bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing personal growth
Authors: Liu Ying (Jessie) , Yin Alexander C.
Published: March 2010

This chapter summarizes the dominant student development theories, notes important noncognitive outcomes, and reviews several assessment instruments that measure student personal growth.
Measurement issues in assessment
Authors: Volkwein J. Fredericks , Yin Alexander C.
Published: March 2010

This chapter summarizes ten selected issues and common problems that arise in most assessment research projects and offers constructive suggestions for assessment researchers.
Reporting research results effectively
Authors: Volkwein J. Fredericks
Published: March 2010

Assessment research is at its best when it packages research results and data so that they can be digested by multiple audiences.
The three‐dimensional nanofiber scaffold culture condition improves viability and function of islets
Authors: Zhao Ming , Song Chun , Zhang Weihui , Hou Yan , Huang Renping , Song Yimin , Xie Wanjun , Shi Yubo , Song Chunfang
Published: March 2010

Significant problems existing in the islet transplantation include a poor survival ability of the islet cells cultured under static conditions in vitro, decreased secretion function, and limited transplantation efficiency. In this study, we cocultured the three‐dimensional (3D) self‐assembling peptide nanofiber hydrogel scaffold with the islets from adult Wistar rats. The nanofiber scaffold constructed a 3D environment for the islets culture. The results of DTZ staining showed that the purity of the islets in the scaffold was >80%. The result of the fluorescent staining with AO‐PI demonstrated that the viability of the islets in the 3D culture environment (within scaffold) was greater than those in the two‐dimensional (2D) culture environment (without scaffold). The islets encapsulated in the 3D peptide nanofiber scaffold exhibited better secretion function. The insulin releasing index in the 3D group was remarkably higher than that in the 2D group. By scanning electron microscopy, it was observed that the 3D self‐assembling peptide nanofiber hydrogel scaffold formed a nano scale fiber with a geometric form and the islets were encapsulated in this scaffold. Our research demonstrated that this nanofiber scaffold provided a favorable 3D environment for the islets to be cultured in vitro and then improve the secretion function and prolong the survival time of the islet in vitro. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Type I collagen promotes proliferation and osteogenesis of human mesenchymal stem cells via activation of ERK and Akt pathways
Authors: Tsai Kuo‐Shu , Kao Shou‐Yen , Wang Chien‐Yuan , Wang Yng‐Jiin , Wang Jung‐Pan , Hung Shih‐Chieh
Published: March 2010

Biomaterials not only serve as scaffolds for bone regeneration, but may also exhibit inductive capability for bone growth. The goal of this study was to identify the best extracellular matrix protein for enhancing osteogenesis by hMSCs (human mesenchymal stem cells) and to investigate the underlying mechanism. Coating with collagen I, but not fibronectin, laminin, gelatin, and poly‐L‐lysine, enhanced late cell proliferation and promoted osteogenesis by hMSCs, as evidenced by an increase in Alizarin Red S staining, alkaline phosphatase activity and mRNA levels of Runx2 and osteocalcin. Coating with collagen I induced activation of ERK and Akt but not FAK, and treatment with PD98059 and LY294002 blocked the activation of ERK and Akt, respectively. Interestingly, LY294002 also blocked ERK activation, indicating the activation of PI3K/ERK pathway upon contact with collagen I. Furthermore, PD98059 or LY294002 abolished collagen I‐induced promotion of osteogenesis by hMSCs. However, blocking antibodies against α2β1 integrins did not inhibit collagen I‐induced osteogenesis by hMSCs. These data demonstrate that collagen I promotes proliferation and osteogenesis of hMSCs via activation of ERK and Akt pathways. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Neural differentiation directed by self‐assembling peptide scaffolds presenting laminin‐derived epitopes
Authors: Li Qianqian , Chau Ying
Published: March 2010

We prepared biofunctionalized matrices for cell growth using (RADA)3IKVAV(RADA)3 ((Arg‐Ala‐Asp‐Ala)3‐Ile‐Lys‐Val‐Ala‐Val‐(Arg‐Ala‐Asp‐Ala)3) and (RADA)4IKVAV ((Arg‐Ala‐Asp‐Ala)4‐Ile‐Lys‐Val‐Ala‐Val), self‐assembling peptides with a laminin‐derived sequence inserted between and attached terminally to the repeats of RADA, respectively. The material–cell interactions were investigated with PC12, a cell line commonly used as a model for studying neural differentiation. The behavior of PC12 and especially the neural differentiation was guided by the presence of IKVAV. Furthermore, the cell–material interactions were dependent on the culture dimensionality and the position of IKVAV in the self‐assembling peptide template. In the two‐dimensional (2‐D) culture, matrices containing IKVAV stimulated significantly longer neurite outgrowths from PC12 cells than did (RADA)4. More pronounced effect was observed in (RADA)3IKVAV(RADA)3 than in (RADA)4IKVAV. In the three‐dimensional (3‐D) culture, neurite outgrowth was not observed in the biofunctionalized matrices. Instead, cells displayed higher proliferation rate and survived longer culture time than in the 2‐D culture, with such enhancement being most significant in (RADA)3IKVAV(RADA)3. Despite the lack of differentiation phenotype, the cells grown in 3‐D biofunctionalized matrices were primed for differentiation, as evident by enhanced neurite outgrowth, increased neurite networking, and up‐regulated expression of differentiation markers upon their reintroduction to the 2‐D culture condition on petri dish. With the ease of incorporating biofunctional epitopes, and the flexibility to support either 2‐D or 3‐D culture, self‐assembling peptides provide versatile scaffolds to study the multiple facets of biomaterial–cell interactions. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
The effect of scanning electrochemical potential on the short‐term impedance of commercially pure titanium in simulated biological conditions
Authors: Ehrensberger Mark T. , Gilbert Jeremy L.
Published: March 2010

The electrochemical history (voltage–time variations) of titanium oxide‐solution interfaces can vary widelyin vivo, particularly where oxide abrasion is present, and it is important to assess the effects of voltage on the impedance behavior of the interface. Potential step impedance analysis (PSIA) utilizes a time and frequency domain methodology to assess the electrochemical impedance of electrified interfaces over a range of voltages. The PSIA method was used to study the combined effects of scanning electrical potential and the presence of solution‐born organic species (protein, amino acids, etc.) on the electrochemical properties of cpTi. The specific solutions used in these scanning PSIA experiments were phosphate buffered saline and cell culture medium supplemented with 10% fetal bovine serum. The results show that electrochemical impedance properties of cpTi are voltage–time history dependent and strongly influenced by electrical potential within the −1000 mV to +1000 mV range studied. Moreover, the presence of biologically relevant molecules in the electrolyte solution alters the impedance properties only at cathodic potentials. Specifically, at cathodic potentials, these organic species have been shown to suppress the cathodic current density, shift the zero current potential in the cathodic direction, and increase the interfacial capacitance, polarization resistance, and the distribution of surface relaxation times. At anodic potentials, the presence of the organic species does not alter any of the electrochemical properties examined. Overall, these results show the importance of understanding of the variation in electrochemical potentials achievablein vivoand the effects voltage history has on interfacial electrochemical behavior. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
The stability of self‐assembled monolayers with time and under biological conditions
Authors: Maciel Joana , Martins M. Cristina L. , Barbosa Mário A.
Published: March 2010

The stability of self‐assembled monolayers (SAMs) of different functionalities (CH3‐, OH‐, and EG4‐) over time under appropriate storage conditions and when immersed in cell culture media was evaluated. X‐ray photoelectron spectroscopy (XPS) was used to detect the oxidized sulfur species (S2p binding energy from 167 to 168 eV) resulting from oxidation of the surfaces. CH3‐terminated SAMs stored for a period of 9 weeks in a nitrogen chamber were not altered. The same did not happen with OH‐ and EG4‐SAMs, for which the XPS spectra evidenced oxidized peaks after 2 weeks. Regarding the stability of these surfaces under biological conditions, 30 min of immersion at 37°C in serum‐free or 10% fetal bovine serum (FBS) supplemented medium did not induce detectable oxidation. However, a small percentage of oxidized sulfur could have been washed out by the media, as confirmed in studies using SAMs immersed in water. Despite the possible rinsing out of oxidized thiols, high amounts of oxidation can still be detected by XPS. SAMs degradation during ethanol sterilization was not detectable by XPS, although a small increase on the wettability of OH‐SAMs was observed. The data suggest that SAMs must be used freshly prepared, being recommended for short‐term biological studies. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Evaluation of scaffold materials for tooth tissue engineering
Authors: Ohara Takayuki , Itaya Toshimitsu , Usami Kazutada , Ando Yusuke , Sakurai Hiroya , Honda Masaki J. , Ueda Minoru , Kagami Hideaki
Published: March 2010

Recently, the possibility of tooth tissue engineering has been reported. Although there are a number of available materials, information about scaffolds for tooth tissue engineering is still limited. To improve the manageability of tooth tissue engineering, the effect of scaffolds on in vivo tooth regeneration was evaluated. Collagen and fibrin were selected for this study based on the biocompatibility to dental papilla‐derived cells and the results were compared with those of polyglycolic acid (PGA) fiber and β‐tricalcium phosphate (β‐TCP) porous block, which are commonly used for tooth, dentin and bone tissue engineering. Isolated porcine tooth germ‐derived cells were seeded onto one of those scaffolds and transplanted to the back of nude mice. Tooth bud‐like structures were observed more frequently in collagen and fibrin gels than on PGA or β‐TCP, while the amount of hard tissue formation was less. The results showed that collagen and fibrin gel support the initial regeneration process of tooth buds possibly due to their ability to support the growth of epithelial and mesenchymal cells. On the other hand, maturation of tooth buds was difficult in fibrin and collagen gels, which may require other factors. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Novel poly(L‐lactic acid)/hyaluronic acid macroporous hybrid scaffolds: Characterization and assessment of cytotoxicity
Authors: Antunes J. C. , Oliveira J. M. , Reis R. L. , Soria J. M. , Gómez‐Ribelles J. L. , Mano J. F.
Published: March 2010

Poly(L‐lactic acid), PLLA, a synthetic biodegradable polyester, is widely accepted in tissue engineering. Hyaluronic acid (HA), a natural polymer, exhibits an excellent biocompatibility, influences cell signaling, proliferation, and differentiation. In this study, HA crosslinking was performed by immersion of the polysaccharide in water–acetone mixtures containing glutaraldehyde (GA). The objective of this work is to produce PLLA scaffolds with the pores coated with HA, that could be beneficial for bone tissue engineering applications. PLLA tridimensional scaffolds were prepared by compression molding followed by salt leaching. After the scaffolds impregnation with soluble HA solutions of distinct concentration, a GA‐crosslinking reaction followed by inactivation of the unreacted GA with glycine was carried out. An increase on surface roughness is shown by scanning electron microscopy (SEM) with the addition of HA. Toluidine blue staining indicates the present of stable crosslinked HA. An estimation of the HA original weight in the hybrid scaffolds was performed using thermal gravimetric analyses. FTIR‐ATR and XPS confirmed the crosslinking reaction. Preliminary in vitro cell culture studies were carried out using a mouse lung fibroblast cell line (L929). SEM micrographs of L929 showed that cells adhered well, spread actively throughout all scaffolds, and grew favorably. A MTS test indicated that cells were viable when cultured onto the surface of all scaffolds, suggesting that the introduction of crosslinked HA did not increase the cytotoxicity of the hybrid scaffolds. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Three‐dimensional macroscopic scaffolds with a gradient in stiffness for functional regeneration of interfacial tissues
Authors: Singh Milind , Dormer Nathan , Salash Jean R. , Christian Jordan M. , Moore David S. , Berkland Cory , Detamore Michael S.
Published: March 2010

A novel approach has been demonstrated to construct biocompatible, macroporous 3‐D tissue engineering scaffolds containing a continuous macroscopic gradient in composition that yields a stiffness gradient along the axis of the scaffold. Polymeric microspheres, made of poly(D,L‐lactic‐co‐glycolic acid) (PLGA), and composite microspheres encapsulating a higher stiffness nano‐phase material (PLGA encapsulating CaCO3 or TiO2 nanoparticles) were used for the construction of microsphere‐based scaffolds. Using controlled infusion of polymeric and composite microspheres, gradient scaffolds displaying an anisotropic macroscopic distribution of CaCO3/TiO2 were fabricated via an ethanol sintering technique. The controllable mechanical characteristics and biocompatible nature of these scaffolds warrants further investigation for interfacial tissue engineering applications. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Mussel adhesive protein fused with cell adhesion recognition motif triggers integrin‐mediated adhesion and signaling for enhanced cell spreading, proliferation, and survival
Authors: Kim Bum Jin , Choi Yoo Seong , Choi Bong‐Hyuk , Lim Seonghye , Song Young Hoon , Cha Hyung Joon
Published: March 2010

Adhesion of cells to a surface is a basic and important requirement in the fields of cell culture and tissue engineering. Previously, we constructed the cell adhesive, fp‐151‐RGD, by fusion of the hybrid mussel adhesive protein, fp‐151, and GRGDSP peptide, one of the major cell adhesion recognition motifs; fp‐151‐RGD efficiently immobilized cells on coated culture surfaces with no protein and surface modifications, and apparently enhanced cell adhesion, proliferation, and spreading abilities. In the present study, we investigated the potential use of fp‐151‐RGD as a biomimetic extracellular matrix material at the molecular level by elucidating its substantial effects on integrin‐mediated adhesion and signaling. Apoptosis derived from serum deprivation was significantly suppressed on the fp‐151‐RGD‐coated surface, indicating that RGD‐induced activation of integrin‐mediated signaling triggers the pathway for cell survival. Analysis of the phosphorylation of focal adhesion kinase clearly demonstrated activation of focal adhesion kinase, a well‐established indicator of integrin‐mediated signaling, on the fp‐151‐RGD‐coated surface, leading to significantly enhanced cell behaviors, including proliferation, spreading and survival, and consequently, more efficient cell culture. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Preparation and tribological properties of polyetheretherketone composites
Authors: Xiong Dangsheng , Xiong Lei , Liu LingLing
Published: March 2010

Polyetheretherketone (PEEK) is a thermoplastic engineering plastic with excellent mechanical properties. In this article, PEEK and its composites filled with ultrahigh‐molecular‐weight polyethylene (UHMWPE) were prepared by vacuum hot‐pressing method. Tribological properties of these materials were investigated by block‐on‐ring friction and wear rig. An alloy (CoCrMo) ring and a ceramic (Si3N4) ring were used as friction pairs. The experiments were conducted under deionized water lubrication (DWL), saline lubrication (SL), and calf serum solution lubrication (CSSL). Worn surfaces morphology was observed and analyzed by metallographic microscope. The results indicated that friction coefficients of PEEK/UHMWPE composites were effectively reduced when compared with pure PEEK. When the materials slid against the alloy (CoCrMo) ring, wear rates of PEEK/UHMWPE were also effectively reduced when compared with pure PEEK. Wear mechanisms of PEEK were mainly ploughing and slight scratches under CSSL condition, whereas the quantity of the ploughing and scratches for PEEK/20%UHMWPE were significantly reduced. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Initial evaluation of bone ingrowth into a novel porous titanium coating
Authors: Wazen Rima M. , Lefebvre Louis‐Philippe , Baril Eric , Nanci Antonio
Published: March 2010

Porous metals (sintered beads and meshes) have been used for many years for different orthopedic applications. Metal foams have been recently developed. These foams have the advantage of being more porous than the traditional coatings. Their high porosity provides more space for bone ingrowth and mechanical interlocking and presents more surface for implant‐bone contact. The objective of this study was to evaluate in vivo bone ingrowth into Ti implants covered with a novel Ti foam coating. This foam contains 50% in volume of interconnected pores and a higher surface area compared to dense Ti. Both coated implants and dense Ti controls were placed transcortically in the rat tibia. The animals were sacrificed at 2 weeks after implantation, and the amount of bone in the implants was determined using backscattered electron imaging and X‐ray microtomography. Already at this time interval, the pores within the Ti foam showed 97.7% bone filling, and the bone‐implant contact area was significantly increased compared to dense Ti controls. These initial results indicate that this novel Ti foam is biocompatible, has the capacity to sustain bone formation, and can potentially improve osseointegration. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
More insights into the CCN3/Connexin43 interaction complex and its role for signaling
Authors: Gellhaus Alexandra , Wotzlaw Christoph , Otto Teresa , Fandrey Joachim , Winterhager Elke
Published: March 2010

Connexin43 (Cx43) forms gap junction channels but also serves as a signaling center by binding to proteins via its C‐terminus. We have previously demonstrated that transfection of Cx43 leads to significantly reduced proliferation of placental tumor cells through upregulating and binding of the growth regulator CCN3 (NOV) at the C‐terminus of Cx43. Here, we combined fluorescence resonance energy transfer (FRET), co‐immunoprecipitation and proliferation and expression assays to characterize the interaction complex of Cx43 and CCN3. FRET measurements confirmed the interaction of CCN3 with wild‐type Cx43 (amino acids 1‐382) and with mutants of Cx43 truncated at the C‐terminus resulting in Cx43 proteins of amino acids 1‐374, 1‐273, 1‐264, 1‐257 in 293T cells. These results matched the co‐immunoprecipitation data. Interestingly, although FRET revealed distinct efficiencies in interaction of Cx43 with CCN3 for all deletion constructs only wild‐type Cx43 and one deletion construct (1‐374) led to increased CCN3 expression. Only these interactions which were associated with increased CCN3 expression resulted in a reduced cell proliferation. Our study provides evidence that only defined binding properties between Cx43 and CCN3 leading to an upregulation of CCN3 are needed for signaling. Furthermore, the data obtained by FRET analysis allowed us to model the 3D structure of the C‐terminus of Cx43 interacting with CCN3. J. Cell. Biochem. 110: 129–140, 2010. © 2010 Wiley‐Liss, Inc.
FGF signalling as a mediator of lineage transitions—Evidence from embryonic stem cell differentiation
Authors: Villegas Santiago Nahuel , Canham Maurice , Brickman Joshua M.
Published: March 2010

The fibroblast growth factor (FGF) signalling pathway is one of the most ubiquitous in biology. It has diverse roles in development, differentiation and cancer. Embryonic stem (ES) cells are in vitro cell lines capable of differentiating into all the lineages of the conceptus. As such they have the capacity to differentiate into derivatives of all three germ layers and to some extent the extra‐embryonic lineages as well. Given the prominent role of FGF signalling in early embryonic development, we explore the role of this pathway in early ES cell differentiation towards the major lineages of the embryo. As early embryonic differentiation is intricately choreographed at the level of morphogenetic movement, adherent ES cell culture affords a unique opportunity to study the basic steps in early lineage specification in the absence of ever shifting complex in vivo microenvironments. Thus recent experiments in ES cell differentiation are able to pinpoint specific FGF dependent lineage transitions that are difficult to resolve in vivo. Here we review the role of FGF signalling in early development alongside the ES cell data and suggest that FGF dependent signalling via phospho‐Erk activation maybe a major mediator of transitions in lineage specification. J. Cell. Biochem. 110: 10–20, 2010. © 2010 Wiley‐Liss, Inc.
Up‐regulation of crystallins is involved in the neuroprotective effect of wolfberry on survival of retinal ganglion cells in rat ocular hypertension model
Authors: Chiu Kin , Zhou Yuan , Yeung Sze‐Chun , Lok Carmen Ka‐Ming , Chan Owen O‐Cheung , Chang Raymond Chuen‐Chung , So Kwok‐Fai , Chiu Jin‐Fu
Published: March 2010

Wolfberry (fruit of Lycium barbarum Linn) has been known for balancing ‘Yin’ and ‘Yang’ in the body, nourishing the liver and kidney, improving visual acuity for more than 2,500 years in oriental countries. The active components in wolfberry include L. barbarum polysaccharide (LBP), zeaxanthine, betaine, cerebroside and trace amounts of zinc, iron, and copper. Each of them confers distinct beneficial effects and together they help to explain widespread use of wolfberry in the eastern world. Earlier study reported the neuroprotective effects of LBP on retinal ganglion cell (RGC) in an experimental model of glaucoma and the underlying in vivo cellular mechanisms of LBP neuroprotection deserve further exploration. In this study, we adopted proteomics, functional genomics, to evaluate pharmacological effects of LBP on the neuronal survival pathways. Among the significantly changed proteins induced by LBP feeding on ocular hypertension (OH) retinas, only proteins in crystallin family were focused in this study. The proteomic results were further confirmed using the Western blotting of the retinas and immunohistochemical staining of the retinal sections. We demonstrated that neuroprotective effect of—wolfberry extract—LBP on the survival of RGCs may be mediated via direct up‐regulation of neuronal survival signal βB2‐crystallin. J. Cell. Biochem. 110: 311–320, 2010. © 2010 Wiley‐Liss, Inc.
Tissue geometry patterns epithelial–mesenchymal transition via intercellular mechanotransduction
Authors: Gomez Esther W. , Chen Qike K. , Gjorevski Nikolce , Nelson Celeste M.
Published: March 2010

Epithelial–mesenchymal transition (EMT) is a phenotypic change in which epithelial cells detach from their neighbors and become motile. Whereas soluble signals such as growth factors and cytokines are responsible for stimulating EMT, here we show that gradients of mechanical stress define the spatial locations at which EMT occurs. When treated with transforming growth factor (TGF)‐β, cells at the corners and edges of square mammary epithelial sheets expressed EMT markers, whereas those in the center did not. Changing the shape of the epithelial sheet altered the spatial pattern of EMT. Traction force microscopy and finite element modeling demonstrated that EMT‐permissive regions experienced the highest mechanical stress. Myocardin‐related transcription factor (MRTF)‐A was localized to the nuclei of cells located in high‐stress regions, and inhibiting cytoskeletal tension or MRTF‐A expression abrogated the spatial patterning of EMT. These data suggest a causal role for tissue geometry and endogenous mechanical stresses in the spatial patterning of EMT. J. Cell. Biochem. 110: 44–51, 2010. © 2010 Wiley‐Liss, Inc.
17β‐estradiol supplementation attenuates ovariectomy‐induced increases in ATGL signaling and reduced perilipin expression in visceral adipose tissue
Authors: Wohlers Lindsay M. , Spangenburg Espen E.
Published: March 2010

Adipocytes from post‐menopausal females have higher basal lipolytic rates than pre‐menopausal females, which contributes to increased risk of developing dyslipidemia following menopause. The purpose of this study was to delineate cellular mechanisms affecting adipose tissue function in the ovariectomized (OVX) mouse and also determine if physical activity or estrogen supplementation alter any detected changes. Female C57/Bl6 mice were placed into SHAM, OVX sedentary (OVX), OVX exercise (OVX‐Ex), and OVX sedentary + 17β‐estradiol (OVX + E2) groups. Visceral fat mass, glycerol, and NEFA levels were significantly higher in OVX mice compared to SHAM animals, but were not elevated in the E2‐treated animals. Voluntary running failed to change circulating levels of glycerol or NEFA in OVX mice, but did partially attenuate the increase in visceral fat mass. Adipose triglyceride lipase (ATGL) protein content was significantly elevated in visceral fat from OVX and OVX‐Ex groups compared to SHAM, while ATGL–CGI‐58 interaction was significantly higher in OVX than SHAM and OVX + E2 mice. No significant differences in HSL phosphorylation were detected between groups, however, ERK1/2 phosphorylation was significantly elevated in the OVX mice. To determine if ERK1/2 function was critical for the increased glycerol levels, visceral fat was treated with MEK inhibitor PD98059, with no differences in glycerol release detected. Perilipin protein content was decreased significantly in OVX and OVX‐Ex mice compared to SHAM. Thus, these data suggest that increased ATGL signaling and reduced perilipin protein content may contribute to increased NEFA and glycerol levels in OVX mice, which are attenuated with E2 treatment, but not by exercise. J. Cell. Biochem. 110: 420–427, 2010. © 2010 Wiley‐Liss, Inc.
Hypoxia decreases sclerostin expression and increases Wnt signaling in osteoblasts
Authors: Genetos Damian C. , Toupadakis Chrisoula A. , Raheja Leah F. , Wong Alice , Papanicolaou Savvas E. , Fyhrie David P. , Loots Gabriela G. , Yellowley Clare E.
Published: March 2010

Mutations in sclerostin function or expression cause sclerosing bone dysplasias, involving decreased antagonism of Wnt/Lrp5 signaling. Conversely, deletion of the VHL tumor suppressor in osteoblasts, which stabilize HIF‐α isoforms and thereby enables HIF‐α/β‐driven gene transcription, increases bone mineral content and cross‐sectional area compared to wild‐type controls. We examined the influence of cellular hypoxia (1% oxygen) upon sclerostin expression and canonical Wnt signaling. Osteoblasts and osteocytes cultured under hypoxia revealed decreased sclerostin transcript and protein, and increased expression and nuclear localization of activated β‐catenin. Similarly, both hypoxia and the hypoxia mimetic DFO increased β‐catenin gene reporter activity. Hypoxia and its mimetics increased expression of the BMP antagonists gremlin and noggin and decreased Smad‐1/5/8 phosphorylation. As a partial explanation for the mechanism of regulation of sclerostin by oxygen, MEF2 reporter assays revealed decreased activity. Modulation of VEGF signaling under normoxia or hypoxia revealed no influence upon Sost transcription. These data suggest that hypoxia inhibits sclerostin expression, through enhanced antagonism of BMP signaling independent of VEGF. J. Cell. Biochem. 110: 457–467, 2010. © 2010 Wiley‐Liss, Inc.
More is less: Inactivation and deletion events and the search for tumor suppressor genes
Authors: Bradley W. Edward C. , Di Paola Domenic , Rampakakis Emmanouil , Zannis‐Hadjopoulos Maria
Published: March 2010

Tumor suppressor genes are frequently inactivated in cancer by large‐scale deletion events or epigenetic silencing, and experimental demonstration of such inactivation has historically been considered as support for assigning tumor suppressive function to a given gene. However, the discovery of a number of chromosomal domains wherein large deletions naturally occur at frequencies up to 100 times the average for the genome as a whole leads us to reevaluate the significance of sporadic deletions found within genes associated with these hotspots. Similarly, our recent demonstration that epigenetic chromatin silencing frequently spreads in cancer cells from gene‐poor into gene‐rich regions with apparent indifference to the gene content of the affected domain raises questions about the pertinence of inactivation as a criterion for ascribing tumor suppressor function to a given gene. We suggest that a number of putative suppressor genes for which inactivation and/or deletion events have been documented may simply be victims of collateral damage when these events occur, and the implication that these genes are being selected against during cancer progression should in some cases be reassessed. J. Cell. Biochem. 110: 281–287, 2010. © 2010 Wiley‐Liss, Inc.
Commentaries on quantum similarity (1): Density gradient quantum similarity
Authors: Carbó‐Dorca Ramon , Mercado Luz Dary
Published: March 2010

Computation of density gradient quantum similarity integrals is analyzed, while comparing such integrals with overlap density quantum similarity measures. Gradient quantum similarity corresponds to another kind of numerical similarity assessment between a pair of molecular frames, which contrarily to the usual up to date quantum similarity definitions are not measures, that is: strictly positive definite integrals. As the density gradient quantum similarity integrals are defined as scalar products of three real functions, they appear to possess a richer structure than the corresponding positive definite density overlap quantum similarity measures, while preserving the overall similarity trends, when the molecular frames are relatively moved in three‐dimensional space. Similarity indices are also studied when simple cases are analyzed in order to perform more comparisons with density overlap quantum similarity. Multiple gradient quantum similarity integrals are also defined. General GTO formulae are given. Numerical results within the atomic shell approximation (ASA) framework are presented as simple examples showing the new performances of the gradient density quantum similarity. Fortran 90 programs illustrating the proposed theoretical development can be downloaded from appropriate websites. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
ForceFit: A code to fit classical force fields to quantum mechanical potential energy surfaces
Authors: Waldher Benjamin , Kuta Jadwiga , Chen Samuel , Henson Neil , Clark Aurora E.
Published: March 2010

The ForceFit program package has been developed for fitting classical force field parameters based upon a force matching algorithm to quantum mechanical gradients of configurations that span the potential energy surface of the system. The program, which runs under UNIX and is written in C++, is an easy‐to‐use, nonproprietary platform that enables gradient fitting of a wide variety of functional force field forms to quantum mechanical information obtained from an array of common electronic structure codes. All aspects of the fitting process are run from a graphical user interface, from the parsing of quantum mechanical data, assembling of a potential energy surface database, setting the force field, and variables to be optimized, choosing a molecular mechanics code for comparison to the reference data, and finally, the initiation of a least squares minimization algorithm. Furthermore, the code is based on a modular templated code design that enables the facile addition of new functionality to the program. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Modeling of diarylalkyl‐imidazole and diarylalkyl‐triazole derivatives as potent aromatase inhibitors for treatment of hormone‐dependent cancer
Authors: Nagar Shuchi , Saha Achintya
Published: March 2010

Aromatase is an enzyme that catalyzes the final step in the conversion of androgen to estrogen. It has become an attractive target for the treatment of estrogen responsive breast cancer. The study has been focused on designing aromatase inhibitors (AIs) that can be selected as probable drug candidate for the treatment of breast cancer. In the present study, long chain diarylalkyl‐imidazole and ‐triazole scaffolds have been considered for exploring pharmacophores as potent AIs using QSAR (Quantitative SAR) and pharmacophore mapping studies. The model generated in linear free energy QSAR study (R2 = 0.905, Q2= 0.885, R2pred(ts) = 0.763) showed the importance of hydrophobicity, size and shape of the molecule, van der Waals surface and hydrogen atom contribution influence the activity. 3D QSAR of comparative molecular field analysis (CoMFA, R2= 0.921, Q2 = 0.741, R2pred(ts)= 0.583) showed that steric and electrostatic features along with hydrophobicity and electronic charge contribution at C4 (Fig. 1) influence on the inhibitory activity. Comparative molecular similarity analysis (CoMSIA, R2 = 0.874, Q2 = 0.716, R2pred(ts) = 0.591) study adjudged the presence of steric, electrostatic and hydrophobic fields together with hydrogen bond (HB) donor and acceptor play significant role in inhibitory activity to aromatase enzyme. Further pharmacophore mapping study (Q2 = 0.947, Δcost = 113.171, R2pred(ts) = 0.857) suggested that presence of HB acceptor, hydrophobicity with aromatic ring, and the importance of steric contribution influence on the activity. The critical distances among the features are also important for the inhibitor activity. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Theoretical studies on the structure and protonation of Cu(II) complexes of a series of tripodal aliphatic tetraamines: Good correlations with the experimental data
Authors: Salehzadeh Sadegh , Bayat Mehdi
Published: March 2010

DFT(B3LYP) studies on first protonation step of a series of Cu(II) complexes of some tripodal tetraamines with general formula N[(CH2)nNH2][(CH2)mNH2][(CH2)pNH2] (n = m = p = 2, tren; n = 3, m = p = 2, pee; n = m = 3, p = 2, ppe; n = m = 3, tpt; n = 2, m = 3, p = 4, epb; and n = m = 3, p = 4; ppb) are reported. First, the gas‐phase proton macroaffinity of all latter complexes was calculated with considering following simple reaction: [Cu(L)]2+(g) + H+(g) → [Cu(HL)]3+(g). The results showed that there is a good correlation between the calculated proton macroaffinities of all complexes with their stability constants in solution. Then, we tried to determine the possible reliable structures for microspecies involved in protonation process of above complexes. The results showed that, similar to the solid state, the [Cu(L)(H2O)]2+ and [Cu(HL)(H2O)2]3+ are most stable species for latter complexes and their protonated form, respectively, at gas phase. We found that there are acceptable correlations between the formation constants of above complexes with both the −$\overline {\Delta E}$ and −$\overline {\Delta G}$ of following reaction: [Cu(L)(H2O)]2+(g) + H+(g) + H2O(g) → [Cu(HL)(H2O)2]3+(g). The −$\overline {\Delta E}$ of the latter reaction can be defined as a theoretically solvent–proton macroaffinity of reactant complexes because they have gained one proton and one molecule of the solvent. The unknown formation constant of [Cu(epb)]2+ complex was also predicted from the observed correlations. In addition, the first proton affinity of all complexes was studied in solution using DPCM and CPCM methods. It was shown that there is an acceptable correlation between the solvent–proton affinities of [Cu(L)(H2O)]2+ complexes with formation constants of [Cu(HL)(H2O)2]3+ complexes in solution. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Molecular docking studies of selected tricyclic and quinone derivatives on trypanothione reductase of Leishmania infantum
Authors: Venkatesan Santhosh Kannan , Shukla Anil Kumar , Dubey Vikash Kumar
Published: March 2010

Visceral leishmaniasis, most lethal form of Leishmaniasis, is caused by Leishmania infantum in the Old world. Current therapeutics for the disease is associated with a risk of high toxicity and development of drug resistant strains. Thiol‐redox metabolism involving trypanothione and trypanothione reductase, key for survival of Leishmania, is a validated target for rational drug design. Recently published structure of trypanothione reductase (TryR) from L. infantum, in oxidized and reduced form along with Sb(III), provides vital clues on active site of the enzyme. In continuation with our attempts to identify potent inhibitors of TryR, we have modeled binding modes of selected tricyclic compounds and quinone derivatives, using AutoDock4. Here, we report a unique binding mode for quinone derivatives and 9‐aminoacridine derivatives, at the FAD binding domain. A conserved hydrogen bonding pattern was observed in all these compounds with residues Thr335, Lys60, His461. With the fact that these residues aid in the orientation of FAD towards the active site forming the core of the FAD binding domain, designing selective and potent compounds that could replace FAD in vivo during the synthesis of Trypanothione reductase can be deployed as an effective strategy in designing new drugs towards Leishmaniasis. We also report the binding of Phenothiazine and 9‐aminoacridine derivatives at the Z site of the protein. The biological significance and possible mode of inhibition by quinone derivatives, which binds to FAD binding domain, along with other compounds are discussed. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Comparison of prenatal ultrasound findings and autopsy findings in fetuses terminated after prenatal diagnosis of malformations: An experience of a clinical genetics center
Authors: Phadke Shubha R. , Gupta Ashutosh
Published: March 2010

Objective.

To compare antenatal diagnosis with post mortem examination findings in the pregnancies terminated after prenatal detection of anomalies and to evaluate the potential benefits of post mortem examination for counseling regarding the risk of recurrence.

Methods.

This is a retrospective study over a 7‐year period from 2001 to 2007. Pregnancies terminated after prenatal identification of fetal malformation were evaluated by post mortem examination of 91 fetuses.

Results.

Fetal autopsy provided a definite diagnosis in 72/91 (79.1%) of the cases. Fetal autopsy confirmed the sonographic findings in 89 of 91 cases (97.8%). In 66 (72.5%) cases there was complete concordance between prenatal and autopsy findings, while in 23 cases there was major concordance. There were 49 cases with isolated malformations, 41 cases with multiple (89) malformations, and, in one case, no malformation was found at autopsy. Of the 89 associated malformations, 39 (43.8%) were detected prenatally and 50 (56.2%) were detected on fetal autopsy. The additional malformations detected on autopsy included 38 major and 12 minor malformations Additional findings helped in redefining the diagnosis and the risk of recurrence in 30 of 91 (33%) cases.

Conclusion.

The present study emphasizes the importance of autopsy in providing accurate etiologic diagnosis necessary for genetic counseling. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2010
Effects of in vivo testosterone manipulation on ovarian morphology, follicular development, and follicle yolk testosterone in the homing pigeon
Authors: Goerlich Vivian C. , Dijkstra Cor , Groothuis Ton G. G.
Published: March 2010

To date, our understanding of the function of testosterone in female reproductive physiology is only marginal although there are indications that testosterone is involved in modulating follicular recruitment, growth, atresia, and ovulation. Studies elevating testosterone in breeding female birds have, in most instances, found detrimental effects, such as delayed clutch initiation or decreased clutch size. In our previous study, testosterone treatment of female homing pigeons delayed clutch initiation without diminishing fecundity. In this study, we explore whether the observed effect might have been caused by testosterone influencing follicle maturation or ovulation. We implanted mature female pigeons with testosterone prior to pairing, which resulted in constant elevation of circulating testosterone concentrations within the physiological range. We killed females after they had laid the first egg and measured ovarian and follicular development. Ovarian mass and pre‐hierarchical yolky follicles were not affected by the treatment; however, testosterone females produced smaller and lighter preovulatory follicles. High plasma testosterone levels at oviposition or a strong temporal increase in testosterone were negatively related to mass and diameter of second follicles. We proposed that sustained elevation of testosterone delays follicular maturation, potentially via negative feedback on the hypothalamo‐pituitary–gonadal axis.

Furthermore, to gain better insight into the regulation of yolk hormone acquisition, we measured testosterone concentrations in the preovulatory follicles. We found no differences between treatment groups but follicle yolk contained much higher levels of testosterone than yolk of un‐incubated eggs, suggesting that hormone measurements performed after oviposition do not correctly reflect maternal allocation. J. Exp. Zool. 313A:328–338, 2010. © 2010 Wiley‐Liss, Inc.
Human bocavirus infection in children with acute respiratory tract infection in India
Authors: Bharaj Preeti , Sullender Wayne M. , Kabra Sushil K. , Broor Shobha
Published: March 2010

Human bocavirus (HBoV) is a new human parvovirus identified in children with respiratory tract disease. Nasopharyngeal aspirates were collected from 305 children <5 years of age with acute respiratory tract infection from April 2005 to March 2007 and screened for the presence of HBoV by two separate sets of a polymerase chain reaction (PCR) described previously. Twenty‐two (7.2%) children who had acute respiratory infection were found to be positive for HBoV by both sets of PCR. The main clinical symptoms were cough (95%), runny nose (64%), and fever (59%). In two samples, HBoV was identified together with respiratory syncytial virus in one sample and influenza A virus in another. HBoV appeared to have no seasonal distribution and is associated with both upper and lower respiratory tract disease in young children in India. J. Med. Virol. 82: 812–816, 2010. © 2010 Wiley‐Liss, Inc.
Genetic variation of prevalent G1P[8] human rotaviruses in South Korea
Authors: Le Van Phan , Chung Yeon‐Chang , Kim Kijeong , Chung Sang‐In , Lim Inseok , Kim Wonyong
Published: March 2010

The human rotavirus G1P[8] strain is one of the most common rotaviruses worldwide, including Korea. Six Korean G1P[8] human rotaviruses, isolated using cell culture techniques, were characterized on the basis of sequence differences in VP7, VP4, VP6, and NSP4 genes to elucidate the evolutionary relationships in the community. All strains had a long RNA electropherotype, supported by VP6 gene analysis, clearly associated with subgroup II specificity. The phylogenetic analysis of VP7 gene sequences showed that they all clustered into lineage I, as reported for G1 strains in Japan, China, Vietnam, and Thailand. In addition, phylogenetic analysis of the VP4 gene showed that they belong to two distinct lineages, P[8]‐II and P[8]‐III. With respect to the NSP4 gene, all strains belonged to genotype B. An understanding of the ecology and molecular evolution of rotaviruses circulating in the country is very important for the development of vaccines and vaccination strategies. This study provides new information concerning the genetic variability of the rotavirus strain G1P[8] occurring most commonly as a vaccine candidate. J. Med. Virol. 82: 886–896, 2010. © 2010 Wiley‐Liss, Inc.
A comparison of two commercially available anti‐HEV IgG kits and a re‐evaluation of anti‐HEV IgG seroprevalence data in developed countries
Authors: Bendall Richard , Ellis Vic , Ijaz Samreen , Ali Rachel , Dalton Harry
Published: March 2010

In developed countries, the incidence of hepatitis E virus (HEV) infection and the resulting seroprevalence are uncertain. Published estimates of seroprevalnce in these populations range from 0.26% to 31%, which may in part reflect the variety of assays used by different studies. This study compared the performance of two commercial assays (Genelabs [Singapore] and Wantai ‘Beijing, China’ HEV IgG EIA kits) and reviewed published estimates of anti‐HEV seroprevalence in developed countries. The assays were compared using the WHO anti‐HEV reference serum, sera from UK‐acquired cases of genotype 3 HEV infections and 500 UK blood donor sera. The PE2 assay was found to be more sensitive than the GL assay (lower limit of detection for HEV IgG 0.25 vs. 2.5 WHO units/ml); it was positive in more sera from proven cases (98% vs. 56%), remained positive for longer post infection and resulted in a substantially higher estimate of seroprevalence in blood donors (16.2% vs. 3.6%). these results suggest that published studies of HEV seroprevalence using the GL assay have underestimated the true figure and that a properly validated method is required to make meaningful comparisons of HEV seroprevalence between populations. J. Med. Virol. 82: 799–805, 2010. © 2010 Wiley‐Liss, Inc.
Viral etiology of respiratory infections in children under 5 years old living in tropical rural areas of Senegal: The EVIRA project
Authors: Niang Mbayame Ndiaye , Diop Ousmane M. , Sarr Fatoumata Diene , Goudiaby Deborah , Malou‐Sompy Hubert , Ndiaye Kader , Vabret Astrid , Baril Laurence
Published: March 2010

Acute respiratory infection is one of the leading causes of child morbidity, especially in developing countries. Viruses are recognized as the predominant causative agents of acute respiratory infections. In Senegal, few data concerning the causes of respiratory infections are available, and those known relate mainly to classical influenza infections. Clinical and virological surveillance of acute respiratory infections was carried out in a rural community in children less than 5 years old. A standardized questionnaire was used and a nasopharyngeal swab sample was collected from each patient. These samples were tested for the detection of 20 respiratory viruses by multiplex RT‐PCR or by viral culture. A total of 82 acute respiratory episodes were included, and 48 (58.5%) were found to be positive, with a total of 55 viral detections; several samples were positive for two (n = 5) or 3 (n = 1) viruses. Ten different viruses were identified: influenza viruses A, B, and C (n = 25), human respiratory syncytial virus type A (n = 13), rhinoviruses (n = 8), human coronaviruses type 229E and NL63 (n = 6), parainfluenza viruses 3 and 4 (n = 2), and bocavirus (n = 1). These results provide evidence on the importance and the diversity of viruses as causative agents of acute respiratory infections in children living in a rural community in Senegal. The establishment of sentinel surveillance sites could help estimate the burden of acute respiratory infection in the pediatric population and should help prepare the health care systems to identify and respond to new viral respiratory emergencies. J. Med. Virol. 82:866–872, 2010. © 2010 Wiley‐Liss, Inc.