bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of coarse grained models for hydrogen bonds in proteins
Authors: De Sancho David , Rey Antonio
Published: February 2007

Backbone hydrogen bonds contribute very importantly to the stability of proteins and therefore they must be appropriately represented in protein folding simulations. Simple models are frequently used in theoretical approaches to this process, but their simplifications are often confronted with the need to be true to the physics of the interactions. Here we study the effects of different levels of coarse graining in the modeling of backbone hydrogen bonds. We study three different models taken from the bibliography in a twofold fashion. First, we calculate the hydrogen bonds in 2gb1, an (α + β)‐protein, and see how different backbone representations and potentials can mimic the effects of real hydrogen bonds both in helices and sheets. Second, we use an evolutionary method for protein fragment assembly to locate the global energy minimum for a set of small β‐proteins with these models. This way, we assess the effects of coarse graining in hydrogen bonding models and show what can be expected from them when used in simulation experiments. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Self‐organizing superimposition algorithm for conformational sampling
Authors: Zhu Fangqiang , Agrafiotis Dimitris K.
Published: February 2007

A novel self‐organizing algorithm for conformational sampling is introduced, in which precomputed conformations of rigid fragments are used as templates to enforce the desired geometry. Starting from completely random coordinates, the algorithm repeatedly superimposes the templates to adjust the positions of the atoms, thereby gradually refining the conformation of the molecule. Combined with pair‐wise adjustments of the atoms to resolve steric clashes, conformations that satisfy all geometric constraints can be generated from this procedure. The algorithm is demonstrated to achieve good performance and promises potential applications on more challenging modeling problems. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Vibalizer: A free, web‐based tool for rapid, quantitative comparison and analysis of calculated vibrational modes
Authors: Grafton Anthony K.
Published: February 2007

This report describes the development and applications of a software package called Vibalizer, the first and only method that provides free, fast, interactive, and quantitative comparison and analysis of calculated vibrational modes. Using simple forms and menus in a web‐based interface, Vibalizer permits the comparison of vibrational modes from different, but similar molecules and also performs rapid calculation and comparison of isotopically substituted molecules' normal modes. Comparing and matching complex vibrational modes can be completed in seconds with Vibalizer, whereas matching vibrational modes manually can take hours and gives only qualitative comparisons subject to human error and differing individual judgments. In addition to these core features, Vibalizer also provides several other useful features, including the ability to automatically determine first‐approximation mode descriptions, to help users analyze the results of vibrational frequency calculations. Because the software can be dimensioned to handle almost arbitrarily large systems, Vibalizer may be of particular use when analyzing the vibrational modes of complex systems such as proteins and extended materials systems. Additionally, the ease of use of the Vibalizer interface and the straightforward interpretation of results may find favor with educators who incorporate molecular modeling into their classrooms. The Vibalizer interface is available for free use at http://www.compchem.org, and it is also available as a locally‐installable package that will run on a Linux‐based web server. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Prediction of GFP spectral properties using artificial neural network
Authors: Nantasenamat Chanin , Isarankura‐Na‐Ayudhya Chartchalerm , Tansila Natta , Naenna Thanakorn , Prachayasittikul Virapong
Published: February 2007

The prediction of the excitation and the emission maxima of green fluorescent protein (GFP) chromophores were investigated by a quantitative structure‐property relationship study. A data set of 19 GFP color variants and an additional data set consisting of 29 synthetic GFP chromophores were collected from the literature. Artificial neural network implementing the back‐propagation algorithm was employed. The proposed computational approach reliably predicted the excitation and the emission maxima of GFP chromophores with correlation coefficient exceeding 0.9. The usefulness of quantum chemical descriptors was revealed by a comparative study with other molecular descriptors. Assignment of appropriate protonation state of the chromophore for the GFP color variants data set was shown to be necessary for good predictive performance. Results suggest that the confinement of the GFP chromophore has no significant influence on the predictive performance of the data set used. A comparative investigation with the traditional modeling methods, particularly multiple linear regression and partial least squares, reveals that artificial neural network is the most suitable modeling approach for the GFP spectral properties. It is anticipated that this methodology has great potential in accelerating the design and engineering of novel GFP color variants of scientific or industrial interest. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
QSAR models based on isomorphic and nonisomorphic data fusion for predicting the blood brain barrier permeability
Authors: Cuadrado Manuel Urbano , Ruiz Irene Luque , Gómez‐Nieto Miguel Ángel
Published: February 2007

A QSAR model for predicting the blood brain barrier permeability (BBBP) in a large and heterogeneous variety of compounds (136 compounds) has been developed using approximate similarity (AS) matrices as predictors and PLS as multivariate regression technique. AS values fuse information of both the isomorphic similarity and nonisomorphic dissimilarity with the purpose of achieving an accurate predictive space. In addition to the fact of applying AS values to heterogeneous data sets, a new concept on graph isomorphism based on the extended maximum common subgraph (EMCS) is defined for the building of AS spaces considering the atoms and bonds, which are bridges between the isomorphic and nonisomorphic substructures. This new isomorphism detection has as objective to take into account the position and nature of the nucleus substituents, thus allowing the development of accurate models for large and diverse sets of compounds. After an outliers study, the training and test stages were made and the results obtained using several AS approaches were compared. Several validation processes were carried out by means of employing several test sets, and high predictive ability was obtained for all the cases (Q2 = 0.81 and standard error in prediction, SEP = 0.29). © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Quantification of red myotomal muscle volume and geometry in the shortfin mako shark (Isurus oxyrinchus) and the salmon shark (Lamna ditropis) using T1‐weighted magnetic resonance imaging
Authors: Perry Cameron N. , Cartamil Daniel P. , Bernal Diego , Sepulveda Chugey A. , Theilmann Rebecca J. , Graham Jeffrey B. , Frank Lawrence R.
Published: February 2007

T1‐weighted magnetic resonance imaging (MRI) in conjunction with image and segmentation analysis (i.e., the process of digitally partitioning tissues based on specified MR image characteristics) was evaluated as a noninvasive alternative for differentiating muscle fiber types and quantifying the amounts of slow, red aerobic muscle in the shortfin mako shark (Isurus oxyrinchus) and the salmon shark (Lamna ditropis). MRI‐determinations of red muscle quantity and position made for the mid‐body sections of three mako sharks (73.5–110 cm fork length, FL) are in close agreement (within the 95% confidence intervals) with data obtained for the same sections by the conventional dissection method involving serial cross‐sectioning and volumetric analyses, and with previously reported findings for this species. The overall distribution of salmon shark red muscle as a function of body fork length was also found to be consistent with previously acquired serial dissection data for this species; however, MR imaging revealed an anterior shift in peak red muscle cross‐sectional area corresponding to an increase in body mass. Moreover, MRI facilitated visualization of the intact and anatomically correct relationship of tendon linking the red muscle and the caudal peduncle. This study thus demonstrates that MRI is effective in acquiring high‐resolution three‐dimensional digital data with high contrast between different fish tissue types. Relative to serial dissection, MRI allows more precise quantification of the position, volume, and other details about the types of muscle within the fish myotome, while conserving specimen structural integrity. J. Morphol., 2007. © 2007 Wiley‐Liss, Inc.
Plasticity of mandibular biomineralization in myostatin‐deficient mice
Authors: Ravosa Matthew J. , Klopp Emily B. , Pinchoff Jessie , Stock Stuart R. , Hamrick Mark W.
Published: February 2007

Compared with the normal or wild‐type condition, knockout mice lacking myostatin (Mstn), a negative regulator of skeletal muscle growth, develop significant increases in relative masticatory muscle mass as well as the ability to generate higher maximal muscle forces. Wild‐type and myostatin‐deficient mice were compared to assess the postweaning influence of elevated masticatory loads because of increased jaw‐adductor muscle and bite forces on the biomineralization of mandibular cortical bone and dental tissues. Microcomputed tomography (microCT) was used to quantify bone density at a series of equidistant external and internal sites in coronal sections for two symphysis and two corpus locations. Discriminant function analyses and nonparametric ANOVAs were used to characterize variation in biomineralization within and between loading cohorts. Multivariate analyses indicated that 95% of the myostatin‐deficient mice and 95% of the normal mice could be distinguished based on biomineralization values at both symphysis and corpus sections. At the corpus, ANOVAs suggest that between‐group differences are due to the tendency for cortical bone mineralization to be higher in myostatin‐deficient mice, coupled with higher levels of dental biomineralization in normal mice. At the symphysis, ANOVAs indicate that between‐group differences are related to significantly elevated bone‐density levels along the articular surface and external cortical bone in the knockout mice. Both patterns, especially those for the symphysis, appear because of the postweaning effects of increased masticatory stresses in the knockout mice versus normal mice. The greater number of symphyseal differences suggest that bone along this jaw joint may be characterized by elevated plasticity. Significant differences in bone‐density levels between normal and myostatin‐deficient mice, coupled with the multivariate differences in patterns of plasticity between the corpus and symphysis, underscore the need for a comprehensive analysis of the plasticity of masticatory tissues vis‐à‐vis altered mechanical loads. J. Morphol., 2007. © 2007 Wiley‐Liss, Inc.
Disulfide bond cleavages observed in SORI‐CID of three nonapeptides complexed with divalent transition‐metal cations
Authors: Mihalca Romulus , van der Burgt Yuri E. M. , Heck Albert J. R. , Heeren Ron M. A.
Published: February 2007

Tandem MS sequencing of peptides that contain a disulfide bond is often hampered when using a slow heating technique. We show that complexation of a transition‐metal ion with a disulfide‐bridge‐containing nonapeptide yields very rich tandem mass spectra, including fragments that involve the cleavage of the disulfide bond up to 56% of the total product ion intensity. On the contrary, MS/MS of the corresponding protonated nonapeptides results predominantly in fragments from the region that is not involved in the disulfide bond. Eleven different combinations of three nonapeptides and three metal ions were measured using Fourier transform ion cyclotron resonance mass spectrometry (FTICR‐MS) combined with sustained off‐resonance irradiation collision induced dissociation (SORI‐CID). All observed fragments are discussed with respect to four different types of product ions: neutral losses, b/y‐fragmentation with and without the disulfide bond cleavage, and losses of internal amino acids without rupture of the disulfide bridge. Furthermore, it is shown that the observed complementary fragment pairs obtained from peptide–metal complexes can be used to determine the region of the binding site of the metal ion. This approach offers an efficient way to cleave disulfide‐bridged structures using low energy MS/MS, which leads to increased sequence coverage and more confidence in peptide or protein assignments. Copyright © 2007 John Wiley & Sons, Ltd.
Applications of LC/MS in structure identifications of small molecules and proteins in drug discovery
Authors: Chen Guodong , Pramanik Birendra N. , Liu Yan‐Hui , Mirza Urooj A.
Published: February 2007

With advancements in ionization methods and instrumentation, liquid chromatography/mass spectrometry (LC/MS) has become a powerful technology for the characterization of small molecules and proteins. This article will illustrate the role of LC/MS analysis in drug discovery process. Examples will be given on high‐throughput analysis, structural analysis of trace level impurities in drug substances, identification of metabolites, and characterization of therapeutic protein products for process improvement. Some unique MS techniques will also be discussed to demonstrate their effectiveness in facilitating structural identifications. Copyright © 2007 John Wiley & Sons, Ltd.
LC‐MS ion maps for the characterization of aniline derivatives of fatty acids and triglycerides in laboratory‐denatured rapeseed oil
Authors: Reig Natalia , Calaf Rosa E. , Messeguer Angel , Morató Anna , Escabros Jordi , Gelpí Emilio , Abian Joaquín
Published: February 2007

In 1981 Spain went through a unique epidemic associated with a food‐borne vector, affecting more than 20 000 people with over 800 deaths, which came to be known as the Toxic Oil Syndrome (TOS). Early epidemiological studies showed a link between this illness and the ingestion of rapeseed oil denatured with 2% aniline. This oil, originally aniline‐denatured for industrial use, was fraudulently processed in an attempt to remove free aniline, and marketed as edible oil. Fatty acid anilides (FAA), monoesters and diesters of 3‐(N‐phenylamino)‐1,2‐propanediol (PAP) are present in oil samples as they arise in the refining process from reactions of aniline with constituent fatty acids and triglycerides of the oil matrix and are the only extraneous compounds found in these samples. To expand the search for the causative agents in TOS‐associated oils and to look for new aniline‐related compounds, an exhaustive characterization of laboratory‐processed oils was undertaken. These oils, in the presence of aniline doped with 14C labelled aniline, were submitted to the laboratory conditions required for the generation of PAPs and FAAs. Laboratory‐generated oil samples were submitted to a liquid‐liquid extraction procedure to remove the unreacted aniline. The extract was processed by double solid‐phase extraction to improve detection limits for minor amine‐containing compounds in oils. The extracts enriched in aniline derivatives were submitted to on‐line HPLC‐UV‐APCI‐MS. Using two‐dimensional ion maps, the components of several families of derivatives were readily identified. Additionally, the extracts were also fractionated by HPLC‐UV and the fractions were analyzed by HPLC‐APCI‐MS/MS to obtain structural information. Standards of some of these compounds were synthesized and analyzed to confirm the results. A total of 115 aniline derivatives from 9 aniline‐related families were identified in these oil samples. These included fatty acid anilides and an extensive array of phenylaminopropanediol esters distributed in eight major compound classes. Copyright © 2007 John Wiley & Sons, Ltd.
Simple and rapid characterization of soybean cultivars by perfusion reversed‐phase HPLC: Application to the estimation of the 11S and 7S globulin contents
Authors: García María Concepción , Heras José María , Marina María Luisa
Published: February 2007

A perfusion RP HPLC method enabling the separation of soybean proteins in an analysis time lower than 3 min has been used to obtain the chromatographic profiles of different soybean cultivars. The chromatograms obtained for each soybean variety presented clear differences that justified the potential use of this method for cultivar characterization. The area percentages obtained were employed as variables for cluster and principal components analysis of these soybeans. The application of these multivariate methods enabled the grouping of the soybeans in different categories. The protein fractions obtained from these soybeans by the application of a fractionation method were also analyzed. The chromatographic profiles obtained enabled the assignment of peaks to the main soybean proteins (7S and 11S globulins). These data were used for the estimation, for the first time, of the 7S and 11S globulin contents in soybean cultivars.
Online preconcentration of arsenic compounds by dynamic pH junction‐capillary electrophoresis
Authors: Jaafar Jafariah , Irwan Zildawarni , Ahamad Rahmalan , Terabe Shigeru , Ikegami Tohru , Tanaka Nobuo
Published: February 2007

An online preconcentration technique by dynamic pH junction was studied to improve the detection limit for anionic arsenic compounds by CE. The main target compound is roxarsone, or 3‐nitro‐4‐hydroxyphenylarsonic acid, which is being used as an animal feed additive. The other inorganic and organoarsenic compounds studied are the possible biotransformation products of roxarsone. The arsenic species were separated by a dynamic pH junction in a fused‐silica capillary using 15 mM phosphate buffer (pH 10.6) as the BGE and 15 mM acetic acid as the sample matrix. CE with UV detection was monitored at a wavelength of 192 nm. The influence of buffer pH and concentration on dynamic pH junction were investigated. The arsenic species focusing resulted in LOD improvement by a factor of 100–800. The combined use of C18 and anion exchange SPE and dynamic pH junction to CE analysis of chicken litter and soils helps to increase the detection sensitivity. Recoveries of spiked samples ranged between 70 and 72%.
Statistical mixture design optimization of extraction media and mobile phase compositions for the characterization of green tea
Authors: Alves de Almeida Aline , Spacino Scarminio Ieda
Published: February 2007

The influence of different solvents on the extraction medium and the RP‐HPLC mobile phase composition were investigated by statistical mixture designs to optimize solvent proportions to prepare the fingerprint of a medicinal herbal extract. For modeling, the number of peaks was used as a measure of fingerprint information. The optimum compositions of solvent to extract chemical substances from green tea and for mobile phase chromatographic analysis were ethyl acetate/ethanol/dichloromethane (20:5:75 v/v/v) and MeOH/ACN/water (7.5:57.5:35 v/v/v), respectively. This system results in 26 peaks in the chromatographic fingerprint. These results show that an incorrect choice of modifiers for mobile phase composition and solvent extraction hampers the detection of a maximum number of peaks and produces a poor chromatographic fingerprint.
Chiral separation of β‐blocker drug nadolol by HPLC – A kinetic and equilibrium study
Authors: Wang Xin , Ching Chi Bun
Published: February 2007

A Chiralpak AD‐H column packed with amylose tris(3,5‐dimethylphenylcarbamate) coated on silica gel was used to study the enantioseparation of nadolol by HPLC. The bed voidage, axial dispersion coefficient, overall mass transfer coefficients as well as equilibrium constants for the chromatographic enantiomeric separation were evaluated by moment analysis on the basis of the solid film linear driving force model. The equilibrium constants were found to be 3.81, 5.24, 9.45 and 19.41 for the stereoisomers (SRS)‐, (SRR)‐, (RSS)‐ and (RSR)‐nadolol, respectively. Their overall mass transfer coefficients were found to be 1841.8, 1254.8, 799.4 and 401.7 min–1 respectively. Temperature effect on the enantiomeric separation and thermodynamic properties including enthalpy and entropy change of binding to the amylose tris(3,5‐dimethylphenylcarbamate) stationary phase were also investigated. The moment analysis and the parameters obtained were used to simulate nadolol elution profiles. The simulated results matched the experimental profiles well, which confirmed the validity of model parameters obtained in this study.
Determination of dopamine and serotonin in human urine samples utilizing microextraction online with liquid chromatography/electrospray tandem mass spectrometry
Authors: El‐Beqqali Aziza , Kussak Anders , Abdel‐Rehim Mohamed
Published: February 2007

A specific LC‐MS‐MS method for the determination of dopamine and serotonin (5‐hydroxytryptamine; 5HT) in human urine is described. The analytes were extracted from urine and preconcentrated by microextraction in a packed syringe (MEPS). The new method is very promising, very easy to use, fully automated, of low cost, and rapid in comparison to previously used methods. The method was validated and the standard curves were evaluated by means of quadratic regression and weighted by inverse of the concentration: 1/x for the calibration range 50–4000 μg/L. The MEPS applied polymer (silica‐C8) could be used more than 300 times. The extraction recovery was about 50%. The results showed close correlation coefficients (r2 >0.999) for all analytes in the calibration range studied. The accuracy of MEPS‐LC‐MS‐MS was 100–101% for dopamine and 99–100% for 5HT. The interday precision (n = 3 days), expressed as the RSD%, was 6.0–7.7% for dopamine and 6.1–11% for 5HT. MEPS reduced the handling time by 12 times compared to a published method.
A GC method for simultaneous analysis of bornesitol, other polyalcohols and sugars in coffee and its substitutes
Authors: Ruiz‐Matute Ana Isabel , Montilla Antonia , del Castillo Maria Dolores , Martínez‐Castro Isabel , Luz Sanz Maria
Published: February 2007

A GC method has been developed for the determination of polyalcohols and sugars in aqueous extracts from green coffee beans, ground roasted coffee beans submitted to either conventional or torrefacto processes, coffee blends and soluble instant coffees. Bornesitol was detected in aqueous coffee extracts for the first time. Mannitol, myo‐inositol, mannose, fructose, galactose, glucose and sucrose have also been determined. Results seem to indicate that coffee manufacturing processes, such as roasting or decaffeination, do not affect the polyalcohol content. Coffee substitutes based on cereals, carob or chicory, have also been studied. The possibility to characterize their presence in coffee extracts was evaluated.
Temperature effects on separation on zirconia columns: Applications to one‐ and two‐dimensional LC separations of phenolic antioxidants
Authors: Cacciola Francesco , Jandera Pavel , Mondello Luigi
Published: February 2007

The effects of temperature and mobile phase on LC chromatographic separation of phenolic antioxidants on zirconia‐based columns were investigated. Unlike silica‐based materials, zirconia columns show excellent thermal stability over a wide range of temperatures and enable high‐temperature separations. Enthalpic and entropic contributions to the retention of phenolic compounds on ZR‐Carbon and ZR‐Carbon C18 columns were determined from retention versus temperature plots in order to elucidate the retention mechanism of sample compounds over the temperature range up to 140°C. High‐temperature liquid chromatography on ZR‐Carbon columns was used for comprehensive LC×LC two‐dimensional separation systems based on the different selectivity of a Zorbax SB micro‐column used in the first dimension and a ZR‐Carbon column used in the second dimension. Two‐dimensional LC×LC systems employing a setup with two alternately operated parallel ZR‐Carbon columns in the second dimension were used for the analysis of phenolic antioxidants in beer and wine samples.
Analysis of aromatic and terpenic constituents of pepper extracts by capillary electrochromatography
Authors: Musenga Alessandro , Mandrioli Roberto , Ferranti Anna , D'Orazio Giovanni , Fanali Salvatore , Raggi Maria Augusta
Published: February 2007

An original method based on CEC has been developed for the determination of aromatic and terpenic compounds in extracts of spices obtained from Piper nigrum. The method is based on the use of a fused silica capillary (effective length: 23.5 cm, internal diameter: 100 μm) packed with a C18 sorbent (packing length: 23 cm, particle size: 5 μm). The mobile phase is a 50 mM, pH 6.0 ammonium acetate/ACN (10:90 v/v) mixture. Applying a 30 kV voltage, the following 11 compounds were separated and analysed: terpinen‐4‐ol, caryophyllene oxide, limonene, α‐pinene, 3‐carene, β‐pinene, α‐humulene, β‐caryophyllene, α‐phellandrene, eugenol and piperine. Compound determination is carried out using a diode‐array detector set at 265 and 338 nm for α‐phellandrene and piperine, respectively, and at 210 nm (reference subtraction at 282 nm) for all the other analytes. The optimised method has been validated with good results in terms of linearity, limits of quantitation, detection and precision. The CEC method was successfully applied to the analysis of essential oils and methanolic extracts of ‘black’, ‘white’ and ‘green’ pepper.
Stable multi-wavelength erbium-doped fiber laser based on a photonic crystal fiber Sagnac loop filter
Authors: Chen D
Published: February 2007

A multi-wavelength erbium-doped fiber laser based on a Sagnac loop filter which is formed by a birefringent and highly nonlinear photonic crystal fiber (PCF), a 3-dB optical coupler and two polarization controllers is proposed. The PCF Sagnac loop filter is used as a comb filter and power-stabilizing and -equilibrizing component in the multi-wavelength erbium-doped fiber laser. Stable multi-wavelength lasing at room temperature is achieved, owing to the contributions of both the birefringent property and the four-wave mixing effect of the PCF.
All-fiber pulsed Raman source based on Yb:Bi fiber laser
Authors: Kurkov A S , Dvoyrin V V , Paramonov V M , Medvedkov O I , Dianov E M
Published: February 2007

All-fiber Raman fiber source emitting at 1254 nm was realized. For the first time to pump Raman converter we have applied Yb:Bi pulsed fiber laser. The P-doped fiber was used as an active medium of the Raman converter. The conversion slope efficiency of 70% and the peak power of 12 W were observed.
Magneto‐motive detection of tissue‐based macrophages by differential phase optical coherence tomography
Authors: Oh Junghwan , Feldman Marc D. , Kim Jihoon , Kang Hyun Wook , Sanghi Pramod , Milner Thomas E.
Published: February 2007

Background and Objectives

A novel method to detect tissue‐based macrophages using a combination of superparamagnetic iron oxide (SPIO) nanoparticles and differential phase optical coherence tomography (DP‐OCT) with an external oscillating magnetic field is reported.

Study Design/Material and Methods

Magnetic force acting on iron‐laden tissue‐based macrophages was varied by applying a sinusoidal current to a solenoid containing a conical iron core that substantially focused and increased magnetic flux density.

Results

Nanoparticle motion was detected with DP‐OCT, which can detect tissue movement with nanometer resolution. Frequency response of iron‐laden tissue movement was twice the modulation frequency since the magnetic force is proportional to the product of magnetic flux density and gradient.

Conclusions

Results of our experiments indicate that DP‐OCT can be used to identify tissue‐based macrophage when excited by an external focused oscillating magnetic field. Lasers Surg. Med. 39:266–272, 2007. © 2007 Wiley‐Liss, Inc.
Metabolic Engineering for Microbial Production and Applications of Copolyesters Consisting of 3‐Hydroxybutyrate and Medium‐Chain‐Length 3‐Hydroxyalkanoates
Authors: Zou Xiang Hui , Chen Guo‐Qiang
Published: February 2007

Poly(hydroxyalkanoate)s (PHAs) are a class of microbially synthesized polyesters that combine biological properties, such as biocompatibility and biodegradability, and non‐bioproperties such as thermoprocessability, piezoelectricity, and nonlinear optical activity. PHA monomer structures and their contents strongly affect the PHA properties. Using metabolic engineering approaches, PHA structures and contents can be manipulated to achieve controllable monomer and PHA cellular contents. This paper focuses on metabolic engineering methods to produce PHA consisting of 3‐hydroxybutyrate (3HB) and medium‐chain‐length 3‐hydroxyalkanoates (3HA) in recombinant microbial systems. This type of copolyester has mechanical and thermal properties similar to conventional plastics such as poly(propylene) and poly(ethylene terephthalate) (PET). In addition, pathways containing engineered PHA synthases have proven to be useful for enhanced PHA production with adjustable PHA monomers and contents. The applications of PHA as implant biomaterials are briefly discussed here. In the very near term, metabolic engineering will help solve many problems in promoting PHA as a new type of plastic material for many applications.

magnified image
Construction of pha‐Operon‐Defined Knockout Mutants of Pseudomonas putida KT2442 and their Applications in Poly(hydroxyalkanoate) Production
Authors: Ouyang Shao‐Ping , Liu Qian , Fang Lei , Chen Guo‐Qiang
Published: February 2007

Pseudomonas putida KT2442 could accumulate medium‐chain‐length poly(hydroxyalkanoate)s (PHA) consisting of 3‐hydroxyhexanoate, 3‐hydroxyoctanoate, 3‐hydroxydecanoate, and 3‐hydroxydodecanoate from a wide range of carbon sources. In this study, the PHA synthase pha operon (phaC1‐phaZ‐phaC2) was knocked out and the vgb gene encoding vitreoscilla hemoglobin protein (VHb), which could enhance oxygen uptake rate especially at low oxygen concentration, was integrated into the P. putida KT2442 genome to replace the deleted fragment. The resulting mutant P. putida KTOY01 or gene‐replaced mutant KTOY02 was used as the host to study PHA synthase properties and PHA production. Different PHA polymerase (PhaC) genes, phaCRe from Rastonia eutropha H16, phaCAc from Aeromonas cavie, and phaC2Ps from Pseudomonas stutzeri 1317, were expressed in the mutant strains to test the PhaC enzyme substrate specificity. The result showed P. putida KTOY01 or KTOY02 could provide not only mcl PHA monomers but also 3‐hydroxybutyrate from fatty acids, which may allow the production of copolyesters poly(3HB‐co‐mcl 3HA). Plasmid pCJY10 containing phaC2Ps, phbA, and phbB genes encoding PHA polymerase, β‐ketothiolase, and acetoacetyl‐CoA reductase, respectively, were transformed into P. putida KTOY01 and KTOY02. Shake‐flask culture showed P. putida KTOY01 or KTOY02 (pCJY10) could accumulate poly(3HB‐co‐mcl 3HA) from glucose. The above result showed pha operon knockout mutant of P. putida KT2442 was a very useful host of great potential not only for studying PhaC synthase, but also for microbial production of copolyesters poly(3HB‐co‐mcl 3HA), which is very difficult to obtain.

magnified image
TiO2 Sphere‐Tube‐Fiber Transition Induced by Oligovaline Concentration Variation
Authors: Mantion Alexandre , Taubert Andreas
Published: February 2007

L‐Valine‐based oligopeptides with the general structure Z‐(L‐Val)n‐OMe or OH (n = 1–4) form stable organogels in a variety of solvents, including the inorganic liquid tetraethylorthosilicate. The acid form Z‐(L‐Val)n‐OH is a less efficient gelator than the methyl ester, but forms stable organogels in aromatic solvents and di‐ and trichloromethane. In all cases the peptides form micrometer long helical fibers with a β‐sheet structure. IR and X‐ray diffraction show that the peptides have closely related structures in the crystalline state and the fibers in the organogels. The gels are efficient templates for the fabrication of complex titania architectures on a (sub)micron length scale: at low peptide concentrations titania spheres form and at higher concentrations one‐dimensional shapes like hollow titania tubes or titania fibers are observed. The tubes are stable towards calcination whereas the fibers (partially) transform into spherical or even bulk particles.

magnified image
Increase of Fluorescence Anisotropy Upon Self‐Assembly in Headgroup‐Labeled Surfactants
Authors: Kastantin Mark , Ananthanarayanan Badriprasad , Lin Brian , Ressl Jan , Black Matthew , Tirrell Matthew
Published: February 2007

The change in fluorescence anisotropy upon micellization in headgroup‐labeled surfactants is investigated. After eliminating the likelihood of depolarizing RET, anisotropy is shown to increase upon self‐assembly due to increased rotational correlation times of the fluorophore. This is shown using two surfactant‐fluorophore systems. Anisotropy in NBD‐labeled phospholipids is studied both in chloroform (unaggregated) and in water (unilamellar vesicles), while in tryptophan‐containing peptide‐amphiphiles, the variation of anisotropy with concentration leads to a reasonable measurement of CAC. Anisotropy increase is shown to be largely the product of increased rotational correlation times for the fluorophore, relative to its τ. These results serve as a basis for future work that measures the amount of depolarizing energy transfer, characterizing distances between similar fluorescent headgroups on mixed micelles.

magnified image
Modeling of Bovine Type‐I Collagen Fibrils: Interaction with Pickling and Retanning Agents
Authors: Bulo Rosa E. , Siggel Lorenz , Molnar Ferenc , Weiss Horst
Published: February 2007

Bovine Type I collagen was investigated, building on a large scale computer model of a collagen fibril in water, and focusing on two stages of the leather manufacturing process. The effects of different salts (NaCl, CaCl2, and Na2SO4) on the swelling behavior of collagen at low pH (the pickling process) were studied. The salts suppress the swelling of the fibrils at low pH and we find specific stabilizing influences for CaCl2 and Na2SO4, due to weak Ca2+/Cl− and strong SO/lysine/arginine interactions, respectively. Using state‐of‐the‐art sampling techniques, such as the metadynamics algorithm, to allow an efficient exploration of configuration space, we were able to investigate the effect of polyacrylate and poly(methyl acrylate) – two polymeric retanning agents – on the fibril. Both polymers interact with the ammonium groups on the surface, but polyacrylate shows significantly stronger interactions. We suggest that it is this stronger interaction that contributes to the reduced suitability of PAA as a tanning agent.

magnified image
Sulfated Glycopolymer Thin Films—Preparation, Characterization, and Biological Activity
Authors: Grombe Ringo , Gouzy Marie F. , Maitz Manfred F. , Freundenberg Uwe , Zschoche Stefan , Simon Frank , Pompe Tilo , Sperling Claudia , Werner Carsten
Published: February 2007

The impact of heparinoid characteristics on model surfaces obtained from immobilization of sole sulfate groups as well as sulfated glycosides, sulfated cellulose, and definite heparin has been investigated. The obtained layers were physico‐chemically characterized regarding film thickness, chemical composition, wettability, and surface morphology. Antithrombin adsorption, studied by fluorescence labeling, revealed a strong dependence on the presence of glycosidic structures and on the molecular weight of the grafted saccharide. On contact with whole blood, the coatings resulted in a diminished plasmatic and cellular coagulation in vitro, which did not reflect well the antithrombin binding. Therefore, more complex activating pathways are discussed.

magnified image
A Flexible Approach to the Preparation of Polymer Scaffolds for Tissue Engineering
Authors: Borgaonkar Poonam , Sharma Sachin , Chen Ming , Bhowmick Sankha , Schmidt Daniel F.
Published: February 2007

Porous polyester thermoset xerogels have been produced via sol–gel chemistry as a first step in the development of sol–gel derived tissue engineering scaffolds templated by replica molding and/or salt leaching. The pore structure of these untemplated thermosets is tunable and can be altered independent of or in tandem with alterations in composition. Cytocompatibility studies on these xerogels imply the effects of both pore size and materials chemistry, with fully aliphatic polyesters with large pore structures allowing the growth of mammalian cells. To the best of our knowledge, this represents the first report examining the preparation and potential of sol–gel derived porous polymer xerogels as tissue engineering scaffolds.

magnified image
Design Parameters and Current Fabrication Approaches for Developing Bioinspired Dry Adhesives
Authors: del Campo Aránzazu , Arzt Eduard
Published: February 2007

The attachment pads of some beetles, spiders, flies, and geckos are covered by a dense array of long hairs with characteristic geometries. This curious surface topography allows them to firmly attach to and easily release from almost any kind of surface. In a technological context, such reversible adhesion could enable robots to walk along walls or ceilings, or lead to new medical devices, disposable plasters, reusable adhesive tapes, etc. Artificial fibrillar surfaces mimicking nature's design have been recently fabricated, but their adhesion performance is still far from that of natural systems. This review describes the progress in this field during the last few years and discusses the issues pending for the future.

magnified image
Synthesis of Magnetite Nanoparticles for Bio‐ and Nanotechnology: Genetic Engineering and Biomimetics of Bacterial Magnetosomes
Authors: Lang Claus , Schüler Dirk , Faivre Damien
Published: February 2007

Magnetotactic bacteria (MTB) have the ability to navigate along the Earth's magnetic field. This so‐called magnetotaxis is a result of the presence of magnetosomes, organelles which comprise nanometer‐sized intracellular crystals of magnetite (Fe3O4) enveloped by a membrane. Because of their unique characteristics, magnetosomes have a high potential for nano‐ and biotechnological applications, which require a specifically designed particle surface. The functionalization of magnetosomes is possible either by chemical modification of purified particles or by genetic engineering of magnetosome membrane proteins. The second approach is potentially superior to chemical approaches as a large variety of biological functions such as protein tags, fluorophores, and enzymes may be directly incorporated in a site‐specific manner during magnetosome biomineralization. An alternative to the bacterial production of magnetosomes are biomimetic approaches, which aim to mimic the bacterial biomineralization pathway in vitro. In MTB a number of magnetosome proteins with putative functions in the biomineralization of the nanoparticles have been identified by genetic and biochemical approaches. The initial results obtained by several groups indicate that some of these proteins have an impact on nanomagnetite properties in vitro. In this article the key features of magnetosomes are discussed, an overview of their potential applications are given, and different strategies are proposed for the functionalization of magnetosome particles and for the biomimetism of their biomineralization pathway.

magnified image
Folate and colorectal cancer: An evidence‐based critical review
Authors: Kim Young‐In
Published: February 2007

Currently available evidence from epidemiologic, animal, and intervention studies does not unequivocally support the role of folate, a water‐soluble B vitamin and important cofactor in one‐carbon transfer, in the development and progression of colorectal cancer (CRC). However, when the portfolio of evidence from these studies is analyzed critically, the overall conclusion supports the inverse association between folate status and CRC risk. It is becoming increasingly evident that folate possesses dual modulatory effects on colorectal carcinogenesis depending on the timing and dose of folate intervention. Folate deficiency has an inhibitory effect whereas folate supplementation has a promoting effect on the progression of established colorectal neoplasms. In contrast, folate deficiency in normal colorectal mucosa appears to predispose it to neoplastic transformation, and modest levels of folic acid supplementation suppress, whereas supraphysiologic supplemental doses enhance, the development of cancer in normal colorectal mucosa. Several potential mechanisms relating to the disruption of one‐carbon transfer reactions exist to support the dual modulatory role of folate in colorectal carcinogenesis. Based on the lack of compelling supportive evidence and on the potential tumor‐promoting effect, routine folic acid supplementation should not be recommended as a chemopreventive measure against CRC at present.
Cover Picture: Macromol. React. Eng. 2/2007
Authors: Di Martino Audrey , Weickert Guenter , McKenna Timothy F.L.
Published: February 2007

Cover: In an effort to better understand the underlying processes in olefin polymerisations, a novel stopped flow reactor system is used to examine the morphology of particles of polyethylene produced on supported catalysts, as well as the evolution of reaction kinetics and polymer properties at extremely short time (i.e. less than 40 ms). Further details can be found in the article by A. Di Martino, G. Weickert, and T. F. L. McKenna* on page 229.
Diaphragmatic paralysis following minor cervical trauma
Authors: Merino‐Ramírez Miguel A. , Juan Gustavo , Ramón Mercedes , Cortijo Julio , Morcillo Esteban J.
Published: February 2007

Two asthmatic patients developed unilateral diaphragmatic paralysis from phrenic nerve injury, in one case following cervical chiropractic manipulation and in the other after a motorcycle accident. Both presented with increased dyspnea and orthopnea. Diagnosis, severity, and level of the lesion were established by neurophysiological methods, which are preferred to chest radiography and diaphragmatic ultrasonography. In spite of only partial electrophysiological recovery of the nerve, both patients were asymptomatic 1 year later. Muscle Nerve, 2007
Novel SOD1 N86K mutation is associated with a severe phenotype in familial ALS
Authors: Beck Marcus , Sendtner Michael , Toyka Klaus V.
Published: February 2007

Familial amyotrophic lateral sclerosis (ALS) is frequently associated with mutations in the SOD1 gene. We identified a rapidly progressive disease in a patient with an inherited ALS. The identified heterozygous T>A exchange in position 1067 in the SOD1 gene results in an amino acid substitution of lysine for asparagine at position 86 (N86K) of the SOD1 protein. The family history suggested that this autosomal dominantly inherited mutation may be associated with rapidly progressive disease. Muscle Nerve, 2007
Diagnostic ultrasound for nerve transection
Authors: Cartwright Michael S. , Chloros George D. , Walker Francis O. , Wiesler Ethan R. , Campbell William W.
Published: February 2007

The current approach for localizing and assessing the severity of traumatic peripheral nerve injuries involves clinical evaluation and electrodiagnostic studies. However, the ability of this approach to determine the extent of nerve damage within the first 6 weeks after trauma is limited. This is problematic because outcome is improved with early surgical intervention after complete nerve transection. This led us to explore alternative techniques, such as imaging, for assessing peripheral nerve injuries. Twelve fresh cadavers were obtained and after inspection 20 arms were deemed suitable for inclusion in the study. Random sites were transected in median, ulnar, and radial nerves, and sham skin incisions were performed throughout the arm. These nerves were then systematically scanned by an ultrasonographer blinded to the nerve transection sites, who made a final decision as to whether the nerve was transected. High‐resolution ultrasound was able to identify transected nerves in the upper extremity with 89% sensitivity and 95% specificity in fresh cadavers. This proof‐of‐concept study shows that ultrasound can accurately identify nerve transection, which should lead to further ultrasound studies in patients with traumatic peripheral nerve injuries. Muscle Nerve, 2007
Elevated brain scyllo‐inositol concentrations in patients with Alzheimer's disease
Authors: Griffith H. Randall , den Hollander Jan A. , Stewart Chris C. , Evanochko William T. , Buchthal Steven D. , Harrell Lindy E. , Zamrini Edward Y. , Brockington John C. , Marson Daniel C.
Published: February 2007

in vivo 1H MRS reveals reduced N‐acetylaspartate (NAA) and elevated myo‐inositol (mI) in patients with mild Alzheimer's disease (AD) and patients with amnestic mild cognitive impairment (MCI). We are unaware of studies that have documented abnormal scyllo‐inositol (sI) levels in patients with AD or patients with MCI, although a previous MRS study in older adults has indicated that sI is a peak of interest to measure in AD. Fifteen patients with mild AD, 26 patients with amnestic MCI, and 19 healthy older adults were recruited to this study. All underwent 1H MRS of the posterior cingulate gyrus of the brain using a 3 T MRI scanner. Increases in the sI/creatine (Cr) ratio were observed in patients with mild AD (P < 0.05). The mI/Cr ratio was raised in patients with mild AD (P < 0.01) and MCI (P < 0.05). Reduced NAA/Cr was detected in patients with mild AD (P < 0.05). The sI/Cr ratio correlated negatively (r = −0.60, P < 0.05) with a measure of clock drawing in patients with mild AD, indicating that impaired cognitive ability in AD is associated with higher concentrations of sI/Cr. In vivo measurement of sI/Cr in the posterior cingulate gyrus of patients with mild AD revealed increases compared with cognitively healthy older adults. Further research on the mechanisms of sI increase in AD is needed. Future studies on the longitudinal course of sI/Cr in MCI and AD appear warranted. Copyright © 2007 John Wiley & Sons, Ltd.
Gadobenate dimeglumine as a contrast agent for MRI of the mouse liver
Authors: Inoue Yusuke , Yoshikawa Kohki , Nomura Yukihiro , Izawa Kiyoko , Shimada Morio , Tojo Arinobu , Ohtomo Kuni
Published: February 2007

We investigated the characteristics and utility of gadobenate dimeglumine (Gd‐BOPTA) for MRI of the mouse liver. Mice were imaged under isoflurane anesthesia using a T1‐weighted, three‐dimensional fast low‐angle shot (3D FLASH) sequence before and after intravenous or subcutaneous injection of Gd‐BOPTA, and the time course of the contrast effect was examined. The appropriate dose for subcutaneous injection was determined visually, and the inter‐ and intra‐observer reproducibilities in liver volumetry were evaluated with and without contrast injection. When mice were imaged sequentially before and after Gd‐BOPTA injection and isoflurane anesthesia was maintained throughout the experiment, a long‐lasting contrast effect was noted in the liver. Subcutaneous injection caused delayed, but favorable, enhancement. Washout from the liver was definitely accelerated in conscious mice in comparison with anesthetized mice. Visual evaluation indicated that a dose of 0.1 mmol/kg was appropriate for clear delineation of the entire liver margin, and the application of Gd‐BOPTA significantly improved the inter‐ and intra‐observer reproducibilities of liver volumetry. In conclusion, the intravenous or subcutaneous injection of Gd‐BOPTA has a favorable contrast effect for the mouse liver, resulting in clear visualization of the liver border and improved reproducibility of liver volumetry. The possible influence of anesthesia on the pharmacokinetics of a contrast agent should be considered in determining the optimal scan timing. Copyright © 2007 John Wiley & Sons, Ltd.