bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of cancer and statin usage—Record linkage study
Authors: Haukka Jari , Sankila Risto , Klaukka Timo , Lonnqvist Jouko , Niskanen Leo , Tanskanen Antti , Wahlbeck Kristian , Tiihonen Jari
Published: April 2009

The consumption of statins (HMG‐CoA reductase inhibitors) has been increasing, and a substantial part of the middle‐aged and elderly population use them continuously. Because a large fraction of the population is exposed, even a small excess of risk with respect to cancer should be considered. We carried out a record‐linkage study in Finland utilizing nationwide databases of reimbursed statin medication and cancer. The study population included all statin users in Finland who had purchased at least 1 prescription between 1996 and 2005 and who had no cancer diagnosis at the date of first purchase. A control population without statin usage was also included. Data consisted of 472,481 pairs of individuals that cumulated 4.2 million person years with an average of 8.8 years of follow‐up. Fifty thousand two hundred ninety‐four cancer cases were observed. Simvastatin and atorvastatin were the most used substances. The most frequent cancers were prostate, breast, lung, colon, and rectum cancer. In general, no association between the utilization of statins and cancer could be detected. In conclusion, this study adds large‐scale, population‐based results about the association between statin utilization and the incidence of cancer. We found neither beneficial nor harmful associations between the usage of statins and cancer.
EGFRvIII‐induced estrogen‐independence, tamoxifen‐resistance phenotype correlates with PgR expression and modulation of apoptotic molecules in breast cancer
Authors: Zhang Yang , Su Hua , Rahimi Massod , Tochihara Ryan , Tang Careen
Published: April 2009

The tumor‐specific, ligand‐independent, constitutively active epidermal growth factor receptor (EGFR) variant, EGFRvIII, remains understudied in breast cancer. Here, we report that expression of EGFRvIII in the ErbB‐2‐overexpressing, estrogen‐dependent MDA‐MB‐361 breast cancer cell line resulted in significant estrogen‐independent tumor growth in ovariectomized, athymic nude mice in comparison to MDA‐MB‐361/wt cells. MDA‐MB‐361/vIII breast cancer cells maintained estrogen‐induced tumor growth, but were tamoxifen‐resistant in the presence of estrogen, while MDA‐MB‐361/wt cells had a significant reduction in tumor growth in the presence of estrogen and tamoxifen. Tamoxifen alone did not have a significant effect on EGFRvIII‐mediated estrogen‐independent tumor growth. Constitutive signaling from the EGFRvIII receptor resulted in an increased activation of both the Akt and MAPK pathways. Compared to estrogen‐dependent, tamoxifen‐sensitive MCF‐7/vIII breast cancer cells, which had unchanged levels of ERα, but an increase in progesterone receptor (PgR) in comparison to MCF‐7/wt cells, MDA‐MB‐361/vIII cells had a reduction in ERα expression as well as a more pronounced reduction in PgR compared with MDA‐MB‐361/wt cells. EGFRvIII expression was also significantly associated with an absence of PgR protein in invasive human breast cancer specimens. Alterations of proapoptotic proteins and antiapoptotic proteins were observed in EGFRvIII transfectants. In conclusion, constitutive signaling through EGFRvIII and its downstream effector proteins crosstalks with the ERα pathway, resulting in loss of PgR expression and alterations in the apoptotic pathway, which may result in the estrogen‐independent, tamoxifen‐resistant phenotype conferred to EGFRvIII‐expressing breast cancer cells. © 2009 UICC
Reduced expression and homozygous deletion of annexin A10 in gastric carcinoma
Authors: Kim Jin , Kim Min A , Jee Chang Do , Jung Eun Ji , Kim Woo Ho
Published: April 2009

Annexins (ANXs) are a family of calcium and phospholipid binding proteins that have been implicated in diverse important biological and physiological process. ANX A10 (ANXA10) is a member of this family, though little is known about its functions. In the present study, array based comparative genomic hybridization (CGH) was used to screen DNA copy number change in gastric cancer cell lines and the results obtained were compared with oligonucleotide microarray data. DNA loss of the ANXA10 locus in chromosome 4q33 was found in several gastric cancer cell lines by array based CGH and these cell lines showed decreased ANXA10 expression by oligonucleotide microarray analysis. Functional analysis using siRNA and full‐length cDNA transfection in gastric cancer cell lines demonstrated that ANXA10 regulates gastric cancer cell proliferation. Of the 585 primary gastric carcinoma tissues examined, ANXA10 expression at the protein level was found to be reduced in 289 (49.4%) cases. Quantitative real‐time PCR analysis validated loss of DNA at the ANXA10 locus in gastric carcinomas with reduced ANXA10 expression. By univariate survival analysis, lack of ANXA10 expression was associated with poor survival (p = 0.016). These results suggest that ANXA10 inactivation by chromosomal deletion may play a role during gastric cancer progression. © 2009 UICC
Effect of bone sialoprotein coating of ceramic and synthetic polymer materials on in vitro osteogenic cell differentiation and in vivo bone formation
Authors: Schaeren Stefan , Jaquiéry Claude , Wolf Francine , Papadimitropoulos Adam , Barbero Andrea , Schultz‐Thater Elke , Heberer Michael , Martin Ivan
Published: April 2009

In this study, we addressed whether Bone Sialoprotein (BSP) coating of various substrates could enhance the in vitro osteogenic differentiation and in vivo bone formation capacity of human Bone Marrow Stromal Cells (BMSC). Moreover, we tested whether synthetic polymer‐based porous scaffolds, despite the absence of a mineral component, could support ectopic bone formation by human BMSC if coated with BSP. Adsorption of recombinant human BSP on tissue culture‐treated polystyrene (TCTP), β‐tricalcium phosphate (Osteologic™) or synthetic polymer (Polyactive™) substrates was dose dependent, but did not consistently accelerate or enhance in vitro BMSC osteogenic differentiation, as assessed by the mRNA expression of osteoblast‐related genes. Similarly, BSP coating of porous β‐tricalcium phosphate scaffolds (Skelite™) did not improve the efficiency of bone tissue formation following loading with BMSC and ectopic implantation in nude mice. Finally, Polyactive™ foams seeded with BMSC did not form bone tissue in the same ectopic assay, even if coated with BSP. We conclude that BSP coating of a variety of substrates is not directly associated with an enhancement of osteoprogenitor cell differentiation in vitro or in vivo, and that presentation of BSP on polymeric materials is not sufficient to prime BMSC functional osteoblastic differentiation in vivo. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Size‐tunable synthesis of stable superparamagnetic iron oxide nanoparticles for potential biomedical applications
Authors: Yu Faquan , Yang Victor C.
Published: April 2009

Dextran‐coated superparamagnetic nanoparticles (MNPs) have widespread biomedical applications. The superparamagnetic behavior, specifically regulated size, and smooth morphology are crucial requirements for essentially all of these applications. Presented herein is an innovative double‐coating strategy that would allow for a size‐controlled synthesis of MNPs. Small monocrystalline iron oxide nanoparticles (MIONs) were first synthesized, which served as the source of superparamagnetic properties. These MIONs were then treated in an acetate buffer containing biocompatible dextran polymer. Under such an environment, the colloidal MIONs would be quickly agglomerated by the acetate ions, and the formed coalescent body of MION would then be stabilized simultaneously by coating with dextran. By regulating the MION or dextran concentration as well as the thermal incubation time, the sizes of these first formed nanoparticles (termed 1st‐NPs) could be readily controlled. A second dextran coating step was further applied to smoothen the 1st‐NPs in attaining a final product (termed 2nd‐NPs). The 2nd‐NPs exhibited robust storage stability because of the additional coating shell. Results successfully confirmed the plausibility of this approach, as these MNPs displayed not only a smooth outline and a narrow size distribution but also the essential superparamagnetic behavior and a significantly prolonged stability on storage. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Uncoupled investigation of scaffold modulus and mesh size on smooth muscle cell behavior
Authors: Munoz‐Pinto Dany J. , Bulick Allen S. , Hahn Mariah S.
Published: April 2009

Although scaffold material properties are known to critically impact cell behavior, it has proven difficult to correlate specific cell responses to isolated scaffold parameters, inhibiting rational design of scaffold material properties. The aim of this study was to validate a systematic approach for evaluating the influence of initial scaffold modulus and mesh size on cell extracellular matrix (ECM) deposition and phenotype. Poly(ethylene glycol) diacrylate (PEGDA) hydrogels were selected for this study because of their tunable material properties. Following screening of six distinct PEGDA hydrogels, three formulations were identified which permitted uncoupled investigation of scaffold mesh size and modulus within the target incremental modulus range of ∼100–300 kPa. Smooth muscle cells (SMCs) were encapsulated within these three formulations, and cell ECM deposition and phenotype were evaluated following 21 days of culture. Although elastin content appeared to be correlated with scaffold mesh size and modulus to a similar degree, levels of collagen and serum response factor (SRF), a key regulator of SMC phenotype, were more strongly correlated with mesh size. To gain insight into the cell signaling underlying these observed correlations, variations in cell metabolic state and in RhoA signaling were semi‐quantitatively evaluated. Both RhoA activity, which is largely modulated by scaffold mechanics in 2D, and cell metabolic activity were highly correlated with hydrogel mesh size. These results indicate that the effects of scaffold mechanics on RhoA activity in 3D may be distinct from those in 2D and underscore the need for uncoupled investigation of scaffold parameters on cell behavior. Furthermore, the present data suggest that RhoA signaling and cell metabolic regulation may be closely linked. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Calcium phosphate/DNA co‐precipitates encapsulated fast‐degrading polymer films for substrate‐mediated gene delivery
Authors: Zhang Qiao , Zhao Dong , Zhang Xian‐Zheng , Cheng Si‐Xue , Zhuo Ren‐Xi
Published: April 2009

Calcium‐phosphate/deoxyribose nucleic acid (Ca‐P/DNA) co‐precipitates were deposited on or encapsulated in fast‐degrading polymer films with surface erosion degradation mechanism to mediate cell transfection. The polymer, cholic acid functionalized star poly(DL‐lactide), was synthesized through the ring‐opening polymerization of DL‐lactide initiated by cholic acid. The releases of DNA from the Ca‐P/DNA co‐precipitates deposited film and the Ca‐P/DNA co‐precipitates encapsulated film were determined and compared. The in vitro gene transfections of HEK293 cells, Hela cells, and NIH 3T3 cells showed that the expression of pGL3‐Luc plasmid could be effectively mediated by the Ca‐P/DNA co‐precipitates deposited and encapsulated polymer films. In addition, the films did not exhibit any additional cytotoxicity to the cells during the transfections, indicating that the fast‐degrading polymer films have great potential in localized gene delivery. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Trypsin‐ligand binding free energies from explicit and implicit solvent simulations with polarizable potential
Authors: Jiao Dian , Zhang Jiajing , Duke Robert E. , Li Guohui , Schnieders Michael J. , Ren Pengyu
Published: April 2009

We have calculated the binding free energies of a series of benzamidine‐like inhibitors to trypsin with a polarizable force field using both explicit and implicit solvent approaches. Free energy perturbation has been performed for the ligands in bulk water and in protein complex with molecular dynamics simulations. The binding free energies calculated from explicit solvent simulations are well within the accuracy of experimental measurement and the direction of change is predicted correctly in all cases. We analyzed the molecular dipole moments of the ligands in gas, water and protein environments. Neither binding affinity nor ligand solvation free energy in bulk water shows much dependence on the molecular dipole moments of the ligands. Substitution of the aromatic or the charged group in the ligand results in considerable change in the solvation energy in bulk water and protein whereas the binding affinity varies insignificantly due to cancellation. The effect of chemical modification on ligand charge distribution is mostly local. Replacing benzene with diazine has minimal impact on the atomic multipoles at the amidinium group. We have also utilized an implicit solvent based end‐state approach to evaluate the binding free energies of these inhibitors. In this approach, the polarizable multipole model combined with Poisson‐Boltzmann/surface area (PMPB/SA) provides the electrostatic interaction energy and the polar solvation free energy. Overall the relative binding free energies obtained from the MM‐PMPB/SA model are in good agreement with the experimental data. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009
Free energy simulations reveal a double mutant avian H5N1 virus hemagglutinin with altered receptor binding specificity
Authors: Das Payel , Li Jingyuan , Royyuru Ajay K. , Zhou Ruhong
Published: April 2009

Historically, influenza pandemics have been triggered when an avian influenza virus or a human/avian reassorted virus acquires the ability to replicate efficiently and become transmissible in the human population. Most critically, the major surface glycoprotein hemagglutinin (HA) must adapt to the usage of human‐like (α‐2,6‐linked) sialylated glycan receptors. Therefore, identification of mutations that can switch the currently circulating H5N1 HA receptor binding specificity from avian to human might provide leads to the emergence of pandemic H5N1 viruses. To define such mutations in the H5 subtype, here we provide a computational framework that combines molecular modeling with extensive free energy simulations. Our results show that the simulated binding affinities are in good agreement with currently available experimental data. Moreover, we predict that one double mutation (V135S and A138S) in HA significantly enhances α‐2,6‐linked receptor recognition by the H5 subtype. Our simulations indicate that this double mutation in H5N1 HA increases the binding affinity to α‐2,6‐linked sialic acid receptors by 2.6 ± 0.7 kcal/mol per HA monomer that primarily arises from the electrostatic interactions. Further analyses reveal that introduction of this double mutation results in a conformational change in the receptor binding pocket of H5N1 HA. As a result, a major rearrangement occurs in the hydrogen‐bonding network of HA with the human receptor, making the human receptor binding pattern of double mutant H5N1 HA surprisingly similar to that observed in human H1N1 HA. These large scale molecular simulations on single and double mutants thus provide new insights into our understanding toward human adaptation of the avian H5N1 virus. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009
Time‐dependent density functional theory study on the electronic excited‐state geometric structure, infrared spectra, and hydrogen bonding of a doubly hydrogen‐bonded complex
Authors: Liu Yufang , Ding Junxia , Liu Ruiqiong , Shi Deheng , Sun Jinfeng
Published: April 2009

The geometric structures and infrared (IR) spectra in the electronically excited state of a novel doubly hydrogen‐bonded complex formed by fluorenone and alcohols, which has been observed by IR spectra in experimental study, are investigated by the time‐dependent density functional theory (TDDFT) method. The geometric structures and IR spectra in both ground state and the S1 state of this doubly hydrogen‐bonded FN‐2MeOH complex are calculated using the DFT and TDDFT methods, respectively. Two intermolecular hydrogen bonds are formed between FN and methanol molecules in the doubly hydrogen‐bonded FN‐2MeOH complex. Moreover, the formation of the second intermolecular hydrogen bond can make the first intermolecular hydrogen bond become slightly weak. Furthermore, it is confirmed that the spectral shoulder at around 1700 cm−1 observed in the IR spectra should be assigned as the doubly hydrogen‐bonded FN‐2MeOH complex from our calculated results. The electronic excited‐state hydrogen bonding dynamics is also studied by monitoring some vibraitonal modes related to the formation of hydrogen bonds in different electronic states. As a result, both the two intermolecular hydrogen bonds are significantly strengthened in the S1 state of the doubly hydrogen‐bonded FN‐2MeOH complex. The hydrogen bond strengthening in the electronically excited state is similar to the previous study on the singly hydrogen‐bonded FN‐MeOH complex and play important role on the photophysics of fluorenone in solutions. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009
Evaluation of the searching abilities of HBOP and HBSITE for binding pocket detection
Authors: Oda Akifumi , Yamaotsu Noriyuki , Hirono Shuichi
Published: April 2009

We evaluated the pocket‐searching abilities of the computer programs HBOP and HBSITE, in which hydrophobic potentials calculated on grid points generated around a protein function as an indicator of the pocket‐like property‐using a test set of 458 experimentally observed structures of protein–ligand complexes. The results were compared with those obtained using the alternative algorithms PASS and SiteID, which only consider geometric properties, and Q‐SiteFinder, which considers not only geometry but also physicochemical properties. The comparison revealed that HBOP and HBSITE could detect experimentally observed ligand‐binding pockets for more test complexes than PASS and SiteID. In addition, the success rate of HBOP for detecting binding pockets was higher than that of Q‐SiteFinder, and that of HBSITE was comparable with that of Q‐SiteFinder. Results of tests for ligand‐unbound state proteins indicated that HBSITE was more appropriate than Q‐SiteFinder for pocket searches of ligand‐unbound proteins, and HBSITE was more robust than Q‐SiteFinder against structural differences between ligand‐bound and ‐unbound state proteins. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009
The subnuclear organization of histone gene regulatory proteins and 3′ end processing factors of normal somatic and embryonic stem cells is compromised in selected human cancer cell types
Authors: Ghule Prachi N. , Dominski Zbigniew , Lian Jane B. , Stein Janet L. , van Wijnen Andre J. , Stein Gary S.
Published: April 2009

Human histone gene expression is controlled at the level of transcription initiation and subsequent 3′end processing to generate non‐polyadenylated stem‐loop containing histone mRNAs. Transcription is controlled at the G1/S phase transition by the Cyclin E/CDK2 mediated induction of p220NPAT/HiNF‐P complexes at subnuclear domains designated Histone Locus Bodies (HLBs) that associate with histone gene clusters. Histone mRNA maturation is mediated by Lsm10 containing U7snRNP complexes. In normal human somatic and embryonic stem cells, the 6p histone locus, the transcription marker p220NPAT and the 3′end processing marker Lsm10 (but not the Cajal Body marker coilin) co‐localize, reflecting the assembly of an integrated factory for histone gene expression. Using in situ immuno‐fluorescence microscopy and fluorescence in situ hybridization (FISH), we show that this subnuclear organization is compromised in some cancer cell lines. In aneuploid cells, the presence of HLBs correlates with the number of histone gene loci. More importantly, the in situ co‐localization of p220NPAT and Lsm10 is disrupted in HeLa S3 cervical carcinoma cells and MCF7 breast adenocarcinoma cells, with most Lsm10 residing in Cajal Bodies. The finding that the subnuclear integration of transcriptional initiation and 3′end processing of histone gene transcripts is deregulated may be causally linked to tumor‐related modifications in molecular pathways controlling histone gene expression during the cell cycle. J. Cell. Physiol. 220: 129–135, 2009. © 2009 Wiley‐Liss, Inc.
Adsorption and desorption behaviour of Pb(II) on a natural kaolin: equilibrium, kinetic and thermodynamic studies
Authors: Tang Qiang , Tang Xiaowu , Li Zhenze , Chen Yunmin , Kou Naiyu , Sun Zufeng
Published: April 2009

BACKGROUND: Pb(II) is common in both waste‐waters and gas emissions. In developing countries, public health problems have been reported concerning Pb(II) pollution, so that stringent measures are required to deal with it.

MAJOR RESULTS: The adsorption and desorption behaviour of Pb(II) has been investigated on a natural Chinese kaolin. Several factors, including initial concentration, pH, equilibration time, dosage and temperature correlated positively with Pb(II) adsorption. The Pb(II) adsorption capacity of natural kaolin was 165.117 mg g−1. A kinetic study shows that Pb(II) adsorption on purified kaolin equilibrates within 35 min. The enthalpy changes of Pb(II) adsorption on purified kaolin were 63.683, 20.488 and 21.371 kJ mol−1 with entropy changes 262.250, 112.210 and 105.120 J mol−1 K−1 for solutions containing 50, 100 and 200 mg L−1 Pb(II) respectively, indicating an endothermic and spontaneous adsorption process. The desorption of Pb(II) from kaolin was difficult with more than 85% Pb(II) removal. Based on X‐ray diffraction (XRD) analysis, the Pb(II) adsorption on natural and purified kaolin was attributed mainly to the magnesite component and complexation with the mineral surface.

CONCLUSIONS: Natural kaolin exhibits a satisfactory performance for adsorption of Pb(II) from aqueous solution. The optimum conditions for adsorption were: ionic strength = 0.01 mol L−1; pH ≥ 7.2; dosage = 10 g L−1; temperature = 25 °C; duration ≥ 16 h (Ci = 80 mg L−1); and the optimum conditions for desorption were ionic strength = 0.1 mol L−1 and pH ≤ 5.0. Copyright © 2009 Society of Chemical Industry
Adsorption of fluoride from aqueous solution by magnesia‐amended silicon dioxide granules
Authors: Zhu Peiyi , Wang Haizeng , Sun Baowei , Deng Peichang , Hou Shaoqin , Yu Yanwei
Published: April 2009

BACKGROUND: A new kind of adsorbent, magnesia‐amended silicon dioxide granules (MAS), has been prepared by wet impregnation of silicon dioxide with magnesium chloride solution. The physicochemical properties were characterized using X‐ray diffraction (XRD), Fourier transform infrared (FT‐IR) and Brunauer, Emmett, Teller (BET) studies. The porous structure and high surface area of these granules make them suitable for sorption. The aim of this study was to show the possibility of defluoridation of water using MAS and to demonstrate the advantage of its use compared with silicon dioxide.

RESULTS: XRD and FT‐IR analysis showed that amorphous magnesia was loaded on silicon dioxide after treating with magnesium chloride solution and calcining at 500 °C. Batch sorption experiments indicated that MAS is more effective than silicon dioxide for fluoride adsorption. The sorption capacities of MAS decreased as the solution pH rose. At pH 3, the maximum defluoridation capacity of MAS was 12.6 mg g−1. The adsorption process fitted the Dubinin–Radushkevich isotherm and kinetic studies revealed that the adsorption followed second‐order rate kinetics.

CONCLUSION: The results indicate that it is feasible to modify both the physical and chemical properties of silicon dioxide with magnesia so that it can be used as a potential adsorbent to adsorb fluoride from aqueous solution. Copyright © 2009 Society of Chemical Industry
Thiotaurine and hypotaurine contents in hydrothermal‐vent polychaetes without thiotrophic endosymbionts: correlation With sulfide exposure
Authors: Yancey Paul H. , Ishikawa Joanne , Meyer Brigitte , Girguis Peter R. , Lee Raymond W.
Published: April 2009

Invertebrates at hydrothermal vents and cold seeps must cope with toxic H2S. One proposed protection mechanism involves taurine derivatives: At vents and seeps, many animals have high levels of hypotaurine and thiotaurine (a product of hypotaurine and HS), originally found in animals with thiotrophic endosymbionts. To further test the role of these compounds, we analyzed them in vent polychaetes without endosymbionts: Paralvinella sulfincola, P. palmiformis and P. pandorae (paralvinellids) and Nicomache venticola (maldanid). P. sulfincola were collected from a high temperature (42–68°C) and a warm site (21–35°C). P. palmiformis and pandorae were from cool sites (12–18°C) and N. venticola were from a cold site (4°C). H2S concentrations in vent effluent largely correlate with temperature. Some specimens were frozen; other ones were kept alive in laboratory chambers, with and without sulfide. Tissues were analyzed for taurine derivatives and other solutes that serve as organic osmolytes. The major osmolyte of all species was glycine. Thiotaurine contents were significantly different among all species, in the order P. sulfincola hot>P. sulfincola warm>P. pandorae>P. palmiformis>N. venticola. P. sulfincola also had high levels of sarcosine; others species had none. Sarcosine and hypotaurine contents of P. sulfincola's branchiae were higher, while glycine contents were lower, than in main body. In P. palmiformis kept in pressure chambers with sulfide, thiotaurine contents were higher and hypotaurine lower than in those kept without sulfide. These results support the hypothesis that conversion of hypotaurine to thiotaurine detoxifies sulfide in vent animals without endosymbionts. J. Exp. Zool. 311A:439–447, 2009. © 2009 Wiley‐Liss, Inc.
Osteoinduction by microbubble‐enhanced transcutaneous sonoporation of human bone morphogenetic protein‐2
Authors: Osawa Kenji , Okubo Yasunori , Nakao Kazumasa , Koyama Noriaki , Bessho Kazuhisa
Published: April 2009

Background

Bone morphogenetic protein‐2 (BMP‐2) is believed to participate in bone healing and regeneration. Previous studies using BMP‐2 in clinical applications have encountered difficulties that include the lack of an efficient, safe and simple delivery system, and expensive proteins and matrices. The gene transfer approach is a promising option for utilizing BMP‐2. Viral vector‐mediated gene transfer is efficient, but safety concerns prevent its clinical application for common diseases. Sonoporation is a simple and inexpensive method that only requires a plasmid and a sonoporation device.

Methods

We used a plasmid‐based human BMP‐2 construct (pCAGGS‐BMP‐2) and examined the induction of bone in the skeletal muscle of mice after plasmid transfer by transcutaneous sonoporation. First, an in vitro study was performed to confirm the expression of BMP‐2 after gene transfer by sonoporation using pCAGGS‐BMP‐2. Next, the BMP‐2 gene was transferred into the skeletal muscle of mice by transcutaneous sonoporation using pCAGGS‐BMP‐2. BMP‐2 production was assessed via immunohistochemistry, and osteoinduction was verified by radiography, histology and biochemical assays.

Results

The presence of human BMP‐2, alkaline phosphatase and osteocalcin mRNA and the production of the alkaline phosphatase were observed in vitro. Moreover, mature bone was observed in mice sonoporated with pCAGGS‐BMP‐2, confirming that transcutaneous sonoporation with pCAGGS‐BMP‐2 caused osteoinduction in the skeletal muscle of mice.

Conclusions

These results suggest the possibility of the effective clinical use of human BMP‐2 gene therapy using transcutaneous sonoporation, and should facilitate clinical applications of BMP‐2 gene therapy. Copyright © 2009 John Wiley & Sons, Ltd.
Facile synthesis of 4‐alkoxycarbonylisoquinoline‐1,3‐diones and 5‐alkoxycarbonyl‐2‐benzazepine‐1,3‐diones via a mild alkaline cyclization
Authors: Billamboz Muriel , Bailly Fabrice , Cotelle Philippe
Published: April 2009

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A series of 4‐methoxycarbonylisoquinoline‐1,3‐diones was obtained from homophthalic acid in four steps. The key step was the quantitative and rapid alkaline cyclization of 2‐methoxycarbonyl‐2‐(2‐methoxycarbonylphenyl) acetamides. Homologation easily afforded in the same conditions 5‐carboxy‐2‐benzazepine‐1,3‐dione. J. Heterocyclic Chem., 46, 392 (2009).
N‐methyl‐D‐aspartate‐stimulated ERK1/2 signaling and the transcriptional up‐regulation of plasticity‐related genes are developmentally regulated following in vitro neuronal maturation
Authors: Zhou Xianju , Moon Changjong , Zheng Fei , Luo Yongneng , Soellner Deborah , Nuñez Joseph L. , Wang Hongbing
Published: April 2009

The general features of neuroplasticity are developmentally regulated. Although it has been hypothesized that the loss of plasticity in mature neurons may be due to synaptic saturation and functional reduction of N‐methyl‐D‐aspartate receptors (NMDAR), the molecular mechanisms remain largely unknown. We examined the effects of NMDAR activation and KCl‐mediated membrane depolarization on ERK1/2 signaling following in vitro maturation of cultured cortical neurons. Although NMDA stimulated a robust increase in intracellular calcium at both DIV (day in vitro) 3 and 14, the activation of ERK1/2 and cAMP responsive element‐binding protein (CREB) was impaired at DIV 14. Specifically, the phosphorylation of ERK1/2 was stimulated by both NMDA and KCl at DIV 3. However, at DIV 14, NMDA‐ but not KCl‐stimulated ERK1/2 and CREB phosphorylation was significantly diminished. Consistently, the NMDA‐induced transcription of ERK/CREB‐regulated genes Bdnf exon 4, Arc, and zif268 was significantly attenuated at DIV 14. Moreover, in comparison with 3 DIV neurons, the phosphorylated‐ERK1/2 in 14 DIV neurons displayed a tremendous increase following maturation and was more susceptible to dephosphorylation. Blocking calcium channels by nifedipine or NMDAR by APV caused a more dramatic ERK dephosphorylation in 14 DIV neurons. We further demonstrate that the loss of plasticity‐related signaling is unrelated to NMDA‐induced cell death of the 14 DIV neurons. Taken together, these results suggest that the attenuation of certain aspects of neuroplasticity following maturation may be due to the reduction of NMDAR‐mediated gene transcription and a saturation of ERK1/2 activity. © 2009 Wiley‐Liss, Inc.
Synoptic forcing of precipitation in the Mackenzie and Yukon River basins
Authors: Cassano Elizabeth N. , Cassano John J.
Published: April 2009

The relationship between near‐surface atmospheric circulation, as characterized by sea level pressure patterns, and precipitation in the Mackenzie and Yukon River basins is presented. A synoptic climatology of sea level pressure patterns based on daily sea level pressure anomalies from the ERA40 reanalysis dataset was created using the method of self‐organizing maps. This objective analysis identified all major near‐surface atmospheric circulation patterns in the region and illustrated the change in dominant circulation patterns throughout the seasons, with strong Aleutian low patterns dominant in the winter and patterns characterized by low pressure over land areas and the Beaufort/Chukchi Seas in the summer. These synoptic patterns were then related to daily precipitation in the Mackenzie and Yukon River basins. The largest daily precipitation values, for both the Mackenzie and Yukon basins, were associated with patterns that occur most frequently in the summer, likely associated with increased frequency of cyclones and convective events that occur over land in that season. During winter, the largest positive precipitation anomalies were along the coastal mountain range in southeastern Alaska associated with Aleutian lows bringing warm, moist flow from the south resulting in upslope flow on the windward side of these mountains. These patterns were responsible for many of the large precipitation events in the winter in the Mackenzie basin. The largest precipitation events in the winter in the Yukon basin occurred with patterns that have a low pressure centre to the southwest of the basin. This synoptic pattern results in southerly flow advecting moisture into the basin to the west of the higher topography which bounds much of the southern boundary of the Yukon watershed. Copyright © 2009 Royal Meteorological Society
Diagnosing warm‐season rainfall variability in Mexico: a classification tree approach
Authors: Englehart Phil J. , Douglas Arthur V.
Published: April 2009

Many observational studies provide evidence that connects seasonal rainfall variations over parts of the subtropical and tropical Americas with the behaviour of large‐scale climate modes. This paper extends these claims based on analysis of a fairly extensive historical rainfall data set (1943–2006) from several locations in Mexico. The paper applies classification tree (CT) analysis to link warm‐season rainfall variability to climate indices, which characterize ENSO state, the NAO, and sea‐level pressure in the eastern North Pacific. While the results generally indicate that a significant part of the variability in warm‐season rainfall over Mexico is conditioned by large‐scale climate modes, there is only limited evidence of simple lag relationships involving Mexican rainfall and antecedent climate behaviour. The main implication here is that advances in warm seasonal rainfall prediction are likely to depend partially on improved capabilities to foreshadow the behaviour of large‐scale climate modes a season or more in advance. Copyright © 2009 Royal Meteorological Society
Effects of 1 to 3 years' treatment with alendronate on mechanical properties of the femoral shaft in a canine model: Implications for subtrochanteric femoral fracture risk
Authors: Burr David B. , Diab Tamim , Koivunemi Andrew , Koivunemi Mark , Allen Matthew R.
Published: April 2009

Bisphosphonate (BP) treatment used to prevent bone loss in postmenopausal osteoporosis has recently been implicated in an apparent increase in subtrochanteric femoral fractures. Previous work showed that BPs can reduce the energy to fracture of cancellous bone, but limited data exist on material‐level mechanical properties of compact bone from the long bones. This study examined intrinsic mechanical properties of the femoral diaphysis of a canine model treated for 1 or 3 years with alendronate at two different doses. Seventy‐two dogs were treated orally with 0.2 mg/kg/day alendronate or 1.0 mg/kg/day alendronate; a control group was administered saline. Prismatic beam specimens were tested in four‐point bending under displacement control, and the intrinsic mechanical properties were calculated. No significant differences were found among groups in any mechanical property at either 1 or 3 years of treatment. We conclude that the material properties of the femoral diaphysis are not degraded following 1 to 3 years treatment with alendronate, even at high doses. Longer periods of treatment have not been studied using clinical doses of alendronate, but such studies need to be carried out to confirm a lack of effect of alendronate on mechanical properties of cortical bone in the subtrochanteric region of the femur. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1288–1292, 2009
Functional sensibility assessment. part II: Effects of sensory improvement on precise pinch force modulation after transverse carpal tunnel release
Authors: Hsu Hsiu‐Yun , Kuo Li‐Chieh , Chiu Haw‐Yen , Jou I‐Ming , Su Fong‐Chin
Published: April 2009

Patients with median nerve compression at the carpal tunnel often have poor sensory afferents. Without adequate sensory modulation control, these patients frequently exhibit clumsy performance and excessive force output in the affected hand. We analyzed precision grip function after the sensory recovery of patients with carpal tunnel syndrome (CTS) who underwent carpal tunnel release (CTR). Thirteen CTS patients were evaluated using a custom‐designed pinch device and conventional sensory tools before and after CTR to measure sensibility, maximum pinch strength, and anticipated pinch force adjustments to movement‐induced load fluctuations in a pinch‐holding‐up activity. Based on these tests, five force‐related parameters and sensory measurements were used to determine improvements in pinch performance after sensory recovery. The force ratio between the exerted pinch force and maximum load force of the lifting object was used to determine pinch force coordination and to prove that CTR enabled precision motor output. The magnitude of peak pinch force indicated an economic force output during manipulations following CTR. The peak pinch force, force ratio, and percentage of maximum pinch force also demonstrated a moderate correlation with the Semmes–Weinstein test. Analysis of these tests revealed that improved sensory function helped restore patients' performance in precise pinch force control evaluations. These results suggest that sensory information plays an important role in adjusting balanced force output in dexterous manipulation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1534–1539, 2009
Lower extremity walking mechanics of young individuals with asymptomatic varus knee alignment
Authors: Barrios Joaquin A. , Davis Irene S. , Higginson Jill S. , Royer Todd D.
Published: April 2009

Varus knee alignment is associated with an increased risk for developing medial knee osteoarthritis (OA). Medial knee OA is commonly associated with altered walking mechanics in the frontal and sagittal planes, as well as altered ground reaction forces. It is unknown whether these mechanics are present in young, asymptomatic individuals with varus knees. We expected that varus‐aligned individuals would generally present with frontal plane mechanics that were similar to those reported for individuals with medial knee OA. The gait mechanics of 17 asymptomatic individuals with varus knees and 17 healthy, normally aligned controls were recorded. Gait parameters associated with medial knee OA were compared between groups. The individuals with varus knees exhibited greater knee external adduction moments, knee adduction, eversion, and lateral ground reaction force than the normally aligned individuals. In addition, those with varus knees also demonstrated increased knee flexion and external knee flexor moments during midstance. These results suggest that individuals with varus knees exhibit some, but not all, of the altered mechanics seen in medial knee OA. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1414–1419, 2009
Raman and surface‐enhanced Raman studies of α‐aminophosphinic inhibitors of metalloenzymes
Authors: Podstawka E. , Dra̧g M. , Oleksyszyn J.
Published: April 2009

Here, we report the nature of new di‐α‐amino (L1–L3) and α‐amino‐α‐hydroxyphosphinic (L4–L6) acids, which are considered potential inhibitors of the aminopeptidase N, adsorbed on a colloidal silver surface by means of surface‐enhanced Raman scattering (SERS) spectroscopy. In order to reveal the adsorption mechanism of these species from their SERS spectra, Fourier‐transform Raman (FT‐RS) spectra of these nonadsorbed molecules were measured. By examining the enhancement, shift in wavenumbers, and changes in breadth of the SERS bands due to the adsorption process, we revealed that the tilted compounds interact with the colloidal silver substrate mainly through the benzene ring, amino group, and phosphinic moiety in the following way. The benzene ring of L2 and L3 is ‘standing up’ on the colloidal silver surface, and the CN bond is almost vertical to it, while the tilt angle between the OPO bond and this surface is greater than 45°. On the other hand, for L1, L4, and L5, the aromatic ring and CN bond are arranged more or less tilted, and the tilt angle between the OPO bond and the silver substrate is smaller than 45°. The elongation of the bond to the benzene ring, the L6 case, produces an almost horizontal orientation of the benzene ring and the OPO bond on the silver nanoparticles.

For these ligands, the complement inhibition IC50 tested in vitro using porcine kidney leucine aminopeptidase was correlated mainly with the behavior of the OPO and CCHN fragments on the silver surface. Copyright © 2009 John Wiley & Sons, Ltd.
Signal processing to evaluate parameters affecting SPE for multi‐residue analysis of personal care products
Authors: Pietrogrande Maria Chiara , Basaglia Giulia , Dondi Francesco
Published: April 2009

This paper discusses the development of a comprehensive method for the simultaneous analysis of personal care products (PCPs) based on SPE and GC‐MS. The method was developed on 29 target compounds to represent PCPs belonging to different chemical classes: surfactants in detergents (alkyl benzenes), fragrances in cosmetics (nitro and polycyclic musks), antioxidants and preservatives (phenols), plasticizers (phthalates) displaying a wide range of volatility, polarity, water solubility. In addition to the conventional C18 stationary phase, a surface modified styrene divinylbenzene polymeric phase (StrataTM X SPE cartridge) has been investigated as suitable for the simultaneous extraction of several PCPs with polar and non‐polar characteristics. For both sorbents different solvent compositions and eluting conditions were tested and compared in order to achieve high extraction efficiency for as many sample components as possible. Comparison of the behavior of the two cartridges reveals that, overall, Strata‐X provides better efficiency with extraction recovery higher than 70% for most of the PCPs investigated. The best results were obtained under the following operative conditions: an evaporation temperature of 40°C, elution on Strata‐X cartridge using a volume of 15 mL of ethyl acetate (EA) as solvent and operating with slow flow rate (–10 KPa). In addition to the conventional method based on peak integration, a chemometric approach based on the computation of the experimental autocovariance function (EACVFtot) was applied to the complex GC‐MS signal: the percentage recovery and information on peak abundance distribution can be evaluated for each procedure step. The PC‐based signal processing proved very helpful in assisting the development of the analytical procedure, since it saves labor and time and increases result reliability in handling GC complex signals.
New synthetic esters with a complex structure considered as tribological fluids
Authors: Mirci Liviu E.
Published: April 2009

The paper presents results concerning synthesis and characterisation as lubricant fluids of some esters of different monocarboxylic acids with variable chain length, along with aliphatic‐aromatic complex alcohols and/or with superior alcohols (exclusive of aliphatic). The monocarboxylic acids taken into account were n‐butyric, n‐octanoic and oleic, respectively, while the alcohols considered were isodecyl and isotridecyl as purely aliphatic, and 2‐phenoxy‐ethanol, 2‐[(o‐sec‐butyl)phenoxy]ethanol and 2‐[(p‐nonyl)phenoxy]ethanol, as part of the complex aliphatic‐aromatic alcohols group. Under these circumstances, it became possible to study the influence of the structure on the main physico‐chemical properties of these synthetic oils as well as on their tribological representative features. The results recorded certified the validity of the proposed research programme. Copyright © 2009 John Wiley & Sons, Ltd.
Is the recipient vein really the main concern? A cohort study of head and neck reconstruction
Authors: Webster Ronaldo Scholze , Chem Roberto Corrêa
Published: April 2009

The aim of this study was to verify the role of the venous drainage system in the pathogenesis of complications in microsurgical head and neck reconstruction. In a nonrandomized cohort study, 52 consecutive cases of complex head and neck microsurgical reconstruction were evaluated. The patients were divided in two groups based on the treatment: the deep (DVDG; n = 30) and superficial (SVDG; n = 22) venous drainage groups. The complications evaluated included vascular obstruction with partial or total loss of the microsurgical flap, inadequate healing (fistulas or suture dehiscence), and infections. The arterial anastomotic site, neoplastic recurrence, use of medications and neoadjuvant radiotherapy, flap selection, tumor histology, smoking/alcoholism, and systemic diseases had no effect on postoperative complications, while the venous component influenced the overall complication rate (chi‐square test, P = 0.006). A protective effect was achieved in the DVDG when the overall complication rate was considered—relative risk (RR) 0.65, 95% confidence interval (CI) 0.45–0.94. The recipient vein should be the surgeon's main concern as it influenced the outcomes of patients undergoing complex microsurgical head and neck reconstruction. A protective effect was observed when the internal jugular vein drainage system was used for this purpose. © 2009 Wiley‐Liss, Inc. Microsurgery 2009.
Hyperbaric oxygen therapy protects the liver from apoptosis caused by ischemia‐reperfusion injury in rats
Authors: Chaves José C. , Fagundes Djalma J. , Simões Manuel De J. , Bertoletto Paulo R. , Oshima Celina T. F. , Taha Murched O. , Simões Ricardo S. , Fagundes Anna L. N.
Published: April 2009

Purpose:

The present paper aimed to investigate the role of hyperbaric oxygen treatment (HBO) and the apoptosis in rat liver ischemia‐reperfusion injury (IRI).

Methods:

Thirty‐seven male Wistar rats were subjected to 30 minutes of hepatic ischemia and 30 minutes of reperfusion and randomly distributed into six groups: G‐I/R (n = 8), control without HBO; G‐HBO/I (n = 8), HBO only during the ischemia period; G‐HBO/R (n = 8), HBO only during the reperfusion period; G‐HBO‐I/R (n = 8), HBO during both the ischemia and reperfusion periods; G‐Sh (n = 3), HBO without ischemia or reperfusion as sham group; G‐C (n = 2) for control of current apoptosis expression on the normal liver tissue. HBO was carried out using a transparent, cylindrical acrylic chamber with a pressure of 2.0 ATA. Hepatic samples were stained for caspase‐3 cleavage.

Results:

Apoptotic cells were identified in all groups. In the hepatic specimens of animals HBO‐treated during ischemia (GHBO‐I), there was a significant decrease (P < 0.001) in the number of cells undergoing apoptosis (1.62 ± 0.91). The apoptotic index showed no significant difference in the animals HBO‐treated during ischemia/reperfusion (5.75 ± 1.28) compared with the G‐I/R (3.5 ± 0.75), which had no HBO treatment. The apoptosis index (11.25 ± 1.90) was significantly higher (P < 0.01) in HBO‐treated animals during the reperfusion period when compared with any of the other groups.

Conclusion:

A favorable effect was obtained when hyperbaric oxygen was administered early during ischemia. The hyperbaric oxygen in later periods of reperfusion was associated with a more severe apoptosis index. © 2009 Wiley‐Liss, Inc. Microsurgery 2009.