bluuebunny/crossref_metadata_2025 huggingface dataset:
CoCo: a web application to display, store and curate ChIP-on-chip data integrated with diverse types of gene expression data
Authors: Girardot Charles , Sklyar Oleg , Grosz Sophie , Huber Wolfgang , Furlong Eileen E. M.
Published: January 2007

Motivation: CoCo, ChIP-on-Chip online, is an open-source web application that supports the annotation and curation of regulatory regions and associated target genes discovered in ChIP-on-chip experiments. CoCo integrates ChIP-on-chip results with diverse types of gene expression data (expression profiling, in situ hybridization) and displays them within a genomic context. Regulatory relationships between the transcription factor-bound regions and putative target genes can be stored and expanded throughout different sessions.

Availability:  http://furlonglab.embl.de/methods/tools/coco

Contact:  charles.girardot@embl.de
snp.plotter: an R-based SNP/haplotype association and linkage disequilibrium plotting package
Authors: Luna Augustin , Nicodemus Kristin K.
Published: January 2007

Summary: snp.plotter is a newly developed R package which produces high-quality plots of results from genetic association studies. The main features of the package include options to display a linkage disequilibrium (LD) plot below the P-value plot using either the r2 or D′ LD metric, to set the X-axis to equal spacing or to use the physical map of markers, and to specify plot labels, colors, symbols and LD heatmap color scheme. snp.plotter can plot single SNP and/or haplotype data and simultaneously plot multiple sets of results. R is a free software environment for statistical computing and graphics available for most platforms. The proposed package provides a simple way to convey both association and LD information in a single appealing graphic for genetic association studies.

Availability: Downloadable R package and example datasets are available at http://cbdb.nimh.nih.gov/~kristin/snp.plotter.html and http://www.r-project.org

Contact:  nicodemusk@mail.nih.gov
Protein–protein interaction site prediction based on conditional random fields
Authors: Li Ming-Hui , Lin Lei , Wang Xiao-Long , Liu Tao
Published: January 2007

Motivation: We are motivated by the fast-growing number of protein structures in the Protein Data Bank with necessary information for prediction of protein–protein interaction sites to develop methods for identification of residues participating in protein–protein interactions. We would like to compare conditional random fields (CRFs)-based method with conventional classification-based methods that omit the relation between two labels of neighboring residues to show the advantages of CRFs-based method in predicting protein–protein interaction sites.

Results: The prediction of protein–protein interaction sites is solved as a sequential labeling problem by applying CRFs with features including protein sequence profile and residue accessible surface area. The CRFs-based method can achieve a comparable performance with state-of-the-art methods, when 1276 nonredundant hetero-complex protein chains are used as training and test set. Experimental result shows that CRFs-based method is a powerful and robust protein–protein interaction site prediction method and can be used to guide biologists to make specific experiments on proteins.

Availability:  http://www.insun.hit.edu.cn/~mhli/site_CRFs/index.html

Contact:  mhli@insun.hit.edu.cn

Supplementary information: Supplementary data are available at Bioinformatics online.
Variational linear comparison bounds for nonlinear composites with anisotropic phases. II. Crystalline materials
Authors: Idiart Martín I , Ponte Castañeda Pedro
Published: January 2007

In part I of this work, bounds were derived for the effective potentials of nonlinear composites with anisotropic constituents, making use of an appropriate generalization of the linear comparison variational method. In this second part, the special case of nonlinear composites with crystalline constituents is considered. First, it is shown that, for this special but very important class of materials, the ‘variational’ bounds of part I are at least as good as an earlier version of the bounds due to deBotton & Ponte Castañeda. Then, the relative merits of these two types of bounds are studied in the context of a model, two-dimensional, porous composite with a power-law crystalline matrix phase, under anti-plane loading conditions. The results show that, indeed, the variational bounds of part I improve, in general, on the earlier bounds, with the former becoming progressively sharper than the latter as the number of slip systems of the crystalline matrix phase increases. In particular, it is shown that, unlike the bounds of deBotton & Ponte Castañeda, the variational bounds of part I are able to recover the variational bound for composites with an isotropic matrix phase, as the number of slip systems, all having the same flow stress, tends to infinity.
Asymptotic behaviour of a reaction–diffusion model with a quiescent stage
Authors: Zhang Kate Fang , Zhao Xiao-Qiang
Published: January 2007

This paper is devoted to the investigation of the asymptotic behaviour for a reaction–diffusion model with a quiescent stage. We first establish the existence of the asymptotic speed of spread and show that it coincides with the minimal wave speed for monotone travelling waves. Then we obtain a threshold result on the global attractivity of either zero or positive steady state in the case where the spatial domain is bounded.
Variation in growth and instar number in field and laboratoryManduca sexta
Authors: Kingsolver Joel G
Published: January 2007

The tobacco hornwormManduca sextahas been an important model system for understanding physiological control of growth, development and metamorphosis of insects for more than half a century. Like allManduca,M. sextatypically has five larval instars, with developmental commitment to metamorphosis occurring early in the 5th (final) instar. Here we show thatM. sextafrom a field population in North Carolina (USA) shows substantial intraspecific variation in the number of larval instars when feeding on a modified artificial diet. Individuals with six instars consistently exhibited slower growth rates during early larval development than individuals with five instars. The frequency of individuals with six instars decreased with increased rearing temperature. In contrast,M. sextafrom a laboratory colony consistently had five instars, and had more rapid larval growth rates thanM. sextafrom the field. We identify a threshold body size at the start of the 5th instar that predicts whether an individual will have five (greater than 600 mg) or six instars (less than 600 mg). Variation in field populations inManducaprovides an important resource for understanding physiological control, developmental plasticity and evolution of growth rate, body size and instar number.
Conspecific sperm precedence in
Callosobruchus subinnotatus
(Coleoptera: Bruchidae): mechanisms and consequences
Authors: Rugman-Jones Paul F , Eady Paul E
Published: January 2007

Conspecific sperm precedence (CSP) has been identified as an important post-copulatory, pre-zygotic mechanism that can act to reduce gene flow between populations. The evolution of CSP is thought to have arisen as a by-product of male and female coevolution in response to intraspecific post-copulatory sexual selection. However, little is known about the mechanisms that generate CSP. When
Callosobruchus subinnotatus
females copulate with both
C. subinnotatus
and
Callosobruchus maculatus
males, regardless of mating order, the majority of eggs are fertilized by conspecific sperm. The low number of heterospecific fertilizations does not result from general differences in the viability of sperm in the female reproductive tract, as heterospecific sperm fertilized equivalent numbers of eggs as conspecific sperm in the absence of sperm competition. Instead, CSP results from disadvantages to heterospecific sperm that are manifest only when in competition with conspecific sperm. CSP in
C. subinnotatus
appears to result from two, not mutually exclusive, mechanisms. First, conspecific sperm are better able to displace heterospecific sperm from female storage. Second, conspecific sperm achieve disproportionately higher numbers of fertilizations relative to their proportional representation in the fertilization set. Thus, we provide evidence of differential sperm use from the female spermatheca.
Asymptotic scaling in turbulent pipe flow
Authors: McKeon B.J , Morrison J.F
Published: January 2007

The streamwise velocity component in turbulent pipe flow is assessed to determine whether it exhibits asymptotic behaviour that is indicative of high Reynolds numbers. The asymptotic behaviour of both the mean velocity (in the form of the log law) and that of the second moment of the streamwise component of velocity in the outer and overlap regions is consistent with the development of spectral regions which indicate inertial scaling. It is shown that an ‘inertial sublayer’ in physical space may be considered as a spatial analogue of the inertial subrange in the velocity spectrum and such behaviour only appears for Reynolds numbers
R
+
>5×10
3
, approximately, much higher than was generally thought.
How training and testing histories affect generalization: a test of simple neural networks
Authors: Ghirlanda Stefano , Enquist Magnus
Published: January 2007

We show that a simple network model of associative learning can reproduce three findings that arise from particular training and testing procedures in generalization experiments: the effect of (i) ‘errorless learning’, (ii) extinction testing on peak shift, and (iii) the central tendency effect. These findings provide a true test of the network model which was developed to account for other phenomena, and highlight the potential of neural networks to study the phenomena that depend on sequences of experiences with many stimuli. Our results suggest that at least some such phenomena, e.g. stimulus range effects, may derive from basic mechanisms of associative memory rather than from more complex memory processes.
Critical threshold effects of benthiscape structure on stream herbivore movement
Authors: Olden Julian D
Published: January 2007

In landscape ecology, substantial theoretical progress has been made in understanding how critical threshold levels of habitat loss may result in sudden changes in landscape connectivity to animal movement. Empirical evidence for such thresholds in real systems, however, remains scarce. Streambed landscapes provide a strong testing ground for studying critical thresholds because organisms are faced with substantial environmental heterogeneity while attempting to overcome the physical force of water. In this study, I report on the results from a series of experiments investigating the influence of habitat abundance and current velocity on the movement dynamics of two stream herbivores (caddisfly larva
Agapetus boulderensis
and snail
Physa
sp.) that differ substantially in how they perceive landscape structure. Specifically, I ask whether critical thresholds to herbivore movement exist in streambed landscapes. By exploiting the pattern recognition capabilities of artificial neural networks, I found that the rate, sinuosity and directionality of movement by
Agapetus
and
Physa
varied nonlinearly according to the abundance of habitat patches, current velocity and habitat–current interaction. Both the study organisms exhibited threshold responses to habitat abundance, yet the location and slope of these thresholds differed between species and with respect to different current velocities. These results suggest that a critical threshold in functional connectivity (i.e. the connection of habitat patches by dispersal) is not an inherent property of the landscape, but in fact emerges from the interplay of species' interactions with landscape structure. Moreover, current velocity interacted with habitat abundance to elicit strong upstream-oriented movement for both the species. This suggests that dispersing individuals may be polarized in the upstream direction and therefore functional connectivity is not equal in all directions. Such results highlight the need for future research addressing the sources of variability of critical threshold effects in ecological phenomena.
ON CENTRAL BANK INDEPENDENCE, WAGE INDEXING AND A MONOPOLY UNION
Authors: Efthimiadis Tilemahos
Published: January 2007

The Rogoff proposition (Quarterly Journal of Economics, 100 (1985), pp. 1169–90) that it is socially optimal to delegate monetary policy to a central banker that is more inflation‐averse than society has been widely accepted and implemented in practice. However, there is a literature that argues that, if there is an inflation‐averse monopoly union in the economy, it is optimal to delegate monetary policy to an ‘ultra‐liberal’ central banker, i.e., a central banker that is interested only in output. In this paper, we examine whether introducing wage indexing into the latter models has any effect on the optimal degree of central bank conservativeness and find that, once a monopoly‐type labour union is introduced, wage indexing does not matter for the determination of the optimal degree of conservativeness of the monetary authority.
ULTRALOW‐EXPANSION CERAMICS IN THE SYSTEM NA2O‐ZRO2P2O5‐SIO2
Authors: Alamo James , ROY Rustum
Published: January 2007

Compositions in the series Na1+xZr2P3‐xSixO12 and Na1+4zZr2‐zP3O12, where x = 0≤x≤1 and z=0≤z≤1/2, have thermal expansions that can be controlled (by selecting the composition) to values in the range <10×10‐7 in a temperature regime of a few hundred degrees. The lowest a values were obtained for x ∼0.33 and z∼0.125.
Effect of Crystallization of the Grain‐Boundary Phase on the Thermal Diffusivity of a Sialon Ceramic
Authors: Bentsen Larry D. , Hasselman D. P. H. , Tien Tseng‐Ying
Published: January 2007

Crystallization of the glassy grain‐boundary phase in a series of sialon ceramics fabricated using a range of hot‐pressing schedules increased the thermal diffusivity at room temperature by an average of ∼10%. For samples made by a given hot‐pressing schedule, the relative difference in thermal diffusivity between composites containing a glassy grain‐boundary phase and those in which this phase had crystallized decreased with increasing temperature. This behavior is attributed to enhanced phonon scattering in the crystalline grain‐boundary phase.
Role of View Factor in the Effective Radiative Thermal Conductivity/Diffusivity of Transparent Materials
Authors: Bentsen Larry D. , Thomas James R. , Hasselman D. P. H.
Published: January 2007

The decrease in size dependence of thermal diffusivity measured by the laser‐flash method with increasing specimen thickness for a lithium aluminosilicate glass‐ceramic is suggested to be attributable in part to the role of the view factor in radiative heat transfer between specimen surfaces. Appropriate expressions for the effective radiative thermal conductivity and diffusivity are derived. Comparison of the observed and predicted specimen size dependence suggests that the view factor should be taken into account.
Small‐Angle X‐Ray Scattering from Hydrating Tricalcium Siliate
Authors: VOLLET D. , CRAIEVICH A. , REGOURD M.
Published: January 2007

The small‐angle X‐ray scattering technique was used to study the evolution of the structure of hydrated tricalcium silicate at room temperature. The changes in specific area of the associated porosity and the evolution of density fluctuations in the solid hydrated phase were deduced from the scattering data. A correlation of these variations with the hydration mechanism was tried.
Summarization of Glassy Spectral Data with Particular Reference to the Boron Anomaly
Authors: PETERSON G. E. , KURKJIAN C. R. , CARNEVALE A.
Published: January 2007

A matrix method is described for summarizing the information in a family of glassy spectra. By means of a singular‐value decomposition we can determine the number of parameters that are needed to describe the data. Frequently this turns out to be very small, often only one or two. These parameters, which can be obtained from the above expansion, can be used for engineering design purposes or can be compared with bulk properties to obtain structural information. This technique is applied to optical absorption spectra of Co2+ in sodium borate glasses, 20‐MHz acoustic‐loss spectra, and infrared‐absorption spectra of sodium borate glasses. Very pronounced discontinuities are observed in the neighborhood of 15% Na2O in all cases. In general they are difficult to observe in the raw data.
Transmission Electron Microscopy and X‐Ray Diffraction of Doped Tricalcium Silicate
Authors: SINCLAIR W. , GROVES G. W.
Published: January 2007

Member of oxides, including MgO, ZnO, La2O3, Al2O3, TiO2, and F were reacted with C3S, either individually or in combination, in order to stabilize a variety of polymorphic forms. The resultant phases were examined by both XRD and TEM. It was found that the results obtained by the conventional means of observing groups of reflections in powder X‐ray diffraction patterns were not in agreement with the structure types identified by electron diffraction. In particular, the rhombohedral form of alite, synthesized by the addition of either ZnO or Al2 O3+ F to C3S, was not observed by TEM although the corresponding X‐ray patterns all displayed single peaks characteristic of the rhombohedral cell. Electron diffraction of C,S doped with 2.02 and 4.43% ZnO gave mono‐clinic patterns, whereas C3S doped with Al + F gave several forms, all of them different from the form produced by ZnO‐doped C3S. The addition of La203 produced a new hexagonal lattice with cell dimensions of a= 2.575 and c= 2.50 nm. When Al + F was incorporated in C3S, the modifications found included the triclinic lattice characteristic of pure C3S, the hexagonal lattice characteristic of La‐doped C3S, and a complex lattice distinguished by the presence of incommensurate doublet reflections and sometimes extra weak spots. A similar incommensurate superlattice was found in alites containing Mg, Al, and a large amount of Ti (0.13 mole). The Jeffery cell for the Mm modification of C3S doped with 1.63% MgO was confirmed.
Displacement Rate and Temperature Effects in Fracture of a Hot‐Pressed Silicon Nitride at 1100° to 1325°C
Authors: KNICKERBOCKER S. H. , ZANGVIL A. , BROWN S. D.
Published: January 2007

An MgO‐fluxed hot‐pressed silicon nitride was fractured in four‐point flexure between 1100° and 1325°C at three crosshead speeds. Above 1200°C, a temperature and strain‐rate dependence of fracture stress and KIc was seen. Scanning and transmission electron microscopy were used to analyze as received and fractured material. A map of temperature vs crosshead speed was drawn showing regions where subcritical cracking was or was not observed and a transition region where microcracks and voids were detected.
Stresses Induced by Differential Sintering in Powder Compacts
Authors: KELLETT BRUCE , LANGE F. F.
Published: January 2007

Stresses created by differential sintering, due to differences in initial bulk density, were determined, to an order of magnitude, by an experiment which estimated the differential sintering phenomenon on a macroscopic level. The experiments entailed determining the shrinkage rates of a powder isostatically pressed to two bulk densities. Using this information, stresses were determined by forcing the slower‐densifying compact to shrink at the same rate as the faster‐densifying compact and measuring the resulting forces with a load cell. Maximum stresses (between 1 and 3 MPa) were observed to occur in the intermediate stage of densification. Despite larger differential strains at higher temperatures, stresses decreased to zero at the latter stage of densification. Viscoelastic experiments, of the stress‐relaxation type, were performed. Results showed that the sintering specimen was more rigid at lower temperatures and more fluidlike at higher temperatures. This explains the development of maximum stresses at intermediate temperatures.
Viral vector vaccines make memory T cells against malaria
Authors: Reyes‐Sandoval Arturo , Harty John T. , Todryk Stephen M.
Published: January 2007

Vaccines that comprise attenuated viral vectors encoding antigens from target pathogens generate potent T‐cell responses. One such pathogen is malaria, and in particular the liver stage of its life cycle. Immunogenicity and efficacy studies in animals and humans have revealed the generation of memory T cells of both the central and effector phenotypes, depending on the viral vectors used in the malaria vaccination regime (viral species and serotype, combination and sequence for prime–boost) and suggest a divergence in their protective role. Being able to influence the memory T‐cell make‐up in a rational manner may allow us to develop more efficacious vaccines.
Impact of class A, B and C CpG‐oligodeoxynucleotides on in vitro activation of innate immune cells in human immunodeficiency virus‐1 infected individuals
Authors: Martinson Jeffrey A. , Tenorio Allan R. , Montoya Carlos J. , Al‐Harthi Lena , Gichinga Carolyne N. , Krieg Arthur M. , Baum Linda L. , Landay Alan L.
Published: January 2007

Oligodeoxynucleotides (ODN) with unmethylated deoxycytidyl‐deoxyguanosine dinucleotides (CpG‐ODNs) stimulate Toll‐like receptor 9 (TLR9) in plasmacytoid dendritic cells (pDC) and B cells and activate innate and adaptive immunity. Three classes of synthetic CpG‐ODNs, class A, B and C, activate cells through TLR9; our goal was to evaluate their effect on cells from human immunodeficiency virus (HIV)‐1+ individuals. We compared the frequencies and the unstimulated activation status of immune effector cells in HIV‐1+ and HIV‐1– individuals. Fewer pDC, myeloid dendritic cells (mDC), B cells, natural killer (NK) cells and invariant natural killer T cells (iNKT) were present in HIV‐1+ peripheral blood mononuclear cells (PBMC) and their baseline activation status was higher than HIV‐1– PBMC. Exposure of HIV‐1+ PBMC to all classes of CpG‐ODNs led to activation and maturation of pDC based on CD86, CD80, and CD83 expression similar to that of cells from HIV‐1– individuals. The percentage of CpG‐ODN stimulated pDC that express CD40 was dramatically higher when cells were obtained from HIV‐1+ than from HIV‐1– individuals. B‐lymphocytes were activated similarly in HIV‐1+ and HIV‐1– individuals. mDC, NK and iNKT cell, which lack TLR9, were indirectly activated. Interferon‐α (IFN‐α) and interferon inducible protein 10 (IP‐10) secretion was induced by class A or C but not class B CpG‐ODN, but the concentrations were less than those produced by HIV‐1– PBMC. HIV‐1 infected individuals have fewer innate effector cells that are chronically activated, but these cells can be further activated by CpG‐ODN, which suggests that synthetic CpG‐ODNs could be used to enhance the immune system in HIV‐1 infected individuals.
Efficacy of intracoronal bleaching techniques with different light activation sources
Authors: Carrasco L. D. , Guerisoli D. M. Z. , Rocha M. J. A. , Pécora J. D. , Fröner I. C.
Published: January 2007

Aim  To evaluate ex vivo the efficacy of 35% hydrogen peroxide for intracoronal bleaching when activated by LEDs, halogen lamp or by the walking bleach technique.

Methodology  Forty extracted human maxillary central incisors had their crowns resected 1 mm below the amelo‐cemental junction and were submitted to artificial staining in centrifuged rat haemolysed blood. A 2‐mm thick glass ionomer cervical plug was placed inside the canal, at the level of the amelo‐cemental junction. Samples were divided randomly into five groups: group I received 35% hydrogen peroxide gel activated by LEDs. Group II received 35% hydrogen peroxide gel activated by a halogen lamp‐based light curing unit. Group III received 35% hydrogen peroxide gel followed by the walking bleach technique. Group IV was neither artificially stained nor bleached (positive control) and group V was stained, but not bleached (negative control). The shade of the teeth was assessed visually by three independent and calibrated evaluators, before and after bleaching. The results were analysed using Kruskal–Wallis one‐way analysis of variance and Dunn's post‐test.

Results  No statistical differences regarding sample shades were found amongst groups for the tested internal bleaching techniques (P > 0.05).

Conclusions  Hydrogen peroxide for intracoronal bleaching when activated either by LEDs, halogen lamp or by the walking bleach technique presented similar efficacy.
In‐frame overlapping genes: the challenges for regulating gene expression
Authors: Yu Jae‐Sung , Kokoska Robert J. , Khemici Vanessa , Steege Deborah A.
Published: January 2007

In‐frame overlapping genes in phage, plasmid and bacterial genomes permit synthesis of more than one form of protein from the same gene. Having one gene entirely within another rather than two separate genes presumably precludes recombination events between the identical sequences. However, studies of such gene pairs indicate that the overlapping arrangement can make regulation of the genes more difficult. Here, we extend studies of in‐frame overlapping genes II and X from filamentous phage f1 to determine if translational controls are required to regulate the gene properly. These genes encode proteins (pII and pX) with essential but opposing roles in phage DNA replication. They must be tightly regulated to maintain production of the proteins at relative steady state levels that permit continuous replication without killing the host. To determine why little or no pX appears to be made on the gene II/X mRNA, gene II translation was lowered by progressively deleting into the gene II initiator region. Increased pX translation resulted, suggesting that elongating ribosomes on the gene II mRNA interfere with internal initiation on the gene X ribosome binding site and limit gene X translation. As judged from systematically lowering the efficiency of suppression at a gene II amber codon upstream from the gene X start, the already modest level of gene II translation would have to be reduced by more than twofold to relieve all interference with internal initiation. Further downregulation of gene X expression proved to be required to maintain pX at levels relative to pII that are tolerated by the cell. Site‐directed mutagenesis and nuclease mapping revealed that the gene X initiation site is sequestered in an extended RNA secondary structure that lowers gene X translation on the two mRNAs encoding it. The more general implications of the results for expression of in‐frame overlapping genes are discussed.
Structural insights on the translation initiation complex: ghosts of a universal initiation complex
Authors: Allen Gregory S. , Frank Joachim
Published: January 2007

All living organisms utilize ribosomes to translate messenger RNA into proteins. Initiation of translation, the process of bringing together mRNA, initiator transfer RNA, and the ribosome, is therefore of critical importance to all living things. Two protein factors, IF1 (a/eIF1A) and IF2 (a/eIF5B), are conserved among all three kingdoms of life and have been called universal initiation factors (Roll‐Mecak et al., 2001). Recent X‐ray, NMR and cryo‐EM structures of the universal factors, alone and in complex with eubacterial ribosomes, point to the structural homology among the initiation factors and initiation complexes. Taken together with genomic and functional evidence, the structural studies allow us to predict some features of eukaryotic and archaeal initiation complexes. Although initiation of translation in eukaryotes and archaea requires more initiation factors than in eubacteria we propose the existence of a common denominator initiation complex with structural and functional homology across all kingdoms of life.
The F plasmid‐encoded TraM protein stimulates relaxosome‐mediated cleavage at oriT through an interaction with TraI
Authors: Ragonese Heather , Haisch Debi , Villareal Ernesto , Choi June‐Hyuk , Matson Steven W.
Published: January 2007

Conjugative DNA transfer is a highly conserved process for the direct transfer of DNA from a donor to a recipient. The conjugative initiator proteins are key players in the DNA processing reactions that initiate DNA transfer – they introduce a site‐ and strand‐specific break in the DNA backbone via a transesterification that leaves the initiator protein covalently bound on the 5′‐end of the cleaved DNA strand. The action of the initiator protein at the origin of transfer (oriT) is governed by auxiliary proteins that alter the architecture of the DNA molecule, allowing binding of the initiator protein. In the F plasmid system, two auxiliary proteins have roles in establishing the relaxosome: the host‐encoded IHF and the plasmid‐encoded TraY. Together, these proteins direct the loading of TraI which contains the catalytic centre for the transesterification. The F‐oriT sequence includes a binding site for another plasmid‐encoded protein, TraM, which is required for DNA transfer. Here the impact of TraM protein on the formation and activity of the F plasmid relaxosome has been examined. Purified TraM stimulates the formation of relaxed DNA in a reaction that requires the minimal components of the relaxosome, TraI, TraY and IHF. Unlike TraY and IHF, TraM is not essential for the formation of the relaxosome in vitro and TraM cannot substitute for either TraY or IHF in this process. The TraM binding site sbmC, along with both IHF binding sites, is essential for stimulation of the relaxase reaction. In addition, stimulation of transesterification appears to require the C‐terminal domain of TraI suggesting that TraM and TraI may interact through this domain on TraI. Taken together, these results provide additional evidence of a role for TraM as a component of the relaxosome, suggest a previously unknown interaction between TraI and TraM, and allow us to propose a molecular role for the C‐terminal domain of TraI.
Multiple co‐regulatory elements and IHF are necessary for the control of fimB expression in response to sialic acid and N‐acetylglucosamine in Escherichia coli K‐12
Authors: Sohanpal Baljinder K. , Friar Simon , Roobol Joanne , Plumbridge Jacqueline A. , Blomfield Ian C.
Published: January 2007

Expression of the FimB recombinase, and hence the OFF‐to‐ON switching of type 1 fimbriation in Escherichia coli, is inhibited by sialic acid (Neu5Ac) and by GlcNAc. NanR (Neu5Ac‐responsive) and NagC (GlcNAc‐6P‐responsive) activate fimB expression by binding to operators (ONR and ONC1 respectively) located more than 600 bp upstream of the fimB promoter within the large (1.4 kb) nanC‐fimB intergenic region. Here it is demonstrated that NagC binding to a second site (ONC2), located 212 bp closer to fimB, also controls fimB expression, and that integration host factor (IHF), which binds midway between ONC1 and ONC2, facilitates NagC binding to its two operator sites. In contrast, IHF does not enhance the ability of NanR to activate fimB expression in the wild‐type background. Neither sequences up to 820 bp upstream of ONR, nor those 270 bp downstream of ONC2, are required for activation by NanR and NagC. However, placing the NanR, IHF and NagC binding sites closer to the fimB promoter enhances the ability of the regulators to activate fimB expression. These results support a refined model for how two potentially key indicators of host inflammation, Neu5Ac and GlcNAc, regulate type 1 fimbriation.
Loss of a conserved 7‐methylguanosine modification in 16S rRNA confers low‐level streptomycin resistance in bacteria
Authors: Okamoto Susumu , Tamaru Aki , Nakajima Chie , Nishimura Kenji , Tanaka Yukinori , Tokuyama Shinji , Suzuki Yasuhiko , Ochi Kozo
Published: January 2007

Streptomycin has been an important drug for the treatment of tuberculosis since its discovery in 1944. But numerous strains of Mycobacterium tuberculosis, the bacterial pathogen that causes tuberculosis, are now streptomycin resistant. Although such resistance is often mediated by mutations within rrs, a 16S rRNA gene or rpsL, which encodes the ribosomal protein S12, these mutations are found in a limited proportion of clinically isolated streptomycin‐resistant M. tuberculosis strains. Here we have succeeded in identifying a mutation that confers low‐level streptomycin resistance to bacteria, including M. tuberculosis. We found that mutations within the gene gidB confer low‐level streptomycin resistance and are an important cause of resistance found in 33% of resistant M. tuberculosis isolates. We further clarified that the gidB gene encodes a conserved 7‐methylguanosine (m7G) methyltransferase specific for the 16S rRNA, apparently at position G527 located in the so‐called 530 loop. Thus, we have identified gidB as a new streptomycin‐resistance locus and uncovered a resistance mechanism that is mediated by loss of a conserved m7G modification in 16S rRNA. The clinical significance of M. tuberculosis gidB mutation also is noteworthy, as gidB mutations emerge spontaneously at a high frequency of 10−6 and, once emerged, result in vigorous emergence of high‐level streptomycin‐resistant mutants at a frequency more than 2000 times greater than that seen in wild‐type strains. Further studies on the precise function of GidB may provide a basis for developing strategies to suppress pathogenic bacteria, including M. tuberculosis.
Heart rate variability is related to pain severity and predominant bowel pattern in women with irritable bowel syndrome
Authors: Cain K. C. , Jarrett M. E. , Burr R. L. , Hertig V. L. , Heitkemper M. M.
Published: January 2007

Abstract  This study examined heart rate variability (HRV) in women with irritable bowel syndrome (IBS) to determine its association with gut pain and predominant bowel pattern. Women with IBS (constipation predominant n = 45, diarrhoea predominant n = 64, alternating n = 56) and healthy controls (n = 50) were recruited from the community. Severity of gut pain was measured retrospectively. The HRV (24 h) was summarized as high‐frequency (HF) power and the ratio of low‐frequency (LF) power to HF power. Among those women with IBS who have severe gut pain, the 15 constipation‐predominant women had lower (P = 0.01) HF power and higher (P = 0.003) LF/HF ratio (geometric means 70 and 7.5, respectively) than the 21 women with diarrhoea‐predominant IBS (286 and 3.1) and controls (224 and 3.9). In contrast, among women without severe pain, there is a smaller and not quite significant difference in the opposite direction. Using a broader definition of pain severity based on several questions nearly doubles the number of subjects in the severe pain group and shows even more significant results. The relationship of predominant bowel pattern to HRV is qualitatively different in the subgroup of patients with more severe pain than in the subgroup with less severe pain.
A bHLH regulatory gene in the common morning glory, Ipomoea purpurea, controls anthocyanin biosynthesis in flowers, proanthocyanidin and phytomelanin pigmentation in seeds, and seed trichome formation
Authors: Park Kyeung‐Il , Ishikawa Naoko , Morita Yasumasa , Choi Jeong‐Doo , Hoshino Atsushi , Iida Shigeru
Published: January 2007

The transcriptional regulators for anthocyanin pigmentation include proteins containing R2R3‐MYB domains, bHLH domains and conserved WD40 repeats, and their interactions determine the set of genes to be expressed. Spontaneous ivory seed (ivs) mutants of Ipomoea purpurea displaying pale pigmented flowers and ivory seeds are caused by insertions of DNA transposons into the bHLH2 gene that encodes a bHLH transcriptional regulator. A partial reduction in the expression of all structural genes encoding enzymes for anthocyanin biosynthesis was observed in the young flower buds of these ivs mutants. The DFR‐B and ANS transcripts were completely abolished in the ivs seed coats, whereas the early biosynthetic genes for flavonol biosynthesis remained active. The production and accumulation of both proanthocyanidin and phytomelanin pigments in the ivory seed coats were drastically reduced. Moreover, the unbranched trichomes in the ivory seeds were smaller in size and fewer in number than those in the wild‐type dark‐brown seeds, and the surface of the epidermis without trichomes in the dark‐brown seeds looked rougher, due to the protruding tangential walls, than that in the ivory seeds. Although the I. purpurea bHLH2 gene is the most closely related to the petunia AN1 gene, whose mutation is known to confer white flowers and to be deficient in acidification of their vacuoles, the vacuolar alkalization in the epidermal flower limbs of I. purpurea ivs mutants appears to occur normally. These results are discussed with regard to the function of bHLH transcriptional regulators controlling flower and seed pigmentation as well as other epidermal traits.
Nitrogen deficiency in Arabidopsis affects galactolipid composition and gene expression and results in accumulation of fatty acid phytyl esters
Authors: Gaude Nicole , Bréhélin Claire , Tischendorf Gilbert , Kessler Felix , Dörmann Peter
Published: January 2007

Nitrogen is an essential nutrient for plants because it represents a major constituent of numerous cellular compounds, including proteins, amino acids, nucleic acids and lipids. While N deprivation is known to have severe consequences for primary carbon metabolism, the effect on chloroplast lipid metabolism has not been analysed in higher plants. Nitrogen limitation in Arabidopsis led to a decrease in the chloroplast galactolipid monogalactosyldiacylglycerol (MGDG) and a concomitant increase in digalactosyldiacylglycerol (DGDG), which correlated with an elevated expression of the DGDG synthase genes DGD1 and DGD2. The amounts of triacylglycerol and free fatty acids increased during N deprivation. Furthermore, phytyl esters accumulated containing medium‐chain fatty acids (12:0, 14:0) and a large amount of hexadecatrienoic acid (16:3). Fatty acid phytyl esters were localized to chloroplasts, in particular to thylakoids and plastoglobules. Different polyunsaturated acyl groups were found in phytyl esters accumulating in Arabidopsis lipid mutants and in other plants, including 16:3 and 18:3 species. Therefore N deficiency in higher plants results in a co‐ordinated breakdown of galactolipids and chlorophyll with deposition of specific fatty acid phytyl esters in thylakoids and plastoglobules of chloroplasts.
The protective effect of rural living against atopy in Mongolia
Authors: Viinanen A. , Munhbayarlah S. , Zevgee T. , Narantsetseg L. , Naidansuren Ts. , Koskenvuo M. , Helenius H. , Terho E. O.
Published: January 2007

Background:  Farm environment in childhood protects against atopy. We investigated in a population‐based study in Mongolia the effects of rural living and migration from rural to urban areas on the risk of atopy.

Methods:  The screening study data of 9453 subjects, aged 10–60 years, were used for taking the sample for the clinical study in which 869 subjects were examined. Asthma, allergic rhinoconjunctivitis and sensitization were clinically defined and their risk factors analysed by logistic regression.

Results:  The risks of allergic rhinoconjunctivitis [adjusted odds ratio (OR) 0.43, 95% confidence interval (CI) 0.19–0.98] and allergic sensitization (OR 0.26, 95% CI 0.13–0.55) were the lowest in subjects living in a village from birth and intermediate in subjects who had relocated from a village to a town (OR for rhinoconjunctivitis 0.68, 95% CI 0.36–1.27, OR for sensitization 0.62, 95% CI 0.35–1.12) compared with subjects living in a town from birth. Simultaneous exposure to herd animals and dung heating decreased the risk of atopy. Keeping animals was a risk‐factor for asthma only in Ulaanbaatar city.

Conclusions:  Continuing farm exposure after childhood may be important in reducing the risk of atopy.
Vaccine‐induced immunity in children after orthotopic liver transplantation: A 12‐yr review of the Swiss national reference center
Authors: Diana Alessandro , Posfay‐Barbe Klara M. , Belli Dominique C. , Siegrist Claire‐Anne
Published: January 2007

Abstract:  Infections represent a significant threat in solid‐organ recipients. However, a certain number of infections can be prevented by immunizing patients before their transplantation. The aim of this study is to determine the level of immunity of children undergoing liver transplantation and to assess their capacity to maintain protective levels after surgery. Charts of 44 children transplanted with deceased donation livers between 1990 and 2002 at the Children's Hospital of Geneva were reviewed. Vaccine antibody responses were established pre‐ and post‐transplantation. Only 43% of patients were up to date for diphtheria, tetanus, acellular pertussis, and polio vaccines at the pretransplantation visit, while 44% of children older than 12 months had received their required measles‐mumps‐rubella vaccines. Six of 44 children had received at least one dose of hepatitis B vaccine, while only two patients had received at least one dose of hepatitis A vaccine. After immunization, and one yr after transplantation, only 14 of 44 patients had detectable anti‐HBs antibodies and seven of 18 had anti‐HAV antibodies. Varicella antibodies were undetectable in 15 of 19 patients immunized prior to transplantation. This study highlights the need to enforce vaccination before transplantation, follow‐up on vaccine‐ induced immunity, and adapt vaccination schedules after liver transplantation in children, especially for non‐live vaccines, which are universally recommended in this population.
Nitazoxanide or CD3+/CD4+ lymphocytes for recovery from severe Cryptosporidium infection after allogeneic bone marrow transplant?
Authors: Faraci M. , Cappelli B. , Morreale G. , Lanino E. , Moroni C. , Bandettini R. , Terranova M. P. , Di Martino D. , Coccia C. , Castagnola E.
Published: January 2007

Abstract:  We describe a case of Cryptosporidium infection occurring in a child after allogeneic SCT for acute non‐lymphoblastic leukemia. This patient presented an intestinal, biliar, and pancreatic Cryptosporidium disease associated with an intestinal aGvHD. The increase in CD3+/CD4+ cells secondary to the reduction of steroid therapy associated with the improvement of aGvHD and the use of antiparasitic treatments (especially nitazoxanide) improved the infection‐related symptoms and led to a complete clearance of the Cryptosporidium.
Seven hundred and fifty‐nine (759) chances to learn: a 3‐year pilot project to analyse transfusion‐related near‐miss events in the Republic of Ireland
Authors: Lundy D. , Laspina S. , Kaplan H. , Rabin Fastman B. , Lawlor E.
Published: January 2007

Background  The National Haemovigilance Office has collected and analysed reports on errors associated with transfusion since 2000. A 3‐year pilot research project in near‐miss event reporting commenced in November 2002.

Materials and Methods  Near‐miss reports from 10 hospital sites were analysed between May 2003 and May 2005. The Medical Event Reporting System for Transfusion Medicine was used to collect and analyse the data. Root cause analysis was used to identify causes of error.

Results  A total of 759 near‐miss events were reported. Near misses are occurring 18 times more frequently than adverse events causing harm. Sample collection was found to be the highest risk step in the work process and was the first site of error in 468 (62%) events. Of these, 13 (3%) involved samples taken from the wrong patient. Medical staff were frequently involved in error. The general wards and emergency department were identified as high‐risk clinical areas, in addition, 78 (10%) events occurred within the transfusion laboratory. Three specific human and two system failures were shown to have been associated with the errors identified in this study.

Conclusions  This study confirms that near‐miss events occur far more frequently than adverse events causing harm. Collecting near‐miss data is an effective means of highlighting human and system failures associated with transfusion that may otherwise go unnoticed. These data can be used to identify areas where resources need to be targeted in order to prevent future harm to patients, improving the overall safety of transfusion.
Recombinant‐activated coagulation factor VIIa (NovoSeven®): current development
Authors: Weiskopf R. B.
Published: January 2007

Recombinant activated coagulation factor VII (rFVIIa) was developed initially for treatment of patients with hemophilia and neutralizing antibodies (“inhibitors”) to coagulation factors VIII or IX. Owing to the unique and selective mechanism of action of rFVIIa and encouraged by clinical experience with other circumstances of inadequate hemostasis, a broad development program has been pursued to test potential efficacy and evaluate safety of this biologic for indications other than hemophilia. This review summarizes the current development of rFVIIa, focusing on results of prospective, randomized clinical trials.
Differences in expression and activity of β,β′‐carotene‐15,15′‐ oxygenase in liver and duodenum of cattle with yellow or white fat
Authors: Morales A. , González A. , Varela‐Echavarría A. , Shimada A. , Mora O.
Published: January 2007

Pasture‐fed cattle show yellow pigmentation of their fat due to β‐carotene stored in this tissue. β,β′‐Carotene‐15,15′‐oxygenase (βCO) is an enzyme expressed in different tissues, and it cleaves β‐carotene into retinal. We compared the expression and activity of βCO in duodenum and liver of cattle with pigmented or non‐pigmented fat. In the duodenum, in situ hybridizations showed expression of βCO in epithelial cells and crypts of the mucosa that was similar in animals from pigmented and non‐pigmented fat; liver showed diffuse signal at lobules, but pigmented animals showed higher signals near the portal space. Analyses by real‐time reverse‐transcription polymerase chain reaction also showed amplification of mRNA for βCO in duodenum and liver, with no difference between pigmented or non‐pigmented animals. Enzyme activity was similar in the duodenum, but pigmented animals had higher enzyme activity (p = 0.004) in liver. Cattle with pigmented fat had higher expression and activity of βCO in liver, but its level was not high enough to prevent the storage of β‐carotene in adipose tissues.
Effects of a dietary application of a yeast cell wall extract on innate and acquired immunity, on oxidative status and growth performance in weanling piglets and on the ileal epithelium in fattened pigs
Authors: Sauerwein H. , Schmitz S. , Hiss S.
Published: January 2007

Potential immunomodulatory effects of a cell wall extract from Saccharomyces cerevisiae (Y; Antaferm MG) were tested in pigs: in trial I, 0.03% Y and in trial II 0.3% Y was used. Based on earlier observations that Y may increase feed intake, two treatment groups, Y‐a (fed ad libitum) and Y‐r (fed restrictively) were studied in comparison with a control group (C) in both trials. Y‐r received the amount of feed consumed by C. Immune status was surveyed by determining phagocytic activity and oxidative burst of neutrophils and blood concentrations of haptoglobin (Hp), and immunoglobulin (Ig) G and A. Oxidative stress was monitored by recording reactive oxygen metabolites (ROM) and total antioxidant capacity. In a third trial, fattened pigs were used for morphological and immunohistochemical studies (IgM and IgA as well as CD and CD T cells) in ileal epithelium. Pigs fed 0.03% Y for 2 weeks prior to slaughter were compared with the C group. Feed intake was identical in the Y‐a and Y‐b groups and data subsets were accordingly pooled. Treatment and time as well as treatment × time interactions were detectable for most of the parameters studied, but a distinct immunomodulatory effect of Y was not consistently identifiable and performance did not improve. In trial III, the intestinal parameters investigated were not different between Y and C.