bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering the acceptor specificity of trehalose phosphorylase for the production of trehalose analogs
Authors: Van der Borght Jef , Soetaert Wim , Desmet Tom 
Published: July 2012

AbstractTrehalose (α‐D‐glucopyranosyl‐(1,1)‐α‐D‐glucopyranoside) is widely used in the food industry, thanks to its protective effect against freezing and dehydration. Analogs of trehalose have the additional benefit that they are not digested and thus do not contribute to our caloric intake. Such trehalose analogs can be produced with the enzyme trehalose phosphorylase, when it is applied in the reverse, synthetic mode. Despite the enzyme's broad acceptor specificity, its catalytic efficiency for alternative monosaccharides is much lower than for glucose. For galactose, this difference is shown here to be caused by a lower Km whereas the kcat for both substrates is equal. Consequently, increasing the affinity was attempted by enzyme engineering of the trehalose phosphorylase from Thermoanaerobacter brockii, using both semirational and random mutagenesis. While a semirational approach proved unsuccessful, high‐throughput screening of an error‐prone PCR library resulted in the discovery of three beneficial mutations that lowered Km two‐ to three‐fold. In addition, it was found that mutation of these positions also leads to an improved catalytic efficiency for mannose and fructose, suggesting their involvement in acceptor promiscuity. Combining the beneficial mutations did not further improve the affinity, and even resulted in a decreased catalytic activity and thermostability. Therefore, enzyme variant R448S is proposed as new biocatalyst for the industrial production of lactotrehalose (α‐D‐glucopyranosyl‐(1,1)‐α‐D‐galactopyranoside). © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012
A mouse neurodegenerative dynein heavy chain mutation alters dynein motility and localization in Neurospora crassa
Authors: Sivagurunathan Senthilkumar , Schnittker Robert R. , Nandini Swaran , Plamann Michael D. , King Stephen J. 
Published: July 2012

AbstractCytoplasmic dynein is responsible for the transport and delivery of cargoes in organisms ranging from humans to fungi. Dysfunction of dynein motor machinery due to mutations in dynein or its activating complex dynactin can result in one of several neurological diseases in mammals. The mouse Legs at odd angles (Loa) mutation in the tail domain of the dynein heavy chain has been shown to lead to progressive neurodegeneration in mice. The mechanism by which the Loa mutation affects dynein function is just beginning to be understood. In this work, we generated the dynein tail mutation observed in Loa mice into the Neurospora crassa genome and utilized cell biological and complementing biochemical approaches to characterize how that tail mutation affected dynein function. We determined that the Loa mutation exhibits several subtle defects upon dynein function in N. crassa that were not seen in mice, including alterations in dynein localization, impaired velocity of vesicle transport, and in the biochemical properties of purified motors. Our work provides new information on the role of the tail domain on dynein function and points out areas of future research that will be of interest to pursue in mammalian systems. © 2012 Wiley Periodicals, Inc.
Combining ISO/IEC 17025:2005 and European Commission Decision 2002/657 audit requirements: A practical way forward
Authors: Kay Jack F. 
Published: July 2012

Laboratories involved in the analyses of veterinary drug residues are under increasing pressure to demonstrate that they produce meaningful and reliable data. Quality assurance and quality control systems are implemented in laboratories to provide evidence of this and these are subject to external assessment to ensure that they are effective.Audits to ISO/IEC 17025:2005, an internationally accepted standard, and subsequent accreditation provide laboratories and their customers with a degree of assurance that the laboratories are operating in control and the data they report can be relied on. However, national or regional authorities may place additional requirements on laboratories to ensure quality data are reported. For example, in the European Union, all official control laboratories involved in veterinary drug residue analyses must also meet the requirements of European Commission Decision 2002/657/EC which sets performance criteria for analytical methods used in this area and these are subject to additional audits by national or regional authorities.All audits place considerable time and resource demands on laboratories and this paper discusses the burden audits place on laboratories and describes a UK initiative to combine these audits to the benefit of both the regulatory authority and the laboratory. © 2012 John Wiley & Sons, Ltd.
The physiological way: Monitoring RNA expression changes as new approach to combat illegal growth promoter application
Authors: Riedmaier Irmgard , Pfaffl Michael W. , Meyer Heinrich H. D. 
Published: July 2012

The use of growth‐promoting agents in food‐producing animals is forbidden in the European Union (EU). Therefore a strict control programme has been developed, detecting residues of all known growth‐promoting agents using chromatographical methods in combination with mass spectrometry or immunoassays. New designed xenobiotic substances or hormone cocktails are difficult to identify with these methods and therefore the development of new sensitive test methods is important.A promising indirect approach is the detection of physiological effects of the administered growth promoters on the molecular level using ‘omic’ technologies. The analysis of the transcriptome on mRNA and miRNA level and thereby identifying biomarkers for the use of anabolic agents is one possible strategy for developing a new screening method. This paper describes the technologies available for gene expression profiling and summarizes the efforts made in the analysis of the transcriptome in order to identify potential gene expression biomarkers for the use of growth promoters in cattle. © 2012 John Wiley & Sons, Ltd.
Complex Formation of Calcium Bis(tetraethylaluminate) with N‐Donor Ligands
Authors: Hülsmann Matthias , Neumann Beate , Stammler Hans‐Georg , Mitzel Norbert W. 
Published: July 2012

AbstractTreatment of calcium bis(tetraethylaluminate) with the bidentate N‐donor ligands tetramethylmethylenediamine (L = TMMDA), tetramethylethylenediamine (L = TMEDA) and N,N′‐dimethylpiperazine (L = DMP) and the tridentate N‐donor ligands 1,3,5‐trialkyl‐1,3,5‐triazacyclohexane {L = cyclo‐[N(R)CH2]3, R = Me (TMTAC), Cy (TCyTAC), tBu (TtBuTAC)} resulted in the formation of complexes of the formulae [Ca(AlEt4)2L]. These compounds were characterised by NMR spectroscopy and elemental analyses. Single crystals suitable for X‐ray diffraction experiments were obtained from the TMMDA, DMP, TCyTAC and TMTAC complexes. In the case of TMTAC, the complex crystallises with two TMTAC ligands bonded to the Ca atom, [Ca(AlEt4)2(TMTAC)2], but in solution only one TMTAC ligand is bonded to the Ca atom. NMR spectroscopy at various temperatures shows the tetraethylaluminate units to be dynamically bonded in these compounds (i.e., they are found to be partially dissociated). This dynamic bonding situation avoids steric overcrowding and – unlike related rare‐earth metal compounds – this behaviour inhibits further degradation reactions. The reaction of calcium bis(tetraethylaluminate) with the NH‐functional diisopropylamine leads to its deprotonation and results in the formation of a dimeric calcium amide [(η2‐AlEt4)2Ca(μ‐NiPr2)2Ca(η2‐AlEt4)2]. This compound was characterised by single‐crystal X‐ray diffraction, NMR spectroscopy and elemental analyses.
Copper‐Catalyzed Decarboxylative Three‐Component Reactions for the Synthesis of Imidazo[1,2‐a]pyridines
Authors: Palani Thiruvengadam , Park Kyungho , Kumar Manian Rajesh , Jung Hyun Ming , Lee Sunwoo 
Published: July 2012

AbstractImidazo[1,2‐a]pyridine derivatives were synthesized through multicomponent coupling reactions of 2‐aminopyridines, aldehydes, and alkynecarboxylic acids in the presence of 10 mol‐% CuI/Cu(OTf)2. Both aryl‐ and alkyl‐substituted alkynecarboxylic acids, including propiolic acid, were good alkyne sources and afforded the desired imidazo[1,2‐a]pyridines in good yields through the decarboxylative coupling reactions. Arylalkynecarboxylic acids were synthesized through palladium‐catalyzed coupling reactions between aryl iodides and propiolic acid and reacted with 2‐aminopyridine and aldehydes, with or without a purification step. In both cases the desired imidazo[1,2‐a]pyridines were obtained in good yields. Mechanistic studies suggested that in the case of propiolic acid the decarboxylative addition predominates over terminal alkyne addition.
Biomagnification of polychlorinated biphenyls in a harbor seal (Phoca vitulina) food web from the strait of Georgia, British Columbia, Canada
Authors: Cullon Donna L. , Yunker Mark B. , Christensen Jennie R. , Macdonald Robie W. , Whiticar Michael J. , Dangerfield Neil J. , Ross Peter S. 
Published: July 2012

Abstract
Polychlorinated biphenyl (PCB) biomagnification was characterized in a harbor seal food web in the Strait of Georgia, British Columbia, Canada. Trophic magnification factors (TMFs) for PCBs averaged 3.6, with a range of 0.7 to 9.4. The TMFs for individual congeners correlated with log KOW (r2 = 0.56, p &lt; 0.001), reflecting the role that physicochemical properties play in driving the biomagnification of PCBs in marine food webs. However, TMFs differed among PCB structure activity groups, clearly indicating an additional role for metabolic transformation of certain PCBs. The known feeding preferences of harbor seals enabled the calculation of trophic level-adjusted biomagnification factors (BMFTL) for PCBs in this species, which averaged 13.4 and ranged from 0.2 to 150.6. Metabolic transformation in seals explained some of the variation in congener-specific biomagnification, with lower BMFTL values for PCB congeners with meta- and parachlorine unsubstituted positions. Principal components analysis revealed the distinct roles played by trophic level, log KOW, and metabolic transformation in explaining the notable differences in PCB patterns among harbor seals, their pups, and their prey. In the present study, the authors estimate there to be approximately 76 kg of PCBs in the biota of the Strait of Georgia, of which 1.6 kg is retained by harbor seals. Environ. Toxicol. Chem. 2012; 31: 2445–2455. © 2012 SETAC
Pathogenic infection confounds induction of the estrogenic biomarker vitellogenin in rainbow trout
Authors: Burki Richard , Krasnov Aleksei , Bettge Kathrin , Rexroad Caird E. , Afanasyev Sergej , Antikainen Mia , Burkhardt-Holm Patricia , Wahli Thomas , Segner Helmut 
Published: July 2012

Abstract
To examine the behavior of the estrogenic biomarker vitellogenin (VTG) under the combined impact of estrogens and pathogens, parasite-infected or noninfected rainbow trout were exposed to two doses of 17β-estradiol (E2). Infected and E2-exposed fish showed significantly lower hepatic VTG mRNA levels than healthy fish. Transcriptome data suggest that this was due to energetic constraints. Reduced responsiveness of the VTG biomarker in parasitized fish might obscure detection of low-level field exposure. Environ. Toxicol. Chem. 2012; 31: 2318–2323. © 2012 SETAC
Elevated methylation of HPV16 DNA is associated with the development of high grade cervical intraepithelial neoplasia
Authors: Mirabello Lisa , Schiffman Mark , Ghosh Arpita , Rodriguez Ana C. , Vasiljevic Natasa , Wentzensen Nicolas , Herrero Rolando , Hildesheim Allan , Wacholder Sholom , Scibior‐Bentkowska Dorota , Burk Robert D. , Lorincz Attila T. 
Published: July 2012

AbstractWe explored the association of human papillomavirus type 16 (HPV16) DNA methylation with age, viral load, viral persistence and risk of incident and prevalent high grade CIN (CIN2+) in serially collected specimens from the Guanacaste, Costa Rica cohort. 273 exfoliated cervical cell specimens (diagnostic and pre‐diagnostic) were selected: (1) 92 with HPV16 DNA clearance (controls), (2) 72 with HPV16 DNA persistence (without CIN2+) and (3) 109 with CIN2+. DNA was extracted, bisulfite converted and methylation was quantified using pyrosequencing assays at 66 CpGs across the HPV genome. The Kruskal‐Wallis test was used to determine significant differences among groups, and receiver operating characteristic curve analyses were used to evaluate how well methylation identified women with CIN2+. In diagnostic specimens, 88% of CpG sites had significantly higher methylation levels in CIN2+ after correction for multiple tests compared with controls. The highest area under the ROC curve (AUC) was 0.82 for CpG site 6457 in L1, and a diagnostic sensitivity of 91% corresponded to a specificity of 60% for CIN2+. Prospectively, 17% of CpG sites had significantly higher methylation in pre‐diagnostic CIN2+ specimens (median time of 3 years before diagnosis) versus controls. The strongest pre‐diagnostic CpG site was 6367 in L1 with an AUC of 0.76. Age‐stratified analyses suggested that women older than the median age of 28 years have an increased risk of precancer associated with high methylation. Higher methylation in CIN2+ cases was not explained by higher viral load. We conclude that elevated levels of HPV16 DNA methylation may be useful to predict concurrently diagnosed as well as future CIN2+.
20(S)‐protopanaxadiol‐aglycone downregulation of the full‐length and splice variants of androgen receptor
Authors: Cao Bo , Liu Xichun , Li Jing , Liu Shuang , Qi Yanfeng , Xiong Zhenggang , Zhang Allen , Wiese Thomas , Fu Xueqi , Gu Jingkai , Rennie Paul S. , Sartor Oliver , Lee Benjamin R. , Ip Clement , Zhao Lijuan , Zhang Haitao , Dong Yan 
Published: July 2012

AbstractAs a public health problem, prostate cancer engenders huge economic and life‐quality burden. Developing effective chemopreventive regimens to alleviate the burden remains a major challenge. Androgen signaling is vital to the development and progression of prostate cancer. Targeting androgen signaling via blocking the production of the potent ligand dihydrotestosterone has been shown to decrease prostate cancer incidence. However, the potential of increasing the incidence of high‐grade prostate cancers has been a concern. Mechanisms of disease progression after the intervention may include increased expression of androgen receptor (AR) in prostate tissue and expression of the constitutively active AR splice variants (AR‐Vs) lacking the ligand‐binding domain. Thus, novel agents targeting the receptor, preferentially both the full‐length and AR‐Vs, are urgently needed. In the present study, we show that ginsenoside 20(S)‐protopanaxadiol‐aglycone (PPD) effectively downregulates the expression and activity of both the full‐length AR and AR‐Vs. The effects of PPD on AR and AR‐Vs are manifested by an immediate drop in proteins followed by a reduction in transcripts, attributed to PPD induction of proteasome‐mediated degradation and inhibition of the transcription of the AR gene. We further show that although PPD inhibits the growth as well as AR expression and activity in LNCaP xenograft tumors, the morphology and AR expression in normal prostates are not affected. This study is the first to show that PPD suppresses androgen signaling through downregulating both the full‐length AR and AR‐Vs, and provides strong rationale for further developing PPD as a promising agent for the prevention and/or treatment of prostate cancer.
Interplay between protein‐modified surface and functional response of osteoblasts
Authors: Chaudhary P. , Pesacreta T. C. , Misra R. D. K. 
Published: July 2012

AbstractThe objective of the study is to elucidate the interplay between fibronectin‐metal hybrid surfaces and osteoblast function. The practical relevance is that a significant initial step in the process of prosthetic integration within a physiological system is the rapid adsorption of proteins, including fibronectin, on the surface of biomedical device. Here, we compare and contrast the cell–substrate interactions on bare and protein‐modified surfaces. The protein adsorption on the surface was beneficial in favorably modulating biological functions including cell attachment, proliferation, and viability. Additionally, immunofluorescence studies demonstrated stronger vinculin signals associated with actin stress fibers in the outer regions of the cells and cellular extensions on protein‐adsorbed surfaces. These results support the hypothesis that protein adsorption on artificial biomedical devices can promote bioactivity and regulate biological functions. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3157–3166, 2012.
In vitro antibacterial evaluation of sol–gel‐derived Zn‐, Ag‐, and (Zn + Ag)‐doped hydroxyapatite coatings against methicillin‐resistant Staphylococcus aureus
Authors: Samani S. , Hossainalipour S. M. , Tamizifar M. , Rezaie H. R. 
Published: July 2012

AbstractHydroxyapatite (HAp) coatings were applied using sol–gel method. Phosphor pentoxide and calcium nitrate were used as phosphorous and calcium precursors, respectively. Zinc nitrate and silver nitrate were used as substitute of calcium in HAp structure. As a base concentration, 1.5 wt %Ag and 2.5 wt %Zn were used. The weight percent of Ag was increased at 0.3 wt% and Zn content was scaled down at 0.5 wt%. Phase analysis and chemical bonds of synthesized materials were studied by XRD and FTIR. Antibacterial activity of Ag‐ and Zn‐doped samples against methicilin‐resistant Staphylococcus aureus (MRSA) were assessed by the plate‐counting method. The XRD and FTIR results proved formation of HAp compound. Colony counting showed that silver and zinc ions prevent proliferation and growth of MRSA. Interestingly, co‐presence of metal ions improves the antibacterial effectiveness of the coatings and the combined effect was greater than sum of the individual effects when each was administered alone. Overall, synergism between antibacterial activities of Zn2+ and Ag+ ions against MRSA can be suggested. Thus, cell toxicity decreases and biocompatibility increases without any decrement in antibacterial activity. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:222–230, 2013.
Ultrashort echo time MR imaging with off‐resonance saturation for characterization of pathologically altered Achilles tendons at 3 T
Authors: Grosse Ulrich , Syha Roland , Martirosian Petros , Wuerslin Christian , Horger Marius , Grözinger Gerd , Schick Fritz , Springer Fabian 
Published: July 2012

AbstractOff‐resonance radiofrequency saturation pulses applied prior to regular excitation in MR sequences can be used to modify signal contrast based on magnetization transfer and direct saturation effects. Clinical applicability and value of ultrashort echo time sequences combined with off‐resonance saturation pulses was tested in 16 healthy and 14 tendinopathic as well as paratendinopathic Achilles tendons in vivo at 3 T. A 3D ultrashort echo time sequence in combination with a gaussian off‐resonance saturation pulse (frequency offset: 1000–5000 Hz) was used to modify the detectable MR signal intensity from the Achilles tendon. Off‐resonance saturation ratio was calculated as the relative reduction in signal intensity under selective off‐resonance saturation in relation to a reference measurement without any saturation pulse. Off‐resonance saturation ratio in tendons of healthy volunteers ranged from 0.52 ± 0.06 (1000 Hz) to 0.24 ± 0.02 (5000 Hz), whereas symptomatic tendinopathic tendons (0.35 ± 0.04 to 0.17 ± 0.02) and asymptomatic tendinopathic tendons (0.41 ± 0.06 to 0.21 ± 0.02) showed significantly lower mean off‐resonance saturation ratio values. Off‐resonance saturation ratio values might provide a sensitive and quantitative marker for assessment of pathological microstructure alterations of the Achilles tendon. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Increasing signal homogeneity and image quality in abdominal imaging at 3 T with very high permittivity materials
Authors: de Heer P. , Brink W. M. , Kooij B. J. , Webb A. G. 
Published: July 2012

AbstractThe appearance of severe signal drop‐outs in abdominal imaging at 3 T arises primarily from areas of very low B transmit field in the body, and is problematic in both obese as well as very thin subjects. In this study, we show how thin patient‐friendly pads containing new high permittivity materials can be designed and optimized, and when placed around the subject increase substantially the B uniformity and the image quality. Results from nine healthy volunteers show that inclusion of these dielectric pads results in statistically significant decreases in the coefficient of variance of the B field, with stronger and more uniform fields being produced. In addition there are statistically significant decreases in time‐averaged power required for scanning. These differences are present in both quadrature‐mode operation (coefficient of variance decrease, P < 0.0001, mean 25.4 ± 10%: power decrease, P = 0.005, mean 14 ± 14%) and also for the RF‐shimmed case (coefficient of variance decrease, P = 0.01, mean 16 ± 13%: power decrease, P = 0.005, mean 22 ± 11%) of a dual‐transmit system. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
A phase field model of dynamic fracture: Robust field updates for the analysis of complex crack patterns
Authors: Hofacker M. , Miehe C. 
Published: July 2012

SUMMARYThe numerical modeling of dynamic failure mechanisms in solids due to fracture based on sharp crack discontinuities suffers in situations with complex crack topologies and demands the formulation of additional branching criteria. This drawback can be overcome by a diffusive crack modeling, which is based on the introduction of a crack phase field. Following our recent works on quasi‐static modeling of phase‐field‐type brittle fracture, we propose in this paper a computational framework for diffusive fracture for dynamic problems that allows the simulation of complex evolving crack topologies. It is based on the introduction of a local history field that contains a maximum reference energy obtained in the deformation history, which may be considered as a measure of the maximum tensile strain in the history. This local variable drives the evolution of the crack phase field. Its introduction provides a very transparent representation of the balance equation that governs the diffusive crack topology. In particular, it allows for the construction of a very robust algorithmic treatment for elastodynamic problems of diffusive fracture. Here, we extend the recently proposed operator split scheme from quasi‐static to dynamic problems. In a typical time step, it successively updates the history field, the crack phase field, and finally the displacement field. We demonstrate the performance of the phase field formulation of fracture by means of representative numerical examples, which show the evolution of complex crack patterns under dynamic loading. Copyright © 2012 John Wiley & Sons, Ltd.