bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing repressor protein levels from expression of gene targets in
Escherichia coli
Authors: Khanin R. , Vinciotti V. , Wit E.
Published: November 2006

The basic underlying problem in reverse engineering of gene regulatory networks from gene expression data is that the expression of a gene encoding the regulator provides only limited information about its protein activity. The proteins, which result from translation, are subject to stringent posttranscriptional control and modification. Often, it is only the modified version of the protein that is capable of activating or repressing its regulatory targets. At present there exists no reliable high-throughput technology to measure the protein activity levels in real-time, and therefore they are, so-to-say, lost in translation. However, these activity levels can be recovered by studying the gene expression of their targets. Here, we describe a computational approach to predict temporal regulator activity levels from the gene expression of its transcriptional targets in a network motif with one regulator and many targets. We consider an example of an SOS repair system, and computationally infer the regulator activity of its master repressor, LexA. The reconstructed activity profile of LexA exhibits a behavior that is similar to the experimentally measured profile of this repressor: after UV irradiation, the amount of LexA substantially decreases within a few minutes, followed by a recovery to its normal level. Our approach can easily be applied to known single-input motifs in other organisms.
Ameiotic recombination in asexual lineages of
Daphnia
Authors: Omilian Angela R. , Cristescu Melania E. A. , Dudycha Jeffry L. , Lynch Michael
Published: November 2006

Despite the enormous theoretical attention given to the evolutionary consequences of sexual reproduction, the validity of the key assumptions on which the theory depends rarely has been evaluated. It is often argued that a reduced ability to purge deleterious mutations condemns asexual lineages to an early extinction. However, most well characterized asexual lineages fail to exhibit the high levels of neutral allelic divergence expected in the absence of recombination. With purely descriptive data, it is difficult to evaluate whether this pattern is a consequence of the rapid demise of asexual lineages, an unusual degree of mutational stability, or recombination. Here, we show in mutation-accumulation lines of asexual
Daphnia
that the rate of loss of nucleotide heterozygosity by ameiotic recombination is substantially greater than the rate of introduction of new variation by mutation. This suggests that the evolutionary potential of asexual diploid species is not only a matter of mutation accumulation and reduced efficiency of selection, but it underscores the limited utility of using neutral allelic divergence as an indicator of ancient asexuality.
Continuous tooth generation in mouse is induced by activated epithelial Wnt/β-catenin signaling
Authors: Järvinen Elina , Salazar-Ciudad Isaac , Birchmeier Walter , Taketo Makoto M. , Jernvall Jukka , Thesleff Irma
Published: November 2006

The single replacement from milk teeth to permanent teeth makes mammalian teeth different from teeth of most nonmammalian vertebrates and other epithelial organs such as hair and feathers, whose continuous replacement has been linked to Wnt signaling. Here we show that mouse tooth buds expressing stabilized β-catenin in epithelium give rise to dozens of teeth. The molar crowns, however, are typically simplified unicusped cones. We demonstrate that the supernumerary teeth develop by a renewal process where new signaling centers, the enamel knots, bud off from the existing dental epithelium. The basic aspects of the unlocked tooth renewal can be reproduced with a computer model on tooth development by increasing the intrinsic level of activator production, supporting the role of β-catenin pathway as an upstream activator of enamel knot formation. These results may implicate Wnt signaling in tooth renewal, a capacity that was all but lost when mammals evolved progressively more complicated tooth shapes.
Rapid and reversible changes in intrahippocampal connectivity during the course of hibernation in European hamsters
Authors: Magariños Ana María , McEwen Bruce S. , Saboureau Michel , Pevet Paul
Published: November 2006

The hippocampal formation is a highly plastic brain structure that undergoes structural remodeling in response to internal and external challenges such as metabolic imbalance and repeated stress. We investigated whether the extreme alterations in metabolic status that occur during the course of hibernation in European hamsters cause structural changes in the dendritic arborizations of the CA3 pyramidal neurons and their main excitatory afferents, the mossy fiber terminals (MFT), that originate in the dentate gyrus. We report that apical, but not basal, dendritic trees of Golgi-impregnated CA3 principal neurons are significantly shorter, less branched, and less spiny in hypothermic hamsters compared with active animals. After the induction of arousal from torpor, within 2 h, the apical dendritic lengths, branching patterns, and spine density estimations returned to levels found in active, euthermic hamsters. The ultrastructure of MFT in hibernating hamsters showed a significant reduction in synaptic vesicle density and in the percentage of MFT area covered by spine profiles. Awakened hamsters showed restoration of MFT morphology to that seen in active animals. MFT of torpid animals also showed a significant increase in the percentage area of mitochondrial profiles that remained higher 3 h after induced arousal from hibernation compared with euthermic controls. Thus, the torpid/awakening cycle of the hibernating European hamster causes a rapid and reversible morphological reorganization of intrahippocampal subregions involved in information processing. The reported reductions in morphological connectivity between the dentate gyrus and the CA3 subregions could underlie the cessation of exploratory activity and spatial navigation skills during hibernation.
Testosterone increases bioavailability of carotenoids: Insights into the honesty of sexual signaling
Authors: Blas J. , Pérez-Rodríguez L. , Bortolotti G. R. , Viñuela J. , Marchant T. A.
Published: November 2006

Androgens and carotenoids play a fundamental role in the expression of secondary sex traits in animals that communicate information on individual quality. In birds, androgens regulate song, aggression, and a variety of sexual ornaments and displays, whereas carotenoids are responsible for the red, yellow, and orange colors of the integument. Parallel, but independent, research lines suggest that the evolutionary stability of each signaling system stems from tradeoffs with immune function: androgens can be immunosuppressive, and carotenoids diverted to coloration prevent their use as immunostimulants. Despite strong similarities in the patterns of sex, age and seasonal variation, social function, and proximate control, there has been little success at integrating potential links between the two signaling systems. These parallel patterns led us to hypothesize that testosterone increases the bioavailability of circulating carotenoids. To test this hypothesis, we manipulated testosterone levels of red-legged partridgesAlectoris rufawhile monitoring carotenoids, color, and immune function. Testosterone treatment increased the concentration of carotenoids in plasma and liver by >20%. Plasma carotenoids were in turn responsible for individual differences in coloration and immune response. Our results provide experimental evidence for a link between testosterone levels and immunoenhancing carotenoids that (i) reconciles conflicting evidence for the immunosuppressive nature of androgens, (ii) provides physiological grounds for a connection between two of the main signaling systems in animals, (iii) explains how these signaling systems can be evolutionary stable and honest, and (iv) may explain the high prevalence of sexual dimorphism in carotenoid-based coloration in animals.
ProteomeCommons.org IO Framework: reading and writing multiple proteomics data formats
Authors: Falkner J. A. , Falkner J. W. , Andrews P. C.
Published: November 2006

Motivation: Effective use of proteomics data, specifically mass spectrometry data, relies on the ability to read and write the many mass spectrometer file formats. Even with mass spectrometer vendor-specific libraries and vendor-neutral file formats, such as mzXML and mzData it can be difficult to extract raw data files in a form suitable for batch processing and basic research. Introduced here are the ProteomeCommons.org Input and Output Framework, abbreviated to IO Framework, which is designed to abstractly represent mass spectrometry data. This project is a public, open-source, free-to-use framework that supports most of the mass spectrometry data formats, including current formats, legacy formats and proprietary formats that require a vendor-specific library in order to operate. The IO Framework includes an on-line tool for non-programmers and a set of libraries that developers may use to convert between various proteomics file formats.

Availability: The current source-code and documentation for the ProteomeCommons.org IO Framework is freely available at

Contact:  jfalkner@umich.edu
PrepMS: TOF MS data graphical preprocessing tool
Authors: Karpievitch Yuliya V. , Hill Elizabeth G. , Smolka Adam J. , Morris Jeffrey S. , Coombes Kevin R. , Baggerly Keith A. , Almeida Jonas S.
Published: November 2006

Summary: We introduce a simple-to-use graphical tool that enables researchers to easily prepare time-of-flight mass spectrometry data for analysis. For ease of use, the graphical executable provides default parameter settings, experimentally determined to work well in most situations. These values, if desired, can be changed by the user. PrepMS is a stand-alone application made freely available (open source), and is under the General Public License (GPL). Its graphical user interface, default parameter settings, and display plots allow PrepMS to be used effectively for data preprocessing, peak detection and visual data quality assessment.

Availability: Stand-alone executable files and Matlab toolbox are available for download at:

Contact:  ykarpi@mdanderson.org

Supplementary information: Supplementary data are available at Bioinformatics online.
SNP2NMD: A database of human single nucleotide polymorphisms causing nonsense-mediated mRNA decay
Authors: Han Areum , Kim Woo-Yeon , Park Seong-Min
Published: November 2006

Summary: Elucidating the effects of genetic polymorphisms on genes and gene networks is an important step in disease association studies. We developed the SNP2NMD database for human SNPs (single nucleotide polymorphisms) that result in PTCs (premature termination codons) and trigger nonsense-mediated mRNA decay (NMD). The SNP2NMD Web interfaces provide extensive genetic information on and graphical views of the queried SNP, gene, and disease terms.

Availability: SNP2NMD is available from , or directly from

Contact:  kimplove@kribb.re.kr, lastmhc@kribb.re.kr

Supplementary information:
A Babel of Judicial Voices? Ruminations from the Bench
Authors: Higgins Rosalyn
Published: November 2006

This Keynote speech examines the implications of the multiplying of judicial institutions and the deepening of international law. Overlapping jurisdiction issues already exist among international courts and tribunals. This raises the question of ‘Whose view prevails?’ But the deepening of international law also requires any given court to ask itself, ‘Which of the many norms now developed are applicable?’ Alternative plausible applicable norms could lead to different solutions. It is ever more apparent that that law is more than ‘bright rules’ that simply need to be applied. This speech discusses potential solutions that have been proposed, such as instituting a judicial hierarchy, using certain provisions of the Vienna Convention on the Law of Treaties, and invoking a hierarchy of norms. It closes with a call for international judges to regard the multiplication of institutions and applicable norms as an opportunity rather than a problem, to read each other's judgments, respect each other's work and try to preserve unity unless context dictates otherwise.
UK OC OK? Interpreting Optimal Classification Scores for the U.K. House of Commons
Authors: Spirling Arthur , McLean Iain
Published: November 2006

Poole's (2000, Non-parametric unfolding of binary choice data. Political Analysis 8:211–37) nonparametric Optimal Classification procedure for binary data produces misleading rank orderings when applied to the modern House of Commons. With simulations and qualitative evidence, we show that the problem arises from the government-versus-opposition nature of British (Westminster) parliamentary politics and the strategic voting that is entailed therein. We suggest that political scientists think seriously about strategic voting in legislatures when interpreting results from such techniques.
Genome-wide detection of human copy number variations using high-density DNA oligonucleotide arrays
Authors: Komura Daisuke , Shen Fan , Ishikawa Shumpei , Fitch Karen R. , Chen Wenwei , Zhang Jane , Liu Guoying , Ihara Sigeo , Nakamura Hiroshi , Hurles Matthew E. , Lee Charles , Scherer Stephen W. , Jones Keith W. , Shapero Michael H. , Huang Jing , Aburatani Hiroyuki
Published: November 2006

Recent reports indicate that copy number variations (CNVs) within the human genome contribute to nucleotide diversity to a larger extent than single nucleotide polymorphisms (SNPs). In addition, the contribution of CNVs to human disease susceptibility may be greater than previously expected, although a complete understanding of the phenotypic consequences of CNVs is incomplete. We have recently reported a comprehensive view of CNVs among 270 HapMap samples using high-density SNP genotyping arrays and BAC array CGH. In this report, we describe a novel algorithm using Affymetrix GeneChip Human Mapping 500K Early Access (500K EA) arrays that identified 1203 CNVs ranging in size from 960 bp to 3.4 Mb. The algorithm consists of three steps: (1) Intensity pre-processing to improve the resolution between pairwise comparisons by directly estimating the allele-specific affinity as well as to reduce signal noise by incorporating probe and target sequence characteristics via an improved version of the Genomic Imbalance Map (GIM) algorithm; (2) CNV extraction using an adapted SW-ARRAY procedure to automatically and robustly detect candidate CNV regions; and (3) copy number inference in which all pairwise comparisons are summarized to more precisely define CNV boundaries and accurately estimate CNV copy number. Independent testing of a subset of CNVs by quantitative PCR and mass spectrometry demonstrated a >90% verification rate. The use of high-resolution oligonucleotide arrays relative to other methods may allow more precise boundary information to be extracted, thereby enabling a more accurate analysis of the relationship between CNVs and other genomic features.
Aminocyclopropane Carboxylic Acid Synthase Is a Regulated Step in Ethylene-Dependent Induced Conifer Defense. Full-Length cDNA Cloning of a Multigene Family, Differential Constitutive, and Wound- and Insect-Induced Expression, and Cellular and Subcellular Localization in Spruce and Douglas Fir
Authors: Ralph Steven G. , Hudgins J.W. , Jancsik Sharon , Franceschi Vincent R. , Bohlmann Jörg
Published: November 2006

In conifer stems, formation of chemical defenses against insects or pathogens involves specialized anatomical structures of the phloem and xylem. Oleoresin terpenoids are formed in resin duct epithelial cells and phenolics accumulate in polyphenolic parenchyma cells. Ethylene signaling has been implicated in the induction of these chemical defenses. Recently, we reported the cloning of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) from spruce (Picea spp.) and Douglas fir (Pseudotsuga menziesii). ACO protein was constitutively expressed in Douglas fir and only weakly induced upon wounding. We now cloned seven full-length and one near full-length cDNA representing four distinct 1-aminocyclopropane-1-carboxylic acid synthases (ACS; ACS1, ACS2, ACS3, and ACS4) from spruce and Douglas fir. Cloning of ACS has not previously been reported for any gymnosperm. Using gene-specific, quantitative real-time polymerase chain reaction, we measured constitutive expression for the four ACS genes and the single-copy ACO gene in various tissues of Sitka spruce (Picea sitchensis) and in white spruce (Picea glauca) somatic embryos. ACO and ACS4 were ubiquitously expressed at high levels; ACS1 was predominantly expressed in developing embryos and ACS2 and ACS3 were expressed only at very low levels. Insect attack or mechanical wounding caused strong induction of ACS2 and ACS3 in Sitka spruce bark, a moderate increase in ACO transcripts, but had no effect on ACS1 and ACS4. ACS protein was also strongly induced following mechanical wounding in Douglas fir and was highly abundant in resin duct epithelial cells and polyphenolic parenchyma cells. These results suggest that ACS, but not ACO, is a regulated step in ethylene-induced conifer defense.
TheArabidopsisHistidine Phosphotransfer Proteins Are Redundant Positive Regulators of Cytokinin Signaling
Authors: Hutchison Claire E. , Li Jie , Argueso Cristiana , Gonzalez Monica , Lee Eurie , Lewis Michael W. , Maxwell Bridey B. , Perdue Tony D. , Schaller G. Eric , Alonso Jose M. , Ecker Joseph R. , Kieber Joseph J.
Published: November 2006

Arabidopsis thaliana histidine phosphotransfer proteins (AHPs) are similar to bacterial and yeast histidine phosphotransfer proteins (HPts), which act in multistep phosphorelay signaling pathways. A phosphorelay pathway is the current model for cytokinin signaling. To assess the role of AHPs in cytokinin signaling, we isolated T-DNA insertions in the five AHP genes that are predicted to encode functional HPts and constructed multiple insertion mutants, including an ahp1,2,3,4,5 quintuple mutant. Single ahp mutants were indistinguishable from wild-type seedlings in cytokinin response assays. However, various higher-order mutants displayed reduced sensitivity to cytokinin in diverse cytokinin assays, indicating both a positive role for AHPs in cytokinin signaling and functional overlap among the AHPs. In contrast with the other four AHPs, AHP4 may play a negative role in some cytokinin responses. The quintuple ahp mutant showed various abnormalities in growth and development, including reduced fertility, increased seed size, reduced vascular development, and a shortened primary root. These data indicate that most of the AHPs are redundant, positive regulators of cytokinin signaling and affect multiple aspects of plant development.
Direct detection of transient α‐helical states in islet amyloid polypeptide
Authors: Williamson Jessica A. , Miranker Andrew D.
Published: November 2006

The protein islet amyloid polypeptide (IAPP) is a glucose metabolism associated hormone cosecreted with insulin by the β‐cells of the pancreas. In humans with type 2 diabetes, IAPP deposits as amyloid fibers. The assembly intermediates of this process are associated with β‐cell death. Here, we examine the rat IAPP sequence variant under physiological solution conditions. Rat IAPP is mechanistically informative for fibrillogenesis, as it samples intermediate‐like states but does not progress to form amyloid. A central challenge was the development of a bacterial expression system to generate isotopically labeled IAPP without terminal tags, but which does include a eukaryotic post‐translational modification. While optical spectroscopy shows IAPP to be natively unfolded, NMR chemical shifts of backbone and β‐carbon resonances reveal the sampling of α‐helical states across a continuous stretch comprising ∼40% of the protein. In addition, the manifestation of nonrandom coil chemical shifts is confirmed by the relative insensitivity of the amide proton chemical shifts to alterations in temperature. Intriguingly, the residues displaying helical propensity are conserved with the human sequence, suggesting a functional role for this conformational bias. The inability of rat IAPP to self assemble can be ascribed, in part, to several slowly exchanging conformations evident as multiple chemical shift assignments in the immediate vicinity of three proline residues residing outside of this helical region.
Improved outcome after relapse in children with acute myeloid leukaemia
Authors: Abrahamsson Jonas , Clausen Niels , Gustafsson Göran , Hovi Liisa , Jonmundsson Gudmundur , Zeller Bernward , Forestier Erik , Heldrup Jesper , Hasle Henrik ,   for the Nordic Society for Paediatric Haematology and Oncology (NOPHO)
Published: November 2006

In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event‐free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty‐six percentage achieved remission with survival after relapse (5 years) 34 ± 4%. Of 122 patients who received re‐induction therapy, 77% entered remission with 40 ± 5% survival. Remission rates were similar for different re‐induction regimens but fludarabine, cytarabine, granulocyte colony‐stimulating factor‐based therapy had low treatment‐related mortality. Prognostic factors for survival were duration of first complete remission (CR1) and stem cell transplantation (SCT) in CR1. In early relapse (<1 year in CR1), survival was 21 ± 5% compared with 48 ± 6% in late relapse. For children receiving re‐induction therapy, survival in early relapse was 29 ± 6% and 51 ± 6% in late. Patients treated in CR1 with SCT, autologous SCT or chemotherapy had a survival of 18 ± 9, 5 ± 5 and 41 ± 5%, respectively. Survival was 62 ± 6% in 64 children given SCT as part of their relapse therapy. A significant proportion of children with relapsed AML can be cured, even those with early relapse. Children who receive re‐induction therapy, enter remission and proceed to SCT can achieve a cure rate of 60%.
Epstein–Barr virus early‐antigen antibodies before allogeneic haematopoietic stem cell transplantation as a marker of risk of post‐transplant lymphoproliferative disorders
Authors: Agbalika Felix , Larghero Jerome , Esperou Helene , Marais Dominique , Robin Marie , Foïs Elena , De Latour Régis Peffault , Gluckman Eliane , Rocha Vanderson , Benbunan Marc , Socié Gerard , Marolleau Jean‐Pierre
Published: November 2006

The occurrence of post‐transplant lymphoproliferative disorders (PTLDs) after allogeneic haematopoietic stem cell transplantation (allo‐HSCT) represents a clinical problem. Pretransplant Epstein–Barr virus serological status and viral load was determined in 21 recipients and 28 control transplanted patients, with (+) and without (−) PTLD, respectively. Early‐antigen immunoglobulin G (EA‐IgG) was detected in 12/21 PTLD+ patients, but only 2/28 PTLD− patients (P = 0·00023, Odds ratio = 17·42). High viral load was detected in peripheral blood mononuclear cells at PTLD diagnosis, independently of deleted LMP1. Detection of EA‐IgG in allo‐HSCT recipients pretransplantation might be considered as risk factor for PTLD development.
Analysis of parotid glands of primary Sjögren's syndrome patients using proteomic technology reveals altered autoantigen composition and novel antigenic targets
Authors: Stea E A , Routsias J G , Samiotaki M , Panayotou G , Papalambros E , Moutsopoulos H M , Tzioufas A G
Published: November 2006

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration, destruction of the salivary and lacrimal glands and production of autoantibodies against a variety of cellular proteins. The aberrant immune response against these autoantigens may begin or extend to other proteins that are not yet defined. Several studies have shown that autoantibody production is taking place in the affected salivary glands. In the present study, using proteomic approaches, we aimed to: (a) identify new autoantigens in the salivary glands of primary SS (pSS) patients and (b) evaluate the epigenetic changes of known autoantigens. Total parotid gland extracts of pSS patients were analysed using two-dimensional gel electrophoresis, sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot with pSS patients' sera or purified autoantibodies and immunoprecipitation using homologous IgG. Identification of the unknown proteins was performed using mass spectrometry (MS). Immunoblot analysis on two-dimensional gels using purified anti-La/SSB antibodies revealed that pSS salivary glands contain high levels of post-translationally modified La/SSB autoantigen, while the native form of the protein is recognized faintly, in contrast to normal controls. Moreover, salivary glands of pSS patients contain post-translationally modified actin that becomes immunogenic in the microenviroment of the affected tissue. The alteration of the physicochemical properties of self-proteins could thus contribute to the break of immune tolerance against them.
Circumferential wall tension due to hypertension plays a pivotal role in aorta remodelling
Authors: Prado Cibele M. , Rossi Marcos A.
Published: November 2006

The present study was carried out to investigate the role of hypertension in the genesis and localization of intimal lesions and medial remodelling found in the prestenotic segment in relation to a severe stenosis of the abdominal aorta just below the diaphragm. Male young rats were divided randomly into operated group, animals submitted to surgical abdominal aorta stenosis, and sham‐operated group, a control group of animals submitted to sham operation to simulate abdominal aorta stenosis. Aortas in the hypertensive prestenotic segment with increased circumferential wall tension associated with normal tensile stress, laminar flow/normal wall shear stress were characterized by enlarged heterogeneous endothelial cells elongated in the direction of the blood flow, diffusely distributed conspicuous neointimal plaques and medial thickening. The immunohistochemical analysis revealed an increased expression of eNOS, iNOS, nitrotyrosine and transforming growth factor‐β (TGF‐β) in endothelial cells and/or smooth muscle cells in this segment. Our findings suggest that increased circumferential wall tension due to hypertension plays a pivotal role in the remodelling of the prestenotic segment through biomechanical effects on oxidative stress and increased TGF‐β expression. Further studies are needed to clarify the intrinsic pathogenetic mechanism of focal distribution of the neointimal plaques in the hypertensive segment.
Biological responses in osteoblast‐like cell line according to thin layer hydroxyapatite coatings on anodized titanium
Authors: SOHN S‐H. , JUN H‐K. , KIM C‐S. , KIM K‐N. , CHUNG S‐M. , SHIN S‐W. , RYU J‐J. , KIM M‐K.
Published: November 2006

summary  Several features of the implant surface, such as roughness, topography and composition play a relevant role in implant integration with bone. This study was conducted in order to determine the effects of various thin layer hydroxyapatite (HA) coatings on anodized Ti surfaces on the biological responses of a human osteoblast‐like cell line (MG63). MG63 cells were cultured on 100 nm HA (100 nm HA coating on anodized surface), 500–700 nm HA (500–700 nm HA coating on anodized surface), 1 μm HA (1 μm HA coating on anodized surface) and anodize (non‐HA coating on anodized surface) Ti. The morphology of these cells was assessed by scanning electron microscopy (SEM). The cDNAs prepared from the total RNAs of the MG63 were hybridized into a human cDNA microarray (1152 elements). The appearances of the surfaces observed by SEM were different on each of the four dental substrate types. MG63 cells cultured on 100 nm HA, 1 μm HA and anodize exhibited cell–matrix interactions. It was 500–700 nm HA surface showing cell–cell interaction. In the expression of genes involved in osseointegration, several genes, including bone morphogenetic protein 2, latent transforming growth factor beta binding protein 1, catenin (cadherin‐associated protein), integrin, PDGFRB and GDF‐1 growth differentiation factor 1 were up‐regulated on the different surfaces. Several genes, including fibroblast growth factor receptor 3, fibroblast growth factor 12 and CD4 were down‐regulated on the different surfaces. The attachment and expression of key osteogenic regulatory genes were enhanced by the surface morphology of the dental materials used.
Biocompatibility of glass–ionomer cements using mouse lymphoma cells in vitro
Authors: RIBEIRO D. A. , MARQUES M. E. A. , SALVADORI D. M. F.
Published: November 2006

summary  Glass–ionomer cements are widely used in dentistry as restorative materials and adhesives for composite restorations. A number of genotoxicity studies have been conducted using these materials with results conflicting so far. Thus, the approach was aimed to look at the genotoxic and cytotoxic potential of three different glass–ionomer cements available commercially (Ketac Cem, Ketac Molar and Vitrebond) by the single cell gel (comet) assay and trypan blue exclusion test, respectively. For this, such materials were exposed to mouse lymphoma cells in vitro for 1 h at 37 °C. Data were assessed by Kruskall–Wallis non‐parametric test. The results showed that all powders assayed did not show genotoxic effects. On the other hand, the liquid from Vitrebond at 0·1% dilution caused an increase of DNA injury. Significant statistically differences (P < 0·05) in cytotoxicity provoked by all powders tested were observed for exposure at 1000 μg mL−1 concentration and 100 μg mL−1 for Ketac Molar. With respect to liquids of glass‐ionomer cements evaluated, the major toxic effect on cell viability was produced at 1%, beginning at the dilution of 0·5% for Vitrebond. Taken together, these results support the notion that some components of glass–ionomer cements show both genotoxic and cytotoxic effects in higher concentrations.
Neoproterozoic A‐type magmatism in the Western Sierras Pampeanas (Argentina): evidence for Rodinia break‐up along a proto‐Iapetus rift?
Authors: Baldo E. , Casquet C. , Pankhurst R.J. , Galindo C. , Rapela C.W. , Fanning C.M. , Dahlquist J. , Murra J.
Published: November 2006

A‐type orthogneisses of mid Neoproterozoic age (774 ± 6 Ma, U‐Pb SHRIMP zircon age), are reported for the first time from the Grenvillian basement of the Western Sierras Pampeanas in Argentina. These anorogenic meta‐igneous rocks represent the latest event of Rodinia break‐up so far recognized in Grenvillian basement exposures across Andean South America. Moreover, they compare well with A‐type granitoids and volcanic rocks along the Appalachian margin of Laurentia (Blue Ridge), thus adding to former evidence that the Western Sierras Pampeanas Grenvillian basement was left on the conjugate rifted margin of eastern Laurentia during Rodinia break‐up and the consequent opening of the Iapetus ocean.
Fluid inclusion evidence for deep burial of the Tertiary accretionary wedge of the Carpathians
Authors: Hurai Vratislav , Marko František , Tokarski Antoni K. , Świerczewska Anna , Kotulová Júlia , Biroň Adrián
Published: November 2006

Hydrothermal quartz from mineralized joints of the Carpathian accretionary wedge contains immiscible aqueous, oil‐condensate, methane and carbon dioxide‐rich fluid inclusions. Distribution patterns of the inclusion trapping PT parameters point to a crack‐seal mechanism during upward and lateral migration of hot methane‐rich fluids from overpressured sediments at the base of the accretionary wedge. A simple equation is proposed to calculate depths from densities and trapping pressures of the buoyant inclusion fluids. In the Carpathian accretionary wedge, the paleofluid pressures of 52–306 MPa correspond to a 5‐ to 11‐km‐thick overburden. Prior to exhumation, thickness of the wedge must have attained 10–25 km, of which only c. 50% was preserved until recently. Anomalously high methane densities (up to 0.43 g cm−3) recorded in the lowermost nappe sheets are provisionally interpreted as a result of supralithostatic overpressure due to thermal cracking of oil and kerogen to methane and pyrobitumen at temperatures above 200 °C.
Apheresis products of the Amicus™ and the AS.TEC 204® cell separators are comparable with regard to dendritic cells derived from the mononuclear cell collection
Authors: Leitner G. C. , Koszik F. , Rudnicki T. , Buchta C. , Worel N. , Fischer M. B. , Schneeberger A. , Hoecker P.
Published: November 2006

Background  In this study, we investigated the quality of autologous mononuclear cells (MNC) collected with two different cell separators using standard MNC‐apheresis procedure modalities. MNCs were purified by density gradient centrifugation and cultured according to standard protocols to generate dendritic cells (DC) and 1 × 107/ml immature DCs were pulsed with tumour lysate for 3 days and subsequently characterized by fluorescent‐activated cell sorter analysis.

Results  No difference was found in the monocyte content of either apheresis product (P = 0·07) and in the overall yield of MNCs (P = 0·7). Mature DCs as defined by their phenotype revealed also no significant difference: Amicus‘, 118 × 106 cells ± 91 vs. AS.TEC 204®, 128 × 106 cells ± 137 (P = 0·55), respectively, although the contamination with platelets (threefold) and red cells (twofold) was significantly higher in the AS.TEC 204 group (P < 0·05) than in the Amicus group.

Conclusion  The Amicus and the AS.TEC 204 are equally capable in providing MNCs for the generation of DCs and the amount of concomitantly collected red cells and platelets had no impact on the final DC yield.
Yield Formation and Plant Metabolism of Spring Barley in Response to Locally Injected Ammonium
Authors: Schittenhelm S. , Menge‐Hartmann U.
Published: November 2006

This study was conducted to elucidate the crop physiological basis for yield differences frequently observed in experiments comparing top‐dressing of N fertilizers with injection of ammonium or ammonium/urea solutions into the soil. The effects of diammonium phosphate (NH4‐N) injected at the two‐leaf stage, calcium nitrate (NO3‐N) broadcasted and incorporated before sowing, and a control without N fertilization (‐N) were assessed from measurements of growth, N‐uptake and N‐partitioning, light interception, gas exchange, leaf anatomy and the activity of key enzymes of N‐metabolism. The experiment was performed with spring barley (Hordeum vulgare L.) grown in 80‐l containers in a vegetation hall in Braunschweig, Germany. The plants in the NH4‐N treatment produced a 20 % higher grain yield than those in the NO3‐N treatment. The grain yield superiority of the NH4‐N plants was attributable to a higher number of ears per plant (+13 %) and more grains per ear (+6 %). The NH4‐N plants exhibited lower concentrations of inorganic cations than plants supplied with NO3‐N. In the NH4‐N treatment, the light penetrated more deeply into the crop canopy and the NH4‐N plants exhibited a higher leaf carbon exchange rate at the different leaf layers than the NO3‐N plants. It is concluded that as opposed to predominantly nitrate nutrition, provision of a persistent source of ammonium enables plants to take advantage of the positive yield effect of mixed N nutrition.
Autopsy case of neuro‐Behçet’s disease with multifocal neutrophilic perivascular inflammation
Authors: Arai Yoshifumi , Kohno Satoshi , Takahashi Yoshitomo , Miyajima Yoshiaki , Tsutusi Yoshihiro
Published: November 2006

We report here an autopsy case of neuro‐Behçet’s disease. The patient was a 28‐year‐old man, who developed a slight fever, right uveitis, and right sensory neural hearing loss at the age of 25. These symptoms relapsed repeatedly despite treatment. Eventually he was admitted to hospital because of progressing neurological deficits such as pyramidal symptoms, somatic sensorial and autonomic disorders, and bulbar palsy. The patient’s condition deteriorated and he died of heart failure. Total clinical course was about three years. In postmortem examination, various‐sized necrotic foci, often accompanied by gliosis and foamy macrophage infiltration, were scattered in the diencephalic region and brain stem. Meningitis was observed on the ventral side of the brain stem as well as inferior cerebral surface. Non‐bacterial or non‐fungal acute perivascular inflammatory foci were also present in the brain stem and cerebellar parenchyma. These histopathological findings suggest that a destructive multifocal neutrophilic inflammation might have caused the neurological deficits. Perivascular inflammation might be important to understanding the pathogenesis of neuro‐Behçet’s disease.
BMP‐15 regulation of ovulation quota in mammals
Authors: SHIMASAKI SHUNICHI
Published: November 2006

Naturally occurring mutations in the oocyte‐specific factor, bone morphogenetic protein‐15 (BMP‐15), cause infertility in women and in ewes. In contrast to these monoovulatory mammals, the targeted deletion of BMP‐15 in polyovulatory mice results in subfertility with only minimal defects in the ovulation process. Given the established role of BMP‐15 in governing the progression of folliculogenesis, it is hypothesized that species‐specific differences in the BMP‐15 system are involved in species‐specific determination of ovulation quota and litter size. Recent data using in vitro cell transfection methodology indicate that, in contrast to human BMP‐15 which is successfully processed and secreted, the mouse BMP‐15 proprotein is resistant to proteolytic cleavage. Thus, no functional mature BMP‐15 is secreted in vitro. Further studies have shown that the functional mature form of BMP‐15 is barely detectable in mouse oocytes in vivo until just before ovulation, when it is markedly increased. The general hypothesis to emerge from these observations is that the species‐specific differences in the defects caused by mutations in the bmp15 gene between monoovulatory ewes and women and polyovulatory mice might be attributed to the timing of the production of BMP‐15 mature protein. (Reprod Med Biol 2006; 5: 245–248)
Chemical removal of zona pellucida versus laser assisted hatching after repeated failures of assisted reproductive technology
Authors: NISHIO EIJI , MORIWAKI TAKAYUKI , YOSHII KUMIKO , UDAGAWA YASUHIRO
Published: November 2006

Background and Aims:  To evaluate outcomes after zona pellucida removal by pronase or laser assisted hatching in women with repeated assisted reproduction failures.

Methods:  Of 389 procedures (January 2004 to November 2005), 203 control cycles had an intact zona, 116 cycles had chemical removal of the zona and 70 cycles had laser assisted hatching. Rates of pregnancy, implantation and abortion were compared, and pregnancy rate was secondarily evaluated for fresh or frozen‐thawed blastocysts.

Results:  Pregnancy rates were 33.5% (68/203) for controls, 29.3% (34/116) for chemical removal and 30.0% (21/70) for laser. Implantation rates were 24.8% (68/274) for controls, 21.8% (34/156) for chemical removal and 30.0% (21/105) for laser. There were no significant differences among groups. Abortion rates were 15.6% (10/64) for controls, 13.9% (5/36) for chemical removal and 14.3% (3/21) for laser. No difference was observed by blastocyst type for control or laser assisted hatching cycles. In the chemical removal group, both pregnancy and implantation rates were higher for frozen‐thawed blastocysts than for fresh blastocysts. (41.5%vs 13.2% and 30.7%vs 11.1%, respectively).

Conclusions:  Assisted hatching did not show a significant benefit. Chemical zona pellucida removal might increase pregnancy rates for frozen‐thawed blastocysts. (Reprod Med Biol 2006; 5: 263–267)
Serum steroids concentration might be used for monitoring the growth of follicles in friendly in vitro fertilization
Authors: HASEGAWA JUNICHI , YANAIHARA ATSUSHI , IWASAKI SHINJI , NEGISHI MOMOKO , SUZUKI NORIO , KAWAMURA TOSHIHIRO , OKAI TAKASHI
Published: November 2006

Background:  Steroid levels have been used as the predictive parameters for oocyte maturation and embryo development. In the present study, estradiol and progesterone concentrations in the follicular fluid and serum were evaluated in conventional in vitro fertilization (IVF; follicle stimulating hormone [FSH] and/or human menopausal gonadotropin [hMG] after pituitary desensitization) and friendly IVF (no stimulation, clomiphene citrate, small dose of FSH or hMG without pituitary desensitization). The purpose of the present study was to evaluate the differences in steroid distribution between conventional and friendly IVF.

Methods:  Concentrations of estradiol, progesterone, FSH, and luteinizing hormone (LH) in serum and follicular fluid were determined in conventional and friendly IVF protocols by an enzyme‐linked immunosorbent assay kit. Correlations between follicular fluid and serum steroid concentrations in these different protocols, and between pregnant cycles and steroid concentrations were evaluated.

Results:  Two hundred and thirty‐four samples of follicular fluid from 74 IVF patients were analyzed. In conventional IVF, there was no relationship in steroid levels in between follicular fluid and serum steroids, whereas serum steroid concentrations correlated with the number of developing follicles. There was a relationship between the serum and follicular fluid estradiol levels (r = 0.467, P < 0.0001) as well as progesterone levels (r = 0.227, P = 0.0488) from friendly IVF patients.

Conclusions:  Serum steroid concentrations were mainly associated with the number of developing follicles. In the cases of friendly IVF, which had a small number of developing follicles, serum steroids might be used to monitor follicular fluid steroid concentrations. (Reprod Med Biol 2006; 5: 277–282)
Comprehensive assessment of the effect of Sphenocentrum jollyanum root extract on male reproductive activity in albino rats
Authors: RAJI YINUSA , FADARE OLAYEMI O. , ADISA RAHMAT A. , SALAMI SHAKIRU A.
Published: November 2006

Aim:  To evaluate the effect of methanol extract from the Sphenocentrum jollyanum root on male reproductive activity.

Methods:  Male albino rats were treated orally with distilled water (vehicle for the extract; control) and 50, 100 and 150 mg kg−1 body weight of Sphenocentrum jollyanum root extract for 8 weeks. Each group had its own recovery. Rats were killed 24 h after the last treatment. Caudal epididymal sperm count, motility, viability, morphology and organ weights were determined. Hematological indices, serum proteins, enzymes, testicular superoxide dismutase (SOD) activity, and testicular and epididymal histology were determined.

Results:  Compared with the control, the extract caused a dose dependent significant (P < 0.05) reduction in progressive motility of spermatozoa, viability and total sperm counts. The number of abnormal spermatozoa and epididymal volume were not statistically significant. There was a significant increase (P < 0.05) in serum testosterone levels in rats treated with 50 (P < 0.01) and 100 mg kg−1 (P < 0.05) of Sphenocentrum jollyanum. There was a significant (P < 0.05) increase in red blood cell count, packed cell volume and hemoglobin concentration, whereas there was no change in white blood cell count, mean total serum protein, albumin and globulin in the sera of Sphenocentrum jollyanum treated rats when compared with the control. The extract caused a significant decrease (P < 0.05) in serum aspartate and alanine aminotransferase activities with a significant increase (P < 0.05) in testicular SOD activity at a dose of 50 mg kg−1 bodyweight. Testicular cytoarchitecture of the extract treated rats showed degeneration of seminiferous tubules, whereas regeneration of germinal epithelium and restructuring of the germinal interstitium occurred in the recovery rats. No lesions were observed in the epididymis of the rats.

Conclusion:  The results suggest that methanol extract of the Sphenocentrum jollyanum root could produce harmful effects on reproductive functions in male albino rats which can be attributed to poor sperm quantity (epididymal sperm count), quality (sperm motility, viability and morphology) and testicular degeneration. The steroidogenic potential of the plant could explain its use as an aphrodisiac agent. (Reprod Med Biol 2006; 5: 283–292)
Npas4, a novel helix–loop–helix PAS domain protein, is regulated in response to cerebral ischemia
Authors: Shamloo Mehrdad , Soriano Liza , Von Schack David , Rickhag Mattias , Chin Daniel J. , Gonzalez‐Zulueta Mirella , Gido Gunilla , Urfer Roman , Wieloch Tadeusz , Nikolich Karoly
Published: November 2006

Basic helix–loop–helix PAS domain proteins form a growing family of transcription factors. These proteins are involved in the process of adaptation to cellular stresses and environmental factors such as a change in oxygen concentration. We describe the identification and characterization of a recently cloned PAS domain protein termed Npas4 in ischemic rat brain. Using gene expression profiling following middle cerebral artery occlusion, we showed that the Npas4 mRNA is differentially expressed in ischemic tissue. The full‐length gene was cloned from rat brain and its spatial and temporal expression characterized with in situ hybridization and Northern blotting. The Npas4 mRNA is specifically expressed in the brain and is highly up‐regulated in ischemic tissues following both focal and global cerebral ischemic insults. Immunohistochemistry revealed a strong expression in the limbic system and thalamus, as well as in layers 3 and 5 in the cortex of the unchallenged brain. When overexpressed in HEK 293 cells, Npas4 appears as a protein of ∼ 100 kDa. In brain samples, however, in addition to the 100 kDa band a specific 200 kDa immunoreactive band was also detected. Ischemic challenge lead to a decrease in the 200 kDa form and a simultaneous increase in the 100 kDa immunoreactivity. This could indicate a novel regulatory mechanism for activation and/or deactivation of this protein in response to ischemic brain injury.
“The Learned Brāhmen, Who Assists Me”: Changing Colonial Relationships in the 18th and 19th Century India
Authors: ALAMGIR ALENA K.
Published: November 2006

Abstract  This article examines the process through which the varied and fluid relationships between English East India Company servants and Indians in the eighteenth‐century transformed into rigidly racist ones in the nineteenth. At the outset, the Company's position in India was precarious and impossible to sustain without intensive help from various Indian elites and experts. Relationships created through these collaborative ties were often (but not always) accompanied by prejudice. Prejudice was frequently expressed as mistrust on the part of the Company servants who complained about Indians' untrustworthiness. Yet for decades prejudice was only one possible modality for relationships between Company servants and Indians; relational fluidity was the default. However, the steps that the Company took on to solve their “mistrust dilemma”– namely, codification of Indian knowledge and modification of Indian institutions in terms of their staffing and methods – set in motion processes that eventually eliminated relational fluidity and replaced it with prejudice as a binding social norm, thus creating a rigidly racist regime.