bluuebunny/crossref_metadata_2025 huggingface dataset:
Stockholm Birth Cohort Study 1953—2003: A new tool for life-course studies
Authors: Stenberg Sten-Åke , Vågerö Denny , Österman Reidar , Arvidsson Emma , Von Otter Cecilia , Janson Carl-Gunnar
Published: June 2006

Aims: To create a new tool for life-course studies of health outcomes as well as social outcomes. Methods: Two anonymous data sets, one a local birth cohort and the other a nationwide registry, covering information from early and middle life, respectively, were matched using a ``key for probability matching'' based on a large number of variables, common to both data sets. The first data set provides social and health information from birth, childhood, and adolescence on boys and girls, born in Stockholm in 1953. The second data set provides information on income, work, and education as well as any inpatient visits and any mortality from mid-life for the entire Swedish population. Results: For 96% of the original cohort it was possible to add data from mid-life. Thus, a new database has been created, referred to as the Stockholm Birth Cohort Study, which provides rich and unique life-course data from birth to age 50 for 14,294 individuals: 7,305 men and 6,989 women. Comparison of matched and unmatched cases in the original cohort suggests that those individuals that could not be matched had slightly more favourable social and intellectual circumstances and had often moved away from Sweden in the 1980s. Conclusion: The new database provides excellent opportunities for life-course studies on health and social outcomes. It allows for studies that have not previously been possible in Sweden or elsewhere. Further, it provides an opportunity for collaborative work with similar databases in Copenhagen and Aberdeen.
Peroxisome biogenesis: the peroxisomal endomembrane system and the role of the ER
Authors: Titorenko Vladimir I. , Mullen Robert T.
Published: June 2006

Peroxisomes have long been viewed as semiautonomous, static, and homogenous organelles that exist outside the secretory and endocytic pathways of vesicular flow. However, growing evidence supports the view that peroxisomes actually constitute a dynamic endomembrane system that originates from the endoplasmic reticulum. This review highlights the various strategies used by evolutionarily diverse organisms for coordinating the flow of membrane-enclosed carriers through the peroxisomal endomembrane system and critically evaluates the dynamics and molecular mechanisms of this multistep process.
The BRAF–MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells
Authors: Sumimoto Hidetoshi , Imabayashi Fumie , Iwata Tomoko , Kawakami Yutaka
Published: June 2006

The mitogen-activated protein kinase (MAPK) pathway is frequently activated in human cancers, leading to malignant phenotypes such as autonomous cellular proliferation. Here, we demonstrate a novel role of the activated MAPK pathway in immune evasion by melanoma cells with the mutation of BRAF, which encodes a MAPKKs, (BRAFV600E). MEK inhibitor U0126 or RNA interference (RNAi) for BRAFV600E decreased production of the immunosuppressive soluble factors interleukin (IL)-10, VEGF, or IL-6 from melanoma cells to levels comparable to those after signal transducer and activator of transcription (STAT)3 inactivation. The suppressive activity of the culture supernatants from the melanoma cells on the production of inflammatory cytokines IL-12 and tumor necrosis factor α by dendritic cells upon lipopolysaccharide stimulation was markedly reduced after transduction with BRAFV600E RNAi, comparable to the effects observed with STAT3 RNAi transduction. No additive or synergistic effects were observed by the simultaneous transduction of RNAi for both BRAFV600E and STAT3. Furthermore, specific DNA binding and transcriptional activity of STAT3 were not affected by down-regulation of the MAPK signaling with the BRAF RNAi. These results indicate that the MAPK signal, along with the STAT3 signal, is essential for immune evasion by human melanomas that have constitutively active MAPK signaling and is a potential molecular target for overcoming melanoma cell evasion of the immune system.
An autosomal dominant major gene confers predisposition to pulmonary tuberculosis in adults
Authors: Baghdadi Jamila El , Orlova Marianna , Alter Andrea , Ranque Brigitte , Chentoufi Mohamed , Lazrak Faouzia , Archane Moulay Idriss , Casanova Jean-Laurent , Benslimane Abdellah , Schurr Erwin , Abel Laurent
Published: June 2006

The molecular basis of genetic predisposition to pulmonary tuberculosis in adults remains largely elusive. Few candidate genes have consistently been implicated in tuberculosis susceptibility, and no conclusive linkage was found in two previous genome-wide screens. We report here a genome-wide linkage study in a total sample of 96 Moroccan multiplex families, including 227 siblings with microbiologically and radiologically proven pulmonary tuberculosis. A genome-wide scan conducted in half the sample (48 families) identified five regions providing suggestive evidence (logarithm of the odds [LOD] score >1.17; P < 0.01) for linkage. These regions were then fine-mapped in the total sample of 96 families. A single region of chromosome 8q12-q13 was significantly linked to tuberculosis (LOD score = 3.49; P = 3 × 10−5), indicating the presence of a major tuberculosis susceptibility gene. Linkage was stronger (LOD score = 3.94; P = 10−5) in the subsample of 39 families in which one parent was also affected by tuberculosis, whereas it was much lower (LOD score = 0.79) in the 57 remaining families without affected parents, supporting a dominant mode of inheritance of the major susceptibility locus. These results provide direct molecular evidence that human pulmonary tuberculosis has a strong genetic basis, and indicate that the genetic component involves at least one major locus with a dominant susceptibility allele.
Polypyrrole-based conducting polymers and interactions with biological tissues
Authors: Ateh D.D , Navsaria H.A , Vadgama P
Published: June 2006

Polypyrrole (PPy) is a conjugated polymer that displays particular electronic properties including conductivity. In biomedical applications, it is usually electrochemically generated with the incorporation of any anionic species including also negatively charged biological macromolecules such as proteins and polysaccharides to give composite materials. In biomedical research, it has mainly been assessed for its role as a reporting interface in biosensors. However, there is an increasing literature on the application of PPy as a potentially electrically addressable tissue/cell support substrate. Here, we review studies that have considered such PPy based conducting polymers in direct contact with biological tissues and conclude that due to its versatile functional properties, it could contribute to a new generation of biomaterials.
Chirality and domain growth in the gyroid mesophase
Authors: Chin Jonathan , Coveney Peter V
Published: June 2006

We describe the first dynamical simulations of domain growth during the self-assembly of the gyroid mesophase from a ternary amphiphilic mixture, using the lattice Boltzmann method. The gyroid is a chiral structure; we demonstrate that, for a symmetric amphiphile with no innate preference for left- or right-handed morphologies, the self-assembly process may give rise to a racemic mixture of domains. We use measurements of the averaged mean curvature to analyse the behaviour of domain walls, and suggest that diffusive domain growth may be present in this system.
Adaptive radiation and hybridization in Wallace's Dreamponds: evidence from sailfin silversides in the Malili Lakes of Sulawesi
Authors: Herder Fabian , Nolte Arne W , Pfaender Jobst , Schwarzer Julia , Hadiaty Renny K , Schliewen Ulrich K
Published: June 2006

Adaptive radiations are extremely useful to understand factors driving speciation. A challenge in speciation research is to distinguish forces creating novelties and those relevant to divergence and adaptation. Recently, hybridization has regained major interest as a potential force leading to functional novelty and to the genesis of new species. Here, we show that introgressive hybridization is a prominent phenomenon in the radiation of sailfin silversides (Teleostei: Atheriniformes: Telmatherinidae) inhabiting the ancient Malili Lakes of Sulawesi, correlating conspicuously with patterns of increased diversity. We found the most diverse lacustrine species-group of the radiation to be heavily introgressed by genotypes originating from streams of the lake system, an effect that has masked the primary phylogenetic pattern of the flock. We conclude that hybridization could have acted as a key factor in the generation of the flock's spectacular diversity. To our knowledge, this is the first empirical evidence for massive reticulate evolution within a complex animal radiation.
Asteroid and comet impacts: the ultimate environmental catastrophe
Authors: Morrison David
Published: June 2006

Cosmic impacts represent the most extreme class of natural hazards, combining a very low probability of occurrence with a capability of killing hundreds of millions and destabilizing global civilization. Fortunately, these disasters are amenable to precise prediction and even (in principle) can be avoided entirely by appropriate application of space technology. However, impacts take place so rarely that they have only recently been recognized as a significant natural hazard. Concerted international action to deal with impacts depends on increased public awareness.
Cuckoos, cowbirds and hosts: adaptations, trade-offs and constraints
Authors: Krüger Oliver
Published: June 2006

The interactions between brood parasitic birds and their host species provide one of the best model systems for coevolution. Despite being intensively studied, the parasite–host system provides ample opportunities to test new predictions from both coevolutionary theory as well as life-history theory in general. I identify four main areas that might be especially fruitful: cuckoo female gentes as alternative reproductive strategies, non-random and nonlinear risks of brood parasitism for host individuals, host parental quality and targeted brood parasitism, and differences and similarities between predation risk and parasitism risk. Rather than being a rare and intriguing system to study coevolutionary processes, I believe that avian brood parasites and their hosts are much more important as extreme cases in the evolution of life-history strategies. They provide unique examples of trade-offs and situations where constraints are either completely removed or particularly severe.
Antigen-43-mediated autoaggregation impairs motility in Escherichia coli
Authors: Ulett Glen C. , Webb Richard I. , Schembri Mark A.
Published: June 2006

Functional interaction between bacterial surface-displayed autoaggregation proteins such as antigen 43 (Ag43) of Escherichia coli and motility organelles such as flagella has not previously been described. Here, it has been demonstrated for the first time that Ag43-mediated aggregation can inhibit bacterial motility. Ag43 overexpression produces a dominant aggregation phenotype that overrides motility in the presence of low levels of flagella. In contrast, induction of an increased flagellation state prevents Ag43-mediated aggregation. This phenomenon was observed in naturally occurring subpopulations of E. coli as phase variants expressing and not expressing Ag43 revealed contrasting motility phenotypes. The effects were shown to be part of a general mechanism because other short adhesins capable of mediating autoaggregation (AIDA-I and TibA) also impaired motility. These novel insights into the function of bacterial autoaggregation proteins suggest that a balance between these two systems, i.e. autoaggregation and flagellation, influences motility.
Occurrence, phylogeny and evolution of ribulose-1,5-bisphosphate carboxylase/oxygenase genes in obligately chemolithoautotrophic sulfur-oxidizing bacteria of the genera Thiomicrospira and Thioalkalimicrobium
Authors: Tourova Tatjana P. , Spiridonova Elizaveta M. , Berg Ivan A. , Kuznetsov Boris B. , Sorokin Dimitry Yu.
Published: June 2006

The occurrence of the different genes encoding ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), the key enzyme of the Calvin–Benson–Bassham cycle of autotrophic CO2fixation, was investigated in the members of the genusThiomicrospiraand the relative genusThioalkalimicrobium, all obligately chemolithoautotrophic sulfur-oxidizingGammaproteobacteria. ThecbbLgene encoding the ‘green-like’ form I RubisCO large subunit was found in all analysed species, while thecbbMgene encoding form II RubisCO was present only inThiomicrospiraspecies. Furthermore, species belonging to theThiomicrospira crunogena16S rRNA-based phylogenetic cluster also possessed two genes of green-like form I RubisCO,cbbL-1andcbbL-2. Both 16S-rRNA- andcbbL-based phylogenies of theThiomicrospira–Thioalkalimicrobium–Hydrogenovibriogroup were congruent, thus supporting its monophyletic origin. On the other hand, it also supports the necessity for taxonomy reorganization of this group into a new family with four genera.
Candida albicans SNO1 and SNZ1 expressed in stationary-phase planktonic yeast cells and base of biofilm
Authors: Uppuluri Priya , Sarmah Bhaskarjyoti , Chaffin W. LaJean
Published: June 2006

The Candida albicans homologues of the most studied Saccharomyces cerevisiae stationary-phase genes, SNO1 and SNZ1, were used to test the hypothesis that, within a biofilm, some cells reach stationary phase within continuously fed, as well as static, C. albicans biofilms grown on dental acrylic. The authors first studied the expression patterns of these two genes in planktonic growth conditions. Using real-time RT-PCR (RT-RTPCR), increased peak expression of both SNZ1 and SNO1 was observed at 5 and 6 days, respectively, in C. albicans grown in suspension culture. SNZ1–yellow fluorescent protein (YFP) and SNO1–YFP were constructed to study expression at the cellular level and protein localization in C. albicans. Snz1p–YFP and Sno1p–YFP localized to the cytoplasm with maximum expression (>90 %) at 5 and 6 days, respectively, in planktonic conditions. When yeast growth was reinitiated, loss of fluorescence began immediately. Germ tubes and hyphae were non-fluorescent. Pseudohyphae began appearing at 9 days in planktonic yeast culture and expressed each protein by 11 days; however, the cells budding from pseudohyphae were not fluorescent. Biofilm was formed in vitro under either static or continuously fed conditions. Increased expression of the two genes was shown by RT-RTPCR, beginning by day 3 and increasing through to day 15 (continuously fed biofilm). Only the bottommost layer of acrylic-adhered cells in the biofilm showed 25 and 40 % fluorescence at 6 and 15 days, respectively. These observations suggest that only a few cells in C. albicans biofilms express genes associated with the planktonic stationary phase and that these are found at the bottom of the biofilm adhered to the surface.
Osmotic stress in Synechocystis sp. PCC 6803: low tolerance towards nonionic osmotic stress results from lacking activation of glucosylglycerol accumulation
Authors: Marin Kay , Stirnberg Marit , Eisenhut Marion , Krämer Reinhard , Hagemann Martin
Published: June 2006

In order to compare the molecular principles of the acclimatization of bacterial cells to salt and nonionic osmotic stress, the moderately halotolerant cyanobacterium Synechocystis sp. PCC 6803 was challenged by salt (NaCl), and the osmolytes sorbitol and maltose. The physiological response towards each of the three compounds was found to be different. After salt addition, the cell volume remained unchanged, and the accumulation of the osmoprotective compound glucosylglycerol (GG) was observed after activation of the key enzyme GgpS at the biochemical and gene (ggpS) expression level. Sorbitol addition had only minor effects on the cell volume. In spite of the fact that the ggpS expression was increased, the GgpS enzyme was not activated, resulting in the absence of GG accumulation. In contrast the cells accumulated sorbitol, which served as a compatible solute and assured a certain osmotic resistance. In comparison to NaCl and sorbitol, the addition of maltose caused a strong decrease in cell volume indicating water efflux. However, no osmolyte accumulation was observed, resulting in an osmosensitive phenotype. Consequently, a successful response of Synechocystis cells to an osmotic challenge is indicative of the de novo synthesis of GG upon salt-dependent activation of the GgpS enzyme or the uptake of external solutes.
Identification and functional analysis of the genes for naphthalenesulfonate catabolism by Sphingomonas xenophaga BN6
Authors: Keck Andreas , Conradt Doris , Mahler Anette , Stolz Andreas , Mattes Ralf , Klein Joachim
Published: June 2006

Sphingomonas xenophagaBN6 degrades various (substituted) naphthalenesulfonates to the corresponding (substituted) salicylates. A gene cluster was identified on the plasmid pBN6 which coded for several enzymes participating in the degradative pathway for naphthalenesulfonates. A DNA fragment of 16 915 bp was sequenced which contained 17 ORFs. The genes encoding the 1,2-dihydroxynaphthalene dioxygenase, 2-hydroxychromene-2-carboxylate isomerase, and 2′-hydroxybenzalpyruvate aldolase of the naphthalenesulfonate pathway were identified on the DNA fragment and the encoded proteins heterologously expressed inEscherichia coli. Also, the genes encoding the ferredoxin and ferredoxin reductase of a multi-component, ring-hydroxylating naphthalenesulfonate dioxygenase were identified by insertional inactivation. The identified genes generally demonstrated the highest degree of homology to enzymes encoded by the phenanthrene-degrading organismSphingomonassp. P2, or the megaplasmid pNL1 of the naphthalene- and biphenyl-degrading strainSphingomonas aromaticivoransF199. The genes ofS. xenophagaBN6 participating in the degradation of naphthalenesulfonates also shared the same organization in three different transcriptional units as the genes involved in the degradation of naphthalene, biphenyl, and phenanthrene previously found inSphingomonassp. P2 andS. aromaticivoransF199. The genes were flanked inS. xenophagaBN6 by ORFs which specify proteins that show the highest homologies to proteins of mobile genetic elements.
Horizontal transfer of the immunoglobulin A1 protease gene (iga) from Streptococcus to Gemella haemolysans
Authors: Takenouchi-Ohkubo Nobuko , Mortensen Lotte M. , Drasbek Kim R. , Kilian Mogens , Poulsen Knud
Published: June 2006

Bacterial IgA1 proteases share the ability to cleave human IgA1 at the hinge region. Nature has developed this trait along at least five independent evolutionary lineages. To obtain further insight into the phylogeny and function of IgA1 proteases, the nucleotide sequence of theigagene that encodes the IgA1 protease was determined from twoStreptococcus mitisstrains and oneGemella haemolysansstrain. Heterologous expression inEscherichia coliconfirmed that the genes encode human IgA1-cleaving activity. IgA1 proteases fromStreptococcusandG. haemolysansshared structural features, including a motif typical for zinc-dependent metalloproteases of clan MA(E) family M26 and an N-terminal signal sequence followed by an LPXTG cell-wall-anchor motif and two putative membrane-spanning domains. In addition, they all harboured a repeat region preceding the active site of the protease. In the streptococcal IgA1 proteases, a G5 domain, which has been suggested to bindN-acetylglucosamine, was identified. Conservation of these structures in otherwise diverse proteases suggests that they are essential to the biological function of the enzyme. The phylogenetic distribution of homologousigagenes and conservation of gene order in theigagene region in differentStreptococcusspecies, combined with the sequence homologies, strongly suggest that theigagene is more ancient inStreptococcusthan inG. haemolysans, and therefore that the IgA1 protease gene was transferred fromStreptococcustoG. haemolysans.
Antimicrobial activity of potato aspartic proteases (StAPs) involves membrane permeabilization
Authors: Mendieta Julieta R. , Pagano Mariana R. , Muñoz Fernando F. , Daleo Gustavo R. , Guevara María G.
Published: June 2006

Solanum tuberosumaspartic proteases (StAPs) with antimicrobial activity are induced after abiotic and biotic stress. In this study the ability ofStAPs to produce a direct antimicrobial effect was investigated. Viability assays demonstrated thatStAPs are able to kill spores ofFusarium solaniandPhytophthora infestansin a dose-dependent manner. Localization experiments with FITC-labelledStAPs proved that the proteins interact directly with the surface of spores and hyphae ofF. solaniandP. infestans. Moreover, incubation of spores and hyphae withStAPs resulted in membrane permeabilization, as shown by the uptake of the fluorescent dye SYTOX Green. It is concluded that the antimicrobial effect ofStAPs againstF. solaniandP. infestansis caused by a direct interaction with the microbial surfaces followed by membrane permeabilization.
Proteus mirabilis isolates of different origins do not show correlation with virulence attributes and can colonize the urinary tract of mice
Authors: Sosa Vanessa , Schlapp Geraldine , Zunino Pablo
Published: June 2006

Proteus mirabilis has been described as an aetiological agent in a wide range of infections, playing an important role in urinary tract infections (UTIs). In this study, a collection of P. mirabilis isolates obtained from clinical and non-clinical sources was analysed in order to determine a possible correlation between origin, virulence factors and in vivo infectivity. Isolates were characterized in vitro, assessing several virulence properties that had been previously associated with P. mirabilis uropathogenicity. Swarming motility, urease production, growth in urine, outer-membrane protein patterns, ability to grow in the presence of different iron sources, haemolysin and haemagglutinin production, and the presence and expression of diverse fimbrial genes, were analysed. In order to evaluate the infectivity of the different isolates, the experimental ascending UTI model in mice was used. Additionally, the Dienes test and the enterobacterial repetitive intergenic consensus (ERIC)-PCR assay were performed to assess the genetic diversity of the isolates. The results of the present study did not show any correlation between distribution of the diverse potential urovirulence factors and isolate source. No significant correlation was observed between infectivity and the origin of the isolates, since they all similarly colonized the urinary tract of the challenged mice. Finally, all isolates showed unique ERIC-PCR patterns, indicating that the isolates were genetically diverse. The results obtained in this study suggest that the source of P. mirabilis strains cannot be correlated with pathogenic attributes, and that the distribution of virulence factors between isolates of different origins may correspond to the opportunistic nature of the organism.
Expression of the Giardia lamblia cyst wall protein 2 in Lactococcus lactis
Authors: Lee Peter , Faubert Gaétan M.
Published: June 2006

In this study, Lactococcus lactis was engineered to express Giardia lamblia cyst wall protein 2 (CWP2) at three different subcellular locations, intracellular, secreted or cell-surface-anchored, using nisin as an inducing agent. CWP2 expression did not appear to be detrimental to L. lactis viability. No particular subcellular location of CWP2 expression offered any advantages over the others with respect to decreased toxicity towards the bacteria. All recombinant lactococci experienced a similar reduction in growth rate when induced. It was determined whether recombinant lactococcal cells engineered for cell surface expression of CWP2 were capable of inducing a CWP2-specific mucosal IgA antibody response. Recombinant lactococci were successful at inducing CWP2-specific IgA antibodies. Moreover, in a pilot challenge experiment, mice immunized with these recombinant lactococci demonstrated a significant (63 %) reduction in cyst output. Thus, it has been demonstrated that G. lamblia CWP2 may be expressed in L. lactis and that recombinant lactococcal cells elicit Giardia-specific antibodies which reduce cyst shedding in a murine model.
A screening system for carbon sources enhancing β-N-acetylglucosaminidase formation in Hypocrea atroviridis (Trichoderma atroviride)
Authors: Seidl Verena , Druzhinina Irina S. , Kubicek Christian P.
Published: June 2006

To identify carbon sources that trigger β-N-acetylglucosaminidase (NAGase) formation in Hypocrea atroviridis (anamorph Trichoderma atroviride), a screening system was designed that consists of a combination of Biolog Phenotype MicroArray plates, which contain 95 different carbon sources, and specific enzyme activity measurements using a chromogenic substrate. The results revealed growth-dependent kinetics of NAGase formation and it was shown that NAGase activities were enhanced on carbon sources sharing certain structural properties, especially on α-glucans (e.g. glycogen, dextrin and maltotriose) and oligosaccharides containing galactose. Enzyme activities were assessed in the wild-type and a H. atroviridis Δnag1 strain to investigate the influence of the two NAGases, Nag1 and Nag2, on total NAGase activity. Reduction of NAGase levels in the Δnag1 strain in comparison to the wild-type was strongly carbon-source and growth-phase dependent, indicating the distinct physiological roles of the two proteins. The transcript abundance of nag1 and nag2 was increased on carbon sources with elevated NAGase activity, indicating transcriptional regulation of these genes. The screening method for the identification of carbon sources that induce enzymes or a gene of interest, as presented in this paper, can be adapted for other purposes if appropriate enzyme or reporter assays are available.
Ultrastructure and gliding motility of Mycoplasma amphoriforme, a possible human respiratory pathogen
Authors: Hatchel Jennifer M. , Balish Rebecca S. , Duley Matthew L. , Balish Mitchell F.
Published: June 2006

Despite their small size and reduced genomes, many mycoplasma cells have complex structures involved in virulence. Mycoplasma pneumoniae has served as a model for the study of virulence factors of a variety of mycoplasma species that cause disease in humans and animals. These cells feature an attachment organelle, which mediates cytadherence and gliding motility and is required for virulence. An essential component of the architecture of the attachment organelle is an internal detergent-insoluble structure, the electron-dense core. Little information is known regarding its underlying mechanisms. Mycoplasma amphoriforme, a close relative of both M. pneumoniae and the avian pathogen Mycoplasma gallisepticum, is a recently discovered organism associated with chronic bronchitis in immunosuppressed individuals. This work describes both the ultrastructure of M. amphoriforme strain A39T as visualized by scanning electron microscopy and the gliding motility characteristics of this organism on glass. Though externally resembling M. gallisepticum, M. amphoriforme cells were found to have a Triton X-100-insoluble structure similar to the M. pneumoniae electron-dense core but with different dimensions. M. amphoriforme also exhibited gliding motility using time-lapse microcinematography; its movement was slower than that of either M. pneumoniae or M. gallisepticum.
Isolation of salt-sensitive mutants of Sinorhizobium meliloti strain Rm1021
Authors: Miller-Williams Mark , Loewen Peter C. , Oresnik Ivan J.
Published: June 2006

The determinants necessary for adaptation to high NaCl concentrations and competition for nodule occupancy inSinorhizobium melilotiwere investigated genetically. Mutations infabGas well assmc02909(transmembrane transglycosylase), trigger factor (tig) andsmc00717(probablyftsE) gave rise to strains that were unable to tolerate high salt and were uncompetitive for nodule occupancy relative to the wild-type. MoreoverexoF1,exoAandpgmdeterminants were determined to be necessary for strain Rm1021 to survive high NaCl and/or MgCl2concentrations. The introduction of anexpR+allele was capable of suppressing the Mg2+sensitivity associated with theexoF1, but not theexoA, mutation in a manner independent of exopolysaccharide II (EPS II)-associated mucoidy. The results also show that the EPS II-associated mucoid phenotype was affected by either Mg2+or K+, but not by Li+, Ca2+, or high osmolarity.
Global gene expression in Escherichia coli K-12 during short-term and long-term adaptation to glucose-limited continuous culture conditions
Authors: Franchini Alessandro G. , Egli Thomas
Published: June 2006

Microarray technology was used to study the cellular events that take place at the transcription level during short-term (physiological) and long-term (genetic) adaptation of the faecal indicator bacterium Escherichia coli K-12 to slow growth under limited nutrient supply. Short-term and long-term adaptation were assessed by comparing the mRNA levels isolated after 40 or 500 h of glucose-limited continuous culture at a dilution rate of 0.3 h−1 with those from batch culture with glucose excess. A large number of genes encoding periplasmic binding proteins were upregulated, indicating that the cells are prepared for high-affinity uptake of all types of carbon sources during glucose-limited growth in continuous culture. All the genes belonging to the maltose (mal/lamB) and galactose (mgl/gal) operons were upregulated. A similar transcription pattern was observed for long-term cultures except that the expression factors were lower than in the short-term adaptation. The patterns of upregulation were confirmed by real-time RT-PCR. A switch from a fully operational citric acid cycle to the PEP-glyoxylate cycle was clearly observed in cells grown in glucose-limited continuous culture when compared to batch-grown cells and this was confirmed by transcriptome analysis. This transcriptome analysis confirms and extends the observations from previous proteome and catabolome studies in the authors' laboratory.
Identifying systems' new initial conditions as influence points for the future
Authors: Aaltonen Mika , Irene Sanders T.
Published: June 2006

Purpose

The purpose of this research paper is to review and contrast traditional foresight methods through the lens of one of the key insights about complex adaptive systems – namely, a system's sensitive dependence on initial conditions.

Design/methodology/approach

Foresight methods have often been criticized about their linear way of looking at the future. Insights from complex adaptive systems research, however, provide a new theory‐driven approach for developing real foresight methods as opposed to traditional forecasting methods based primarily on linear extrapolation. This serves as a starting point for the re‐analysis and re‐classification of the foresight methods, presented profoundly in the American Council for the United Nation's University Millennium Project's Futures Research Methodology – V2.0.

Findings

The findings of the analysis show which foresight methods actually present the future as a continuation of the present, and which instead are able to identify a system's new and emerging initial conditions; and what kind of possible understanding of the system the methods offer to the user.

Research limitations/implications

This research paper provides a new perspective to reopen the discussion about the necessary qualities of foresight methods. This paper argues that instead of trying to forecast the future the foresight methods should help us to see and influence the future as it is emerging.

Practical implications

Discussion and guidelines for methodological work and an introduction of complex systems concept‐tools map, a new set of methods and the way how it could be used together with Futures Research Methodology – V2.0 represent vast implications for organizations' foresight practices.

Originality/value

The origins of novelty are two: the complex adaptive systems perspective to discuss foresight methods, and the presentation of the new set of methods to support and complement Futures Research Methodology – V2.0.
Constructing and using scenarios to forecast demand for future mobile communications services
Authors: Forge Simon , Blackman Colin , Bohlin Erik
Published: June 2006

Purpose

Aims to present a pragmatic method for long‐term forecasting and to illustrate its usage with the results of a recent case study to forecast future demand for mobile communications services.

Design/methodology/approach

A scenario construction methodology is explained in detail. The case material presented here is drawn from a forecasting exercise for the European Commission between September 2004 and April 2005 examining potential demand for mobile communications services up to 2020.

Findings

The formalized method and a synopsis of the actual scenarios generated in the case study are given here in outline. The paper also indicates how needs analysis was used in conjunction with the scenarios to generate a list of potential services and their use, which formed the basis of detailed traffic estimates. Certain aspects of the method and its results have been incorporated by the ITU working committees into their detailed preparations for the World Radiocommunication Conference's negotiations in 2007.

Research limitations/implications

This paper can only give a brief description of the scenarios and provides only limited detail on how the scenarios were subsequently used to generate forecasts of demand for mobile communication services.

Originality/value

The paper demonstrates a socio‐economic forecasting method based on scenarios and their use in forecasting demand within the telecommunications sector.
Lipopolysaccharide exposure makes allergic airway inflammation and hyper‐responsiveness less responsive to dexamethasone and inhibition of iNOS
Authors: Komlósi Z. I. , Pozsonyi É. , Tábi T. , Szökő É. , Nagy A. , Bartos B. , Kozma G. T. , Tamási L. , Orosz M. , Magyar P. , Losonczy G.
Published: June 2006

Allergic airway disease can be refractory to anti‐inflammatory treatment, whose cause is unclarified. Therefore, in the present experiment, we have tested the hypothesis that co‐exposure to lipopolysacharide (Lps) and allergen results in glucocorticoid‐resistant eosinophil airway inflammation and hyper‐responsiveness (AHR). Ovalbumin (Ova)‐sensitized BALB/c mice were primed with 10 μg intranasal Lps 24 h before the start of Ova challenges (20 min on 3 consecutive days). Dexamethasone (5 mg/kg/day) was given on the last 2 days of Ova challenges. AHR, cellular build‐up, cytokine and nitrite concentrations of bronchoalveolar lavage fluid (BALF) and lung histology were examined. To assess the role of iNOS‐derived NO in airway responsiveness, mice were treated with a selective inhibitor of this enzyme (1400W) 2 h before AHR measurements. More severe eosinophil inflammation and higher nitrite formation were found in Lps‐primed than in non‐primed allergized mice. After Lps priming, AHR and concentrations of T‐helper type 2 cytokines in BALF were decreased, but still remained significantly higher than in controls. Eosinophil inflammation was partially, while nitrite production and AHR were observed to be largely dexamethasone resistant in Lps‐primed allergized animals. 1400W effectively and rapidly diminished the AHR in Ova‐sensitized and challenged mice, but failed to affect it after Lps priming plus allergization. In conclusion, Lps inhalation may exaggerate eosinophil inflammation and reduce responsiveness to anti‐inflammatory treatment in allergic airway disease.
Exploiting the potential of routine data to better understand the disease burden posed by allergic disorders
Authors: Anandan C. , Simpson C. R. , Fischbacher C. , Sheikh A.
Published: June 2006

The Department of Health and Scottish Executive are currently undertaking independent reviews of allergy services in England (and Wales) and Scotland. Each review will assess the disease burden posed by allergic problems, involving secondary analyses of routine National Health Service (NHS) datasets. Major suggestions for re‐structuring and/or re‐focusing the NHS efforts to better deal with allergic disease are anticipated. The UK has some of the best datasets of routine health data in the world, but despite their strengths, they have important limitations. These include gaps in data collection, particularly in relation to monitoring of Accident & Emergency and out‐patient consultations, and in‐patient prescribing, thereby resulting in considerable under‐estimates of hospital workload. The current gaps in service monitoring are likely to under‐estimate the burden and workload associated with allergic problems, particularly in secondary care. One major limitation of existing data sources is the general inability to link individual patient level data between different datasets. By unlocking this potential there are very considerable potential gains to be made. Data linkage techniques currently being developed in the UK offer exciting new possibilities of looking across the primary‐, secondary‐ and tertiary‐care interfaces and also assessing short‐and long‐term social and educational outcomes in relation to allergic disorders. The current reviews of allergy services being undertaken need to be cognisant of these inherent limitations of existing data sources and would do well to recommend strategic initiatives that could enhance the availability, accessibility and quality of these datasets. Ideally, this should include investment in central data repositories staffed by teams with the necessary technical and statistical expertise, which would also take responsibility for progressing data linkage capabilities.
Follistatin is a candidate endogenous negative regulator of activin A in experimental allergic asthma
Authors: Hardy C. L. , O'Connor A. E. , Yao J. , Sebire K. , De Kretser D. M. , Rolland J. M. , Anderson G. P. , Phillips D. J. , O'Hehir R. E.
Published: June 2006

Background
Activin A is a member of the transforming growth factor‐β superfamily which is directly implicated in airway structural change and inflammation in asthma. In vitro, the biological effects of activin A are neutralized by the soluble binding protein follistatin.

Objective
To determine the potential of endogenous follistatin to suppress activin A in vivo by analysing their relative tissue and kinetic compartmentalization during the effector phase of subchronic Th2‐driven mucosal inflammation in a murine model of allergic asthma.

Methods
Eosinophilic mucosal inflammation was elicited by triggering Th2 recall responses by antigen challenge in ovalbumin‐sensitized BALB/c mice. The kinetics and distribution of activin A and follistatin protein were assessed in lung tissue and bronchoalveolar lavage fluid and measured in relation to airway eosinophilia, goblet cell metaplasia and Th2 cytokine production in mediastinal lymph nodes.

Results
Follistatin was released concurrently with activin A suggesting it acts as an endogenous regulator: peak BAL concentrations coincided with maximal airway eosinophilia, and frequency of IL‐4, IL‐5 and IL‐13 producing cells in mediastinal lymph nodes but induction lagged behind the onset of inflammation. Follistatin and activin A immunoreactivity were lost in airway epithelial cells in parallel with goblet cell metaplasia. Exogenous follistatin inhibited the allergen‐specific Th2 immune response in mediastinal lymph nodes and mucus production in the lung.

Conclusion
Follistatin is preformed in the normal lung and released in concert with activin A suggesting it serves as an endogenous regulator. Disturbance of the fine balance between activin A and its endogenous inhibitor follistatin may be a determinant of the severity of allergic inflammation or tissue phenotypic shift in asthma.
Advances in the pathology of COPD
Authors: Wright J L , Churg A
Published: June 2006

Chronic obstructive pulmonary disease encompasses alterations in the parenchyma, airways and vascular compartments. This review is designed to help surgical pathologists evaluate the lungs of subjects who have clinical manifestations of airflow obstruction so that appropriate clinical–pathological correlations can be performed.
Gastric mucin phenotype defines tumour progression and prognosis of intrahepatic cholangiocarcinoma: gastric foveolar type is associated with aggressive tumour behaviour
Authors: Aishima S , Kuroda Y , Nishihara Y , Taguchi K , Taketomi A , Maehara Y , Tsuneyoshi M
Published: June 2006

Aims : To identify the role of mucus core protein (MUC) in intrahepatic cholangiocarcinoma (ICC).

Methods and results : We examined the expression profile of MUC2, MUC5AC and MUC6 by immunohistochemical staining in 100 ICCs and compared the clinicopathological factors and the immunohistochemical results. The expression frequency was: MUC2, 9%; MUC5AC, 40%; and MUC6, 21%. According to the gastric mucin expression profile, ICCs were classified into the following groups: null type (n = 43), gastric foveolar type (n = 36), pyloric gland type (n = 11) and gastric combined type (n = 10). Half of the gastric foveolar type and the gastric combined type were located in the hilar region, but the other types were predominant at the periphery (P = 0.0004). Well‐differentiated components were more often detected in the gastric combined type and the pyloric gland type (P = 0.0281). The gastric foveolar type was associated with a higher incidence of lymph node metastasis (P < 0.0001). The pyloric gland type was associated with better survival and the gastric foveolar type was associated with worse survival. The gastric mucin phenotype was an independent prognostic factor by multivariate survival analysis.

Conclusion : The gastric foveolar type of ICC was more often associated with aggressive tumour development, whereas the pyloric gland type exhibited less aggressive behaviour.
The relation of pepsinogen group II (PGII) expression to intestinal metaplasia and gastric cancer
Authors: Stemmermann G N , Nomura A M Y
Published: June 2006

Aims : A substantial minority of intestinal metaplasia (IM)‐associated stomach cancers express a gastric product—pepsinogen group II (PGII). The aim of this study was to examine PGII expression as it relates to IM and to tumour heterogeneity.

Methods and results : The extent of IM was divided into four levels: none, minimal, moderate, extensive. Stomach specimens (N = 165) were stained for PGII and two tumour markers, epidermal growth factor receptor (EGFr) and p53. PGII was more likely to be expressed with moderate or extensive IM than with minimal or no IM (P = 0.05). Cancers that expressed PGII were more likely to be of high stage than those that did not (P = 0.035). Of 25 cases that expressed all three markers (PGII, EGFr, p53), 20 (80%) had stage 3 or 4 disease, compared with 11 (37%) advanced cancers expressing none of the markers (P = 0.001). Cancers expressing one or two markers were between these extremes.

Conclusions : PGII+ cancers in IM‐associated gastric cancers may derive from residual gastric glands, or may arise from postinduction reversion to a gastric phenotype from intestinalized cells. This is supported by the more frequent association of PGII expression with the most extensive degrees of IM and its association with high‐stage cancers that display heterogeneity in tumour marker expression.
Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast
Authors: Fulford L G , Easton D F , Reis‐Filho J S , Sofronis A , Gillett C E , Lakhani S R , Hanby A
Published: June 2006

Aims : Cytokeratin (CK) 14, a myoepithelial marker, is also expressed in a proportion of breast carcinomas. There is evidence that these tumours show a differing metastatic pattern and clinical outcome from other invasive ductal carcinomas (IDCs) and may need different management. Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC.

Methods and results : A detailed histological review of 453 grade 3 IDCs revealed 88 (19.4%) that expressed CK14. Assessment was made independently by two pathologists using a standardized ‘tick‐box’ proforma covering grade, architectural and cytological features. The results were analysed using logistic regression to identify features that predicted for basal phenotype. Concordance between the two pathologists was fair to good for most parameters (κ 0.4–0.6). On multiple logistic regression, the basal phenotype was highly significantly associated with the presence of a central scar (P = 0.005), tumour necrosis (P < 0.0001), presence of spindle cells (P = 0.006) or squamous metaplasia (P < 0.0001), high total mitotic count (> 40 per 10 high‐power field) (P = 0.0002) and high nuclear–cytoplasmic ratio (P = 0.0002).

Conclusions : Specific morphological features are strongly associated with basal‐like breast carcinoma. These could be used in routine diagnostic practice to identify this important subset of tumours.
Extracellular superoxide dismutase has a highly specific localization in idiopathic pulmonary fibrosis/usual interstitial pneumonia
Authors: Kinnula V L , Hodgson U A , Lakari E K , Tan R J , Sormunen R T , Soini Y M , Kakko S J , Laitinen T H , Oury T D , Pääkkö P K
Published: June 2006

Aims : Recent studies suggest the importance of oxidant stress in the progression of pulmonary fibrosis. The aim of this study was to investigate extracellular superoxide dismutase (ECSOD), the major antioxidant enzyme of the extracellular matrix of human lung, in biopsy‐proven idiopathic pulmonary fibrosis (IPF) related to usual interstitial pneumonia (UIP).

Methods and results : Fibrotic areas and fibroblastic foci in UIP lungs were notable for absence of ECSOD by immunohistochemistry. Western blotting showed significantly lowered immunoreactivity of ECSOD in fibrotic compared with non‐fibrotic areas of the diseased lung. The only cell type that showed intense ECSOD positivity in UIP was the interstitial mast cell. In order to investigate the mechanism for ECSOD depletion in fibrotic areas, alveolar epithelial cells were exposed to tumour necrosis factor‐α and transforming growth factor (TGF)‐β1; TGF‐β suggested a trend towards decreased synthesis. Patients with UIP were also assessed to determine whether this disease is associated with a naturally occurring mutation in ECSOD (Arg213Gly) which leads to a loss of tissue binding of ECSOD. No significant differences could be found in the allele or genotype frequencies of this polymorphism between 63 UIP patients and 61 control subjects.

Conclusion : Overall, consistent with several other antioxidant enzymes, ECSOD is very low in fibrotic areas of UIP, which may further increase the oxidant burden in this disease.