffold contained open and interconnected pore structures, and the boundary between both parts was tightly connected without any gaps. It was found that the structure of the combination scaffold was analogous to that of natural bone based on micro‐computed tomography analysis. Additionally, the dense, uniform apatite layer was formed on the surface of the HA/PLA biphasic scaffold through a biomimetic process, and DEX was successfully released from the PLA of the biphasic scaffold over a 1‐month period. This release caused human embryonic palatal mesenchyme cells to proliferate, differentiate, produce ECM, and form tissue in vitro. Therefore, it was concluded that this functionally graded scaffold is similar to natural bone and represents a potential bone‐substitute material. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Enhancement of the capability of hydroxyapatite formation on Zr with anodic ZrO2 nanotubular arrays via an effective dipping pretreatment
Authors: Wang Lu‐Ning , Adams Alissa , Luo Jing‐Li
Published: September 2011

Hydroxyapatite (HA) depositions on metallic biomedical implants are widely applied to generate bioactive surfaces in simulated biological environments. Highly ordered anodic ZrO2 nanotubes have attracted increasing interest for biomedical applications. However, previous reports showed that at least 14–28 days were required to obtain HA coating on ZrO2 nanotubular arrays under biomimetic condition, thus capability to grow HA coating on ZrO2 nanotubular at room temperature needs to be enhanced. In the present work, we demonstrate that ZrO2 nanotubular arrays are suitable for an effective dipping treatment to induce more rapid HA coating. A series of ZrO2 nanotubular arrays having different dimensions were fabricated in fluoride containing electrolyte. Then, we used a dipping treatment for biomimetic formation of an adhesive HA coating on the nanotubular arrays. The coatings formed rapidly using this procedure under biomimetic conditions and did not require a high‐temperature annealing process. The as‐formed ZrO2 nanotubular arrays were treated using several dip‐and‐dry steps, through which the nanotubular arrays were filled and covered with calcium phosphate (CaP) nucleation sites. The specimens readily grew HA once immersed in the simulated biological fluid after 2 days immersion. The carbonated HA coating had several micron thickness after 8 days of immersion while only a thin layer of CaP were observed on annealed ZrO2 nanotubes immersed in the same solution for the same duration. Tensile testing showed that bonding strength between HA coating and substrate was 21.6 ± 1.6 MPa. This treatment dramatically improves efficiency for promoting HA formation on anodic ZrO2 nanotubes at room temperature. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Cogrinding significance for calcium carbonate–calcium phosphate mixed cement. II. Effect on cement properties
Authors: Tadier Solène , Bolay Nadine Le , Fullana Sophie Girod , Cazalbou Sophie , Charvillat Cédric , Labarrère Michel , Boitel Daniel , Rey Christian , Combes Christèle
Published: September 2011

In the present study, we aim to evaluate the contribution of the cogrinding process in controlling calcium carbonate‐dicalcium phosphate dihydrate cement properties. We set a method designed to evaluate phase separation, usually occurring during paste extrusion, which is quantitative, reliable, and discriminating and points out the determining role of cogrinding to limit filter‐pressing. We show that solid‐phase cogrinding leads to synergistic positive effects on cement injectability, mechanical properties, and radio‐opacity. It allows maintaining a low (<0.4 kg) and constant load during the extrusion of paste, and the paste's composition remains constant and close to that of the initial paste. Analogous behavior was observed when adding a third component into the solid phase, especially SrCO3 as a contrasting agent. Moreover, the cement's mechanical properties can be enhanced by lowering the L/S ratio because of the lower plastic limit. Finally, unloaded or Sr‐loaded cements show uniform and increased optical density because of the enhanced homogeneity of dry component distribution. Interestingly, this study reveals that cogrinding improves and controls essential cement properties and involves processing parameters that could be easily scaled up. This constitutes a decisive advantage for the development of calcium carbonate‐calcium phosphate mixed cements and, more generally, of injectable multicomponent bone cements that meet a surgeon's requirements. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Phase morphology, physical properties, and biodegradation behavior of novel PLA/PHBHHx blends
Authors: Zhao Qiang , Wang Shufang , Kong Meimei , Geng Weitao , Li Robert K.Y. , Song Cunjiang , Kong Deling
Published: September 2011

In this study, two biodegradable polyesters [i.e., polylactic acid (PLA) and poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBHHx)] with complementarity in terms of mechanical performance have been combined, and a series of blends with a broad range of compositions has been prepared by thermal compounding. The evolution of phase morphologies with the variation of compositions has been characterized by using Fourier transform infrared spectroscopic imaging together with scanning electron microscope analyses. Thermal, mechanical, and biodegradation properties of the PLA/PHBHHx blends were systematically investigated. Mechanical properties were further analyzed by using theoretical models and correlated with the results of the morphology/structure and compatibility of the blends. Results indicate that PLA/PHBHHx blends are immiscible but can be compatible to some extent at certain compositions (e.g., PLA/PHBHHx (w/w) = 80/20 and 20/80). The physical properties of the blend could be fine tuned by adjusting the blend composition. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.