bluuebunny/crossref_metadata_2025 huggingface dataset:
Immature hematopoietic cells display selective requirements for adhesion‐ and degranulation‐promoting adaptor protein in development and homeostatsis
Authors: Dluzniewska Joanna , Zou Liangxing , Harmon Ian R. , Ellingson Marc T. , Peterson Erik J.
Published: October 2007

Adhesion‐ and degranulation‐promoting adaptor protein (ADAP) modulates T cell development and function and promotes TCR signaling. Regulation of ADAP protein expression during thymopoiesis and in development of other hematopoietic lineages has not been explored. Using intracellular staining, we detected ADAP protein in bone marrow lymphocyte precursors. Like its binding partner SH2‐containing leukocyte phosphoprotein of 76 kDa, ADAP is dynamically regulated during thymocyte positive selection. ADAP is also found in unconventional thymocytes, including NKT, CD8αα, and TCRγδ T cells. In peripheral T cells, ADAP is up‐regulated after TCR stimulation and with acquisition of memory status. Although absent in splenic B cells, ADAP is present in pro‐B cells, as well as in BM erythrocyte and myeloid progenitors. Studies with radiation chimeras show that ADAP is dispensable for NKT, CD8αα and TCRγδ T cell development, while confirming that ADAP is required for optimal development of conventional TCRαβ T cells in the thymus. Interestingly, ADAP is necessary for CD8αα homeostasis in the small intestinal epithelium, yet is dispensable for optimal reconstitution of splenic B cell populations. Our observations highlight the dynamic regulation of ADAP during T cell maturation and document expression patterns that suggest a possible role for ADAP in development of non‐T hematopoietic lineages.
Role of T cells in a murine model of Escherichia coli sepsis
Authors: van Schaik Sandrijn M. , Abbas Abul K.
Published: October 2007

To study the role of T cells in gram‐negative sepsis, we developed a mouse model in which i.v. injection of Escherichia coli results in severe systemic illness, with high mortality rates after day 5. A large proportion of both CD4+ and CD8+ T cells are activated within 1 day after infection, as evidenced by up‐regulation of CD69 and down‐regulation of CD62L. Even more surprisingly, T cell‐deficient mice exhibit markedly decreased disease severity compared to WT mice, indicating a pathogenic role of T cells. Mice lacking IFN‐γ also show diminished disease, and exhibit reduced T cell activation. Therefore, the pathogenic role of T cells may be mediated by IFN‐γ. Both T cell‐ and IFN‐γ‐deficient mice have reduced serum IL‐6 levels compared to WT mice, suggesting that T cells may stimulate innate immune responses, resulting in enhancement of disease. These data indicate an important role for T cells in a mouse model of E. coli sepsis, and reveal an unexpected early and pathogenic T cell response to this bacterial infection.
Oxidation of 3,4‐Diaryl‐2,5‐dihydrothiophenes to 3,4‐Diarylthiophenes Using CuBr2: Simple and Efficient Preparation of 3,4‐Diarylthiophenes
Authors: Dang Yizhe , Chen Yi
Published: October 2007

A class of 3,4‐diarylthiophenes was prepared in excellent yield (80–91 %) by oxidation of 3,4‐diaryl‐2,5‐dihydrothiophenes with CuBr2. The approach is also available for the synthesis of 3,4‐diarylpyrroles and 3,4‐diarylfuran. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Determination of tocopherols in vegetable oils by CEC using methacrylate ester‐based monolithic columns
Authors: Lerma‐García María Jesús , Simó‐Alfonso Ernesto F. , Ramis‐Ramos Guillermo , Herrero‐Martínez José Manuel
Published: October 2007

The separation and determination of tocopherols (Ts) in vegetable oils by CEC using methacrylate ester‐based monolithic columns has been developed. The effects of pore size of the monolithic columns were studied, and the composition of mobile phase was optimized. The optimal pore size of the monolith was obtained with 12 wt% 1,4‐butanediol in the polymerization mixture. Excellent resolution between tocopherols was achieved within 10 min analysis time with a 99:1 v/v MeOH–aqueous buffer containing 5 mM tris(hydroxymethyl)aminomethane at pH 8.0. The LODs were lower than 2.3 μg/mL, and interday and column‐to‐column reproducibilities at 25 μg/mL were better than 5.6%. Using a 93:7 v/v MeOH–aqueous buffer, both tocopherols and tocotrienols (T3s) of grapeseed and palm oils were resolved. Application to the detection of olive oil adulteration with low‐cost edible oils was demonstrated.
Postcolumn reactor using a laser‐drilled capillary for light‐emitting diode‐induced fluorescence detection in CE
Authors: Yamamoto Daisuke , Kaneta Takashi , Imasaka Totaro
Published: October 2007

This study investigated a novel postcolumn reactor for fluorescence detection in CE. A laser‐drilled capillary, with an aperture made by laser ablation, was used for mixing derivatization reagents with the analytes separated by CZE. The derivatization reagents, o‐phthaldialdehyde (OPA), and 2‐mercaptoethanol, were introduced into the capillary through the aperture and reacted with the analytes after CZE separation. High voltages were applied to both the inlet reservoir and the reservoir filled with the derivatization reagents. Thus, the flow rate of the derivatization reagents was controlled by the electric potential that was applied to the reservoir of the derivatization reagents. A UV light‐emitting diode was used as an excitation light source for the fluorescence detection of OPA derivatives. A commercially available tee connector was compared with the laser‐drilled capillary. The results implied that the dead volume of the laser‐drilled capillary was less than that of the tee connector, since the laser‐drilled capillary suppressed band broadening more efficiently. The LODs for amino acids were determined to be ˜5 μM. The method was applied to the determination of amino acids in a Japanese beverage.
Lignan profile in seeds of modern and old Italian soft wheat (Triticum aestivum L.) cultivars as revealed by CE‐MS analyses
Authors: Dinelli Giovanni , Marotti Ilaria , Bosi Sara , Benedettelli Stefano , Ghiselli Lisetta , Cortacero‐Ramírez Sonia , Carrasco‐Pancorbo Alegría , Segura‐Carretero Antonio , Fernández‐Gutiérrez Alberto
Published: October 2007

The health‐promoting effects of whole‐grain consumption have been attributed in part to their unique phytochemical contents and profiles. Wheat is an important component of the human diet; however, little is known about the phytochemical profiles of different wheat varieties, especially of old wheats. The objective of this study was to investigate the distribution of lignans, a class of phytochemicals with proved health benefit effects, of four modern and six old Italian soft wheat (Triticum aestivum L.) cultivars. In this work, we describe the first analytical method involving CE coupled to MS (CE‐MS) used to identify and quantify lignan compounds in grains of different cultivars of wheat. Total lignan content determined by CE‐ESI‐MS was 2.60 ± 0.21 and 5.00 ± 1.30 μg/g dry seed weight for modern and old cultivars, respectively. Secoisolariciresinol and pinoresinol were detected in all ten investigated soft wheat cultivars, whereas arctigenin, hinokinin, and syringaresinol were exclusively detected in old genotypes. Significant differences between modern and old cultivars were also observed for the number of glycosidic forms. Results highlighted the high content and unique composition in lignans of old cultivars suggesting their uses into a wide range of regular and speciality food products naturally enriched with health‐promoting compounds.
Identification of novel angiotensin‐converting enzyme‐inhibitory peptides from ovine milk proteins by CE‐MS and chromatographic techniques
Authors: Gómez‐Ruiz José Ángel , Ramos Mercedes , Recio Isidra
Published: October 2007

In this report, we present the use of CE‐MS as complement to RP separation for the identification of novel angiotensin‐converting enzyme‐inhibitory (ACEI) peptides from a complex milk protein hydrolysate. As preliminary step, fast protein LC (FPLC) was used to isolate the different casein fractions from raw ovine milk. Enzymatic hydrolysis of these fractions was performed by using proteolytic enzymes of gastrointestinal origin. The most active hydrolysate, corresponding to κ‐casein hydrolyzed with pepsin, chymotrypsin, and trypsin, was fractionated by RP‐HPLC and the peptides contained in the active fractions were sequenced by CE coupled to IT‐MS (CE‐MS). The use of CE‐MS allowed the identification of short peptides with ACEI activity included in the scarcely retained fraction obtained by semipreparative RP‐HPLC. Among the identified peptides, those with hydrophobic or positively charged residues at the C‐terminal tripeptide were chemically synthesized to determine their ACEI activity. This procedure allowed us to identify four novel potent ACEI peptides from κ‐casein with sequences IAK, YQQRPVA, WQVLPNAVPAK, and HPHPHLSF. These active sequences could be obtained by enzymatic hydrolysis either of the individual κ‐casein fraction or the total casein fraction from ovine milk.
Processing of nonconventional DNA strand break ends
Authors: Wilson David M.
Published: October 2007

Single‐strand breaks (SSBs) are one of the most common forms of genetic damage, arising from attack of DNA by reactive oxygen species or as intended or inadvertent products of normal cellular DNA metabolic events. Recent evidence linking defects in the enzymatic processing of nonconventional DNA SSBs, i.e., lesions incompatible with polymerase or ligase reactions, with inherited neurodegenerative disorders, reveals the importance of SSB repair in disease manifestation. I review herein the major eukaryotic enzymes (with an emphasis on the human proteins) responsible for the “clean‐up” of DNA breaks harboring 3′‐ or 5′‐blocking termini, and the cellular and disease ramifications of unrepaired SSB damage. Environ. Mol. Mutagen., 2007. Published 2007 Wiley‐Liss, Inc.
DNA adducts from alkoxyallylbenzene herb and spice constituents in cultured human (HepG2) cells
Authors: Zhou Guo‐Dong , Moorthy Bhagavatula , Bi Jia , Donnelly Kirby C. , Randerath Kurt
Published: October 2007

Alkoxy derivatives of allylbenzene, including safrole, estragole, methyleugenol, myristicin, dill apiol, and parsley apiol, are important herb and spice constituents. Human exposure occurs mainly through consumption of food and drinks. Safrole, estragole, and methyleugenol are weak animal carcinogens. Experimental data reveal the genotoxicity and/or carcinogenicity of some allylbenzenes; however, except for safrole, the potential capacity of allylbenzenes for forming adducts in human cellular DNA has not been investigated. In the present study, we have exposed metabolically competent human hepatoma (HepG2) cells to three concentrations (50, 150, and 450 μM) of each of the six aforementioned allylbenzenes and shown by the monophosphate 32P‐postlabeling assay that each compound formed DNA adducts. With the exception of methyleugenol, DNA adduction was dose dependent, decreasing in the order, estragole > methyleugenol > safrole ≈ myristicin > dill apiol > parsley apiol. These results demonstrate that safrole, estragole, methyleugenol, myristicin, dill apiol, and parsley apiol are capable of altering the DNA in these cells and thus may contribute to human carcinogenesis. Environ. Mol. Mutagen., 2007. © 2007 Wiley‐Liss, Inc.
Cortical glucose metabolism correlates negatively with delta‐slowing and spike‐frequency in epilepsy associated with tuberous sclerosis
Authors: Nishida Masaaki , Asano Eishi , Juhász Csaba , Muzik Otto , Sood Sandeep , Chugani Harry T.
Published: October 2007

The mechanism of altered glucose metabolism seen on positron emission tomography (PET) in focal epilepsy is not fully understood. We determined the association between interictal glucose metabolism and interictal neuronal activity, using PET and electrocorticography (ECoG) measures derived from 865 intracranial electrode sites in 11 children with focal epilepsy associated with tuberous sclerosis complex (TSC) (age: 0.5–16 years) undergoing epilepsy surgery. A multiple linear regression analysis was applied to each patient, to determine whether the glucose uptake at each electrode site on interictal PET was predicted by ECoG amplitude powers and interictal spike‐frequency measured in the given electrode site. The regression slopes as well as R‐square values (an indicator of fitness of the regression models) were finally averaged across the 11 patients. The mean regression slope for delta amplitude power was −0.0025 (95% CI: −0.0045 to −0.0004; P = 0.02 based on one‐sample t‐test) and that for spike frequency was −0.023 (95% CI: −0.042 to −0.0038; P = 0.02). On the other hand, the mean regression slopes for the remaining ECoG amplitude powers (theta, alpha, sigma, beta, and gamma activities) were not significantly different from zero. The mean R‐square value was 0.39. These results suggest that increased delta‐slowing and frequent spike activity were independently and additively associated with glucose hypometabolism in children with focal epilepsy associated with TSC. Association between frequent interictal spike activity and low glucose metabolism may be attributed to slow‐wave components following spike discharges on ECoG recording, and a substantial proportion of the variance in regional glucose metabolism on PET could be explained by electrophysiological traits derived from conventional subdural ECoG recording. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Visual field and task influence illusory figure responses
Authors: Bakar Afiza Abu , Liu Lichan , Conci Markus , Elliott Mark A. , Ioannides Andreas A.
Published: October 2007

In normal viewing conditions, many objects are often hidden or occluded by others, therefore restricting the information that enters the eye. One ability that the human visual system has developed to compensate for this visual limitation is to relate the surrounding elements to globally interpret the whole scene. The appearance of illusory figures (IF) based on surrounding elements also relies on this similar function. In the present study, we hypothesized that different mechanisms may be used by the brain to process IF from the center and periphery of the visual field. We compared magnetoencephalographic responses to IFs presented at different parts of the visual field under three task loads. For central presentation, IF specific responses peaked first in V1/V2 (96–101 ms), and then in the lateral occipital complex (LOC; 132–141 ms), independent of task. For peripheral presentation, the relative modulation towards IF was markedly reduced in V1/V2 and LOC while prominent activation peaks now shifted to the Fusiform Gyrus (from 200 ms onwards). Additionally, the type of task influenced processing at early stages beginning in V1/V2 (87 ms). Our results show that retinal eccentricity plays a crucial role in IF processing: figural completion at the center of the visual field is achieved in an ‘automatic’ and seemingly effortless fashion whereas peripheral stimulus locations necessitate higher‐order object completion stages which rely more heavily on attentional demands. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
Differential contributions of the anterior temporal and medial temporal lobe to the retrieval of memory for person identity information
Authors: Tsukiura Takashi , Suzuki Chisato , Shigemune Yayoi , Mochizuki‐Kawai Hiroko
Published: October 2007

Although previous studies have suggested the importance of the bilateral anterior temporal (ATL) and medial temporal lobes (MTL) in the retrieval of person identity information, there is little evidence concerning how these regions differentially contribute to the process. Here we investigated this question using functional magnetic resonance imaging (fMRI). Before scanning, subjects learned associations among faces (F), names (N), and job titles (as a form of person‐related semantics, S). During retrieval with fMRI, subjects were presented with previously learned and new S stimuli, and judged whether the stimuli were old or new. Successful retrieval (H) trials were divided into three conditions: retrieval of S and associated F and N (HSFN); retrieval of S and associated F (HSF); and retrieval of S only (HS). The left ATL was significantly activated in HSFN, compared to HSF or HS, whereas the right ATL and MTL were significantly activated in HSFN and HSF relative to HS. In addition, activity in bilateral ATL was significantly correlated with reaction time for HSFN, whereas we found no significant correlation between activity in the right MTL and reaction time in any condition. The present findings suggest that the left ATL may mediate associations between names and person‐related semantic information, whereas the right ATL mediates the association between faces and person‐related semantic information in memory for person identity information. In addition, activation of the right MTL region implies that this area may contribute to a more general relational processing of associative components, including memory for person identity information. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
Representation of UV‐B‐induced thermal and mechanical hyperalgesia in the human brain: A functional MRI study
Authors: Seifert Frank , Jungfer Isabella , Schmelz Martin , Maihöfner Christian
Published: October 2007

Surrogate models of pain and hyperalgesia allow the investigation of underlying mechanisms in healthy volunteers. Here, we investigated brain activation patterns during mechanical and heat hyperalgesia in an inflammatory human pain model using functional magnetic resonance imaging. Heat and mechanical hyperalgesia were induced on the right forearm by UV‐B application in 14 healthy subjects. All four conditions (nonsensitized heat and nonsensitized mechanical pain, sensitized heat and sensitized mechanical pain) were perceptually matched. A 2 × 2 factorial analysis was performed. Areas with main effect of sensitization were insula, anterior cingulate cortex (ACC), prefrontal cortices (PFC), parietal association cortices (PA), thalamus, and basal ganglia. A main effect of modality with more activation during heat hyperalgesia was found in primary somatosensory cortex (S1), ACC, PFC, and PA. A main effect of modality with more activation during mechanical hyperalgesia was found in secondary somatosensory cortices, posterior insula, and contralateral inferior frontal cortex (IFC). An interaction of sensitization and modality was found bilaterally in IFC. Areas with similar effects of sensitization in both stimulus modalities were ACC, bilateral anterior insula and bilateral IFC. We conclude that different types of hyperalgesia in a human surrogate model of inflammatory pain produce different brain activation patterns. This is partly due to a differential processing of thermal and mechanical pain and an interaction of sensitization and modality in the caudal portion of the IFC. Finally, the data provide evidence for the existence of a common “sensitization network” consisting of ACC, bilateral anterior insula, and parts of the IFC. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
The analysis of efficiency among a small number of organisations: How inferences can be improved by exploiting patient‐level data
Authors: Olsen Kim Rose , Street Andrew
Published: October 2007

Those responsible for monitoring and managing the performance of health‐care organisations face the common problem that the relationship between observed performance and effort is difficult to establish. A solution is to compare the performance of multiple organisations, but this requires a sufficient number of comparators. Faced with a small sample, it may be possible to exploit other information sources. Multilevel regression models are applied to analyse the performance of six Danish vascular departments in 2004 using a patient‐level data set. We find that treatment costs are higher for smokers, older patients, patients with cerebrovascular and pulmonal diseases and for those subject to acute hospitalisation and with longer lengths of stay. Costs are lower for patients who are having follow‐up surgery and for patients who receive some form of home care, suggesting that there may be some substitution of care input between vascular departments and other care providers.

We estimate the relative efficiency of each department. The construction of confidence intervals allows the six departments to be sorted into two groups containing the least and most efficient departments. Conclusions about relative efficiency are robust to model specification, choice of estimator and hold at the 95% confidence level. Copyright © 2007 John Wiley & Sons, Ltd.
A note on the dynamic interaction between waiting times and waiting lists
Authors: Siciliani Luigi
Published: October 2007

Waiting times are commonly used as a rationing device in health care and the public sector. We develop a stylised model, which predicts the dynamics of waiting times and waiting lists over time as a function of differing demand and supply parameters. We show that a path with decreasing waiting time and increasing waiting list over certain time intervals is a possible solution, which is consistent with some empirical evidence. Copyright © 2007 John Wiley & Sons, Ltd.
On the determinants of Central Bank independence in open economies
Authors: D'Amato Marcello , Pistoresi Barbara , Salsano Francesco
Published: October 2007

We test some positive implications of the commitment hypothesis for the design of monetary institutions in open economies, by studying the determinants of Central Bank independence on a sample of 55 countries, for the period 1980–1989. We document fairly consistent empirical evidence in support of the hypothesis that strategic commitment is indeed important to understand cross‐country variation in the level of Central Bank degree of dependence. We also address the related question why only highly industrialized countries have relied on such a solution to the inflationary bias of monetary policy whereas other countries have not. Data suggest that the answer is related to the presence and the size of world‐wide common features in the business cycle at country level. Copyright © 2007 John Wiley & Sons, Ltd.
Wear in molded tibial inserts: Knee simulator study of H1900 and GUR1050 polyethylenes
Authors: Tsukamoto Riichiro , Williams Paul Allen , Shoji Hiromu , Hirakawa Kazuo , Yamamoto Kengo , Tsukamoto Mikiko , Clarke Ian C.
Published: October 2007

Hi‐fax 1900™ tibial inserts were used in the IB‐1 total knee replacement (TKR) beginning 1978, soon followed by the AGC design. Such direct compression molded (DCM) inserts was relatively immune to oxidation. Unfortunately the Hi‐fax 1900™ resin (H1900) was taken off the market in year 2004. As an alternate, GUR1050 was introduced in the Vanguard™ TKR. However there appeared to be little or no wear comparisons of molded inserts. Therefore the study aim was to compare wear performance of GUR1050 to the historical H1900. The hypothesis was that Hi‐fax and GUR1050 would show comparable wear performance. The Vanguard™ was a posterior‐cruciate sacrificing design (Biomet Inc.). All tibial inserts were sterilized by gamma‐radiation (3.2 Mrad) under argon. A 6‐channel, displacement–controlled knee simulator was used with serum lubricant (protein concentration 20 mg/mL). Wear assessments were by gravimetric methods and linear regression techniques. The gross weight‐loss trends over 2.5 Mc duration demonstrated excellent linear behavior with good agreement between TKR sets (<±10%). Fluid sorption artifacts in control represented less than 5% of gross wear magnitudes. Thus suitable corrections could be made in determining net wear. The H1900 and GUR1050inserts demonstrated net wear‐rates of 3.6 and 3.4 mm3/Mc, respectively. This difference was not found to be statistically significant. This wear study demonstrated that GUR1050 inserts were indistinguishable from the Hi‐fax 1900 in terms of laboratory wear performance, proving our hypothesis. Given the excellent clinical history of DCM Hi‐fax 1900, the GUR1050 should be an ideal candidate for TKR. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Differentiation ofVitis viniferavarieties by MALDI‐MS analysis of the grape seed proteins
Authors: Pesavento Ivana Chiara , Bertazzo Antonella , Flamini Riccardo , Vedova Antonio Dalla , De Rosso Mirko , Seraglia Roberta , Traldi Pietro
Published: October 2007

Until now the study of pathogenic related proteins in grape juice and wine, performed by ESI‐MS, LC/ESI‐MS, and MALDI/MS, has been proposed for differentiation of varieties. In fact, chitinases and thaumatin‐like proteins persist through the vinification process and cause hazes and sediments in bottled wines. An additional instrument, potentially suitable for the grape varieties differentiation, has been developed by MALDI/MS for the grape seed protein analysis. The hydrosoluble protein profiles of seeds extract from three differentVitis viniferagrape (red and white) varieties were analyzed and compared. In order to evaluate the environmental conditions and harvest effects, the seed protein profiles of one grape variety from different locations and harvests were studied. Copyright © 2007 John Wiley & Sons, Ltd.
The Last Glacial Maximum British–Irish Ice Sheet: a reconstruction using digital terrain mapping
Authors: Fretwell P. T. , Smith D. E. , Harrison S.
Published: October 2007

The use of digital terrain mapping in determining the anatomy of the Late Devensian British–Irish Ice Sheet at a resolution of 500 m cell size is illustrated for Boulton et al.'s 1985 and 1991 models and Lambeck's 1995 model of the ice sheet at its maximum extent as an independent ice mass. Area and volume of the ice sheet are given for each model and the spatial pattern of ice thickness shown in maps. The analyses show that if no account is taken of topography beneath the ice surface, models will seriously overestimate ice volume. It is suggested that as reconstructions of the ice sheet improve, detailed models of ice thickness at the resolution given in this paper may be of value in determining the contribution of the ice sheet to sea surface changes as well as in determining the effects of ice loading on glacio‐isostasy, neotectonics and possibly on paraglacial processes in areas of high relief. Copyright © 2007 John Wiley & Sons, Ltd.
Separation of a sphere from a flat in the presence of couple stress fluids
Authors: Elsharkawy Abdallah A. , AL‐Fadhalah Khaled J.
Published: October 2007

A mathematical model for couple stress fluid is presented to analyse the separation flow of a fully flooded sphere from a flat under the condition of constant load. Assuming the lubricant between the sphere and the flat to contain additives, the couple stress effect, presented by the characteristic length of the additives, has been considered to account for the non‐Newtonian behaviour. In addition, the effect of the sphere inertia on accelerating the separation process has been considered. Compared with the Newtonian fluid case, the results of the numerical solution indicated that the separation time increases with increasing the characteristic length of the additives. It was also found that the additive characteristic length has negligible effect on the thickness of the lubricant film at the separation point. Copyright © 2007 John Wiley & Sons, Ltd.
Transmission ratio distortion at the growth hormone gene (GH1) in bovine preimplantation embryos: An in vitro culture‐induced phenomenon?
Authors: Murphy Angela M. , Meade Kieran G. , Hayes Patricia A. , Park Stephen D.E. , Evans Alex C.O. , Lonergan Patrick , MacHugh David E.
Published: October 2007

The growth hormone gene (GH1) and its polypeptide product (GH) have a crucial role in reproduction, embryogenesis and general development. A polymorphism present in the fifth exon of the bovine GH1 gene (GH1 p.Leu127Val) has been associated with GH release and milk production in cattle. The objective of the present study was to examine the genotype frequencies of the GH1 p.Leu127Val polymorphism in bovine blastocysts produced in vitro and in vivo to determine if allelic variation of the GH1 gene affects embryo development and survival. A heterozygous (p.Leu127/Val127) sire was used for in vitro fertilization of oocytes of unknown maternal genotype (n = 104) and known maternal genotype (n = 115). PCR amplification and genotyping of the GH1 gene from Day 8 blastocysts derived from these fertilized oocytes demonstrated that there was significant over‐representation from the expected Mendelian ratio of GH1 p.Leu127/Leu127 homozygotes from oocytes of known maternal genotype (P = 0.006). Contrary to this, analysis of in vivo‐produced bovine blastocysts of known parental GH1 genotype (n = 69) did not reveal an overrepresentation of GH1 p.Leu127/Leu127 homozygotes. These results suggest that developing in vitro‐produced embryos are exposed to a selection process, probably due to a less favorable culture environment, that acts to increase the number of GH1 p.Leu127/Leu127 homozygotes, thereby giving rise to the observed transmission ratio distortion (TRD) of GH1 genotypes when compared to in vivo produced embryos. Mol. Reprod. Dev. 75: 715–722, 2008. © 2007 Wiley‐Liss, Inc.
Differential expression of genes for transcription factors in theca and granulosa cells following selection of a dominant follicle in cattle
Authors: Zielak A.E. , Canty M.J. , Forde N. , Coussens P.M. , Smith G.W. , Lonergan P. , Ireland J.J. , Evans A.C.O.
Published: October 2007

Transcription factors inhibit or assist RNA polymerases in the initiation and maintenance of transcription; however, the cell specific expression and roles of transcription factors within bovine ovarian follicles during development are unknown. The aim of present study was to determine if the expression of transcription factors in theca and granulosa cells differ between the dominant and the largest subordinate follicles at different stages of the follicle wave. We used a bovine cDNA microarray to screen granulosa and theca cells from dominant and subordinate follicles for differential expression of genes coding for transcription factors. Expression was confirmed using reverse transcription polymerase chain reaction and differences in mRNA abundance further examined at Emergence, Selection and Dominance stages of the follicle wave. We have identified five genes encoding for transcription factors that have not been previously described in developing follicles with greater mRNA abundance in subordinate compared to dominant follicles. The genes (and their putative roles) are CEBP‐β (responsible for luteinization), SRF (cell survival), FKHRL1 (stimulates apoptosis), NCOR1 (modulation of the actions of the oestradiol receptor) and Midnolin (control of development via regulation of mRNA transport in cells). Mol. Reprod. Dev. 75: 904–914, 2008. © 2007 Wiley‐Liss, Inc.
Fractionated manganese‐enhanced MRI
Authors: Bock Nicholas A. , Paiva Fernando F. , Silva Afonso C.
Published: October 2007

We investigated the use of manganese‐enhanced MRI (MEMRI) with fractionated doses as a way to retain the unique properties of manganese as a neuronal contrast agent while lessening its toxic effects in animals. First, we followed the signal enhancement on T1‐weighted images of the brains of rats receiving 30 mg/kg fractions of MnCl2 · 4H2O every 48 h and found that the signal increased in regions with consecutive fractionated doses and ultimately saturated. Second, we used T1 mapping to test whether the amount of MRI‐visible manganese that accumulated depended on the concentration of manganese in the fractions. For a fixed cumulative dose of 180 mg/kg MnCl2 · 4H2O, increasing fraction doses of 6 × 30 mg/kg, 3 × 60 mg/kg, 2 × 90 mg/kg and 1 × 180 mg/kg produced progressively shorter T1 values. The adverse systemic health effects, including complications at the injection site and poor animal well‐being, also rose with the fraction dose. Thus, fractionated MEMRI can be used to balance the properties of manganese as a contrast agent in animals against its toxic effects. Published in 2007 by John Wiley & Sons, Ltd.
Smooth finite element methods: Convergence, accuracy and properties
Authors: Nguyen‐Xuan Hung , Bordas Stéphane , Nguyen‐Dang Hung
Published: October 2007

A stabilized conforming nodal integration finite element method based on strain smoothing stabilization is presented. The integration of the stiffness matrix is performed on the boundaries of the finite elements. A rigorous variational framework based on the Hu–Washizu assumed strain variational form is developed.

We prove that solutions yielded by the proposed method are in a space bounded by the standard, finite element solution (infinite number of subcells) and a quasi‐equilibrium finite element solution (a single subcell). We show elsewhere the equivalence of the one‐subcell element with a quasi‐equilibrium finite element, leading to a global a posteriori error estimate.

We apply the method to compressible and incompressible linear elasticity problems. The method can always achieve higher accuracy and convergence rates than the standard finite element method, especially in the presence of incompressibility, singularities or distorted meshes, for a slightly smaller computational cost.

It is shown numerically that the one‐cell smoothed four‐noded quadrilateral finite element has a convergence rate of 2.0 in the energy norm for problems with smooth solutions, which is remarkable. For problems with rough solutions, this element always converges faster than the standard finite element and is free of volumetric locking without any modification of integration scheme. Copyright © 2007 John Wiley & Sons, Ltd.
Implicit boundary method for finite element analysis using non‐conforming mesh or grid
Authors: Kumar Ashok V. , Padmanabhan Sanjeev , Burla Ravi
Published: October 2007

In the finite element method (FEM), a mesh is used for representing the geometry of the analysis and for representing the test and trial functions by piece‐wise interpolation. Recently, analysis techniques that use structured grids have been developed to avoid the need for a conforming mesh. The boundaries of the analysis domain are represented using implicit equations while a structured grid is used to interpolate functions. Such a method for analysis using structured grids is presented here in which the analysis domain is constructed by Boolean combination of step functions. Implicit equations of the boundary are used in the construction of trial and test functions such that essential boundary conditions are guaranteed to be satisfied. Furthermore, these functions are constructed such that internal elements, through which no boundary passes, have the same stiffness matrix. This approach has been applied to solve linear elastostatic problems and the results are compared with analytical and finite element analysis solutions to show that the method gives solutions that are similar to the FEM in quality but is less computationally expensive for dense mesh/grid and avoids the need for a conforming mesh. Copyright © 2007 John Wiley & Sons, Ltd.
Methylmalonic acidaemia leads to increased production of reactive oxygen species and induction of apoptosis through the mitochondrial/caspase pathway
Authors: Richard E , Alvarez‐Barrientos A , Pérez B , Desviat LR , Ugarte M
Published: October 2007

Methylmalonic acidaemia (MMA) is a heterogeneous group of rare genetic metabolic disorders caused by defects related to intracellular cobalamin (vitamin B12) metabolism. Increasing evidence has emerged suggesting that free radical generation is involved in the pathophysiology of neurodegenerative diseases, including some inborn errors of metabolism. We have previously identified in MMA patients several differentially expressed proteins involved in oxidative stress [mitochondrial superoxide dismutase (MnSOD) and mitochondrial glycerophosphate dehydrogenase (mGPDH)] and apoptosis by a proteomic approach. We have now extensively evaluated various parameters related to oxidative stress and apoptosis in cultured fibroblasts from a spectrum of patients with methylmalonic acidaemia. Fibroblasts from several MMA patients showed a significant increase in intracellular reactive oxygen species (ROS) content and in MnSOD expression level with respect to controls, suggesting a cellular response to intrinsic ROS stress. Moreover, we have demonstrated, using siRNA, that mGPDH is an important ROS generator in MMA patients. Cells from patients with MMA had a higher rate of apoptosis than those of controls and there was evidence that this process primarily involves the mitochondrial/caspase‐dependent pathway. ROS level–phenotype correlation revealed that patients with severe neonatalcblBdisorder had elevated intracellular ROS content. These findings support the possible role of oxidative stress in the pathophysiology of methylmalonic acidaemia. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Epigenetic inactivation of microRNA gene hsa‐mir‐9‐1 in human breast cancer
Authors: Lehmann U , Hasemeier B , Christgen M , Müller M , Römermann D , Länger F , Kreipe H
Published: October 2007

MicroRNAs (miRNAs) represent a new class of small non‐coding RNAs regulating gene expression by inducing RNA degradation or interfering with translation. Aberrant miRNA expression has been described for several human malignancies and tumour suppressor functions have been ascribed to this new class of small regulatory RNAs. Accordingly, inactivation due to deletion or mutation has been found in human malignancies. Here, we describe the role of aberrant hypermethylation as an additional mechanism for miRNA gene inactivation in human breast cancer. Aberrant hypermethylation was shown for mir‐9‐1, mir‐124a3, mir‐148, mir‐152, and mir‐663 in 34–86% of cases in a series of 71 primary human breast cancer specimens. For comprehensive methylation analysis, combined bisulphite restriction analysis, bisulphite sequencing, and Pyrosequencing™ were employed. miRNA gene hypermethylation correlated strongly with methylation of known tumour suppressor genes (p = 0.003). After treatment of various breast cancer cell lines with the demethylating agent 5‐aza‐2′‐deoxycytidine, reduction of mir‐9‐1 gene methylation and concomitant reactivation of expression could be observed. For the mir‐9‐1 gene, which is already hypermethylated in pre‐invasive intraductal lesions, a good correlation between quantitative methylation level and reduction of expression could be demonstrated in a subset of primary human breast cancer specimen (r = 0.8). In conclusion, this study demonstrates that various microRNA genes are also affected by epigenetic inactivation due to aberrant hypermethylation and that this is an early and frequent event in breast cancer development. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mortality in schizophrenia
Authors: Auquier Pascal , Lançon Christophe , Rouillon Frédéric , Lader Malcolm
Published: October 2007

Schizophrenia is a life‐threatening disease associated with mortality rates that are two to three times higher than those expected/observed in the general population. It is associated with high levels of suicide, particularly in young male patients soon after diagnosis. Delays in treating schizophrenia could contribute to the high number of suicides during this period. However, approximately two‐thirds of the excess mortality is caused by natural deaths. Patients with schizophrenia die from the same diseases as people in the general population. The number of deaths caused by cardiovascular disease, as in the general population, is high and could be reduced by the modification of certain lifestyle factors, such as diet and exercise. Careful monitoring of patients' weight, blood pressure, blood glucose levels and serum lipid levels will not only provide an opportunity to educate patients about lifestyle choices that contribute to cardiovascular disease but will also give them a better chance of receiving early treatment for disorders that contribute to cardiovascular disease, such as obesity, type 2 diabetes, hypertension and dyslipidaemia. Careful selection of antipsychotic drugs, some of which are associated with side effects such as weight gain and cardiac disorders, will also help reduce co‐morbidity and mortality among patients with schizophrenia. Copyright © 2007 John Wiley & Sons, Ltd.
Screening statins for possible carcinogenic risk: up to 9 years of follow‐up of 361 859 recipients
Authors: Friedman Gary D. , Flick E. Dawn , Udaltsova Natalia , Chan Pharm D James , Quesenberry Charles P. , Habel Laurel A.
Published: October 2007

Purpose

Determine the risk of cancer in statin users.

Methods

Risk of cancer in up to 9.4 years after first recorded receipt of statins was evaluated in subscribers of an integrated health care program in northern California. Statin use and cancer development were ascertained from the program's pharmacy records and cancer registry from August 1994 to December 2003.

Results

Most of the 361 859 statin users received lovastatin, simvastatin or both. Results are presented from analyses with 2‐year lag and use for over 5 years. Most of the observed associations were likely due to chance or confounding. The few associations that seemed less readily explainable were increased risk of cancers of the thyroid, esophagus and urinary tract and decreased risk of colon cancer in men. Increased risk of lung cancer was the only nominally statistically significant positive association in women and could be partially attributable to their smoking habits.

Conclusions

Overall this study provided no strong evidence of either causation or prevention of cancer by statins. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis of a [60]fullerene‐functionalized poly(vinyl chloride) derivative by stereospecific chemical modification of PVC
Authors: Martínez Gerardo , Gómez Marián A. , Gómez Rafael , Segura José L.
Published: October 2007

The covalent attachment of [60]fullerene (C60) to two poly(vinyl chloride) (PVC) samples with different isotactic content is achieved by direct reaction in o‐dichlorobenzene (o‐DCB) solution in the presence of AIBN. The extent of fullerenation is controlled by varying the C60 feed ratio. The pendant C60‐chemically modified PVC polymers are soluble in tetrahydrofuran (THF) and have been characterized by UV–vis, NMR, FTIR, DSC, TGA, cyclic voltammetry, and SEM. The quantitative microstructural analysis after covalent attachment of the bulky C60 moiety to the PVC has been followed by 13C NMR spectroscopy. From the results it can be concluded that the modification of PVC by graft reaction through free radical reaction proceeds by a stereoselective mechanism. This conclusion has been confirmed on the basis of the increase of the glass‐transition temperature (Tg) and the thermal stability of the C60‐chemical modified PVC samples. The fullerenated PVCs obtained show good electron acceptor properties, as evidenced by electrochemical investigations. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5408–5419, 2007
Synthesis, characterization, and cross‐linking of a library of statistical copolymers based on 2‐“soy alkyl”‐2‐oxazoline and 2‐ethyl‐2‐oxazoline
Authors: Hoogenboom Richard , Thijs Hanneke M. L. , Fijten Martin W. M. , Schubert Ulrich S.
Published: October 2007

The synthesis of statistical copolymers consisting of 2‐ethyl‐2‐oxazoline (EtOx) and 2‐“soy alkyl”‐2‐oxazoline (SoyOx) via a microwave‐assisted cationic ring‐opening polymerization procedure is described. The majority of the resulting copolymers revealed polydispersity indices below 1.30. The reactivity ratios (rEtOx 1.4 ± 0.3; rSoyOx = 1.7 ± 0.3) revealed a clustered monomer distribution throughout the polymer chains. The thermal and surface properties of the pEtOx‐stat‐SoyOx copolymers were analyzed before and after UV‐curing demonstrating the decreased chain mobility after cross‐linking. In addition, the cross‐linked materials showed shape‐persistent swelling upon absorption of water from the air, whereby as little as 5 mol % SoyOx was found to provide efficient cross‐linking. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5371,–5379, 2007
Conservative management of a ruptured pulmonary hydatid cyst
Authors: Zampoli M. , Zar H.
Published: October 2007

Pulmonary hydatid cysts in children frequently develop complications such as infection and air leaks. Surgery combined with medical therapy remains the standard form of treatment. We report a 7‐year‐old child who developed rupture of a large pulmonary hydatid cyst following chest trauma; conservative management resulted in successful expulsion of the cyst. Pediatr Pulmonol. 2007; 42:1229–1232. © 2007 Wiley‐Liss, Inc.
Use of Doppler ultrasonography in the assessment of bronchodilator response in acute bronchiolitis
Authors: Kalogeropoulou Christina , Anthracopoulos Michael B. , Yarmenitis Spiridon , Kanellopoulos Theodore , Eliopoulou Maria , Papanastasiou Dimitris
Published: October 2007

Measurement of the response of acute bronchiolitis (AB) to bronchodilators relies on clinical signs and pulse oximetry. We hypothesized that Doppler ultrasonographic indices of hepatic venous flow may prove to be an objective tool in the assessment of the effect of inhaled salbutamol in infants hospitalized for AB. Previously healthy infants hospitalized for their first episode of AB were prospectively studied. Composite clinical score (CCS, retractions plus wheezing/crackles) and hemoglobin oxygen saturation (SaO2) were measured before, and 15‐min post‐salbutamol nebulization (0.15 mg/kg, minimum 1.5 mg). Peak velocities at the middle hepatic vein (PV‐HV) and right renal vein (PV‐RV), as well as peripheral‐to‐middle hepatic vein transit time (TT) of an ultrasound contrast agent were also measured by Doppler ultrasonography pre‐ and post‐nebulization. Nineteen infants were studied. Mean CCS decreased by 0.37 (95% confidence interval [CI]: 0.08–0.66, P = 0.015) and mean SaO2 increased by 0.68% (95%CI: 0.17–1.19, P = 0.01) post‐bronchodilator treatment. Mean TT increased by 9.54 sec (95%CI: 5.95–13.13, P < 0.0001) and PV‐HV increased by 16.49 cm/sec (95%CI: 9.07–23.91, P = 0.0002); PV‐RV did not change. TT (r = 0.51, P = 0.009), but not PV‐HV, correlated negatively with CCS. There was a strong positive correlation between pre‐ and post‐salbutamol TT values (r = 0.92, P < 0.0001). The most likely explanation for these findings is post‐salbutamol abolishment of shunting at the pulmonary capillary bed. We conclude that the peripheral‐to‐middle hepatic vein prolongation of TT measured by Doppler ultrasonography after salbutamol administration in infants with AB can be used as a bedside tool in the objective assessment of clinical response to medication in these patients. Pediatr Pulmonol. 2007; 42:1159–1165. © 2007 Wiley‐Liss, Inc.