bluuebunny/crossref_metadata_2025 huggingface dataset:
Anisotropic low-temperature piezoresistance in (311)A GaAs two-dimensional holes
Authors: Habib B. , Shabani J. , De Poortere E. P. , Shayegan M. , Winkler R.
Published: July 2007

The authors report low-temperature resistance measurements in a modulation-doped, (311)A GaAs two-dimensional hole system as a function of applied in-plane strain. The data reveal a strong but anisotropic piezoresistance whose magnitude depends on the density as well as the direction along which the resistance is measured. At a density of 1.6×1011cm−2 and for a strain of about 2×10−4 applied along the [011¯], e.g., the resistance measured along this direction changes by nearly a factor of 2, while the resistance change in the [2¯33] direction is less than 10% and has the opposite sign. The accurate energy band calculations indicate a pronounced and anisotropic deformation of the heavy-hole dispersion with strain, qualitatively consistent with the experimental data. The extremely anisotropic magnitude of the piezoresistance, however, lacks a quantitative explanation.
Quantum-confinement effect in individual Ge1−xSnx quantum dots on Si(111) substrates covered with ultrathin SiO2 films using scanning tunneling spectroscopy
Authors: Nakamura Yoshiaki , Masada Akiko , Ichikawa Masakazu
Published: July 2007

The authors observed a quantum-confinement effect in individual Ge1−xSnx quantum dots (QDs) on Si (111) substrates covered with ultrathin SiO2 films using scanning tunneling spectroscopy at room temperature. The quantum-confinement effect was featured by an increase in the energy band gap of ∼1.5eV with a decrease in QD diameter from 35to4nm. The peaks for quantum levels of QDs became broader with a decrease in the height-diameter aspect ratio of QDs, demonstrating the gradual emergence of two dimensionality in density of states of quasi zero-dimensional QDs with the QD flattening.
Estimation of shrub height for fuel-type mapping combining airborne LiDAR and simultaneous color infrared ortho imaging
Authors: Riaño David , Chuvieco Emilio , Ustin Susan L. , Salas Javier , Rodríguez-Pérez José R. , Ribeiro Luis M. , Viegas Domingos X. , Moreno José M. , Fernández Helena
Published: July 2007

A fuel-type map of a predominantly shrub-land area in central Portugal was generated for a fire research experimental site, by combining airborne light detection and ranging (LiDAR), and simultaneous color infrared ortho imaging. Since the vegetation canopy and the ground are too close together to be easily discerned by LiDAR pulses, standard methods of processing LiDAR data did not provide an accurate estimate of shrub height. It was demonstrated that the standard process to generate the digital ground model (DGM) sometimes contained height values for the top of the shrub canopy rather than from the ground. Improvement of the DGM was based on separating canopy from ground hits using color infrared ortho imaging to detect shrub cover, which was measured simultaneously with the LiDAR data. Potentially erroneous data in the DGM was identified using two criteria: low vegetation height and high Normalized Difference Vegetation Index (NDVI), a commonly used spectral index to identify vegetated areas. Based on the height of surrounding pixels, a second interpolation of the DGM was performed to extract those erroneously identified as ground in the standard method. The estimation of the shrub height improved significantly after this correction, and increased determination coefficients from R2 = 0.48 to 0.65. However, the estimated shrub heights were still less than those observed in the field.
Analysis of Alaskan burn severity patterns using remotely sensed data
Authors: Duffy Paul A. , Epting Justin , Graham Jonathan M. , Rupp T. Scott , McGuire A. David
Published: July 2007

Wildland fire is the dominant large-scale disturbance mechanism in the Alaskan boreal forest, and it strongly influences forest structure and function. In this research, patterns of burn severity in the Alaskan boreal forest are characterised using 24 fires. First, the relationship between burn severity and area burned is quantified using a linear regression. Second, the spatial correlation of burn severity as a function of topography is modelled using a variogram analysis. Finally, the relationship between vegetation type and spatial patterns of burn severity is quantified using linear models where variograms account for spatial correlation. These results show that: 1) average burn severity increases with the natural logarithm of the area of the wildfire, 2) burn severity is more variable in topographically complex landscapes than in flat landscapes, and 3) there is a significant relationship between burn severity and vegetation type in flat landscapes but not in topographically complex landscapes. These results strengthen the argument that differential flammability of vegetation exists in some boreal landscapes of Alaska. Additionally, these results suggest that through feedbacks between vegetation and burn severity, the distribution of forest vegetation through time is likely more stable in flat terrain than it is in areas with more complex topography.
Src phosphorylation of cortactin enhances actin assembly
Authors: Tehrani Shandiz , Tomasevic Nenad , Weed Scott , Sakowicz Roman , Cooper John A.
Published: July 2007

Src kinase mediates growth factor signaling and causes oncogenic transformation, which includes dramatic changes in the actin cytoskeleton, cell shape, and motility. Cortactin was discovered as a substrate for Src. How phosphorylation of cortactin can enhance actin assembly is unknown. Here, using an actin assembly system reconstituted from purified components, we demonstrate for the first time a biochemical mechanism by which Src phosphorylation of cortactin affects actin assembly. The adaptor Nck is an important component of the system, linking phosphorylated cortactin with neuronal WASp (N-WASp) and WASp-interacting protein (WIP) to activate Arp2/3 complex.
Cell division is essential for elimination of the yeast [
PSI
+
] prion by guanidine hydrochloride
Authors: Byrne Lee J. , Cox Brian S. , Cole Diana J. , Ridout Martin S. , Morgan Byron J. T. , Tuite Mick F.
Published: July 2007

Guanidine hydrochloride (Gdn·HCl) blocks the propagation of yeast prions by inhibiting Hsp104, a molecular chaperone that is absolutely required for yeast prion propagation. We had previously proposed that ongoing cell division is required for Gdn·HCl-induced loss of the [
PSI
+
] prion. Subsequently, Wu
et al.
[Wu Y, Greene LE, Masison DC, Eisenberg E (2005)
Proc Natl Acad Sci USA
102:12789–12794] claimed to show that Gdn·HCl can eliminate the [
PSI
+
] prion from α-factor-arrested cells leading them to propose that in Gdn·HCl-treated cells the prion aggregates are degraded by an Hsp104-independent mechanism. Here we demonstrate that the results of Wu
et al.
can be explained by an unusually high rate of α-factor-induced cell death in the [
PSI
+
] strain (780-1D) used in their studies. What appeared to be no growth in their experiments was actually no increase in total cell number in a dividing culture through a counterbalancing level of cell death. Using media-exchange experiments, we provide further support for our original proposal that elimination of the [
PSI
+
] prion by Gdn·HCl requires ongoing cell division and that prions are not destroyed during or after the evident curing phase.
Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces the indolocarbazole skeleton
Authors: Makino Masatomo , Sugimoto Hiroshi , Shiro Yoshitsugu , Asamizu Shumpei , Onaka Hiroyasu , Nagano Shingo
Published: July 2007

Staurosporine isolated from
Streptomyces
sp. TP-A0274 is a member of the family of indolocarbazole alkaloids that exhibit strong antitumor activity. A key step in staurosporine biosynthesis is the formation of the indolocarbazole core by intramolecular C–C bond formation and oxidative decarboxylation of chromopyrrolic acid (CPA) catalyzed by cytochrome P450 StaP (StaP, CYP245A1). In this study, we report x-ray crystal structures of CPA-bound and -free forms of StaP. Upon substrate binding, StaP adopts a more ordered conformation, and conformational rearrangements of residues in the active site are also observed. Hydrogen-bonding interactions of two carboxyl groups and T-shaped π–π interactions with indole rings hold the substrate in the substrate-binding cavity with a conformation perpendicular to the heme plane. Based on the crystal structure of StaP–CPA complex, we propose that C–C bond formation occurs through an indole cation radical intermediate that is equivalent to cytochrome
c
peroxidase compound I [Sivaraja M, Goodin DB, Smith M, Hoffman BM (1989)
Science
245:738–740]. The subsequent oxidative decarboxylation reaction is also discussed based on the crystal structure. Our crystallographic study shows the first crystal structures of enzymes involved in formation of the indolocarbazole core and provides valuable insights into the process of staurosporine biosynthesis, combinatorial biosynthesis of indolocarbazoles, and the diversity of cytochrome P450 chemistry.
Insulin-like growth factor binding protein 2 promotes glioma development and progression
Authors: Dunlap Sarah M. , Celestino Joseph , Wang Hua , Jiang Rongcai , Holland Eric C. , Fuller Gregory N. , Zhang Wei
Published: July 2007

Overexpression of insulin-like growth factor binding protein 2 (IGFBP2) is associated with progression in many types of human cancer. In this study we used a glial-specific transgenic mouse model to examine the active role of IGFBP2 in tumorigenesis and progression. Our studies show that IGFBP2 coexpression results in progression to a higher-grade glioma in platelet-derived growth factor β (PDGFB)-driven tumors. These anaplastic oligodendrogliomas are characterized by increased cellularity, vascular proliferation, small regions of necrosis, increased mitotic activity, and increased activation of the Akt pathway. Combined expression of IGFBP2 or Akt with K-Ras was required to form astrocytomas, indicating that activation of two separate pathways is necessary for gliomagenesis. In
ex vivo
experiments, blockade of Akt by an inhibitor led to decreased viability of cells coexpressing IGFBP2 versus PDGFB expression alone. Thus, this study provides definitive evidence that IGFBP2 plays a key role in activation of the Akt pathway and collaborates with K-Ras or PDGFB in the development and progression of two major types of glioma.
Buffering of deoxyribonucleotide pool homeostasis by threonine metabolism
Authors: Hartman John L.
Published: July 2007

Synergistically interacting gene mutations reveal buffering relationships that provide growth homeostasis through their compensation of one another. This analysis in
Saccharomyces cerevisiae
revealed genetic modules involved in tricarboxylic acid cycle regulation (
RTG1
,
RTG2
,
RTG3
), threonine biosynthesis (
HOM3
,
HOM2
,
HOM6
,
THR1
,
THR4
), amino acid permease trafficking (
LST4
,
LST7
), and threonine catabolism (
GLY1
). These modules contribute to a molecular circuit that regulates threonine metabolism and buffers deficiency in deoxyribonucleotide biosynthesis. Phenotypic, genetic, and biochemical evidence for this buffering circuit was obtained through analysis of deletion mutants, titratable alleles of ribonucleotide reductase genes, and measurements of intracellular deoxyribonucleotide pool concentrations. This circuit provides experimental evidence, in eukaryotes, for the presence of a high-flux backbone of metabolism, which was previously predicted from
in silico
modeling of global metabolism in bacteria. This part of the high-flux backbone appears to buffer deficiency in ribonucleotide reductase by enabling a compensatory increase in
de novo
purine biosynthesis that provides additional rate-limiting substrates for dNTP production and DNA synthesis. Hypotheses regarding unexpected connections between these metabolic pathways were facilitated by genome-wide but also highly quantitative phenotypic assessment of interactions. Validation of these hypotheses substantiates the added benefit of quantitative phenotyping for identifying subtleties in gene interaction networks that modulate cellular phenotypes.
THE DISTRIBUTION AND RETURN OF SOCIAL CAPITAL: EVIDENCE FROM SWEDEN
Authors: Behtoui Alireza
Published: July 2007

This paper studies the role of social capital in the status attainment process and examines the link between the hiring process and the potential pool of social capital embedded in a person's network. The analysis is based on a sample of people newly employed by the municipal services in Malmö, the third largest city in Sweden. Jobs in this sector of labour market are mainly low-paid, and are dominated by women and immigrants. The position generator method is used to measure social capital, understood as assets captured by individuals in social networks. The findings demonstrate that access to social capital is positively related to work experience, a higher educational level, having a partner, and active membership of voluntary associations. It is also apparent that being an immigrant is associated with a substantial social capital deficit. Regarding the return on capital, the results show that both human capital and social capital were rewarded with higher wages and more adequate jobs. Furthermore, we found that social capital is associated with better labour market outcomes, whether or not respondents reported that they obtained their current jobs using informal job-search methods. Results also show similar returns on access to social capital for natives and immigrants.
LEARNING FROM OTHERS AND RECEIVING SUPPORT: THE IMPACT OF PERSONAL NETWORKS ON FERTILITY INTENTIONS IN POLAND
Authors: Bühler Christoph , Fratczak Ewa
Published: July 2007

Research about fertility has focused in the main on studying separately the influence of communication networks and social capital on reproductive behavior, but it has rarely tried to integrate both network properties theoretically or analytically. We therefore discuss a general model of purposeful behavior that perceives individuals’ subjective perceptions of the utilities of different courses of action to be affected by structures of interpersonal influence. Resources needed to realize desired goals are furthermore shaped by exchange relationships that build social capital. These considerations are empirically applied to explanations of the intentions of 758 Polish men and women ever to have a first, second, or third child. Personal networks are especially relevant for the considerations to have a first or second child. The intentions of childless respondents are positively influenced by network partners who are at a similar stage of their reproductive biographies or who have already taken the step of having a first child. However, respondents with one child have a higher probability of intending to have a second child the more they have access to fertility-related social capital.
SPEEDING UP OR HOLDING BACK?: INSTITUTIONAL FACTORS IN THE DEVELOPMENT OF CHILDCARE PROVISION IN SPAIN
Authors: León Margarita
Published: July 2007

This paper looks at childcare provision in Spain from the perspective of policies for the reconciliation of work and family life. The goal is to understand how social care – and childcare in particular – has been placed within the different policy domains of the welfare state, and how this condition affects its opportunities for policy development and innovation. As a point of reference, the study takes into consideration the recent EU benchmark regarding childcare provision in the context of the European Employment Strategy. The investigation looks at the impact of the institutional configuration of the welfare system and the labour market on the development of childcare provision and policies for the reconciliation of work and family. The paper suggests that, given a strong policy legacy in family policy and social services, childcare provision is expanding under the decentralized education system although it has not been articulated in terms of policies for the reconciliation of work and family life, which impacts on female employment. Legislative changes improving the conditions of female employees who give birth have recently been introduced in labour law, although the structure of the labour market and practices in employment relations pose obstacles to their effective implementation.
THE EUROPEAN SOCIO-ECONOMIC CLASSIFICATION: A NEW SOCIAL CLASS SCHEMA FOR COMPARATIVE EUROPEAN RESEARCH
Authors: Rose David , Harrison Eric
Published: July 2007

As a result of an initiative by the European Statistical Office as part of its Statistical Harmonisation Programme, a prototype of a common European Socio-economic Classification (ESeC) has been created. ESeC is a categorical social class schema based on the concept of employment relations. The paper explains the conceptual basis of ESeC, describes the categories of the classification and how they may be collapsed for analytic purposes, as well as indicating how it is operationalised. The operational variants of ESeC, depending on the data available for its construction, are also discussed. In the second part of the paper some key findings of comparative analyses which use ESeC to examine issues relating to unemployment, education, poverty, deprivation and health across the EU are summarised. These analyses demonstrate the potential of ESeC as a major advance for an improved understanding of the patterns of European social inequalities. As such, this new classification should be of vital importance to both academic and policy researchers.
Heterotrophic microbial communities use ancient carbon following glacial retreat
Authors: Bardgett Richard D , Richter Andreas , Bol Roland , Garnett Mark H , Bäumler Rupert , Xu Xingliang , Lopez-Capel Elisa , Manning David A.C , Hobbs Phil J , Hartley Ian R , Wanek Wolfgang
Published: July 2007

When glaciers retreat they expose barren substrates that become colonized by organisms, beginning the process of primary succession. Recent studies reveal that heterotrophic microbial communities occur in newly exposed glacial substrates before autotrophic succession begins. This raises questions about how heterotrophic microbial communities function in the absence of carbon inputs from autotrophs. We measured patterns of soil organic matter development and changes in microbial community composition and carbon use along a 150-year chronosequence of a retreating glacier in the Austrian Alps. We found that soil microbial communities of recently deglaciated terrain differed markedly from those of later successional stages, being of lower biomass and higher abundance of bacteria relative to fungi. Moreover, we found that these initial microbial communities used ancient and recalcitrant carbon as an energy source, along with modern carbon. Only after more than 50 years of organic matter accumulation did the soil microbial community change to one supported primarily by modern carbon, most likely from recent plant production. Our findings suggest the existence of an initial stage of heterotrophic microbial community development that precedes autotrophic community assembly and is sustained, in part, by ancient carbon.
Impact of scale on the effectiveness of disease control strategies for epidemics with cryptic infection in a dynamical landscape: an example for a crop disease
Authors: Gilligan Christopher A , Truscott James E , Stacey Adrian J
Published: July 2007

We use a spatially explicit, stochastic model to analyse the effectiveness of different scales of local control strategies in containing the long-term, multi-seasonal spread of a crop disease through a dynamically changing population of susceptible crops in which there is cryptic infection. The model distinguishes between susceptible, infested and symptomatic fields. It is motivated by rhizomania disease on sugar beet in the UK as an exemplar of a spatially structured and partially asymptomatic epidemic. Our results show the importance of matching the scales of local control strategies to prevent intensification and regional spread of disease with the inherent temporal and spatial scales of an epidemic. A simple field-scale containment strategy, whereby the susceptible crop is no longer grown on fields showing symptoms, fails for this system with cryptic infection because the locally applied control lags behind the epidemic. A farm-scale strategy, whereby growers respond to the disease status of neighbouring farms by transferring their quota for sugar beet to farmers in regions of reduced risk, succeeds. We conclude that a soil-borne pathogen such as rhizomania could be managed by movement of susceptible crops in the landscape using a strategy that matches the temporal and spatial scales of the epidemic and which take account of risk aversion among growers. We show some parallels and differences in effectiveness between a ‘culling’ strategy involving crop removal around emerging foci and the local deployment of partially resistant varieties that reduce amplification and transmission of inoculum. Some relationships between the control of plant and livestock diseases are briefly discussed.
Multidimensional linear diffusion for image enhancement on a type II quantum computer
Authors: Coffey Mark W , Colburn Gabriel G
Published: July 2007

We describe how multidimensional linear diffusion with application to image processing could be carried out on a hybrid classical–quantum computer. We present the quantum-lattice-gas-based algorithms, their effective finite difference approximations and representative simulation results. The methods for two-dimensional diffusion processing are particularly relevant to image enhancement tasks. We additionally demonstrate an extension to constrained linear diffusion that provides for non-uniform image smoothing. The simulation results and accompanying analysis support the utility of both classical and classical–quantum lattice gases for image enhancement. The diffusion modelling has applicability to many other fields including biological and physical science.
Potential for female kin associations in wild western gorillas despite female dispersal
Authors: Bradley Brenda J , Doran-Sheehy Diane M , Vigilant Linda
Published: July 2007

Female philopatry and male dispersal are the norm for most mammals, and females that remain in their natal region often derive foraging or social benefits from proximity to female kin. However, other factors, such as constraints on group size or a shortage of potential mates, may promote female dispersal even when female kin associations would be beneficial. In these cases, female kin associations might develop, not through female philopatry, but through female emigration to the same group. To date, little attention has been focused on the potential for kin-biased behaviour between females in female-dispersing species. Here we investigate the genetic relationships among adults in eight wild groups of unhabituated western gorillas (Gorilla gorilla) at the Mondika Research Center using microsatellite genotyping of DNA collected from hair and faeces. We found that almost half (40%) of adult females had an adult female relative in the same group and average within-group relatedness among females was significantly higher than that expected under a model of random dispersal. This provides the first genetic evidence that females can maintain social associations with female relatives in spite of routine natal and secondary dispersal. In addition, we show that females appear to avoid related silverback males when making dispersal decisions, suggesting that a strategy of non-random female dispersal may also function to avoid inbreeding.
Molecular cloning of Brassica rapa nitrilases and their expression during clubroot development
Authors: ISHIKAWA TOSHIKI , OKAZAKI KEIICHI , KURODA HARUKA , ITOH KIMIKO , MITSUI TOSHIAKI , HORI HIDETAKA
Published: July 2007

Three isoforms of nitrilase were cloned from turnip, Brassica rapa L., and their expression during clubroot development caused by Plasmodiophora brassicae was investigated. The isoforms were designated BrNIT‐T1, BrNIT‐T2 and BrNIT‐T4 based on homology to known nitrilases. BrNIT‐T1 and BrNIT‐T2 have 80% homology to three nitrilases from Arabidopsis thaliana (AtNIT1, AtNIT2 and AtNIT3). BrNIT‐T4 showed 90% homology to AtNIT4. To confirm their enzyme activity, the recombinant proteins were expressed in Escherichia coli. The recombinant BrNIT‐T1 and BrNIT‐T2 but not BrNIT‐T4 converted indole‐3‐acetonitrile to indole‐3‐acetic acid, an endogenous plant auxin, although kinetic analysis showed that indole‐3‐acetonitrile is a poor substrate compared with various aliphatic and aromatic nitriles. By contrast, the recombinant BrNIT‐T4 specifically converted β‐cyano‐l‐alanine to aspartic acid and asparagine and these findings agree with the idea that it is involved in the cyanide detoxification pathway. Real‐time PCR analysis clearly showed that these isoforms were differentially expressed during clubroot development. BrNIT‐T1 transcripts were very low in non‐infected roots but were enhanced up to 100‐fold in infected roots exhibiting club growth. By contrast, BrNIT‐T2 transcripts remained at a very low level during clubroot formation. All these results clearly indicate the specific involvement of BrNIT‐T1 in clubroot formation. The BrNIT‐T4 transcripts were substantially reduced in the clubroot‐growing phase, but thereafter they increased rapidly to a level found in non‐infected roots as the clubroot growth reached a plateau. These findings suggest the specific involvement of BrNIT‐T4 in clubroot maturation. In fully developed clubs, the BrNIT‐T1 and BrNIT‐T2 transcripts also increased. Free indole‐3‐acetic acid (IAA) content increased in the early and the latest phase of infected roots compared with non‐infected roots, but decreased substantially at the middle phase. Thus, free IAA may play a role in the initiation and maturation of clubroot. Total IAA content was significantly higher in infected roots than in non‐infected roots throughout clubroot development and IAA conjugation/conjugate hydrolysis system as well as BrNIT‐Ts appear to be involved in clubroot development.
Bortezomib in combination with intermediate‐dose dexamethasone and continuous low‐dose oral cyclophosphamide for relapsed multiple myeloma
Authors: Kropff Martin , Bisping Guido , Schuck Elke , Liebisch Peter , Lang Nicola , Hentrich Markus , Dechow Tobias , Kröger Nicolaus , Salwender Hans , Metzner Bernd , Sezer Orhan , Engelhardt Monika , Wolf Hans‐Heinrich , Einsele Hermann , Volpert Sarah , Heinecke Achim , Berdel Wolfgang E. , Kienast Joachim ,   on behalf of the Deutsche Studiengruppe Multiples Myelom, DSMM
Published: July 2007

A phase 2 trial was performed to study the combination of bortezomib (VELCADE®) with intermediate‐dose dexamethasone (DEX), and continuous low‐dose oral cyclophosphamide (CY) in patients with relapsed multiple myeloma (MM). Fifty‐four patients with advanced MM were enroled to receive eight 3‐week treatment cycles with bortezomib 1·3 mg/m2 on days 1, 4, 8, and 11, followed by three 5‐week cycles with bortezomib 1·3 mg/m2 on days 1, 8, 15, and 22. Within all cycles, DEX 20 mg/d was given orally on the day of bortezomib injection and the day thereafter. In addition, patients received CY continuous oral treatment at a dose of 50 mg/d p.o. once daily. Fifty patients completing at least one treatment cycle were evaluable for response. Complete, partial, and minor responses occurred in 16%, 66% and 8% of patients, respectively; overall response rate 90% (efficacy analysis). Median event‐free survival was 12 months, with a median overall survival of 22 months. Adverse events (AE) of grades 3 or 4 occurring in at least 10% of patients comprised leucopenia, infection, herpes zoster, thrombocytopenia, neuropathy and fatigue. Bortezomib combined with DEX and CY is a highly effective treatment for relapsed MM at an acceptable rate of grade 3/4 AE. Antiviral prophylaxis appears to be mandatory.
Activation of Wnt/β‐catenin pathway mediates growth and survival in B‐cell progenitor acute lymphoblastic leukaemia
Authors: Khan Naveed I. , Bradstock Kenneth F. , Bendall Linda J.
Published: July 2007

This study investigated the response of acute lymphoblastic leukaemia (ALL) cells to Wnt proteins. Accumulation of β‐catenin was measured by Western blotting and immunofluorescence microscopy. Reverse transcription polymerase chain reaction (RT‐PCR) analysis of B‐cell progenitor acute lymphoblastic leukaemia (ALL) cells revealed expression of Wnt genes, including WNT2B in 33%, WNT5A in 42%, WNT10B in 58% and WNT16B in 25% of cases. The Wnt receptors, (Frizzled) FZD7 and FZD8 were also expressed in most cases while FZD3, FZD4 and FZD9 were occasionally detected. Stimulation of ALL cells with Wnt‐3a activated canonical Wnt signalling with increased expression and nuclear translocation of β‐catenin. This resulted in a 1·7‐ to 5·3‐fold increase in cell proliferation, which was associated with enhanced cell cycle entry. A significant increase in the survival of ALL cells under conditions of serum deprivation was also observed. Microarray analysis and quantitative RT‐PCR revealed that activation of the Wnt/β‐catenin pathway led to altered expression of genes involved in cell cycle regulation and apoptosis in normal and leukaemic B‐cell progenitors. Our results demonstrate that Wnt‐3a provides proliferative and survival cues in ALL cells. This data suggests that targeting the Wnt signalling pathway may be a useful therapeutic strategy in ALL.
Intranasal delivery of whole influenza vaccine prevents subsequent allergen‐induced sensitization and airway hyper‐reactivity in mice
Authors: Minne A. , Jaworska J. , Gerhold K. , Ahrens B. , Avagyan A. , Vanbever R. , Matricardi P. M. , Schmidt A. C. , Hamelmann E.
Published: July 2007

Background
Infection with influenza virus has been associated with seemingly opposing effects on the development of asthma. However, there are no data about the effects of mucosal vaccination with inactivated influenza on the inception of allergic asthma.

Objective
To assess the immunological effects of inhaled inactivated influenza vaccine, using two different types of flu vaccines, on the inception of allergic sensitization and allergen‐mediated airway disease in a mouse model.

Methods
BALB/c mice were intranasally or intratracheally vaccinated with whole or split influenza virus vaccine (days −1 or −1, 27) before systemic sensitization with ovalbumin (OVA) (days 1, 14) and repeated airway allergen challenges (days 28–30). Allergen sensitization (IgE serum levels), airway inflammation (differential cells in bronchoalveolar lavage fluid) and airway hyper‐reactivity (AHR) (in vivo lung function) were analysed.

Results
The intranasal instillation of whole influenza vaccine before allergen sensitization significantly reduced the serum levels of total and OVA‐specific IgE as well as allergen‐induced AHR. Prevention was due to an allergen‐specific shift from a predominant T helper (Th)2‐ towards a Th1‐immune response. Application of split influenza vaccine did not show the same preventive effect.

Conclusion
Intranasal administration of inactivated whole influenza vaccine reduced subsequent allergen sensitization and prevented allergen‐induced AHR. Our results show that the composition of the influenza vaccine has a major influence on subsequent development of allergen‐induced sensitization and AHR, and suggest that mucosal inactivated whole influenza vaccination may represent a step towards the development of a preventive strategy for atopic asthma.
Transforming growth factor‐β2 polymorphisms are associated with childhood atopic asthma
Authors: Hatsushika K. , Hirota T. , Harada M. , Sakashita M. , Kanzaki M. , Takano S. , Doi S. , Fujita K. , Enomoto T. , Ebisawa M. , Yoshihara S. , Sagara H. , Fukuda T. , Masuyama K. , Katoh R. , Matsumoto K. , Saito H. , Ogawa H. , Tamari M. , Nakao A.
Published: July 2007

Background
Transforming growth factor (TGF)‐β plays an important role in the regulation of airway inflammation and remodelling in asthma. Recent studies suggest that TGF‐β2 is a predominant isoform expressed in severe asthma and it is also associated with airway remodelling.

Objective
To determine whether the polymorphisms in TGF‐β2 are associated with childhood atopic bronchial asthma in a Japanese population.

Methods
We identified a total of eight polymorphisms and characterized the linkage disequilibrium (LD) mapping of the gene. Three variants in the promoter and 3′UTR were genotyped, and we conducted an association study of TGF‐β2 (childhood atopic asthma n=297, normal controls n=555). An association analysis of these variants and an expression and functional analysis were performed.

Results
3′UTR 94862T >A was found to be significantly associated with the risk of childhood atopic asthma (P=0.00041). The −109→ACAA ins promoter variant was also associated with the risk of childhood atopic asthma (P=0.0037). TGF‐β2 expression was observed in both the normal and asthmatic bronchial epithelium, and both real‐time PCR and an ELISA showed a significant basal and TGF‐β1‐induced TGF‐β2 expression in the bronchial epithelial cell line BEAS2B. Furthermore, the promoter variant −109→ACAA ins increased the TGF‐β2 promoter‐reporter activity in BEAS2B cells.

Conclusions
Our data suggest that TGF‐β2 may therefore be involved in the development of childhood atopic asthma by means of functional genetic polymorphism. The polymorphisms in TGF‐β2 may become important information for asthma susceptibility in children.
A non‐linear regularized constrained impedance inversion
Authors: Zhang Hongbing , Shang Zuoping , Yang Changchun
Published: July 2007

Inversion for seismic impedance is an inherently complicated problem. It is ill‐posed and band‐limited. Thus the inversion results are non‐unique and the process is unstable. Combining regularization with constraints using sonic and density log data can help to reduce these problems. To achieve this, we developed an inversion method by constructing a new objective function, including edge‐preserving regularization and a soft constraint based on a Markov random field. The method includes the selection of proper initial values of the regularization parameters by a statistical method, and it adaptively adjusts the regularization parameters by the maximum likelihood method in a fast simulated‐annealing procedure to improve the inversion result and the convergence speed. Moreover, the method uses two kinds of regularization parameter: a ‘weighting factor’λ and a ‘scaling parameter’δ. We tested the method on both synthetic and field data examples. Tests on 2D synthetic data indicate that the inversion results, especially the aspects of the discontinuity, are significantly different for different regularization functions. The initial values of the regularization parameters are either too large or too small to avoid either an unstable or an over‐smoothed result, and they affect the convergence speed. When selecting the initial values of λ, the type of the regularization function should be considered. The results obtained by constant regularization parameters are smoother than those obtained by adaptively adjusting the regularization parameters. The inversion results of the field data provide more detailed information about the layers, and they match the impedance curves calculated from the well logs at the three wells, over most portions of the curves.
Heterozygosity–fitness correlations in a bottlenecked island species: a case study on the Seychelles warbler
Authors: BROUWER L. , KOMDEUR J. , RICHARDSON D. S.
Published: July 2007

We used capture–mark–recapture models to investigate the effects of both individual and parental heterozygosity, measured at microsatellite loci on the survival of Seychelles warblers (Acrocephalus sechellensis), an endemic island species which went through a severe population bottleneck in the middle of the last century. We found that an individual's survival was not correlated with multilocus heterozygosity, or with heterozygosity at any specific locus. However, maternal, but not paternal, multilocus heterozygosity was positively associated with offspring survival, but only in years with low survival probabilities. A nestling cross‐fostering experiment showed that this was a direct maternal effect as there was an effect of the genetic mother's, but not of the social mother's, heterozygosity. Heterozygosity–fitness correlations at microsatellite markers were generally assumed to reflect genome‐wide effects. Although this might be true in partially inbred populations, such correlations may also arise as a result of local effects with specific markers being closely linked to genes which determine fitness. However, heterozygosity at the individual microsatellite loci was not correlated and therefore does not seem to reflect genome‐wide heterozygosity. This suggests that even in a small bottlenecked population, heterozygosity–fitness correlations may not be caused by genome‐wide effects. Support for the local effects hypothesis was also equivocal; although three specific loci were associated with offspring survival, including all single‐locus heterozygosities as independent predictors for the variation in survival was not supported by the data. Furthermore, in contrast to the local effects hypothesis, the loci which contributed most to the heterozygosity–survival relationship were not more polymorphic than the other loci. This study highlights the difficulties in distinguishing between the two hypotheses.
Functional analysis of the translation factor aIF2/5B in the thermophilic archaeon Sulfolobus solfataricus
Authors: Maone Enzo , Di Stefano Michele , Berardi Alessandra , Benelli Dario , Marzi Stefano , La Teana Anna , Londei Paola
Published: July 2007

The protein IF2/eIF5B is one of the few translation initiation factors shared by all three primary domains of life (bacteria, archaea, eukarya). Despite its phylogenetic conservation, the factor is known to present marked functional divergences in the bacteria and the eukarya. In this work, the function in translation of the archaeal homologue (aIF2/5B) has been analysed in detail for the first time using a variety of in vitro assays. The results revealed that the protein is a ribosome‐dependent GTPase which strongly stimulates the binding of initiator tRNA to the ribosomes even in the absence of other factors. In agreement with this finding, aIF2/5B enhances the translation of both leadered and leaderless mRNAs when expressed in a cell‐free protein‐synthesizing system. Moreover, the degree of functional conservation of the IF2‐like factors in the archaeal and bacterial lineages was investigated by analysing the behaviour of ‘chimeric’ proteins produced by swapping domains between the Sulfolobus solfataricus aIF2/5B factor and the IF2 protein of the thermophilic bacterium Bacillus stearothermophilus. Beside evidencing similarities and differences between the archaeal and bacterial factors, these experiments have provided insight into the common role played by the IF2/5B proteins in all extant cells.
A small RNA downregulates LamB maltoporin in Salmonella
Authors: Bossi Lionello , Figueroa‐Bossi Nara
Published: July 2007

In Escherichia coli and Salmonella enterica, activation of σE‐dependent envelope stress response leads to the abrupt decline in the synthesis of all major outer membrane proteins (OMPs). Recent studies found that two σE‐controlled small RNAs (sRNAs), MicA and RybB, downregulate a number of OMPs. While RybB targets several different mRNAs, including ompC and ompD, MicA was up to date thought to act solely on ompA. Here we present evidence showing that MicA downregulates a second Salmonella OMP: LamB maltoporine. In strains overexpressing σE, MicA accumulation leads to a significant decrease in LamB protein and mRNA levels, as well as a reduction in β‐galactosidase activity in a strain carrying a lamB–lacZ translational fusion. The latter findings provided the basis for a genetic screen that allowed isolating point mutations in the micA gene and in its σE promoter. All alleles obtained displayed their altered regulatory phenotype from their natural chromosomal location. LamB downregulation by MicA requires a functional Hfq protein. Besides this role, confined to σE‐activated conditions, we show that loss of Hfq results in the accumulation of a lamB‐malM dimeric precursor and of malM mRNA during unchallenged growth. This suggests that Hfq normally intervenes in a mechanism that uncouples expression of the malK‐lamB‐malM operon, causing the distal portion of the transcript to be clipped off and degraded.
Fixed drug eruption to cetirizine with positive lesional patch tests to the three piperazine derivatives
Authors: Cravo Mariana , Gonçalo Margarida , Figueiredo Américo
Published: July 2007

Background  The H1‐antihistamine cetirizine, a piperazine derivative widely used in daily practice, is rarely the cause of cutaneous drug reaction. Nevertheless, four cases of fixed drug eruption (FDE) as a result of this drug have been described recently. We present the case of a 45‐year‐old woman with a multilocalized FDE following oral intake of cetirizine for allergic rhinitis.

Methods  Patch testing with hydroxyzine 1% and 10% in petrolatum (Chemotechnique), and with powdered Zyrtec® (cetirizine) and Xyzal® (levocetirizine) pills, prepared at 20% in water and at 20% in petrolatum, was performed in both residual lesions and healthy skin.

Results  Positive results (++) to these drugs (24 h occlusion and readings at days 2 and 3) were obtained in residual lesions only. These results allowed us to confirm the drug responsible for this FDE and to study cross‐reactions between antihistamines of the same chemical family.

Conclusions  To the best of our knowledge, this is the first report of FDE to cetirizine with positive patch testing to hydroxyzine, cetirizine, and levocetirizine. This case highlights the importance of patch testing in the study of cutaneous drug reactions, namely FDE.
Cutaneous manifestations of dengue viral infection in Punjab (north India)
Authors: Thomas Emy Aby , John Mary , Bhatia Anuradha
Published: July 2007

Background  Dengue infection is emerging as a public health problem in India. Despite numerous studies, there is a paucity of literature regarding the cutaneous manifestations of dengue. This study was performed to investigate the prevalence and type of cutaneous manifestations in dengue viral infection.

Methods  Two hundred and fifty‐six patients with febrile illness, admitted to the Christian Medical College and Hospital, Ludhiana, India, were studied. On the basis of the clinical criteria and laboratory tests, 124 patients were diagnosed with dengue viral infection, and these patients were investigated in detail. Serologic tests were attempted in only 84 patients, and all of these samples tested positive for anti‐dengue immunoglobulin M (IgM) antibodies.

Results  Of the 124 patients with dengue infection, 41 (23.1%) were classified with dengue fever (DF) and 83 (66.9%) with dengue hemorrhagic fever (DHF), four (3.2%) of whom had dengue shock syndrome (DSS). Cutaneous involvement was seen in 46.8% of patients, the most common symptom being maculopapular/morbilliform eruption (48.3%), followed by ecchymotic (27.6%), petechial (13.8%), and macular/scarlatiniform (10.3%) eruption. Maculopapular eruption was observed more in DF, whereas petechiae, ecchymosis, and mucosal involvement were seen more in DHF; 72.4% of patients with cutaneous manifestations were asymptomatic, and 27.6% had pruritus. Involvement was generalized in 48.3% of patients, with the limbs and trunk involved in 32.8% and 18.9% of patients, respectively. Mucosal involvement was seen in 29.8% of patients, with conjunctival involvement being the most common (20.9%), followed by the lips (4.8%), palate (2.4%), and tongue (1.6%).

Conclusions  This study describes the variety of cutaneous features associated with dengue viral infection which may evolve during the course of the disease. As a significant proportion of patients showed cutaneous features, these manifestations, together with simple laboratory tests, will be helpful in the early diagnosis of dengue viral infection.
Postglacial intra‐lacustrine divergence of Icelandic threespine stickleback morphs in three neovolcanic lakes
Authors: ÓLAFSDÓTTIR G. Á. , SNORRASON S. S. , RITCHIE M. G.
Published: July 2007

The geographical context of divergence and local adaptation of lacustrine fish is controversial. Despite recent theoretical support for sympatric and parapatric divergence, empirical studies providing unequivocal support for this remain scant. An important component of such a case would be where multiple lakes have different morphs and a range of markers, both mitochondrial and nuclear, show monophyly within lakes. Here we describe such a situation for threespine sticklebacks in three lakes in Iceland. By analysing the variation at nuclear and mitochondrial markers in several freshwater and marine populations as well as three pairs of intra‐lacustrine morphs we infer their phylogenetic relationships and colonization pattern. There were high levels of microsatellite variation in all populations and no evidence was found for either repeated colonization of marine fish or colonization from distinct glacial refugia. Intra‐lacustrine threespine stickleback morphs in all three lakes show significant genetic divergence probably indicating restricted gene flow.
Arc mRNA induction in striatal efferent neurons associated with response learning
Authors: Daberkow D. P. , Riedy M. D. , Kesner R. P. , Keefe K. A.
Published: July 2007

The dorsal striatum is involved in motor‐response learning, but the extent to which distinct populations of striatal efferent neurons are differentially involved in such learning is unknown. Activity‐regulated, cytoskeleton‐associated (Arc) protein is an effector immediate–early gene implicated in synaptic plasticity. We examined arc mRNA expression in striatopallidal vs. striatonigral efferent neurons in dorsomedial and dorsolateral striatum of rats engaged in reversal learning on a T‐maze motor‐response task. Male Sprague–Dawley rats learned to turn right or left for 3 days. Half of the rats then underwent reversal training. The remaining rats were yoked to rats undergoing reversal training, such that they ran the same number of trials but ran them as continued‐acquisition trials. Brains were removed and processed using double‐label fluorescent in situ hybridization for arc and preproenkephalin (PPE) mRNA. In the reversal, but not the continued‐acquisition, group there was a significant relation between the overall arc mRNA signal in dorsomedial striatum and the number of trials run, with rats reaching criterion in fewer trials having higher levels of arc mRNA expression. A similar relation was seen between the numbers of PPE+ and PPE– neurons in dorsomedial striatum with cytoplasmic arc mRNA expression. Interestingly, in behaviourally activated animals significantly more PPE– neurons had cytoplasmic arc mRNA expression. These data suggest that Arc in both striatonigral and striatopallidal efferent neurons is involved in striatal synaptic plasticity mediating motor‐response learning in the T‐maze and that there is differential processing of arc mRNA in distinct subpopulations of striatal efferent neurons.