bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue response and orbital floor regeneration using cyclic acetal hydrogels
Authors: Betz Martha W. , Caccamese John F. , Coletti Domenick P. , Sauk John J. , Fisher John P.
Published: July 2008

Orbital floor injuries are a common form of traumatic craniofacial injury that may not heal properly through the body's endogenous response. Reconstruction is often necessary, and an optimal method does not exist. We propose a tissue engineering approach for orbital bone repair based upon a cyclic acetal biomaterial formed from 5‐ethyl‐5‐(hydroxymethyl)‐β,β‐dimethyl‐1,3‐dioxane‐2‐ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). The EHD monomer and PEGDA polymer may be fabricated into an EH‐PEG hydrogel by radical polymerization. The objectives of this work were to study (1) the tissue response to EH‐PEG hydrogels in an orbital bone defect and (2) the induction of bone formation by delivery of bone morphogenetic protein‐2 (BMP‐2) from EH‐PEG hydrogels. EH‐PEG hydrogels were fabricated and implanted into an 8‐mm rabbit orbital floor defect. Experimental groups included unloaded EH‐PEG hydrogels, and EH‐PEG hydrogels containing 0.25 μg and 2.5 μg BMP‐2/implant. Results demonstrated that the unloaded hydrogel was initially bordered by a fibrin clot and then by fibrous encapsulation. BMP‐2 loaded EH‐PEG hydrogels, independent of concentration, were surrounded by fibroblasts at both time points. Histological analysis also demonstrated that significant bone growth was present at the 2.5 μg BMP‐2/implant group at 28 days. This work demonstrates that the EH‐PEG construct is a viable option for use and delivery of BMP‐2 in vivo. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Synthesis, characterization, and biocompatibility of novel injectable, biodegradable, and in situ crosslinkable polycarbonate‐based macromers
Authors: Sharifi Shahriar , Imani Mohammad , Mirzadeh Hamid , Atai Mohammad , Ziaee Farshid , Bakhshi Raheleh
Published: July 2008

A series of novel self‐crosslinkable and biodegradable polymers, poly(hexamethylene carbonate‐fumarate) and poly(hexamethylene carbonate) diacrylate, and their amphiphilic copolymers with polyethylene glycol, poly(ethylene glycol fumarate‐co‐hexamethylene carbonate‐fumarate) (PEGF‐co‐PHMCF), were developed for tissue engineering using propylene oxide as an acid scavenger. The synthesized polymers are white, which makes them more suitable for self‐crosslinking via photopolymerization. These novel polymers were fully characterized using nuclear magnetic resonance spectroscopy, Fourier‐transform infrared spectroscopy, gel permeation chromatography, differential scanning calorimetry, and rheometry. The cytocompatibility of the photocrosslinked networks were evaluated by [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] assay. These polymers can be used as precursors to prepare polymer networks and scaffolds with controlled hydrophilicity, biodegradability, and mechanical characteristics. Results obtained suggest that these polymers are potentially useful as injectable and photocrosslinkable materials for cell delivery, tissue engineering, and drug delivery applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
In vitro osteogenic potential of human bone marrow stromal cells cultivated in porous scaffolds from mineralized collagen
Authors: Bernhardt A. , Lode A. , Mietrach C. , Hempel U. , Hanke T. , Gelinsky M.
Published: July 2008

Porous 3D structures from mineralized collagen were fabricated applying a procedure in which collagen fibril reassembly and precipitation of nanocrystalline hydroxyapatite (HA) occur simultaneously. The resulting matrices were evaluated in vitro with respect to their suitability as scaffolds for bone tissue engineering. We found a high capacity of the material to bind serum proteins as well as to absorb Ca2+ ions, which could be advantageous to promote cell attachment, growth, and differentiation. Human bone marrow stromal cells (hBMSCs) were seeded onto the 3D scaffolds and cultivated for 4 weeks in the presence and absence of osteogenic supplements. We studied viability, proliferation, and osteogenic differentiation in terms of total lactate dehydrogenase (LDH) activity, DNA content, and alkaline phosphatase (ALP) activity. Furthermore, the expression for bone‐related genes (ALP, bone sialo protein II (BSP II), and osteocalcin) was analyzed. In our investigation we found a 2.5‐fold to 5‐fold raise in DNA content and an increase of ALP activity for osteogenic induced hBMSC on collagen HA scaffolds. The expression of ALP and BSP II in these cells was also stimulated in the course of cultivation; however, we did not detect an upregulation of osteocalcin gene expression. These data suggest, that porous collagen HA scaffolds are suitable for the expansion and osteogenic differentiation of hBMSC and are therefore promising candidates for application as bone grafts. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
The influence of Young's modulus of loaded implants on bone remodeling: An experimental and numerical study in the goat knee
Authors: Stoppie Nele , Van Oosterwyck Hans , Jansen John , Wolke Joop , Wevers Martine , Naert Ignace
Published: July 2008

The aim of this study was to examine the influence of the Young's modulus of the implant material on the bone remodeling in a loaded condition. A combined animal experimental and computational study was set up. The animal experimental group comprised of 16 Saanen goats, each receiving one titanium implant (Young's modulus 110 GPa) and one high‐density polyethylene (HDPE) implant (Young's modulus 1 GPa) in the left femoral condyle. Both types of implants received a titanium coating of 100 nm thickness. The implants protruded in the knee joint space and were directly weight bearing. The first group of eight goats was sacrificed after 6 weeks of loading and the second group of eight goats after 6 months of loading. The 16 femoral condyles with the 32 implants were prepared for microfocus computed tomography (micro‐CT) scanning and histological sectioning. Three‐dimensional trabecular bone parameters were calculated on the micro‐CT images for the zones neck, middle, and apex of the implant. The percent of bone contact with the implant was measured on longitudinal histological sections. An axisymmetric finite element (FE) model was created to compare peri‐implant bone strains and relative motion between a titanium and a HDPE implant for the experimental loading condition, and to assess the influence of different bone‐implant interface (contact) conditions. From the statistical analysis of the 3D bone parameters, the difference between the titanium and HDPE implants was not significantly different (p > 0.05) between the zones (neck, middle, and apex) for both groups of goats. The implants could be considered in their entirety. After 6 weeks of loading, the PE implant presented lower connectivity and smaller marrow spaces in the circular region of 0–500 μm. In the region 500–1500 μm more bone volume was present for the PE implant. After 6 months, the PE implants showed more bone volume and thicker trabeculae than the titanium implants for the entire length of the implant. This effect was already present in the smallest region of interest, 0–500 μm. After 6 months more fibrous encapsulation was found around titanium implants. FE results demonstrated a substantial influence of the interface conditions on peri‐implant strains and relative motion. For interface conditions that were representative for the early postoperative situation (involving press‐fit and friction), differences in peri‐implant bone strain distributions between titanium and HDPE could be related to the experimentally observed differences in amounts of bone and fibrous encapsulation. In contrast, differences in relative motion did not seem to play a role. Both the experimental and computational results suggest that implant stiffness can affect the peri‐implant tissue response, which may be related to differences in peri‐implant strains. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Regional variations in the viscoelastic compressive properties of the temporomandibular joint disc and implications toward tissue engineering
Authors: Lumpkins Sarah B. , McFetridge Peter S.
Published: July 2008

Evidence from experimental and finite element studies have shown that the temporomandibular joint disc is heavily loaded during normal physiological function. Several studies have been carried out to investigate the response of the disc to tensile and static compressive forces. However, there is limited information that elucidates the dynamic characteristics of the disc under in vivo loading conditions. These investigations assessed the effect of physiologically relevant applied strain amplitudes and frequencies to determine regional mechanical properties of the disc. Cyclic tests on porcine TMJ discs were carried out over a period of 15 cycles, and the resultant compressive moduli and energy dissipation properties of the disc were reported. Results showed that modulus values were more dependent on strain amplitude than on frequency, and modulus values exhibited a strong regional variation. Clear hysteresis loops were evident in each set of testing parameters, and the only statistically significant regional variation in energy dissipation was between the central and medial regions. From these investigations, a more detailed understanding of the spatial mechanical properties of the TMJ disc has been achieved under physiologically relevant loading conditions. Combined with studies on other loading modalities of the disc, these results will serve as a benchmark for future TMJ disc tissue engineering endeavors. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Cellular responses to degradable cyclic acetal modified PEG hydrogels
Authors: Kaihara Sachiko , Matsumura Shuichi , Fisher John P.
Published: July 2008

In this study, high viability of bone marrow stromal stem cells (BMSCs) encapsulated in a synthetic, poly[poly(ethylene glycol)‐co‐cyclic acetal] (PECA) hydrogel has been reported. This novel degradable hydrogel, which contains cyclic acetal as degradable segments and poly(ethylene glycol) (PEG) as hydrophilic segments, has been designed to limit the release of acidic products during hydrolytic degradation. PECAs with three different molecular weights (PECA 600, 1000, and 2000) were prepared to evaluate the effect of polymer main chain molecular weight on the viability and morphology of BMSCs embedded in PECA hydrogels as well as the viability of BMSCs exposed to PECA degradation products. Results demonstrated high BMSC viability when incubated in control media with PECA, while a significant decrease in viability was noted after 4 days when incubated in media augmented with PEG diacrylate. There was no effect of PECA molecular weight on the differentiation and cytotoxicity of degradation products up to 4 days, indicating that the degradation products' terminal carbonyl groups do not significantly affect cell viability and differentiation. BMSC viability when embedded on PECA hydrogels was evaluated by a LIVE/DEAD assay, and confirmed high viability up to 14 days. Gene expression analysis confirmed that BMSCs embedded in PECA hydrogels undergo osteogenic differentiation. Histological analysis also showed that cell morphology was significantly influenced by hydrogel swelling degree, which is itself controllable by the molecular weights of PECA main chains. These results indicate that PECA hydrogels may be utilized as scaffolds for regeneration of bone‐like tissues. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Pulsed electric field as a potential new method for microbial inactivation in scaffold materials for tissue engineering: The effect on collagen as a scaffold
Authors: Smith Sharon , Griffiths Sarah , MacGregor Scott , Beveridge Joe , Anderson John , van der Walle Chris , Grant M. Helen
Published: July 2008

Hybrid scaffolds for tissue engineering are becoming increasingly complex through incorporation of biologically active biomacromolecules. There is a need to develop a compatible sterilization method that is capable of killing microorganisms, without adversely affecting the labile scaffold biomaterials or biomacromolecular components. Pulsed electric field (PEF) treatment has been successful as a nonthermal microbial inactivation–pasteurization method within the food industry. We have previously demonstrated that PEF treatment inactivates E. coli seeded in collagen gels. Here, we show that PEF treatment does not affect the structural integrity of the collagen molecule or its adsorption to polystyrene and hydroxyapatite surfaces. Moreover, osteoblast cells cultured on PEF‐treated collagen, which was coated onto two‐ and three‐dimensional scaffolds, retained their normal morphology, growth rate, and functionality. PEF treatment, therefore, shows great potential to be used as a sterilization method for collagen‐based biomaterials. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Comparison of new bone formation, implant integration, and biocompatibility between RGD‐hydroxyapatite and pure hydroxyapatite coating for cementless joint prostheses—An experimental study in rabbits
Authors: Bitschnau Achim , Alt Volker , Böhner Felicitas , Heerich Katharina Elisabeth , Margesin Erika , Hartmann Sonja , Sewing Andreas , Meyer Christof , Wenisch Sabine , Schnettler Reinhard
Published: July 2008

This is the first work to report on additional Arginin‐Glycin‐Aspartat (RGD) coating on precoated hydroxyapatite (HA) surfaces regarding new bone formation, implant bone contact, and biocompatibility compared to pure HA coating and uncoated stainless K‐wires. There were 39 rabbits in total with 6 animals for the RGD‐HA and HA group for the 4 week time period and 9 animals for each of the 3 implant groups for the 12 week observation. A 2.0 K‐wire either with RGD‐HA or with pure HA coating or uncoated was placed into the intramedullary canal of the tibia. After 4 and 12 weeks, the tibiae were harvested and three different areas of the tibia were assessed for quantitative and qualitative histology for new bone formation, direct implant bone contact, and formation of multinucleated giant cells. Both RGD‐HA and pure HA coating showed statistically higher new bone formation and implant bone contact after 12 weeks than the uncoated K‐wire. There were no significant differences between the RGD‐HA and the pure HA coating in new bone formation and direct implant bone contact after 4 and 12 weeks. The number of multinucleated giant did not differ significantly between the RGD‐HA and HA group after both time points. Overall, no significant effects of an additional RGD coating on HA surfaces were detected in this model after 12 weeks. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Recellularization of biological heart valves with human vascular cells: In vitro hemocompatibility assessment
Authors: Schopka Simon , Schmid Franz‐Xaver , Hirt Stephan , Birnbaum Dietrich E. , Schmid Christof , Lehle Karla
Published: July 2008

Coverage of cardiovascular bioprostheses with autologous endothelium is used for the purpose of improving blood compatibility. The aim of our study was to analyze endothelialization potential of glutaraldehyde‐fixed heart valves, cellular functions of seeded endothelial cells (EC), and the impact of a two‐stage seeding protocol using human vascular fibroblasts (FB) and EC from saphenous veins (HSVEC) on cellular functional properties invitro. Adherence and morphology of adhered cells were assessed by scanning electronic microscopy and immunohistochemistry. Reproducible, complete surface coverage with EC was established on decellularized and glutaraldehyde‐fixed bovine pericardium. Analyzing functional properties of cells directly adhered to biomaterial revealed nonproliferative cells, which were capable of inflammatory stimulation in terms of TNF‐induced increase in interleukin‐6 secretion and adhesion of inflammatory cells. Furthermore, EC showed sustained antithrombotic properties quantified by platelet adhesion onto EC and prostacyclin secretion by EC. Preseeding with vascular fibroblasts using a two‐stage seeding protocol induced EC proliferation and improved inflammatory and anti‐thrombotic functions. Cardiovascular biomaterials differ significantly in their potential to allow for adhesion of human EC. Successfully endothelialized biomaterial, however, revealed cellular properties which are likely to be favorable to improving performance of biomaterials. Two‐stage seeding adds regenerative potential and improves cell functions of adherent EC. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Fretting crevice corrosion of stainless steel stem–CoCr femoral head connections: Comparisons of materials, initial moisture, and offset length
Authors: Gilbert Jeremy L. , Mehta Manav , Pinder Bryan
Published: July 2008

Modular tapers continue to be used in a wide variety of orthopedic implants. In this study, stainless steel (ASTM F‐1568) femoral hip stems combined with Co‐Cr‐Mo alloy heads (SS/CoCr) were tested in an in vitro fretting corrosion test set‐up to assess the propensity for mechanically assisted corrosion. Three different aspects of the modular design were evaluated in this study: (1) material combination compared to CoCr/CoCr, (2) wet versus dry assembly for SS/CoCr couples, and (3) 0‐ and 6‐mm head offset for SS/CoCr couples. Fretting corrosion tests over a range of cyclic loads up to 3300 N were performed, and continuous cyclic loading at 3300 N for 1 M cycles were performed on each group (n = 5). Fretting micromotion was measured as a function of cyclic load on select couples to detect the nature and extent of motion present. The results showed that SS/CoCr couples were more susceptible to fretting corrosion than CoCr/CoCr couples, that dry assembly does not prevent fretting corrosion from taking place but raises the onset load, and that 6‐mm offset heads had higher visual evidence of fretting damage but showed mixed statistical results in terms of onset loads and OCP shifts and currents compared to the 0‐mm offset samples. Current and voltage excursions over 1million cycles tended to diminish towards their unloaded control levels but did not fully recover until cyclic loading ceased. Micromotion measurements indicated fretting motions in the range of 10–25 μm where 0‐mm heads tended to piston on the trunion, while 6 mm heads tended to rock. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
A 3‐year analysis of plateletpheresis donor deferral pattern in a tertiary health care institute: Assessing the current donor selection criteria in Indian scenario
Authors: Tondon Rashmi , Pandey Prashant , Chaudhry Rajendra
Published: July 2008

Introduction: This study reports the frequency and nature of plateletpheresis deferrals and evaluates donors with low platelet count and hemoglobin levels so as to assess the possibility of reentry without hampering donor safety. Materials and methods: Three‐year retrospective data of plateletpheresis deferral was collected. Data from actual procedures was also reviewed to analyze the safety of performing plateletpheresis in donors with low hemoglobin and platelet values. Results: Four hundred sixteen donors were deferred for various reasons among 1,515 screened (27.5%), of which 69.7% deferrals were because of low platelet count (55.8%) and less hemoglobin levels. Among the low platelet count donor group, 20.3% had a count between 141 and 149 × 109/L and 41.8% below 120 × 109/L. Of the 14% donors deferred for low hemoglobin, 62.1% had values in the range of 11.5–12.4 g/dL with normal mean corpuscular volume and red cell distribution width in most (86.2%) of them. Expected blood loss in each procedure varied between 20 and 30 mL, whereas RBC contamination in the product varied from 0 to 1.6 mL in 538 procedures. There were 176 donations with predonation platelet count <180 × 109/L (32.7%). None of the 14 procedures performed on donors with platelet count of 150 × 109/L showed evidence of thrombocytopenia or donor reaction. Conclusion: Lowering the cut‐off value for plateletpheresis from 12.5 g/dL to 11.5 g/dL has no deleterious effect on donor safety as the blood loss is minimal. One‐fifth deferrals can be reconsidered if the criteria of plateletpheresis donor selection are relaxed for hemoglobin and platelet count. J. Clin. Apheresis, 2008. © 2008 Wiley‐Liss, Inc.
Genetic and epigenetic regulation in nuclear microenvironments for biological control in cancer
Authors: Stein Gary S. , Zaidi Sayyed K. , Stein Janet L. , Lian Jane B. , van Wijnen Andre J. , Montecino Martin , Young Daniel W. , Javed Amjad , Pratap Jitesh , Choi Je‐Yong , Ali Syed A. , Pande Sandhya , Hassan Mohammad Q.
Published: July 2008

The regulatory machinery that governs genetic and epigenetic control of gene expression is compartmentalized in nuclear microenvironments. Temporal and spatial parameters of regulatory complex organization and assembly are functionally linked to biological control and are compromised with the onset and progression of tumorigenesis providing a novel platform for cancer diagnosis and treatment. J. Cell. Biochem. 104: 2016–2026, 2008. © 2008 Wiley‐Liss, Inc.
Dexamethasone and corticosterone induce similar, but not identical, muscle wasting responses in cultured L6 and C2C12 myotubes
Authors: Menconi Michael , Gonnella Patricia , Petkova Victoria , Lecker Stewart , Hasselgren Per‐Olof
Published: July 2008

Dexamethasone‐treated L6 (a rat cell line) and C2C12 (a mouse cell line) myotubes are frequently used as in vitro models of muscle wasting. We compared the effects of different concentrations of dexamethasone and corticosterone (the naturally occurring glucocorticoid in rodents) on protein breakdown rates, myotube size, and atrogin‐1 and MuRF1 mRNA levels in the two cell lines. In addition, the expression of the glucocorticoid receptor (GR) and its role in glucocorticoid‐induced metabolic changes were determined. Treatment with dexamethasone or corticosterone resulted in dose‐dependent increases in protein degradation rates in both L6 and C2C12 myotubes accompanied by 25–30% reduction of myotube diameter. The same treatments increased atrogin‐1 mRNA levels in L6 and C2C12 myotubes but, surprisingly, upregulated the expression of MuRF1 in L6 myotubes only. Both cell types expressed the GR and treatment with dexamethasone or corticosterone downregulated total cellular GR levels while increasing nuclear translocation of the GR in both L6 and C2C12 myotubes. The GR antagonist RU38486 inhibited the dexamethasone‐ and corticosterone‐induced increases in atrogin‐1 and MuRF1 expression in L6 myotubes but not in C2C12 myotubes. Interestingly, RU38486 exerted agonist effects in the C2C12, but not in the L6 myotubes. The present results suggest that muscle wasting‐related responses to dexamethasone and corticosterone are similar, but not identical, in L6 and C2C12 myotubes. Most notably, the regulation by glucocorticoids of MuRF1 and the role of the GR may be different in the two cell lines. These differences need to be taken into account when cultured myotubes are used in future studies to further explore mechanisms of muscle wasting. J. Cell. Biochem. 105: 353–364, 2008. © 2008 Wiley‐Liss, Inc.
Sex steroid hormones induce acylation stimulating protein resistance in 3T3‐L1 adipocytes
Authors: Wen Yu , Wang HongWei , MacLaren Robin , Lu HuiLing , Hu Xiu‐Fen , Cianflone Katherine
Published: July 2008

Acylation stimulating protein (ASP) stimulates triglyceride synthesis and glucose transport via its receptor C5L2. In human studies, ASP is increased in insulin resistant states such as obesity, diabetes, polycystic ovary syndrome and late pregnancy (the latter two associated with altered sex hormones). The aims were (i) to evaluate ASP response and C5L2 expression following treatment with sex steroid hormones and (ii) to identify mechanisms of ASP resistance using 3T3‐L1 adipocytes and preadipocytes. Overnight incubation with physiological progesterone (PROG) concentrations induced dose‐dependent inhibition of ASP‐stimulated glucose transport in adipocytes (188 ± 11% +ASP, 100 ± 4% control, 129 ± 18% to 85 ± 7% [ASP + PROG 10−8 to 10−6 M] and preadipocytes (263 ± 18% +ASP, 100 ± 3% control, 170 ± 11% to 167 ± 4% [ASP + PROG 10−8 to 10−6 M]), while estradiol and testosterone (TEST) were effective only at the highest concentration (10−6 M). In adipocytes, dose‐dependent maximal C5L2 mRNA decreases were 39–75% (P = 0.003), with decreased cell‐surface C5L2 of −22% and −27% (10−6 M PROG and TEST, respectively) with no change in preadipocytes. Adipocytes treated with PROG displayed decreases in G proteins: Gβ (−55%), Gαq/11 (−56%) as well as complete inhibition of ASP stimulation. PROG significantly decreased basal levels of phosphorylated PKCα (p‐PKCα) while there was no change in p‐ PKCζ. ASP increased p‐PKCα and PKCζ to 161% (P < 0.0.001) and 160% (P < 0.01), a stimulation effectively blocked by PROG (10−8 and 10−6 M) and TEST (10−6 M). Sex steroid hormone‐induced ASP resistance via C5L2 may contribute to altered adipose tissue function and insulin resistance phenotype in humans. J. Cell. Biochem. 105: 404–413, 2008. © 2008 Wiley‐Liss, Inc.
Glycogen synthase kinase‐3β regulates ΔNp63 gene transcription through the β‐catenin signaling pathway
Authors: Chu Wing‐Keung , Dai Pei‐Min , Li Hsin‐Lun , Chen Jan‐Kan
Published: July 2008

Overexpression of ΔNp63 has been observed in a number of human cancers, suggesting a role for ΔNp63 in carcinogenesis. In the present study, we show that inhibition of glycogen synthase kinase‐3β (GSK‐3β) by lithium chloride (LiCl) elicited a stimulatory effect on ΔNp63 promoter activity in HEK 293T cells. Exposure to LiCl induced ΔNp63 promoter activation as well as ΔNp63 protein expression in the cells. The effect of GSK‐3β on ΔNp63 expression was further confirmed by the use of two highly specific GSK‐3β inhibitors, SB216763 and SB415286. Further study showed the presence of a putative β‐catenin responsive element (β‐catenin‐RE) in the ΔNp63 promoter region, and the stimulation of ΔNp63 promoter activity by GSK‐3β inhibitor is markedly abolished by mutation or deletion of the putative β‐catenin‐RE. Data are also presented to show that β‐catenin acts together with Lef‐1 to influence ΔNp63 promoter activity and protein expression. J. Cell. Biochem. 105: 447–453, 2008. © 2008 Wiley‐Liss, Inc.
Wnt5a induces homodimerization and activation of Ror2 receptor tyrosine kinase
Authors: Liu Yan , Rubin Boris , Bodine Peter V.N. , Billiard Julia
Published: July 2008

Wnts are secreted glycoproteins that control vital biological processes, including embryogenesis, organogenesis and tumorigenesis. Wnts are classified into several subfamilies depending on the signaling pathways they activate, with the canonical subfamily activating the Wnt/β‐catenin pathway and the non‐canonical subfamily activating a variety of other pathways, including the Wnt/calcium signaling and the small GTPase/c‐Jun NH2‐terminal kinase pathway. Wnts bind to a membrane receptor Frizzled and a co‐receptor, the low‐density lipoprotein receptor related protein. More recently, both canonical and non‐canonical Wnts were shown to bind the Ror2 receptor tyrosine kinase. Ror2 is an orphan receptor that plays crucial roles in skeletal morphogenesis and promotes osteoblast differentiation and bone formation. Here we examine the effects of a canonical Wnt3a and a non‐canonical Wnt5a on the signaling of the Ror2 receptor. We demonstrate that even though both Wnt5a and Wnt3a bound Ror2, only Wnt5a induced Ror2 homo‐dimerization and tyrosine phosphorylation in U2OS human osteoblastic cells. Furthermore, Wnt5a treatment also resulted in increased phosphorylation of the Ror2 substrate, 14‐3‐3β scaffold protein, indicating that Wnt5a binding causes activation of the Ror2 signaling cascade. Functionally, Wnt5a recapitulated the Ror2 activation phenotype, enhancing bone formation in the mouse calvarial bone explant cultures and potentiating osteoblastic differentiation of human mesenchymal stem cells. The effect of Wnt5a on osteoblastic differentiation was largely abolished upon Ror2 down‐regulation. Thus we show that Wnt5a activates the classical receptor tyrosine kinase signaling cascade through the Ror2 receptor in cells of osteoblastic origin. J. Cell. Biochem. 105: 497–502, 2008. © 2008 Wiley‐Liss, Inc.
Global dynamics and transition state theories: Comparative study of reaction rate constants for gas‐phase chemical reactions
Authors: Ju Li‐Ping , Han Ke‐Li , Zhang John Z. H.
Published: July 2008

In this review article, we present a systematic comparison of the theoretical rate constants for a range of bimolecular reactions that are calculated by using three different classes of theoretical methods: quantum dynamics (QD), quasi‐classical trajectory (QCT), and transition state theory (TST) approaches. The study shows that the difference of rate constants between TST results and those of the global dynamics methods (QD and QCT) are seen to be related to a number of factors including the number of degrees‐of‐freedom (DOF), the density of states at transition state (TS), etc. For reactions with more DOF and higher density of states at the TS, it is found that the rate constants from TST calculations are systematically higher than those obtained from global dynamics calculations, indicating large recrossing effect for these systems. The physical insight of this phenomenon is elucidated in the present review. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Dispersion in the Mott insulator UO2: A comparison of photoemission spectroscopy and screened hybrid density functional theory
Authors: Roy Lindsay E. , Durakiewicz Tomasz , Martin Richard L. , Peralta Juan E. , Scuseria Gustavo E. , Olson Cliff G. , Joyce John J. , Guziewicz Ela
Published: July 2008

We present a comparison between the screened hybrid density functional theory of Heyd, Scuseria, and Enzerhof (HSE06) and high‐resolution photoemission (PES) measurement on a single crystal of UO2. Angle‐resolved photoemission data show a slight dispersion in the f‐orbital derived bands in good agreement with the HSE band structure. The effect of spin‐orbit coupling on the HSE band gap has also been calculated and found to be negligible. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Modeling the structure‐property relationships of nanoneedles: A journey toward nanomedicine
Authors: Poater Albert , Saliner Ana Gallegos , Carbó‐Dorca Ramon , Poater Jordi , Solà Miquel , Cavallo Luigi , Worth Andrew P.
Published: July 2008

Innovative biomedical techniques operational at the nanoscale level are being developed in therapeutics, including advanced drug delivery systems and targeted nanotherapy. Ultrathin needles provide a low invasive and highly selective means for molecular delivery and cell manipulation. This article studies the geometry and the stability of a family of packed carbon nanoneedles (CNNs) formed by units of 4, 6, and 8 carbons, by using quantum chemistry computational modeling methods. At the limit of infinite‐length, these CNNs might act as semiconductors, especially when the number of terminal units is increased. CNNs are also potentially able to stabilize ions around their structure. Therefore, due to the apolar characteristics of CNNs and their ability to carry ionic species, they would be suitable to act as drug carriers through nonpolar biologic media. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
A novel method for enzyme design
Authors: Zhu Xiaolei , Lai Luhua
Published: July 2008

Rational design of enzymes is a stringent test of our understanding of protein structure and function relationship, which also has numerous potential applications. We present a novel method for enzyme design that can find good candidate protein scaffolds in a protein‐ligand database based on vector matching of key residues. Residues in the vicinity of the active site were also compared according to a similarity score between the scaffold protein and the target enzyme. Suitable scaffold proteins were selected, and the side chains of residues around the active sites were rebuilt using a previously developed side‐chain packing program. Triose phosphate isomerase (TIM) was used as a validation test for enzyme design. Selected scaffold proteins were found to accommodate the enzyme active sites and successfully form a good transition state complex. This method overcomes the limitations of the current enzyme design methods that use limited number of protein scaffold and based on the position of ligands. As there are a large number of protein scaffolds available in the Protein Data Band, this method should be widely applicable for various types of enzyme design. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Accelerating molecular dynamic simulation on the cell processor and Playstation 3
Authors: Luttmann Edgar , Ensign Daniel L. , Vaidyanathan Vishal , Houston Mike , Rimon Noam , Øland Jeppe , Jayachandran Guha , Friedrichs Mark , Pande Vijay S.
Published: July 2008

Implementation of molecular dynamics (MD) calculations on novel architectures will vastly increase its power to calculate the physical properties of complex systems. Herein, we detail algorithmic advances developed to accelerate MD simulations on the Cell processor, a commodity processor found in PlayStation 3 (PS3). In particular, we discuss issues regarding memory accessversuscomputation and the types of calculations which are best suited for streaming processors such as the Cell, focusing on implicit solvation models. We conclude with a comparison of improved performance on the PS3's Cell processor over more traditional processors. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Scientific method, abduction, and clinical reasoning
Authors: Haig Brian D.
Published: July 2008

This special issue of the Journal of Clinical Psychology comprises six theoretical papers that are concerned with the interconnected topics of scientific method, abductive inference, and clinical reasoning. The first four papers deal with the nature and limitations of a broad abductive theory of scientific method, and its application to clinical reasoning and case formulation. These are followed by three papers which in turn consider the prospects of using explanatory criteria to appraise competing models of psychopathy, examine the merits of a number of different psychometric perspectives on the assessment of psychopathology, and reject a core supposition of the orthodox approach to hypothesis testing. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64: 1–6, 2008.
Psychological services for returning veterans and their families: evolving conceptualizations of the sequelae of war‐zone experiences
Authors: Sammons Morgan T. , Batten Sonja V.
Published: July 2008

The provision of effective and timely behavioral health care for veterans returning from the conflicts in Iraq and Afghanistan has become the focus of national attention. In this special issue, attempts to provide psychological care for service members and their families are examined in light of three key constructs. First, it is contended that at no other time in history has more attention been paid to the psychological consequences of engaging in combat. Second, for the first time in recorded warfare, psychological morbidity is likely to far outstrip physical injury associated with combat. Finally, although posttraumatic stress disorder and traumatic brain injury are serious concerns, most service members return without significant physical or psychological injury and will be able to return to functioning without notable problems. Accurate diagnosis, a focus on resilience, and the expectation of readjustment are essential precepts that should guide clinical efforts and resource allocation. © 2008 Wiley Periodicals, Inc. J Clin Psychol: In Session 64:1–7, 2008.
Couple therapy with combat veterans and their partners
Authors: Erbes Christopher R. , Polusny Melissa A. , MacDermid Shelley , Compton Jill S.
Published: July 2008

Service members returning from Iraq and Afghanistan face psychological challenges that can exert profound effects on families and couples, but can also be treated within a systemic context. Couple therapy offers a means of increasing social support, decreasing interpersonal conflict, and addressing the experiential avoidance that maintains posttraumatic symptoms. For combat veterans and their partners, we present an adaptation of integrative behavioral couple therapy (IBCT) that reduces conflict and encourages intimacy through acceptance and skills strategies. By doing so, IBCT exposes service members in couple therapy to emotions, interpersonal situations, and activities that facilitate recovery from combat‐related distress. We illustrate common presenting problems in this population and the utilization of IBCT with a case example. © 2008 Wiley Periodicals, Inc. J Clin Psychol: In Session 64:1‐12, 2008.
Formation of Kv2.1‐FAK complex as a mechanism of FAK activation, cell polarization and enhanced motility
Authors: Wei Jian‐Feng , Wei Ling , Zhou Xin , Lu Zhong‐Yang , Francis Kevin , Hu Xin‐Yang , Liu Yu , Xiong Wen‐Cheng , Zhang Xiao , Banik Naren L. , Zheng Shu‐Sen , Yu Shan Ping
Published: July 2008

Focal adhesion kinase (FAK) plays key roles in cell adhesion and migration. We now report that the delayed rectifier Kv2.1 potassium channel, through its LD‐like motif in N‐terminus, may interact with FAK and enhance phosphorylation of FAK397 and FAK576/577. Overlapping distribution of Kv2.1 and FAK was observed on soma and proximal dendrites of cortical neurons. FAK expression promotes a polarized membrane distribution of the Kv2.1 channel. In Kv2.1‐transfected CHO cells, formation of the Kv2.1‐FAK complex was stimulated by fibronectin/integrin and inhibited by the K+ channel blocker tetraethylammonium (TEA). FAK phosphorylation was minimized by shRNA knockdown of the Kv2.1 channel, point mutations of the N‐terminus, and TEA, respectively. Cell migration morphology was altered by Kv2.1 knockdown or TEA, hindering cell migration activity. In wound healing tests in vitro and a traumatic injury animal model, Kv2.1 expression and co‐localization of Kv2.1 and FAK significantly enhanced directional cell migration and wound closure. It is suggested that the Kv2.1 channel may function as a promoting signal for FAK activation and cell motility. J. Cell. Physiol. 217: 544–557, 2008. © 2008 Wiley‐Liss, Inc.
Induction of serum‐ and glucocorticoid‐induced kinase‐1 (SGK1) by cAMP regulates increases in α‐ENaC
Authors: Vasquez Margarita M. , Castro Robert , Seidner Steven R. , Henson Barbara M. , Ashton Daniel J. , Mustafa Shamimunisa B.
Published: July 2008

α‐ENaC expression and activity is regulated by a variety of hormones including β‐adrenergic agonists via the second messenger cAMP. We evaluated the early intermediate pathways involved in the up‐regulation of SGK1 by DbcAMP and whether SGK1 is a prerequisite for induction of α‐ENaC expression. Submandibular gland epithelial (SMG‐C6) cells treated with DbcAMP (1 mM) induced both SGK1 mRNA and protein expression. DbcAMP‐stimulated SGK1 mRNA expression was decreased by actinomycin D and mRNA and protein expressions were attenuated by PKA inhibitors (H‐89 and KT5720). Inhibition of PI3‐K with either LY294002 or dominant negative PI3‐K reduced DbcAMP‐stimulated SGK1 protein and mRNA levels, attenuated the phosphorylation of CREB (a cAMP‐activated transcription factor) and decreased α‐ENaC protein levels and Na+ transport. In addition, the combination of PKA inhibitors with dominant negative PI3‐K synergistically inhibited DbcAMP‐induced Na+ transport. Inhibition of SGK1 expression by siRNA decreased but did not obliterate DbcAMP‐induced α‐ENaC expression. Thus, in a cell line which endogenously exhibits minimal α‐ENaC expression, induction of SGK1 by DbcAMP occurs via the PI3‐K and PKA pathways. Increased α‐ENaC levels and function are partly dependent upon the early induction of SGK1 expression. J. Cell. Physiol. 217: 632–642, 2008. © 2008 Wiley‐Liss, Inc.
Selective iron removal from spent passivation baths by ion exchange
Authors: Fernández‐Olmo I , Ortiz A , Urtiaga A , Ortiz I
Published: July 2008

BACKGROUND: Post‐treatment of zinc plated surfaces is required to provide corrosion protection; for this purpose chromium passivation is usually used. In the EU, the older hexavalent chromium passivation baths have been replaced by trivalent chromium conversion coatings. However, the life of Cr(III) passivation baths is reduced due to iron and zinc impurities generated in the process. Thus, the objective of this work was to investigate the regeneration of spent passivation baths from the plating industry by ion exchange using a new chelating resin (Purolite S‐957).

RESULTS: Three genuine passivation baths with different iron and zinc concentrations were investigated; the effect of loading flow rate, temperature and resin regeneration conditions on the uptake of iron ions was also studied. The removal performance of iron was increased at higher temperature (55 °C) and lower flow rates. The best regeneration conditions were found to be 6 bed volumes (BV) of 30 wt% HCl.

CONCLUSION: This work has shown that iron can be selectively removed from trivalent chromium passivation baths using a new chelating resin (Purolite S‐957) and no addition of chromium (III) is required. Low feed flow rate and high bath temperature (up to 55 °C) are recommended for high iron uptake. Copyright © 2008 Society of Chemical Industry
Prenatal diagnosis of ectopic intrathoracic kidney in a fetus with a left diaphragmatic hernia
Authors: Panda Britta , Rosenberg Victor , Cornfeld Daniel , Stiller Robert
Published: July 2008

Intrathoracic renal ectopia as a result of a congenital diaphragmatic hernia (CDH) is a rare congenital anomaly. We present a case in which the prenatal diagnosis of an ectopic intrathoracic kidney was made on routine anatomical survey at 28 weeks' gestation. Color doppler sonography imaging revealed the renal artery coursing into the infant's thorax and was consistent with CDH, but fetal MRI suggested an intact diaphragm. However, neonatal evaluation confirmed the diagnosis of intrathoracic kidney with posterior CDH, which was repaired without complication. In contrast to diaphragmatic hernia with liver or bowel herniation, infants with intrathoracic ectopic kidneys generally do well. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009
Cryo‐X‐ray analysis—A novel tool to better understand the physicochemical reactions at the bioglass/biological fluid interface
Authors: Balamurugan Anbalagan , Benhayoune Hicham , Kannan Sanjeevi , Laquerriere Patrice , Michel Jean , Balossier Gerard , Ferreira José M.F.
Published: July 2008

The present study deals with the short‐term physicochemical reactions at the interface between bioactive glass particles [55SiO2‐20CaO‐9P2O5‐12Na2O‐4MgO. mol%] and biological fluid (Dulbecco Modified Eagle's Medium (DMEM)). The physicochemical reactions within the interface are characterized by scanning transmission electron microscopy (TEM) (STEM) associated with Energy‐dispersive X‐ray spectroscopy (EDXS). Microanalysis of diffusible ions such as sodium, potassium, or oxygen requires a special care. In the present investigation the cryo‐technique was adopted as a suitable tool for the specimen preparation and characterization. Cryosectioning is essential for preserving the native distribution of ions so that meaningful information about the local concentrations can be obtained by elemental microanalysis. The bioglass particles immersed in biological fluid for 24 h revealed five reaction stages: (i) dealkalization of the surface by cationic exchange (Na+, Ca2+ with H+ or H3O+); (ii) loss of soluble silica in the form of Si(OH)4 to the solution resulting from the breakdown of SiOSi bonds (iii); repolymerization of Si(OH)4 leading to condensation of SiO2); (iv) migration of Ca2+ and PO43− to the surface through the SiO2‐rich layer to form CaO‐P2O5 film; (v) crystallization of the amorphous CaO‐P2O5 by incorporating OH or CO32− anions with the formation of three different surface layers on the bioactive glass periphery. The thickness of each layer is ≈300 nm and from the inner part to the periphery they consist of SiOH, which permits the diffusion of Ca2+ and PO43− ions and the formation of the middle CaP layer, and finally the outer layer composed of NaO, which acts as an ion exchange layer between Na+ ions and H+ or H3O+ from the solution. Microsc. Res. Tech., 2008. © 2008 Wiley‐Liss, Inc.
Restricted transgene persistence after lentiviral vector‐mediated fetal gene transfer in the pregnant rabbit model
Authors: Moreno Rafael , Rosal Marta , Martinez Itziar , Vilardell Felip , Gonzalez Juan Ramón , Petriz Jordi , Hernandez‐Andrade Edgard , Gratacós Eduard , Aran Josep M.
Published: July 2008

Background

Prenatal gene transfer may enable early causal intervention for the treatment or prevention of many devastating diseases. Nevertheless, permanent correction of most inherited disorders requires a sustained level of expression from the therapeutic transgene, which could theoretically be achieved with integrating vectors.

Methods

Rabbit fetuses received 8.5 × 106 HIV‐based recombinant lentivirus particles containing the enhanced green fluorescent protein (EGFP) transgene by intrahepatic, intra‐amniotic or intraperitoneal injection at 22 days of gestation. Provirus presence and transgene expression in rabbit tissues were evaluated at both 1.5 and 16 weeks post‐in utero intervention by polymerase chain reaction (PCR) and reverse transcriptase‐PCR, respectively. Moreover, we assessed persistence of EGFP by immunohistochemistry. Enzyme‐linked immunosorbent assays confirmed the development of antibodies specific against both the viral vector and the reporter protein.

Results

Regardless of the route of administration employed, lentiviral vector‐based in utero gene transfer was safe and reached 85% of the intervened fetuses at birth. However, the integrated provirus frequency was significantly reduced to 50% of that in young rabbits at 16 weeks post‐treatment. In these animals, EGFP expression was evident in many tissues, including cytokeratin 5‐rich basal cells from stratified and pseudostratified epithelia, suggesting that the lentiviral vector might have reached progenitor cells. Conversely, we identified the presence of immune‐inflammatory infiltrates in several EGFP‐expressing tissues. Moreover, almost 70% of the lentiviral vector‐treated rabbits elicited a humoral immune response against the viral envelope and/or the EGFP.

Conclusions

At two‐thirds gestational age, the adaptive immune system of the rabbit appears a relevant factor limiting transgene persistence and expression following lentiviral vector‐mediated in utero gene transfer. Copyright © 2008 John Wiley & Sons, Ltd.